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In Silico Design: Those Accentuate Assembly of HIV-1 Capsid-Juniper Publishers

JUNIPER PUBLISHERS-OPEN ACCESS JOURNAL OF DRUG DESIGNING & DEVELOPMENT

Abstract

Considering the significance of RNA genome in the HIV infection, its release can be forbidden by inhibiting encapsulated Capsid (CA) "core". In this context, design of new molecules that interact with HIV-1 CA assembly was made by conducting 3D-QSAR and Pharmacophore studies on a stockpile of fifty eight molecules. The supramolecular interactions of these inhibitors with the receptors active site amino acids Glu 35, Gly 60, His62, Gln 63, Ala 65, and Val 136 has been characterized using docking studies. The combined five point Pharmacophore hypothesis AHHRR, and 3D-QSAR CoMFA (Comparative molecular field analysis) and CoMSIA (Comparative molecular similarity indices analysis) has shown good statistical partial least square factors. The association of generated 3D-QSAR and PHASE pharmacophore hypothesis has provided structural insights to explore new molecules with enhanced CA assembly activity.

Keywords:     Human immunodeficiency Virus type-1 (HIV-1); Capsid protein (CA); Common pharmacophore hypothesis (CPHs); Pharmacophore alignment and scoring engine (PHASE); Comparative molecular field analysis (CoMFA); Comparative molecular similarity indices analysis (CoMSIA) emphasize   

Introduction

Capsid protein (CA) of Human immunodeficiency Virus type- 1 (HIV-1) is a fullerene cone accomplished with approximately 250 hexamers and 12 pentamers that plays a prominent role in the initial stages of post host cell entry and in virus assembly [1-4]. Proteolytic cleavage of Gag (Matrix, Capsid and Nucleo capsid) polyprotein releases CA which reassembles to form a conical "core" that encloses the viral RNA genome [5-7]. The assembly process of CA protein is associated with the N-terminal domain (CANTD residues 1-145) and C-terminal domain (CACTD residues 151-231). The CANTD aid in virion maturation by self associating into hexameric rings and incorporation of the cellular protein cyclophilin A (CypA). While CACTD contributes to Gag-Gag interactions [8-10]. Once the virus enters the cell, the core disassembles and releases ribonucleoprotien complex, resulting in the formation of reverse transcription complexes [11-14]. However, virions with deformed core structured are defective in initiating reverse transcription and exhibit reduced infectivity [15]. It is believed that the N-terminus of CA can refold to form a new y-hairpin helix by cleavage of CA from matrix protein (MA), which is stabilized by a buried salt bridge between Proline-1 of CA and the carboxyl side chain of Asp51. The renovation from tubular to spherical forms can be induced by changing the pH from 7.0 to 6.8 [16,17]. Several small molecule inhibitors like CAP-1, NYAD-1 a peptide inhibitor, bevirimat, a triterpene derivative have been reported to interfere with CA function on binding to the N-terminal domain of CA in both its mature and immature forms [18-25]. Pharmacophore mapping was performed by using Pharmacophore Alignment and Scoring Engine (PHASE) to evaluate features necessary for the ligand to interact with a receptor [26]. The pharmacophore may be used as a query in searching 3D databases containing "drug like" small organic molecules and also aid in exploring and engineering of new scaffold with high potency [27]. To investigate the mode of recognition and interaction mechanism of HIV-1 CA inhibitors with CA protein, molecular docking studies are performed. Further 3D-QSAR studies were performed by using CoMFA and CoMSIA analysis.   

Methodology

Ligand construction and preparation

A stockpile of fifty eight 1,5-dihydrobenzo[b][1,4]diazepine- 2,4-dione derivatives [28-30] (Figure 1) with their experimental information were collected from the literature. Outlining the three dimensional structures of these ligands using Maestro build panel in Schrodinger Suite, all possible low energy states are generated at physiological pH range of 7 +/- 2 in the Ligprep module of Schrödinger.

Generation ofthe common pharmacophore hypothesis (CPH)

The pharmacophore hypothesis and alignment were carried out by PHASE [31] (version 2.5, 2011; Schrodinger, LLC, New York, NY). Considering the significance of EC50 in biological activity [32,33] and we have converted E C50 into the corresponding pEC50 (-logE C50), and randomly selected thirty five molecules as training set to generate Pharmacophore models. PHASE defines chemical features of ligand that facilitate non covalent bonding between the ligand and target receptor. PHASE models are created by applying Partial Least Squares (PLS) regression. The accuracy of the models improves with an increase in the number of PLS factors [34]. The PLS regression analysis was carried out using three PLS factors and possible statistical parameters are evaluated. The test set predictions were described as Q2 root mean squared error and Pearson correlation coefficient (R) value. The regression value is calculated using the formula;

Where are the average observed and predicted pEC50 values of the test set molecules.

(Figure1).

Docking studies

The X-ray structure of CANTD in complex with the benzodiazepine inhibitor (PDB: 4E91) [35] was retrieved from Protein Data Bank (http://www.rcsb.org/). Protein was prepared by using protein preparation wizard in Schrodinger. [36] GLIDE 5.6 (Grid-based ligand docking with energies) docking was performed by generating a grid (10 Å x10 Å x10 Å) around the active site of capsid assembly inhibitor. Rigid receptor docking protocols of Glide, namely Standard Precision (SP) and Extra Precision (XP) were employed to gain insight into the binding modes of all inhibitors. Further, to account for the receptor flexibility, a computationally intensive Induced Fit Docking (IFD) was performed. To validate the docking protocol, co-crystallized ligand benzodiazepinedione was re-docked and its atomic root mean square deviation (RMSD) was calculated [37-39].

Prime/MM-GBSA calculations

The relative binding free energies for best ranking molecules in XP mode are calculated by Molecular Mechanics Generalized Born Surface Area (MM/GBSA) using Prime. The dock pose features that are locally optimized features from glide were minimized from prime and complex energies were calculated using OPLS_2005 force field. The relative binding free energy ΔGbind was estimated according to equation.

ΔGbind=Ecomplex (minimized)-[Eligand (unbound, minimized) + Ereceptor (unbound, minimized)]

ΔGbind is the calculated relative free energy which includes both ligand and receptor strain energy. Ecomplex (minimized) is MM-GBSA energy of the minimized complex, Eligand (unbound, minimized) is the MM-GBSA energy of the ligand after removing it from the complex and allowing it to relax. Ereceptor (unbound, minimized) is the MM-GBSA energy of protein after separating it from the ligand.

CoMFA and CoMSIA Models

CoMFA and CoMSIA studies are performed by aligning data set molecules and are evaluated for thier steric, electrostatic and hydrogen bond effect on bioactivities using SYBYLX-2.1[40,41]. Gasteiger Huckle charges were assigned for all the inhibitors [42]. For CoMFA, the overlapped molecules were placed in a rectangular grid points separated by 2 A. The van der Waals potential and columbic terms, representing the steric and electrostatic fields, were calculated using standard Tripos force field [43]. The regression analysis was carried out using set of variables, and cross validated the PLS method (leave-one-out). The final model (noncross-validated conventional analysis) was developed with the optimal number of components which poses the highest q2 value.

For CoMSIA, five physicochemical properties namely steric, electrostatic, hydrophobic, hydrogen bond donor and acceptor were calculated. The CoMFA or CoMSIA descriptors were used as independent variables and pEC50 values as dependent variables in partial least square analysis. [34] The predictive correlation coefficient (r2pred ) based on the test molecules, is computed with the formula r2pred = (SD-PRESS)/SD, where SD is the sum of the squared deviations between the biological activities of test set and mean activities of the training set molecules. PRESS is the sum of squared deviation between predicted and observed activity for each molecule in the test set.

ADME prediction

The ADME (absorption, distribution, metabolism and excretion) properties of designed molecules were evaluated computationally using Qik Prop module of Schrodinger [44]. The physically significant descriptors and pharmaceutically relevant properties of organic molecules with compliance to Lipinski's rule of five were calculated by Qik prop.   

Results and Discussion

The hexameric architecture of capsid relay on three basic type of interactions. (i) CANTD-CANTD six fold symmetric interfaces that create the hexameric rings [45]. (ii) CANTD- CACTD intermolecular interface that reinforces the hexamer [8-10] and (iii) CACTD-CACTD dimeric interface that links the hexameric rings to form the lattice [46-50]. The current study is mainly focused on hexamer formation of CA by disrupting the intermolecular interaction of CANTD and hence in silico methods employed are restricted to N-terminal domain only. The X-ray crystal structure (4E91) of HIV-1 CANTD is a single chain containing the N-terminal domain. Sundquist reported intermolecular N-terminal domain interactions between Phe-32, Glu35, Gly60, His62, Gln63, and Ala65 residues of helices 1 and 2 [51]. The perturbation of intermolecular N-terminal domain interaction involves in disruption of NTD-NTD interaction and hence inhibits CA assembly [52].

Pharmacophore generation

PHASE analysis for a set of 58 molecules derived five point CPHs belonging to AHHRR, AHRRR. Thirty five molecules in the training set were aligned on these CPHs and evaluated for PLS analysis using three PLS factors. The predictivity of each hypothesis was cross validated by the test set of twenty three molecules. The variants named AHHRR (model A1) and AHRRR (model B1) in Figure 2 showed better statistical significance than AHHRR (A2), AHHRR (A3) and AHHRR (A4). Since all the five pharmacophore hypothesis capitulate a statistically significant data as shown in Table 1, the hypothesis AHHRR (A1) with good survival score 3.549, with significant R2 of 0.926 and Q2 of 0.824 was considered in this work. From the above results it is confirmed that the obtained PHASE model (r2 > 0.5, q2 > 0.6, [(r2- r02)/r2 < 0.1, 0.85 ≤ k ≤ 1.15 and rm2 > 0.5) was in the acceptable range.

The hydrogen bond acceptor A2, and the phenyl ring R12 was found to be significant for the activity. The carbonyl group at second position can form hydrogen bond interaction with His 62 residue in the active site, while the aromatic ring at third position contributes to hydrophobicity. The hypothesis AHHRR (AJ was fit into the molecular skeleton of highest active molecule of capsid assembly inhibitor 50g. The distance and angles between the five features of the best two models AHHRR (AJ and AHRRR (BJ are shown in Table 1 & 2 (provided in supplementary data). The pharmacophore model implies that molecules which would fit the AHHRR (A1) sites may consequence in stronger interactions with the active site residues. The distance and the angle maps of the best two models are represented in Figure S1 given in supplementary data. The field contribution (blue and red cube contours) of the best two models are represented in Figure 3. The blue cubes represent that substitution of hydrophobic favored groups while red cubes represent disfavored region. Scatter plot of experimental and phase predicted pEC50 is shown in (Figure 2-4) (Table 1).

A-Hydrogen bond acceptor, H- Hydrophobic/non-polar group, R- Aromatic ring, R2-correlation coefficient, F- variance ratio, Q2-predicted activities for training set, SD- standard deviation of regression.

Molecular docking studies and Prime MM/GBSA calculations

To evaluate the validity of docking protocol, root mean square deviation (RMSD) calculations were performed. The crystal ligand was haul out from the complex (PDB id: 4E91) and subsequently re-docked into the receptor. Best dock pose from docking studies differ from the original conformation by 0.216 A, substantiating the robustness of docking protocol to enumerate the experimental binding mode. Figure 5 shows the overlay of the X-ray crystal structures (colored in cyan) of capsid assembly inhibitor and the re-docked pose (colored in plum) (Figure 5).

Fifty eight molecules with benzodiazepine scaffold which were reported to exhibit inhibitory effect on assembly process of HIV-1 capsid (Figure 1) are chosen for docking studies. The binding orientation of these has shown hydrogen bond interactions with Glu35, Gly60, His 62, Gln 63, Ala 65, Val 135 and Tyr 145 amino acid residues and are said to exhibit HIV-1 replication with a novel mechanism of action [52]. This compounds bind to the N-terminal domain (NTD) of the viral capsid protein (CA) and is believed to prevent its ensemble into conical core that is trivial for virion maturation and viral infectivity [53].

The hydrogen bond interaction with His 62 and Phe 32 residues of helices 1 and 2 are plays a crucial role since they hinder the hexameric lattice organization by interrupting intermolecular N-terminal interaction. SP dock pose of highest active molecule 50g display polar H-bond interaction with His 62 (Figure 6a), while XP dock pose exhibit additional n-n stacking interaction with Phe 32. (Figure 6b) The IFD dock pose for the same 50g molecule reveal polar hydrogen bonding interaction with Phe 32 and His 62 residues (Figure 6c). Application of different docking protocols i.e., SP, XP and IFD resulted in variable dock scores, of which IFD has shown more refined scores. Increase in dock scores in IFD protocol is possibly due to additional flexibility attributed to the protein, which allow more interactions with active site residues. However, some deviations have been observed in IFD scores of 45f and 53h which were lower than XP dock scores which might be due to steric clashes.

The relative binding affinities of protein ligand complexes were assessed by Molecular mechanics with generalized born surface area (MM/GBSA). The ΔGbind value of highest active molecule 50g was found to be -134.50 that is slightly higher than the lead molecule 54 which was screened through CA assembly assay. It is imperative to evaluate statistical correlation between the different computational parameters and experimental pEC50 values to validate the applicability of in silico studies in predicting the HIV-1 CA inhibitors. These inhibitors showed a statistically significant correlation of -0.579 for XP docking, -0.614 for prime MMGBSA (Figure 7). The list of inhibitors along with their pEC50, SP, XP and IFD dock scores, ΔGbind values from PRIME along with predicted CoMFA and CoMSIA values have been tabulated in Table 2.

(SP, XP, IFD) and binding energy (ΔGbind).

*test set molecules.

3D-QSAR model

The 3D-QSAR CoMFA and CoMSIA analysis was performed by aligning the dock poses of all fifty eight molecules (Figure 8). A training set of thirty five molecules (which has been selected for generating PHASE models) were also chosen for constructing CoMFA and CoMSIA models. The best predictions were obtained with CoMFA standard model q2 value of 0.607, r2 value of 0.968 and CoMSIA with q2 value of 0.616 and r2 value of 0.954 respectively. The predictivity of the model was cross validated by the test set of twenty three molecules. The predictive correlation coefficient r2 pred of 0.576 for CoMFA and 0.528 for CoMSIA explains good predictive ability of the models. The scatter plot of actual and predicted pEC50 values for training and test set of CoMFA and CoMSIA studies are shown in Figure 9a and Figure 9b. The results of CoMFA and CoMSIA are listed in Table 3.

q2 = correlation coefficient from leave one out method.ONC = Optimum number of components, SEE=Standard error of estimate, F = Fisher value, r2Pred= predictive r2 on test set.

CoMFA and CoMSIA contour maps

To visualize the information derived from the 3D-QSAR models, contour maps were generated. The contour plots are representation of the lattice points in the grid and the difference in the lattice points is strongly connected with the difference in the receptor binding affinity. Whereas molecular fields defines the favorable and unfavorable interaction energies of aligned molecules with a probe atom traversing across the lattice points, suggesting the modification required to design new potent molecules.

The CoMFA contours indicate the region in space where the molecule would favorably or unfavorably interact with the receptor, while CoMSIA contours indicate the areas within the specified region where the presence of groups with particular physicochemical property binds to the receptor. Therefore the most potent inhibitor among the series 50g was displayed on the maps for visualization.

The steric contours of CoMFA and CoMSIA Figure 10(a) and Figure 10(b) indicate the regions where sterically bulky substituent might have favorable (green) and unfavorable (yellow) effects on the activity of the inhibitor. The methoxy and hydroxyl substitutions are necessary to have good interactions with the receptor, and pyrazole ring is less sterically crowded, substitutions at this position with a bulky group facilitate increase in the activity. The electrostatic contours of CoMFA and CoMSIA Figure 10(c) and Figure 10(d) suggest that increasing the negative charge in red region will have a propensity for increase in binding affinity towards the receptor. The hydrophobic contour of CoMSIA Figure 11(a) recommends the substituent's like CF3 and phenyl are accountable for the hydrophobic activity. Any modification of C F3 and phenyl would result in a decrease of activity. The H-bond acceptor and H-bond donor contours of CoMSIA imply the regions with cyan acceptor favored and magenta donor favored regions are liable for activity as depicted in Figure 11(b) and Figure 11(c) (Figure 6-10) (Table 2,3).

Design of new molecules

As the first hit molecule screened through Capsid assembly assay was compound 54 with an enamine side chain at 3rd position was reported to be chemically instable by Lee Fader [28], and the SAR studies were performed by replacing the assay was compound 54 with an enamine side chain at 3rd position was reported to be chemically instable by Lee Fader [28], and the SAR studies were performed by replacing the enamine side chain with more polar groups like 2-methoxyethyl, 2-hydroxyethyl chains which resulted in no loss of potency thus confirmed that small substitutions at this position can be tolerated [29]. In this article designing of new molecules was attempted by substitution on phenyl ring at 5th position but results were not industrious in terms of compliance to PHASE. These observations lead us to a conclusion that the substitution at R1, R2 and R3 of phenyl moiety at third position are well tolerated and therefore were targeted for isosteric substitution (Figure 11).

The sterically favored pyrazole at R3, that showed single interaction with His 62 has been substituted with 1,2,4 triazole and electronegative favored methoxy (-OMe) group in 50g has been replaced with methyl sulfonate (-SO2Me) of N10, showed equivalent dock scores and facilitate newer interactions with Val 27 and Val 59. This implies that improved electronegativity on the substituents showed higher affinity. Increase in aliphatic carbon chain on diazapine nitrogen with propyl (N1-N6) and isobutyl (N7-N ) accounts for increased hydrophobicity. Considering the structural necessities depicted in Figure 12, we have designed ten new molecules which adhere to PHASE as well as CoMFA and CoMSIA. Docking studies revealed that the designed molecules Figure 13 show good interaction with the active site amino acids. The structures of newly designed molecules and their possible interactions are tinted in Figure 14. The pharmacokinetic data of newly designed molecules is illustrated in Table 3 (provided in supplementary data).

Design of new molecules by retaining quinoline scaffold. The quinolines not only exhibited antibacterial, antimalarial but also shown to inhibit HIV-1 activity by involving in assembly process. Hence new molecules are designed with a view to interact with N-terminal domain of HIV-1 Capsid, they too have shown the similar interactions as that of reported molecules. The docks pose C1 with its ligand interactions are depicted in the Figure 14. The oxygen of carbonyl carbon forms hydrogen bond interaction with amine of Phe 32, where as the amine of quinoline forms hydrogen bond interaction with the His 62 amino acids within the active site.

Prediction of ADME properties

The newly designed molecules were analyzed for their drug- likeness by assessing their physiochemical properties (Table S3 provided in supplementary data) and by applying Lipinski's rule of five. This rule states that the molecule should have molecular weight < 650 Daltons, H-bond donors <5, H-bond acceptors < 10, and a log P of <5. For the selected 10 molecules the partition coefficient (QPlogPo/w), water solubility (QPlogS) and MDCK cell permeability (QPPMDCK) properties have been estimated. All these pharmacokinetic parameters were found to be within the acceptable range.   

Conclusion

In summary, Docking studies guided by the receptor, predicted the binding conformations, and binding free energies for a series of fifty eight benzodiazepenedione inhibitors against HIV-1 capsid which are well correlated with their reported inhibitory activities, The docking results for the newly designed molecules provide additional hydrogen bond interactions with residues Val 27, Val 59 and Gly 60 along with His 62, Phe 32. The higher binding affinities of designed molecules N1, N2, N9 and N10 may be attributed to the additional hydrophobic interaction. Pharmacophore generation and 3D QSAR CoMFA and CoMSIA field distribution are in good conformity with the structural requirements of the active site of capsid assembly inhibitors that allows conception of a plausible template for designing novel potent inhibitors. The predicted activities of newly designed molecules for both CoMFA and CoMSIA are found to be equivalent to that of the highest active molecule 50g and expected to be active against HIV-1 Capsid assembly (Figure 14).   

Acknowledgment

We gratefully acknowledge support for this research from DST-SERB (SB/EMEQ-004/2013), We are thankful to Department of chemistry, UCS, Osmania University Hyderabad, India where the research was carried out. We also acknowledge Schrodinger Inc. for GLIDE software. We also express our gratitude to Tripos for providing the Sybyl software for performing 3D-QSAR studies.

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[juniperpublishersoceanography]

Effects of Artificial Illumination on Intertidal Communities As A Consequence of Coastal Urbanisation- Juniper Publishers

Abstract

Coastal urbanization is often accompanied by the replacement of natural substrata by artificial structures, which causes coastal habitat modifications, losses of species richness, diversity and microhabitats diversity and favours the settlement of non-native species. The impact that coastal defence structures cause in the intertidal community is further favoured by the anthropic pressures produced in heavily populated areas (such as pollution or the collection of intertidal organisms). Among these, the effect of artificial lights on intertidal communities is practically unknown, even though that the behaviour of many intertidal vagile organisms is synchronized with circatidal and circadian rhythms. Considering that large areas of natural and artificial habitats are exposed to artificial illumination, this review exposes the current knowledge in this matter in order to evaluate the importance of this disregarded impact. Nocturnal lighting can increase stress in intertidal communities, modifying the predation rates and community dynamics. Likewise, lights may favour visual foragers and favour crepuscular behaviours. In consequence, light pollution should be considered in future conservation strategies and more ecological coastal structure designs.

Keywords: Coastal urbanization; Artificial lights; Intertidal community; Anthropic pressures; Vagile benthos

Introduction

Coastal modification is one of the principal sources of impact on intertidal communities around the world [1]. Usually, the alterations include punctual perturbations, such as the construction and reparation of coastal defence structures, and permanent and more deleterious long term perturbations, such as the replacement of the natural rocky intertidal with artificial substrata. And the colonization of the new surfaces by the marine benthic species is usually slowed and limited by the design of these structures, which usually have a lower microhabitat diversity than natural nearby areas [1,2]. Also, these modified coastlines are often heavily populated, which means increased collection rates and pollution. Among the different sources of stress affecting intertidal communities, the illumination from adjacent urban areas and roads has been largely unattended [3]. Light pollution is a global environmental issue and large areas of natural and artificial habitats are exposed to artificial lighting [4]. In this matter, the recent popularization of low-consumption LEDs (light-emitting diodes) will increase the amount of artificial light emitted nearshore in the 479nm spectrum, which is used by the majority of bioluminescent organisms [4-6].

The increased intensity of artificial light as compared to moonlight can also favour crepuscular foraging behaviours in beach ecosystems [7], affect the activity of birds [3] and alter the settlement of sessile organisms larvae [6,8] and the foraging behaviour of vagile organisms [9]. Endogenous and exogenous circadian rhythms have been observed in many intertidal vagile organisms and activity peaks are usually synchronized by circatidal and circadian cycles [10]. Some endangered species within the intertidal have a regular feeding activity also during the night [11], being more sensitive to alterations in food intake by light pollution with relevant implications in conservation biology. Furthermore, some intertidal and subtidal species use lighting clues to determine the timing of larvae release, which could increase their sensitivity to nocturnal lighting stresses [12,13]. Therefore, light pollution influences the behaviour of coastal communities at multiple levels and, depending on intensity and spectrum, can interfere more or less severely in ecological processes and community structuring [3-5]. The effect on intertidal and subtidal benthic communities is largely unknown and biological responses of flora and fauna should be considered in future studies [5,9]. Above all, light pollution should be taken into account and minimized in future actuations and coastal structures designs in order to decrease stress in coastal areas.

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[juniperpublishersophthalmology]

Endophthalmitis after Lower Lid Blepharoplasty; A Rare Complication-Juniper Publishers

Case Presentation

A 22-year- old man referred to the emergency ward because of vision loss in his right eye five days after bilateral lower lid blepharoplasty, his right eye showed ciliary injection, cornea showed mild edema and anterior chamber showed 4+cells and faint hypopyon in slit lamp examination, There was severe chemosis, without any site of laceration. However, fundus examination showed severe fibrinous reaction and vitritis. (Figures 1-5 are related to the post-operative status.)

Discussion

Based on the diagnosis of undetermined uveitis the patient underwent diagnostic vitrectomy, interestingly there was a site of laceration in the posterior fundus, leading to peritomy and its repair associated with severe vitreous inflammation and retinal necrosis and vasculitis. The patient underwent pars plana vitrectomy associated with intra vitreal antibiotic injection and silicone oil injection; the culture of the vitreous documented staphylococcus aurous in the vitreous sample. This rare complication has been rarely described in the literature [1,2].

    Conclusion

Although rare, doing blepharoplasty a common cosmetic in inexperienced hand could lead to a severe devastating intra ocular complication.” For more Open Access Journals in Juniper Publishers please click on: https://juniperpublishers.comFor more articles in  JOJ Ophthalmology (JOJO) please click on: https://juniperpublishers.com/jojo/index.phpFor more about juniper publishers  please click on: https://www.juniperpublishersgroup.com/

[journalofsportsmedicine]

Clinical Definition and Pathophysiology of Osteoporosis: A Brief Review-Juniper Publishers

Introduction

With the field of medical science making constant and dramatic improvements in the treatment and prevention of disease progression, life expectancies in the United States are beginning to increase dramatically, with the elderly population demonstrating the greatest expansion [1]. With this dramatic increase in the elderly population, new and unfounded challenges in managing, treating, and caring for this sector of the population have begun presenting themselves at rates exponential to those of just 20 years ago. In 1990, the American Medical Association stated that “one of the most important tasks that the medical community faces today is to prepare for the problems in caring for the elderly in the 1990’s and the 21st century” [2]. The emphasis of this particular study was on the need to develop and sustain means of special care for the growing population of the elderly, who suffered from such diseases as osteoporosis.

Osteoporosis, which is literally defined as “porous bones,” is a degenerative disorder responsible for the dramatic decrease in bone density, and loss of bone tissue, over time [3]. The primary cause of this particular ailment is attributed to the excessive losses in bone protein and mineral content, specifically calcium [4]. With the ensuing decrease in bone mass and density, there is a significant decrease in overall skeletal strength, increasing the risk of fractures and breaks due to the increased fragility of bone [3,5]. Osteoporosis is diagnosed within individuals presenting a bone mineral density greater than 2.5 standard deviations below the age-predicted norm, as identified using dual X-ray absorptiometry DEXA [6].

By first understanding the basics of bone physiology, researchers have been able to identify physiological factors responsible for osteoporotic progression and development. Bone tissue is constantly in flux, somewhere between resorption and formation, changing shape as a consequence of external, and internal, stressors to which it is exposed [7]. During resorption, osteoclasts digest old bone, while osteoblasts are responsible for deposition and formation of new bone to the matrix. As an individual advance in age from adolescence to early adulthood, a positive balance between formation and removal exists, with greater amounts of bone accumulating than being destroyed. Maximum mass and strength are attained somewhere around 30 years of age, with various extraneous factors influencing the specific time point of maximal density. Once the zenith of bone formation has been attained, a negative balance exists, favoring bone resorption, yielding a progressive decline in bone mineral density and strength with advancing age [7]. Primary osteoporosis is a consequence of the acceleration of this normal aging process, whereas secondary osteoporosis, still caused by an acceleration of bone resorption, can be attributed to outside disease processes or prolonged medication use and/or abuse [3].

Most commonly, osteoporosis will occur in elderly individuals of both sexes, as well as in women following menopause [3]. Additionally, osteoporosis has been found prevalent in younger individuals, both males and females, suffering from disordered eating habits, one of the three key factors in the female athlete triad [8]. The disease directly affects greater than 50% of males and females greater than 75 years of age, with women being more than five times as likely to develop the disease as a consequence of reduced estrogen, a “bone-protecting” hormone, which is no longer produced in significant quantities, following menopause [4-6]. Greater than 44 million people in North America, both males and females, are at risk for developing osteoporosis [9]. The disease itself is responsible for greater than 1.5 million fractures annually, with the most common point of injury being in the hip, spine, and wrist and Often, many of these fractures will require hospitalization and major surgery to reduce the risk of permanent disability and potential death due to complications [9]. Researchers have estimated that greater than one in five American women, and 13-25% of males over the age of 50 currently have osteoporosis [10].

The primary known causes of osteoporosis in the older sect of the population are a drop in estrogen in females attributed to menopause, and a decline in testosterone in males attributed to advancing age [3]. Calcium and phosphate, two essential minerals for normal bone formation and function, are reabsorbed by the body at a rate exceeding that of their deposition as an individual progress in age. This decline in mineral content yields a dramatic decrease in bone mineral density, resulting in brittle, fragile bones that are far more prone to fractures [3,6,9]. In addition to decreased bone mineral density attributed to hormonal declines and fluctuations attributed to age, there exist a litany of other causes of osteoporosis, including but not limited to: confinement to a bed; rheumatoid arthritis; chronic kidney disease; eating disorders; prolonged use of corticosteroid medications, including prednisone; hyperparathyroidism; and Vitamin D deficiency [3,6,11]. Additionally, white women, specifically those with a family history of osteoporosis, demonstrate a significantly above average risk of developing osteoporosis [12]. Additional risk factors for developing osteoporosis include: amenorrhea, or an absence of the menstrual cycle; high levels of alcohol consumption; a family history of osteoporosis; prior hormonal treatment of prostate or breast cancer; low body weight; chronic smoking; or, low dietary calcium consumption [3,6,11].

While no symptoms present themselves in the earliest stages of the disease, there are a variety of manifestations of osteoporosis that present themselves during later points in the progression of the disease state. Some of the symptoms include: bone pain and tenderness; fractures with minimal to no trauma or stress exposure; declination in height by as much as 6”, attributed to reduced vertebral density concomitant to increased fractures of the spinal bones, as well as progression of kyphosis; as well as low back and neck pain [13]. While Osteoporosis is an incurable progressive disease, there are a variety of treatment paths that can be followed to treat the signs and symptoms of the disease. Ultimately, the goals of osteoporosis treatment include: controlling for, and reducing pain attributed to the disease; slowing down, and potentially stopping, bone loss; reduce and prevent bone fractures with both medication and physical training intervention; and, minimizing the risk of falls that may cause fractures [14,15].

Pharmacological treatments include: biphosphonates, calcitonin, hormone replacement therapy, parathyroid hormone, and Raloxifene. Biphosphanates are the primary medication utilized to both prevent and treat osteoporosis in post-menopausal women [14]. Biphosphatanes can be taken orally e.g. alendronate, ibandronate, and risedronate, or given intravenously. Some of the side-effects include osteonecrossi of the jaw and atypical femur fractures [14]. Calcitonin, administered either intravenously or intra-nasally, is a medication that slows the rate of bone loss and can aid in reducing bone pain [16]. While effective, calcitonin is not as effective as biphosphanates in the treatment of osteoporosis. Hormone replacement therapy which typically entails estrogen and parathyroid hormone (Teriparatide) injections, has declined significantly in application and utilization in recent years [14]. Risk factors associated with hormone replacement therapy include ineffective treatment and sub-optimal recovery when compared to alternative treatments [17]. Finally, Raloxifene, which is similar to the drug tamoxifen, used in the treatment of breast cancer, has been shown to reduce the risk of spinal fractures by almost 50% [18]. Additionally, raloxifene has been shown to have moderate protective effects against heart disease and breast cancer. Adversely, raloxifene supplementation demonstrates an increased risk of developing deep venous thrombosis and/or pulmonary emboli [18].

Non-pharmacological interventions include dramatic lifestyle alterations, including diet and exercise modifications, as well as cessation of detrimental behaviors. Regular exercise can dramatically decrease the risk of bone fractures in people suffering from osteoporosis. Exercise interventions demonstrated to have beneficial effects in the treatment of osteoporosis include: weight-bearing exercises like walking, jogging and dancing; resistance exercises including free-weights and resistance bands; and, balance exercises like tai chi and yoga [3]. It is essential to avoid any high risk activities that would increase the risk of falling to prevent potentially debilitating fractures. Regarding nutrient intake, it is essential to ensure a well-balanced diet, rich in phytonutrients and calcium to ensure optimal conditions for healthy skeletal remodeling [10]. Researchers recommend individuals consume a minimum of 1,200 milligrams of calcium and 800-1,000 international units of Vitamin D3 on a daily basis [18,s19]. Some foods identified as high in calcium and Vitamin D include: cheese; ice-cream; green, leafy vegetables; low-fat milk; salmon and sardines; tofu; and, yogurt [19]. Additionally, researchers highly recommend cessation of detrimental habits which significantly contribute to osteoporotic development. Some of these habits include: smoking; alcohol consumption; walking during icy conditions; and, leading a sedentary lifestyle [19].

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Recycling of Liquid waste for effective and satisfactory Pretreatment in Cotton wet Processing - Juniper Publishers

Abstract

Textile industries are focusing on minimizing their production costs by using sustainable technologies and by inventing new methods. Pretreatment is the heart of textile wet processing. Most of the Textile Companies are using combined pretreatment process with exhaust and semi-continuous method. After the treatment is over, the bath with residual chemicals are drained out into effluent treatment plant. In this study, an attempt has been made to reuse the residual chemicals by replenishing the measured amounts of chemicals again for combined pretreatment process. The concentration of the main chemicals, after pretreatment, before draining was analyzed and quantified. In case of pretreatment process in a Jigger machine, the liquor is drained out after three turns (6 ends) with residual chemicals, then the concentrations of H2O2 and NaOH was assessed in that. In case of pad-roll bleaching, the fabric roll is rotated in the steaming chamber for twelve hours and washed in a counter current washing machine, then the concentration of chemicals was analyzed after washing is over. Based on the chemical analysis results, by replenishing with measured amounts of chemicals, pretreatment is done in both laboratory scales repeatedly up to four times without changing water and on the bulk production; it has been done by mixing used water and fresh water. The effectiveness of pretreatment was evaluated in terms of absorbency, whiteness, yellowness and the effect in subsequent reactive dyeing and pigment printing in terms of colour strength, colour difference and fastness properties after each pretreatment. It was observed that acceptable results which can fulfill the requirements of the products can be obtained by reusing the pretreatment bath.

Keywords: Pretreatment; Reuse; Replenishing; Jigger; Pad-roll

Introduction

To remove impurities from cotton, a massive amount of water is required in this process per day. It is estimated that on an average, almost 100 liters of water is used to process only 1kg of textile goods and thus the water consumption of an average sized textile mill having capacity only 8 tons/day is about 1.6 million liters per day [1]. Among the textile fibers, about 48% are cotton fibers that we consume as clothing materials all over the globe [2]. All the cotton goods as woven or knit, all goes through the pretreatment process like desizing, scouring, bleaching etc. before dyeing process. These pretreatment processes create huge pretreatment liquor and wash liquor which the industries discharge as textile effluent. All the chemicals used in desizing, scouring and bleaching of cotton fabric do not fully react with it. As a result, pretreatment liquor contains some residual chemicals like caustic soda, peroxide and other auxiliary chemicals [3,4].

The conventional three step pre-treatment process for cotton fabric consists of desizing, scouring and bleaching. Desizing of a grey fabric removes previously added size or starchy material which can be done by using water (rot steeping), acid, enzyme, oxidation chemicals and alkali. Scouring uses alkali to remove oils, fats and waxes to improve the absorbency whereas bleaching uses oxidizing agents to improve the whiteness of the fabric. In a conventional process, scouring and bleaching is done once which results in underutilization of alkali and hydrogen peroxide. But in most of the companies, all these three processes are combined into one, which is a single stage pretreatment process by using jiggers and pad- roll bleaching machines. In case of Jiggers, all the liquor after six ends chemical rotation are drained out; and in case of pad- roll bleaching, after 6-12 hours of rotation in the reaction chamber, the residual chemicals are washed out in washing machine. Most of the time the textile industry uses combined pretreatment process by pad- roll bleaching machine and jiggers. The main chemicals used are NaOH, H2O2, Organic stabilizer, wetting agent and Optical Brightening Agent (OBA). The drained-out liquors and wash water can be replenished by adding measured amounts of chemicals and reused again and again based on the concentration of chemicals required for pretreatment process. The textile industry utilizes abundant water in pretreatment, dyeing and finishing processes. There is a need to adopt economical practices for the use of water in textile industries. The quantity of water required for textile processing is large and varies from mill to mill depending on the fabrics produced and processed, the quantity and quality of the fabric, processes carried out and the sources of water. The longer the processing sequences, the higher will be the quantity of water required. Bulk of the water is utilized in washing at the end of each process [5].

Recent experiences with water reuse in the textile industry indicate that recycled water, having impurity levels above historically accepted limits, can be used to produce first-quality goods. The minimum water quality for process reuse, therefore, is defined as the treated wastewater containing the highest level or concentration of impurities that will consistently produce an end-product of first quality [6]. The needs of water recycling & reuse in wet processing has necessitated an appropriate, cost effective water recycling method for reducing the pollution level and fresh water consumption rate [7]. Conservation of water and chemicals by reusing the same bath for several times in cotton pretreatments as desizing, scouring and bleaching [8- 10], reuse of clarified print washes water in washing blankets and screens of the print machine [11], reuse of alkali containing mercerizing wash liquor for scouring and bleaching [12], reuse of the chemicals used in scouring and bleaching of cotton knit [13], reuse of bleaching bath where this bath was also reused four times [14], same liquor bath used for eight times [15], use of unexhausted alkali and oxidizing agent in the scouring and bleaching wastewater respectively to desize a new grey fabric [16], reuse of bleach liquour for eight times [15], reusing of bleaching liquor for scouring [8], reusing of washing water [9,17], reuse of wash water for desizing, scouring and bleaching [18], reusing of washing liquor for desizing [19] are some of studies carried out with considerable success in industrial practice.

The present work is to find the possibilities of reusing the textile pretreatment liquor or wash liquor in disizing, scouring and bleaching of cotton fabric. It is an appropriate, cost effective recycling method for reduction in chemical consumption, fresh water and the pollution level. The pretreatment liquor or wash liquor from single bath was collected periodically and analyzed for presence of useful chemicals and their strength. Then, they will be used for the purpose of combined desizing, scouring and bleaching by replenishing with required quantity of necessary chemicals. Combined pretreated and subsequently dyed fabric samples were assessed for the performances and compared against the samples prepared by conventional method. The focus of this project is on recycling and reusing water and chemicals in the textile pre-treatment process without prior waste water treatment.

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Materials and Methods

Materials

100% cotton fabric (plain-weave, 21 Ne, 24 ends per inch, 18 picks per inch, areal density of 147g/m2), Jiggers, pad-roll machine, chemicals such as hydrogen per oxide, caustic soda, Organic stabilizer, wetting agent, optical brightening agents, acetic acid, C.I Reactive Blue 19, C.I Pigment Blue 15, sequestering agent, iodine solution, phenolphthalein indicator, Sulphuric acid, hydrochloric acid, common salt, soda ash, potassium per manganate, binder, thickener, emulsifier were used for the study.

Methods

Method -1 1) Collecting the drain out pretreatment bath from jiggers after three turns (6 ends). 2) Analyzing chemicals concentration of hydrogen per oxide (H2O2) and caustic soda (NaOH) by titration method. 3) Replenishing the drain bath by adding measured amounts of H2O2, caustic soda, Organic stabilizer and wetting agent based on the titration results of caustic soda and H2O2concentration. 4) Doing combined pretreatment of cotton fabric with the replenished water. 5) Checking and comparing the treated fabric parameters with the conventional treated fabric. 6) Collecting the drain out bath for the second time and repeating procedure 2, 3 and 4. 7) The above procedure will be repeated up to three or four times depending on the concentration of chemicals in the drained-out bath. Method - 2 To avoid and minimize contamination of the fabric due to degraded starch and other impurities in the used liquor, it is thought that better to mix used liquor and fresh water in different proportions. These mixing with fresh water can be used for full bleached fabric rather than the one to be dyed / printed. The following three blends of used and fresh water were used. 1) Mixing 70% used water and 30% fresh water 2) Mixing 50 % used water and 50 % fresh water 3) Mixing 30 % used water and 70 % fresh water The chemical concentrations already analyzed in the above method 1 were used for calculating the requirements in this method. Combined pretreatment is done by different jiggers and pad-roll bleaching machine. The chemical recipes which are used in Jiggers 50 % concentrated H2O2 - 5gpl, Flake caustic soda (NaOH) - 4gpl, Organic Stabilizer-1g/l, Wetting agent - 1gpl

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Evaluation

The fabric absorbency was assessed by the following three methods such as, water drop test (AATCC/ASTM Test Method TS-0180), wicking height (AATCC Test Method 197) and sinking time test (AATCC Test Method 17-1994) methods. Desizing efficiency was evaluated for the presence of residual starch by Tegewa scale rating test which involves iodine absorption and change of colour from no colour change (no starch present) to pale blue to bluish violet (presence of starch size or a blend of starch and synthetic size) to Brown (presence of modified starch or a blend of starch/PVA size) and scale ranging from 8 (best, no starch) to Pale blue to Bluish violet to 1 (Brown). The whiteness index was evaluated as per CIE standard method. The CIE Whiteness Index value (CIE WI) will be determined for the bleached fabric using AATCC test method using a Colour eye Reflectance spectrophotometer 3100 under illuminants D-65, day light and TL84 at 2° Observer and Yellowness index as per ASTM method E313.

To understand the effect of the above results on the dyeing behavior, reactive dyeing has been done by using C.I Reactive Blue 19 by dyeing in 1% (on weight fabric) shade for all treated fabrics. As recommended by the dye supplier, the dyeing was done by exhaust dyeing method at 60oC for 60 minutes. After dyeing is over, the samples were evaluated for color strength (K/S) value, color difference (ⵠE), percent reflectance using Colour eye Reflectance spectrophotometer 3100 and Wash fastness, rubbing fastness, Light fastness by following the standard procedures viz. IS: 764:79 Test Method 3, AATCC Test Method 8, AATCC Test Method 16 - Option 3 respectively.

Results and Discussion

Chemical analysis

The residual liquor after 6 ends in Jigger were collected and analyzed for two main chemicals, hydrogen per oxide (H2O2) and caustic soda (NaOH) concentration by titration method. The results are presented in Table 1. As observed from Table 1, out of 5g/l H2O2 and 4g/l NaOH, 1.58g/l and 1.61g/l respectively are still present unutilized that can reused in a single Jigger treatment. The pH is in the acceptable range for of oxidative bleaching that is around 11.30. The treatment after replenishing is done based on the analysis results. The first analysis was done with the liquor after the conventional pretreatment is over and second analysis is also done with the liquor after first analysis is over, third and fourth analysis are also done from second and third liquor respectively. Above fourth analysis it was not possible as more than 90 % of the water was consumed in replenishing process from once up to four times. Without replacing water, by adding the above measured chemicals, combined pretreatment is done up to four times in the laboratory scale.

The results from Table 2 show that there is no significant difference between the conventional one and the replenished pretreatment in terms of absorbency which is in the order of acceptable level. The drop test results of all samples are less than five seconds. The sinking time test for the conventional and the average values of the replenished is similar. The Tegawa scale rating results shows 8 for the conventional and 5 to 6 for the replenished, the difference is because of hydrolysed starch in the form of dextrin or glucose present in used liquor that is interfering. However, it was found that the samples prepared with used liquor after replenishing can be used for full bleaching, dyeing and printing purpose.

As shown in Table 3 and Figure1, Figure 2, the conventional and the replenished average values are within the acceptable range for the degree of whiteness. In day light as illuminant, the whiteness index was 141.89 and 137.25 for conventional and replenished respectively. The yellowness index value is negative which shows that the whiteness index is higher and as whiteness index increases yellowness index decreases. The differences of yellowness index between conventional and replenished average graphs of two samples are almost over lapped, which means, the difference is insignificant.

Dyeing performance

The dyeing performance of treated samples is evaluated with similar shade and dyestuff. Dyeing have also been done all the above pretreated fabrics by using, C.I Reactive Blue19 of 1% owf. The dyed samples are tested for K/S value (color strength), % Reflectance and Color difference values with 2° observer and under D65, TL84 and daylight light source by using spectrophotometer at 620nm wave length (λmax). From the results presented in Table 4 and in Figure 3, it is clear that pretreatment with replenished liquor gives little lesser colour strength. The conventional showed a % Reflectance of 10.78 % and replenished average was 11.41 %, due to the fact that, as the K/S value increases percent reflectance decreases. The Colour strength was 3.69 for the conventional and ranging from 3.30 to 3.61 with average of 3.44 for the replenished pretreated & dyed. Color difference between conventional and replenished pretreated was 1.61 to 2.32 with average of 1.7 to 1.9 under all light sources which is quite significant.

The fastness properties of both the conventional and replenished pretreated & dyed samples have good results as it is shown by the grey scale readings in Table 5. The washing fastness results of both staining and fading rating was in the range of 4-5 and 4-5 dry & 4 wet rubbing values for both conventional and replenished average. The laboratory results are not reproducible in bulk stage in general. The main reasons are: a. Material to liquor ratio (MLR) difference between laboratory tests and bulk. 1:20 was used in laboratory, but at the bulk in jiggers it was about 1:5.

b. Temperature and time have also an effect in reproducibility of bulk production. c. For ready- for- dyeing fabric, there must be a separate desizing process before scouring, but in some factories desizing is not done. The above all results may be reproduced if a soft flow machine.

Bulk Results

Keeping the laboratory results in mind and considering contamination of water because of decomposed starch present in liquor, the following experiments have been done on the mass production machines by using small jiggers. The drainedout liquor was used for pretreatment again in Jigger that had a capacity of 300 liters of solution and can load 135kg of fabric.

The collected liquor had 1.6g/l of H2O2 out of 5g/l and 1.4g/l of NaOH out of 4g/l. The remaining amounts of chemicals and other auxiliary chemicals were added to make up the conventional recipe before using again jigger. Then, as shown in the Table 6, the pretreatment was carried out and the performance was assessed and compared with conventional. The chemical amounts in Table 6 are based on the standard recipe, H2O2 -5g/l, NaOH -4g/l, Organic stabilizer- 20% of H2O2, wetting agent- 1g/l and OBA - 0.6g/l.

With these, after doing pretreatment on jigger, whiteness and yellowness index are checked and compared with the conventional with same chemical recipes. In addition to this, on the treated fabrics, pigment printing has been done with C.I Pigment Blue 15 and the performance was assessed in terms of fastness, color strength, color difference and percent reflectance. The whiteness and yellowness index values of the bulk samples are summarized in Table 7 and in Figure 4. It is clear that the whiteness index is decreasing, and yellowness index is increasing from the conventional to fourth replenished pretreated. The reason for this is the decomposed starches in the used liquor are reacting with per oxide and interfering in the overall process. Even though, it was a decreased result, the variation is not too much and it can be used for printing, grounding and off-white fabric. To make more white fabric per oxide amount must be increased to compensate the reaction. C.I Pigment Blue 15 printed samples K/S value (color strength); % reflectance and Color difference values were tested at 600nm wavelength (λmax) Table 8.

The K/S values of the printed samples showed very minor variation between conventional and replenished pretreated. It is 4.80 for the reference and 4.59 for the replenished (average). The reflectance values showed a little increase, but the difference is less than 1 Table 9. The color difference was around 1.1 under three light sources. The fastness properties of the printed samples are within acceptable range based on gray scale value. Both staining and fading of washing fastness it 4; dry rubbing and wet rubbing staining values have 4 and 3 respectively Figure 5

*Both Change in colour and staining on white

Conclusion

Based on the results, it can be concluded that pretreatment liquor and wash liquor can be reused in the pretreatment process of cotton instead of fresh water. The pretreatment liquor and wash liquor can safely be reused after replenishing with measured amounts of H2O2, NaOH and other auxiliary chemicals based on the analysis results for the scouring-bleaching purpose of next batch with satisfactory bleaching, printing and dyeing performance. As a result, the reuse of pretreatment liquor ensures saving of a lot of chemicals consumption, water consumption as well as reduce waste water discharge and effluent load and the reuse of wash liquor ensures the reduced consumption of huge amount of fresh water.

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Dairy Cow Welfare, Heat Stress and Climate Change- Juniper Publishers

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Abstract

There has been widespread concern in the media regarding the impact that livestock have on global warming, particularly with methane from ruminants noted as a potent greenhouse gas. Less public debate has occurred however, on the potentially negative impact that global warming will have, indeed is having, on livestock welfare. Here we will first briefly discuss the effect of livestock husbandry on climate change before moving to a more detailed discussion of the effect that a warmer climate is likely to have, again is currently having, on the physiology and welfare of cattle across the world. Finally, we will briefly discuss measures that can be taken to reduce the impact of temperature increase on dairy cattle.

Introduction

Recent research has estimated that while cattle provide just 18% of the world’s dietary calories and 37% of protein, they use a huge proportion (83%) of agricultural land and produce 60% of agricultural greenhouse gas emissions [1]. Understandably, given these figures, most public concern regarding cattle and climate change has focussed on the animals as an important causative agent with broadcast media highlighting the problem [2]. Public understanding of the impact of global warming on cattle welfare is significantly less, although some newspapers have noted the problem [3]. The effects of heat stress on beef and dairy cattle have been recognised by the farming industry for some time but the link with increasing ambient temperature is only recently being highlighted. Here we look at the effects of heat stress on cattle and the impact that global warming will have, indeed is already having, on cattle welfare.

Heat Stress and the Lactating Cow

The lactating dairy cow already has an increased internal temperature through her milk production (Figure 1). Heat production through metabolic functions is estimated to account for around a third of the energy intake of a 600kg cow producing 40kg of milk daily with a far level of 4% [4]. A study comparing cows that were non-lactating, or at low (18.5kg/d) or high (31.6 kg/d) milk yield showed that low and high yielding cows generated 27 and 48% more heat than nonlactating cows even though they had a lower body weight [5]. Whilst in cold environments dissipation of such body heat is not a problem, during periods of elevated ambient temperature, heat loss can be a significant problem for dairy cattle. The limiting factor for cattle at peak lactation is energy intake and a common management practice is to increase energy density of the diet by decreasing forage and giving a mixed ration with a high energy density. A side effect of feeding such a high energy ration is that of increased heat production; Reynolds and colleagues showed that heat production for heifers ingesting 4 and 7kg dry matter per day was around 40 and 56MJ/d respectively [6].

The irony, if we are aiming to increase dietary intake in cattle living on the metabolic knife edge of maximum productivity, is that heat stress leads to reduced feed intake, decreased activity and increase in peripheral blood flow to aid perspiration [7] while decreasing portal blood flow taking nutrients from the intestines to the liver [8]. Lough’s 1990 paper also showed a reduced vascular supply to the mammary gland in times of heat stress, reducing milk production. Other effects of heat stress on lactation include a decline in plasma somatotrophin and triiodothyronine and thyroxine [9]. Heat stress alters blood acid-base balance, since panting animals lose carbon dioxide and thus have a respiratory alkalosis [10]. Compensation for this involves increased renal excretion of bicarbonate in times of heat stress, leading to a paradoxical metabolic acidosis during the cooler hours of nighttime. This in turn leads to a loss of bicarbonate buffering capacity which can be critical if cattle are being fed high grain rations. To add to the cow’s electrolyte compromise, potassium loss through increased sweating can lead to hypokalaemia [11].

What impact do these metabolic changes in heat stress have on the affective status of the animal? As far back as 1968 Collins and Weiner suggested that acute heat stress had emotional effects on dairy cattle [12] and subsequent work confirmed that heatstressed cattle have higher cortisol levels than animals kept in cooler environments [13]. Animals with a reduce dry matter intake during heat stress are not only physiological stressed, losing body weight, but also emotionally affected by hunger [14]. We know that cattle given a limited grazing period have higher plasma levels of ghrelin, the ‘hunger hormone’ [15] and it is reasonable to assume that cattle reducing their dietary intake through heat stress will experience the same endocrinologic and affective state. Thirst too is a classic response to heat stress and providing adequate water is essential [16] with chilled drinking water alleviating both thermal issues and thirst [17,18]. Stermer’s research [17] was undertaken more than thirty years ago and yet it must be asked how many farms are providing chilled water for their dairy cattle in times of heat stress. Such information is difficult to access, but this author’s impression is that few are.

What influence does heat stress have on lameness and pain in dairy cattle? Heat-stressed cattle increase their standing time to allow greater body surface area to be exposed to the air for heat loss by convection. Lying time is reduced by 30% with higher ambient temperatures [19] and increased periods of standing have been suggested as a significant risk factor for lameness which is already a substantial cause of pain in a sizeable proportion of dairy cattle [20]. It has been suggested that the conflict between whether to stand up and increase cooling or to lie and relieve pain form lameness might be a significant factor in frustration in dairy cattle, a potentially important affective influence on their welfare [21]. Leg stomping, weight repositioning and butting, potential behavioural indicators of frustration, have been noted in cattle deprived of the opportunity to lie [22] and it would be a valuable exercise to assess the prevalence of such behaviours in heat stressed cattle as compared with the same animals in cooler environments.

Heat stress also reduces fertility in cattle. While results of research on the effect of heat stress on reproductive endocrine status have been varied, plasma luteinising hormone pulses have been shown to be of lower amplitude and frequency in periods of high ambient temperature [23] and plasma oestradiol concentrations are lowered by heat stress in dairy cows. Plasma progesterone levels are influenced by food intake and hepatic metabolism as well as luteal function, so the influence of heat stress on progesterone production is complex, but effects of heat stress on this hormone will affect the survival of an implanting fetus in the uterine wall as well as oocyte formation with deleterious effects on oocyte maturation and embryonic death.

Opportunities to Alleviate These Issues

Ambient temperature increases are to be expected in the future, so one must ask what measures can be put in place to manage heat stress in cattle. A personal experience might be worth noting here. On a visit to the Department of Veterinary Medicine in the University of Khartoum, Sudan I was at first horrified to see Holstein Friesian cattle, imported from Holland, kept in the elevated temperatures of this African country. Inspection of the farms however showed the use of large water misting fans to cool the cattle (Figure 2). This together with adequate provision of shade allowed the cattle to live comfortably. Indeed, the human inhabitants of Khartoum have borrowed that technology and now use water-cooling fans in up-market restaurants in the city! It is not only equatorial Africa which is using such technology in the livestock industry. American and Australian dairy farms are now also using fan assisted cooling and sprinklers more and more [24]. With an estimated reduction in lactation of up to 35% in midlactating heat-stressed cows it has been suggested that the US dairy industry is losing between $900 and $1500 million annually [25]. Clearly reducing heat stress is not only a welfare issue, but also a commercial imperative.

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Juniper publishers have been established with the aim of spreading quality scientific information to the research community throughout the universe. We, as Open Access publishers, strive to offer the best in class online science publications. Open Access process eliminates the barriers associated with the older publication models, thus matching up with the rapidity of the twenty-first century. Our main areas of interest lie in the fields of science, engineering and other related areas. Juniper Publishers is a platform for professors and researchers who aspire to give out quality information based on their research and expertise, in an attempt to aid scholars/researchers in their field of interest with the latest information.

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Generation Windrush: diasporic landscapes and settlement- Juniper Publishers

The Windrush scandal

In April 2018, the British government faced widespread public anger and outcry against, and later acknowledged, the mistreatment of hundreds of British Caribbean residents who had settled in the United Kingdom following the Second World War [1]. Migrants from the then British colonies in the Caribbean had been encouraged to cross the Atlantic by the British government and industriesand were offered work permits to help re-build an economy and society decimated by war. West Indian migrants arriving between 1948 and the early 1970s came to be known as the ‘Windrush Generation’, named after the first 492 adults and children arriving from Jamaica, who disembarked from the passenger ship HMT Empire Windrush at Tilbury Docks, London on 22ndJune1948.

Migrants and settlers from Caribbean societies have shaped British history and society for centuries, and the transatlantic Caribbean diaspora has been built up via layered and interwoven social, cultural, economic and political landscapes of connection and subtle divergence [2]. The Windrush Generation’s contributions to the multiculturalism of British life today have been formative and striking [3,4]. Windrush writers and artists, such as Sam Selvon & Linton Kwesi Johnson [5,6]- LKJ - have themselves generated a substantial oeuvre of Black British writing and cultural energy that lies as much at the heart of British society, as do the economic contributions of the early Windrush migrant workers and subsequent generations. Since many children arrived and settled in the United Kingdom legally via their parents’ passports, the exact number of the Windrush Generation is not clear, but it amounts to thousands, reinforcing the quantitative and qualitative Caribbean underpinnings of British society today(Figure 1).

Given that such deep and positive influences of the Windrush Generation are widely celebrated, it seemed all the more outrageous and perplexing that since 2012, the British government’s ‘hostile environment’ policy has created great insecurity and uncertainty among many lawful British Caribbean residents. This antagonistic agenda constituted a set of administrative and legislative measures designed to make staying in the United Kingdom more difficult for residents without full citizenship, even if they were entitled to such rights(Figure 2). This proved to be the case for many Windrush settlers and their children, who have faced restricted access to welfare services, internship, and actual or threatened deportation back to the Caribbean, even after five decades of legal residence in the United Kingdom.

Just as writers and artists such as LKJ and Selvon have relayed the hardships of arriving and living in Britain during the Windrush era, and riled at ongoing legacies of empire and slavery, the current targets of this only recently revoked crackdown - May 2018 - are now making their own political and cultural voices heard. New oral and visual diasporic landscapes of resistance and cries for justice are being formed. This live topography reflects longstanding tensions of diasporic landscapes experienced by earlier migrants crossing the Atlantic in the reverse direction from Britain. Those stressed are felt in the need to create a new sense of dwelling and self in strange lands by making fresh pathways, generating mobile identities, while also collating past memories and seeking stasis and settlement in place.

    Diaspora, mobility and settlement

Disaporic landscapes explore the intimacies between body and place that mobility continues to create, reflecting spatial scales of embodiment, while highlighting intersections of complex identities with diverse historical and physical trajectories. These embodied landscapes underpin experiences of migration and settlement, reflecting closely Machado’s understanding that individual and collective diasporas are rarely pre-determined, always in motion - ‘there is no road, the road is made by walking’:

Caminante, son tus huellas

el camino, y nada más;

caminante, no hay camino,

se hace camino al andar.

Al andar se hace camino,

y al volver la vista atrás

se ve la senda que nunca

se ha de volver a pisar.

Machado’s serial optimism of re-creation and progressive enlightenment through movement runs counter to more pessimistic or stressed contexts and accounts of diaspora formation and memory. Such tensions are reflected in twentieth and twenty-first century-transatlantic diasporic writings, as well as many before, en route from Britain to North America. Robert Louis Stevenson’s experiences as an emigrant to the United States reflect the more downbeat context of mobility that can shape sombre realisations and intimacies of footfall and motion, through troubling or troubled landscapes. While voyaging across the Atlantic, Stevenson’s thoughts were not of an open future, but of a lost past and curtailed present: ‘… all now belonging for ten days to one small iron country on the deep. We were a company of the rejected… We were a shipful of failures, the broken men of England’. The historical intimacy of his Scottish ancestry is subsumed into the hard, momentary present of a ship’s metal hulk. For Stevenson and many others, the flight from home, albeit to build another, was not youthful and full of hope, but engendered a desperate and despondent setting. Acquaintances were scraped together, rather than friendships forged. These intimacies of knowledge and experience, generated by movement, embodied as much distance as proximity; exclusion and inclusion shared in uneven doses. A century beforehand, Johnson [7] had referred to the making of this new Scottish diaspora in the Americas as a dilution of energy, a loss of heat from a waning national hearth: …for a nation scattered in the boundless regions of America resembles rays diverging from a focus. All the rays remain, but the heat is gone. Their power consisted in their concentration: when they dispersed, they have no effect. It may be thought that they are happier by the change; but they are not happy as a nation, for they are a nation no longer… they must want that security, that dignity, that happiness, whatever it be, which a prosperous community throws back upon individuals(Figure 3).

Traumatic tensions of optimism and pessimism, celebratory recollection and solemn commemoration of place, person and movement are revealed. Transdisciplinary approaches to memory, mobility and mindsets reflect Bergson’s [8] thesis on spontaneous (la mémoire spontanée) and voluntary (la mémoire volontaire) processes of recollection. While time, he suggests runs with a linear, irreversible current, the embodiment of human memory transcends both time and space. The migrant and settler’s memory acts vertically, as fleeting, unexpected glimpses of the past and future that cut across and into present constructions of place and senses of belonging. Human memory unites past and present in one place, joining or displacing the individual or collective in the context of the moment and with intimate depths of human experience, knowledge and identity.

The experiences of ‘Generation Windrush’ are many miles and eras way from the writing of these two, now celebrated, Scottish writers. Connections, however, may be found in charting a series of pathways through visceral and emotive landscapes, offering the reader and writer a series of routes by which to figure out diverse memories and narratives of diasporic identities. The process of creating a path to a place generates the disaporic landscapes revealed historically and today, and which are emerging now in poignant new political and cultural forms as British society as whole comes to terms with the woefully misguided notion of a ‘hostile environment’. ‘Landscape’ is often understood as a noun connoting fixity, yet diasporic literature reveals the word as a ‘hidden verb’:the landscapes are dynamic and cause commotion; they are ‘bristling’ with identities, memories and the transformative effects of moving through place[9-12].

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[juniperpublishers-endocrinology]

Small Pheochromocytomas: Clinical, Diagnostic and Perioperative Issues of Disease- Juniper Publishers

Abstract

Small Pheochromocytomas: Clinical, Diagnostic and Perioperative Issues of Disease

Introduction: Pheochromocytoma (P) is considered as relatively rare adrenal tumor with clinical manifestation after reaching the size of 4-6cm. Meanwhile, it’s supposing that small P can be not rare found within different diagnostic imagination. Some of these, being clinically silent, can cause serious cardio-vascular risk undergoing unrelated medical procedures. We compared clinical course, peculiarities of diagnostics and treatment of small P (less than 3cm) and bigger P on the basement of own clinical experience among patients underwent adrenalectomy on proven or suspected P.

Material and methods: Group of small P was comprised by 14 patients aged from 21 to 62 years with mean size of tumor 23mm (range: 4-29mm). Control group consisted of 35 patients corresponded on age (23-75 years) with mean P diameter of 56mm (range: 30-127mm). Small P comprised 8% of all 175 patients with P operated on during the last 19 years in endocrine surgery hospital from the whole group of 967 adrenalectomies. Prevalence of women and right side lesions characterized both groups.

Discussion: Principal differences between groups were less prominent clinical activity (any symptoms were detected in half of small P) with less level of catecholamines and metanefrines in lab examination of serum and urea of small P patients. Computed tomography was often the first but not targeted diagnostic step. Silent clinical course was the main reason that small P have been discovered predominantly incidentally with no blockage of alpha-adrenergic receptors before surgery in 6 of 14 patients. Most of them had a critical elevation of blood pressure during operation (43% against 9% in control group; p<0.05). Despite small size and mild catecholamine excess in small P group, 4 from 14 patients (29%) experienced episodes of potentially harmful hypertensive crisis during unrelated medical procedures in the past. All small P were treated successfully by laparoscopic adrenalectomy. Most of patients became free from hypertension.

Conclusion: Small P may carry actual risk of unexpected hypertensive crisis during any unrelated medical procedures. The clinical course of small P is hidden in half of patients and laboratory investigations are interfered with mild elevation of biochemical markers. Laparoscopic adrenalectomy is safe mode of treatment of small P in case of adequate preparation.

Keywords: Pheochromocytoma; Small size; Diagnostics; Peculiarities; Laparoscopic adrenalectomy

Introduction

Pheochromocytoma (P) is considered as relatively rare adrenal tumor which typically demonstrates clinical manifestation after reaching the size of 4-6cm. The rate of P among adrenal incidentalomas is about 5 %, and on autopsy among died from all causes 1:1000 [1]. Meanwhile, it’s supposing that small P can be not rare found within different diagnostic imagination. Some of these, being clinically silent, can cause serious cardio-vascular risk undergoing unrelated medical procedures [2].

Half of P are discovered only at autopsy despite most of them demonstrated bright clinical symptoms [2,3]. From this point of view the case of 34th USA President Dwight David Eisenhower, whose diagnosis of small P was revealed only postmortem, is a very illustrative example. He suffered from poor controlled arterial hypertension for a long time and sustained 4 myocardial infarction [4].

Purpose

To compare clinical course, peculiarities of diagnostics and treatment of small P (less than 3cm) and bigger P on the basement of own clinical experience among patients underwent adrenalectomy due proven or suspected diagnosis.

Material and Methods

There was a retrospective study with randomized historical control group. All together during 1.01.1997-1.08.2016 years in Department of Endocrine Surgery of Ukrainian Research Center for Endocrine Surgery of Public Health Ministry 967 adrenalectomies have been performed. Tumors arisen from adrenal medulla comprised 18.1% (175 cases). Patients were aged from 8 to 75 years with female prevalence (74.3%). Size of P mostly exceeds 30mm ranged from 3.8mm to 127mm (mean 47.99±2.93mm). Adrenalectomy was performed initially through open conventional lumbotomy, but during last decade predominantly by laparoscopic methodic (71.4% among all cases).

The group of small P was comprised by 14 patients aged from 21 to 62 years with mean size of tumor 23 mm (range: 4-29mm). Control group consisted of 35 patients corresponded on age (23-75 years) with mean tumor diameter of 56mm (range: 30-127mm). Small P comprised 8% of all 175 patients with P operated on during the last 19 years in endocrine surgery hospital from the whole group of 967 adrenalectomies. Prevalence of women and right side lesions characterized both groups. We excluded from both groups all cases of malignant P, family forms, bilateral P, children and pregnant.

After laboratory confirmation of diagnosis patients were prepared by alpha-adrenoblockers till stable normalization of BP. Computed tomography was the main method of visualization (in most cases – on «Toshiba Aquilion 64» CT). Laparoscopic adrenalectomy was performed by well known traditional methodic of M. Gagner [7] with authors modification [8]. Statistics for compared groups of study based on paired “t” test. Difference considered significant if P was less than 0.05.

Results and Discussion

Typical presentation of P in group of small P was the incidentally discovered on CT adrenal tumor of high native attenuation (mean - +31.06±3.52HU) – Figure 1. Macroscopically small P looks like homogenous solid tumor of grey or grey-cherry color defined by thin capsule (Figure 2). Clinical and laboratory data of studied groups are presented in Table 1.

The less prominent clinical activity (any symptoms were detected in half of small P) with less level of catecholamines and metanefrines in lab examination of serum and urea of small P patients represented the principal difference between groups. Computed tomography was often the first but not targeted diagnostic step. Silent clinical course was the main reason that small P have been discovered predominantly incidentally with no blockage of alpha-adrenergic receptors before surgery in 6 of 14 patients. Most of them had a critical elevation of blood pressure during operation (43% against 9% in control group).

Despite small size and mild catecholamine excess in group of small P, 4 from 14 patients (29%) experienced some episodes of potentially harmful hypertensive crisis during unrelated medical procedures in the past. All small P were treated with successful laparoscopic adrenalectomy. Most of patients became free from arterial hypertension.

Discussion

Our study confirmed opinion of some authors that even small P can bring significant risk for patients in case of stressful situation or unrelated medical procedures [5,6]. Despite existing information about significant rate of “hidden” P in population [1,9], targeted screening of P among patients with elevated BP or sympathetic crisis is not recommended routinely. Yu R et al. [5] supposed that small P could carry the 17% cardio-vascular risk in case of unrelated surgical or dentistry manipulation, that is equal to P of regular size. We found two fold differences in such risk for small and bigger P (29% against 69%), but it even more than found previous authors and allow us strongly recommend surgical operation for all such patients, as it sounds from other investigators [5,6]. Some authors recommend adrenal venous sampling with glucagon stimulation test in patients with negative visualization but clinical suspicion to catecholamine producing tumor, that prove presence of P in 36 from 41 patients[6]. Mere than half of those patients became normotensive after operation. We also observed normalization of BP in ¾ of operated patients within first months after adrenalectomy. Laparoscopic methodic of adrenalectomy for patients with P is well recognized type of surgery all around the world [1,7,8], all the more for small tumors, and we confirm it one more time on our clinical series [9].

Conclusion

Pheochromocytomas of size less than 3cm is not exclusive catecholamine producing tumors and comprise 8 % of operated on P in large clinical series. Small P may carry actual risk of unexpected hypertensive crisis during any unrelated medical procedures. The clinical course of small P is hidden in half of patients and laboratory investigations are interfered with mild elevation of biochemical markers. Laparoscopic adrenalectomy is reliable and safe mode of treatment of small P in case of adequate preparation with alpha-blockers.

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[juniperpublishersna]

Antimicrobial Peptide Elicitors (APEs) and Inhibitors (APIs): Challenges and Opportunities in Personalized Medicine-Juniper Publishers

JUNIPER PUBLISHERS-OPEN ACCESS JOURNAL OF DRUG DESIGNING & DEVELOPMENT

Abstract

Antimicrobial Peptide Elicitors [APEs) and inhibitors (APIs) are physical [class I), chemical [class II) or biological agents [class III) that either up or downregulate human antimicrobial peptide expression respectively. The up or downregulation of anti-microbial peptides (APs) is related to the origin and/or severity of several diseases, including tuberculosis, HIV/AIDS, cancer and psoriasis among others which lead to opportunities for drug design. The development of these "first in class” molecules in the so-called "host-directed therapy”, together with companion diagnostics offer unique opportunities to increase efficacy and minimizing toxicity in future clinical settings. In this context, APIs and APEs could help in current treatment schemes with reduced risk of side effects or in new schemes as e.g. MDR-TB clinical trials. The efficacy and safety of APEs and APIs remain to be demonstrated in the clinic, but this new class of molecules holds great opportunities to personalized medicine.

Keywords:   Antimicrobial peptide elicitor; Beta defensin; Cathelicidin, DEFB1; LL-37; Cancer, Diabetes; HIV/AIDS; Psoriasis; Personalized medicine

Abbreviations:  1KGP: 1000 Genomes Project; DEFB1: Human Beta Defensin 1 Gene; ENCODE: Encyclopedia of DNA Elements; hBD-1: Human β-Defensin-1 Peptide; MDR-TB: Multi-Drug Resistant TB; rSNP: Regulatory SNP; SNP: Single Nucleotide Polymorphism; T1R: Type 1 Reaction;TB: Tuberculosis   

Introduction

Antimicrobial Peptide Elicitors [APEs) and inhibitors [APIs) are physical [class I), chemical [class II) or biological agents [class III) that up or down regulate human anti-microbial peptide expression respectively [1]. The up or down regulation of anti-microbial peptides [APs) are related in origin and/or severity to several diseases [1-3], which leads to opportunities for drug design and development of this first in class molecules in the so-called "host-directed therapy" Nylen, F 2017. In this context, APIs and APEs could help in current treatment schemes with reduced risk of side effects, or in new schemes as e.g. MDR- TB clinical trials.

Challenges and opportunities

APEs and APIs in the future clinical setting: Even when a submitted patent Prado 2013 Innate Immun and a cell assay for high-throughput screening [HTS) has been published to discover APEs Nylen 2004 and 2017 these methods have a limitation in that they attempt to represent all human ethnic variants with just one promoter from one cell line from only one donor. These assays are useful to discover effective APEs for the donor but not necessarily for other patients, even if from the same ethnic background or family. Furthermore, we do not know the extent to which the different responses among cell lines are due to the disease status per se or because those cell lines come from genetically different individuals Prado 2013 Innate Immun.

In recent years, we have been able to making predictions by generating in silico representative promoters of determinate ethnic origin based on the most frequent alleles of each SNP and to predict which signalling routes are not altered by regulatory SNPs [rSNPs). After that, propose the APE/API that could be more effective in that target population, also with future application in N=1 clinical trials [Flores Saiffe Farias A, Chavez Alvarez R, Prado Montes de Oca E, in preparation). Also due to the advantages of performing the customized regulatory SNP prediction [rSNP) with in silico analysis [based on the in-vitro evidence ENCODE and 1KGPamong other projects) of the promoters of patients and/or a target ethnic group Flores Saiffe 2015, there is a unique unthinkable years ago) to develop simultaneously both lead molecules and their companion diagnostics as y "pharmacogenomics" panels. Most potential drugs fail in Phase II trials, and at least 50% of these are due to lack of efficacy and 25% due to toxicity Plenge 2013. The in silico prediction of that efficacy and toxicity can now be determined before the design of a clinical trial and more easily explained by SNPs [and other genetic variants) functionality, originated by interindividual or inter-ethnic genetic differences. Our above mentioned software together with additional databases, methods and software to predict drug side effects Niu 2015, Toropov 2014, Zhang 2015 could pave the way to the effective application of APEs/APIs in the clinic with personalized medicine as the background rationale.

A novel indirect approach: The use of APEs and APIs is promising and innovative because it is theoretically more difficult for a pathogen to develop a way to overcome these agents, because in most cases they are not antimicrobial per se but act indirectly up on a) induction, b) up regulation or c) down regulation of anti Microbial peptides Prado 2013, Innate Immun. These can be novel molecules or well-known molecules such as vitamin C with novel role as an APE Cruz Diaz 2015. APEs could be useful in the treatment of diseases caused or modified by AP deficiencies such as shigellosis, Crohn's disease, HIV/ AIDS, atopic dermatitis, lepromatous leprosy and cancer, among others Prado 2013 Innate Immun. In the case of leprosy, for example, the challenge is to find specific and mild inhibitors as APIs that combat T inflammatory response of type 1 reactions [T1R) without compromising the host immune system or use APIs for hepcidinin combination with APEs for both cathelicidin and defensins [11]. Alternatively, in tuberculosis [TB) research, there could be an opportunity to test APEs of DEFB1[hBD-1 peptide), DEFB4 [hBD-2) and CAMP genes [LL-37) in clinical trials of multidrug resistant variant tuberculosis [MDR-TB), because there is a need and justification to try novel approaches when in the past other drugs/therapeutic schemes have fail Khusro A, 2016.   

Conclusion

APIs and APEs could help in current treatment schemes with reduced risk of side effects or as completely new approaches as e.g. MDR-TB. The efficacy and safety of APEs and APIs remain to be demonstrated in the clinic setting, but this new class of molecules with their companion diagnostics, even with great challenges to overcome, holds great promise for the future of personalized medicine.   

Acknowledgement

Results of my research group regarding APEs/APIs and the rSNP prediction software [SNP Clinic v.1.0) have been supported by the Public Education Ministry [SEP) and National Council of Science and Technology Sectorial Funds [CONACYT, Mexico) [grant numbers CB-2008-01-10581 and CB-2014-01-222618), Intellectual property PROPIN-COECYTJAL 2014 [grant number 2870), Aguascalientes State-CONACYT Mixed Funds [grant numberAGS-2010-C02-143938), Personalized Medicine National Laboratory Special Fund [grant number C-491/2016-271627). The funding sources had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; nor in the decision to submit the article for publication. Special thanks to wellcome Trust [UK) for advanced courses fellowships [2006, 2009, 2012 and 2013) and EMBL/EBI fellowships [2013, 2015). EPM is a Level I Fellow of the National Researchers System [SNI, CONACYT). This work is dedicated to the loving memory of Carrillo Rodríguez KE, Obledo Vázquez NO, Dávila Vázquez G, GÓmez Romero J and LÓpez LÓpez A.  ��

Conflict of Interest

Dr. Prado Montes de Oca and collaborators are pursuing two patents related to the methods for the enzymatic synthesis of a novel API and APEs as well as their applications.

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[juniperpublishersoceanography]

An Acoustic Archival Tag for Long-Range Tracking Of Small Fishes- Juniper Publishers

Abstract

This mini review describes the development of an acoustic tag for long-range (tens to hundreds of kilometers) tracking of small fishes or other marine animals. Tracking is achieved by standard RAFOS triangulation using the arrival times of unique sound signals emitted by moored sources. The tag also records temperature and pressure. All functions of the tag are controlled by an application specific microchip. The collected acoustic and sensor data are stored in a non-volatile memory. A cylindrical hydrophone of 25.4mm length and 10.7mm diameter also serves as housing for all electronic components. Power is provided by 2 button cell batteries, which enable an active tag lifetime of approximately two years.

Introduction

Much has been learned about the behavior of fishes during the past few decades through various kinds of data storage tags (DSTs), which were attached either externally to the back of the fish, or subcutaneously (e.g. Metcalfe [1], Block [2]). By recording in-situ physical parameters such as temperature, depth and light intensity, the geographical position can be inferred on the basis of retrospective analysis of known hydrographic features of the animal's environment or light level for surface species. However, such retrospective positioning is invariably imprecise because physical features may vary only slightly (horizontally, and vertically in higher latitudes) or be poorly known (at least for purposes of retrospective positioning). During the first decade of the new millennium, a new technology emerged, which allowed equipping the tags with compact high frequency acoustic transmitters, each transmitting a unique ID code. When a fish tagged with such a transmitter passed within the acoustic range of a moored stationary receiver, a record of that event was kept. While fish cannot be tracked continuously this way, this widely used technology provided valuable insight into the overall range and timing of their movements [3].

To track submerged objects over much longer distances, Rossby [4] pioneered a new approach more than 30 years ago with his SOFAR floats, that passively listened for scheduled acoustic transmissions from anchored sound sources (Rossby [5], whose narrow-band emissions, centered at 260Hz, could be detected tens to hundreds of kilometers away depending on the physical conditions of the sound channel. The selected 260Hz range renders signal absorption insignificant and avoids most of the low- frequency ambient noise Urick [6], Wenz [7]. Each RAFOS float keeps a record of the arrival times of the precisely timed sound signatures. The source distance can then retroactively be inferred by multiplying the travel time of each sound signature by its known propagation speed.

The Fish Tag

Thanks to the continuing reduction of the transistor dimensions in microelectronic circuits (Moore's Law), it is now possible to implement the complex acoustic arrival time detector of a RAFOS float on a tiny microchip. While in its most active mode when the tag is searching for sound signatures, the chip dissipates approximately 70|iW, but the stand-by power is not more than 4|iW. Assuming a realistic duty cycle of 10% (e.g. searching for sound signatures for 6 minutes every hour), the average power dissipation amounts to just 10-11|iW. Two 1.5-volt button cell batteries of 80mAh capacity can thus keep the system running for more than 2 years. The microchip also houses a thermal sensor as well as a pressure sensor interface to assess depth. The sensors utilized in the fish tag yield a resolution of 0.05 °C and approximately 0.7 PSI (~0.5m), respectively. If so desired, pressure and temperature can be sampled more frequently than searching for sound signatures. A more detailed description of the chip's features and its design can be found in reference Fischer [8].

Accurate timing is critically important in any time-of-flight based positioning system. Since the fish tag’s energy capacity is severely limited, it uses a low power commercial watch crystal oscillator circuit as the clock source. To avoid severe clock deviations, the fish tag timer employs a digital correction unit, which allows adjusting for offset errors stemming from the manufacturing process and compensating for the expected temperature deviations. The 6-bit digital correction scheme limits timing errors to ±0.95ppm or ±0.6 seconds per week. The remaining clock deviations can be mitigated by utilizing the travel time differences from three source to determine the position hyperbolically. One can then retroactively determine the clock correction needed to obtain the right travel time [9].

The assembly of the tag is a relatively straightforward matter. The custom microchip is surface mounted on a tiny printed circuit board (PCB) together will all other electronic components, i.e., the watch crystal oscillator, the nonvolatile memory chips and 3 filter capacitors. This PCB is only 8mm wide and fits tightly inside the hydrophone cylinder, which also serves as the tag's housing. The circular pressure sensor board is attached perpendicular to the PCB and forms one of the two end plates of the cylindrical tag. Figure 1 depicts a RAFOS sound source together with one of the 4 cm long prototype tags without its final polyurethane coat.

Field Test Results

A series of field tests have been conducted during the course of this project to validate the performance of the tag in its various stages. The first was a preliminary test designed to evaluate the critically important analog preamplifier and the potential tracking range. In this experiment, source and receiver were kept below the surface mixed layer at ~40 and 30m, respectively, on the New England shelf south of Nantucket. At a distance of 70km from the acoustic source, the records revealed a robust in-band signal-to- noise ratio of approximately 6dB [10].

Encouraged by the positive early test results, the project continued. But it was not until this past summer that first complete prototype tags became available. This paved the way for a more comprehensive test conducted approximately 50km south of the Mississippi delta in the Gulf of Mexico. The logistics of this experiment were simple. The tags were attached to the ends of two 30m long ropes, which in turn were tied to 2 surface drifters equipped with GPS trackers. The sound source was kept on the host vessel, the Endeavor, and lowered repeatedly to a depth of approximately 25m from the Starboard side at various distances starting at ~130km.

The submerged tags recorded an almost uniform water temperature around 27 °C during the 40-hour test period. This warm surface layer provided for less than ideal acoustic conditions, since it bends the acoustic energy away from the surface. But a thin fresh water lens of Mississippi origin created a shallow surface sound channel such that transmissions could be detected as far as 60km away. The source level was measured with a calibrated hydrophone to be 180dB re 1μPa at 1m. It was therefore no surprise that none of the tags detected a signal emitted from any of the three farthest source sites located 72 -130km away.

4-8 sound signatures were emitted at each source site. The recordings revealed a remarkably small spread in signal propagation times, 0.053-0.132 seconds. This corresponds to a spatial uncertainty range of not more than 200m.

Conclusion

The presented fish tag, with a length of approximately 4cm similar in size to other archival tags, operates according to standard RAFOS tracking principles: it detects and records the arrival times of signals transmitted from moored sound sources. Navigational accuracy is determined by how well clock errors in the tag can be controlled, but can be kept quite small thanks to knowing total drift error and temperature of the crystal clock during mission. The two main drawbacks of the presented tagging technology are the cost for the sound infrastructure and the need to retrieve the tag to upload the archived data. At a future time, we will explore how to avoid the second drawback by adapting the tag to a miniature satellite transmitter and a release mechanism, which allows the device to float to the surface at the end of mission. The added bulk means this technology will be best suited to larger species.

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[juniperpublishersophthalmology]

Juniper Publishers- JOJ Ophthalmology

Keratoconus Progression Diagnosis Evidenced by Corneal Epithelium Mapping- Juniper Publishers

Case Report

Background

We are reporting a case of a 16y.o. (y.o.b. 1996) young gentleman that we have followed for keratoconus in our center about a year ago. His first visit occurred on February, 2011. At this time he was informed about the different options such as collagen cross-linking, INTACS, the Athens Protocol (the combination of topography-guided partial ablation PRK with CXL), and lamellar keratoplasty. Following a complete clinical investigation, recommendation was given that the 0S be treated with cross-linking with simultaneous partial topography-guided excimer surface ablation (Athens Protocol) [1], which was performed in May, 2011.

The 0D had reasonable good correction (BCVA 20/20) and therefore, due to his age and good corneal thickness (CCT in the vicinity of 500μim), we recommended for him to follow eight months to a year's time in order to evaluate a possible progression and the possibility of intervention. This paper is about our investigation of the 0D keratoconus progression not only by optical anterior segment imaging technologies, but also by the epithelium mapping, which supported our findings relating to correlation of keratectasia and elevated corneal overall epithelium.

Methods and technologies

Anterior-segment imaging of keratometric, topometric and topographic parameters can be an important tool in the decisionmaking process and prompt action. The optical instruments involved in this report were Biometry by I0L Master (Carl Zeiss Meditec Inc., USA), Anterior-Segment 0ptical Coherence Tomography (AS OCT) by Optovue RTVue (Optovue Inc. Fremont, CA), Placido topography and Scheimpflug topography by Wave light (Erlagen, Germany), specifically the Topolyzerand the Pentacam High Resolution (Oculus Optikgerate GmbH), a.k.a. Oculyzer II, which is a Pentacam HR that has been specially configured to export topometric data to Alcon's refractive suite [2]. The ultrasound bio microscopy (UBM) instrument was the Artemis II + superior (Artemis Medical Technologies Inc. Vancouver, British Columbia, Canada) [3]. To our knowledge this is the first such documented case combining these optical modalities with epithelium mapping by HF ultrasound for keratoconus screening in the peer-reviewed literature.

Patient follow-up

The initial anterior segment parameters recorded during the first visit (late February, 2011) are summarized in (Figure 1 &Table 1). Based on these findings, astigmatism was determined -1.25 D, with the flat axis was determined at 21°. We saw the patient several months later (late January, 2012). The data (Figure 2 & Table 2), indicated keratoconic progression, despite that overall corneal thickness was found increased by an average of 13μim. For example, the difference with the Pentacam (Oculyzer II) preimposed on the old and newer topometric measurement showed a change in the central steepening. For example, sagittal curvature increased, K1 (flat axis) by +0.2 D and K2 (steep axis) by +0.8 D. Likewise, anterior surface elevation was found increased by approximately + 13μim, also there was change between lowest elevation to pupil center (20711, -13 -> +3μiM, 2012 -18 -> +8μim). Based on these findings, astigmatism was determined at 40°:

We decided to further evaluate this finding because on topometric terms this finding suggested progression of the keratoconus. We obtained Artemis II+ HF UBM corneal epithelium mapping. Careful evaluation of the UBM findings revealed that the epithelium (Figure 3) was overall thicker compared to a population of 33 patients (50 eyes) [4]. The patient’s epithelium featured mean thickness 56μm (normal population 50.8μim), central thickness 60μm (normal population 52.1μm), and average peripheral thickness 50μm (normal population 49.54μm), while over the cone (located superiorly - temporal) the epithelium was thicker, at 53μm.

    Discussion

We feel that this is a good example where the -at first sight- progression of keratoconus is accompanied by epithelium whose thickness is overall thicker than the control population, particularly at the pupil center by a significant amount (+8μm). This would be impossible to establish with Scheimpflug imaging maps alone. It appears the HF Ultrasound is able, by giving the specific epithelium maps to point to that direction. Obviously, for the definite diagnosis of this theory would be re-evaluation of the cornea with Oculyzer and UBM. In case where the epithelium returned to a thinner thickness we would expect that the Pentacam maps would flatten and that would establish that there is no actual progression of the keratoconus. It is interesting to compare the posterior curvature maps of past and current and see in these maps that there is a change in posterior curvature. One has to take into account that the increase of irregularity by the epithelium thickening may be the factor that creates this bias.

    Acknowledgement

Dr. Kanellopoulos is a Consultant to Alcon Wave light.

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[journalofsportsmedicine]

Juniper Publishers - Open Access of Journal of Physical Fitness, Medicine & Treatment in Sports

Research Article

Evaluation of Physical Education Faculty of University of Mazandaran

Morteza Dousti1*, Sepideh Delkhah2 and Abolfazl darvishi3

1Assotiate professor, Department of Sports, University of Mazandaran, Iran

2MA of Sport Management, Education and Train of Mazandaran, Iran

3PhD student, Department of Sports, University of Mazandaran, Iran

Submission:   February 28, 2018;    Published:  March 13, 2018

*Corresponding author: M Dousti, Department of Sports, Assistant Professor, University of Mazandara, Iran; Email: M_dostipasha@yahoo.com

How to cite this article: Morteza Dousti, Sepideh Delkhah, Abolfazl darvishi. Evaluation of Physical Education Faculty of University of Mazandaran. J Phy Fit Treatment & Sports. 2018; 2(2): 555583 DOI: 10.19080/JPFMTS.2018.02.555583   

Abstract

CIPP model has provided a comprehensive framework for evaluation in different areas including curriculum. The overall objective of this study is to assess the Physical Education College of Mazandaran University based on (CIPP) model. This study is a Descriptive survey and data collection method is of field survey. All the students and teachers of Physical Education College of Mazandaran University had formed the population of this research, of which there were 418 students and 17 teachers according to the statistics of the education center. Based on Cochran sampling formula 200 students were selected by simple random sampling and also 16 teachers were totally selected. To collect the data, the questionnaire of the assessment of CIPP model by Ali Mohammadi was used. The questionnaire consists of 19 questions. 2 questions about the context factors, 6 questions related to Input factors, 5 questions related to the process factors, and 6 questions related to the product factors. Researcher has used Cronbach's alpha coefficient to assess the reliability of the questionnaire. In this research the questionnaire was given to a group of 30 samples, and its values were obtained as α =0/88. Kolmogorov-Smirnov test was used to assess the normality of the data distribution, and one-sample t-test and binomial test were used to check the major and minor questions. The results showed that from the perspective of both students and professors of the context factors, input, process and product of Physical Education College of Mazandaran University is away from the desired point (3/5). As the result of the research, it is recommended that due to the distance with the desired point in the fog, context factors, input, process and product should revise in order to reach the desired point.

Keywords:   (CIPP) Model; Evaluation; Physical Education; Desired point

    Introduction

Higher Education System In terms of organizations and functions should be evaluated occasionally in the course of its evolution. Thus, in line with changes and developments in the organization and educational systems, existence of a tool is needed for evaluating their performance and measuring the rate of achieving their goals. The research provides evaluation of important information about the costs, benefits and problems associated with alternative programs. Assessments are also done to assist managers in making good decisions in relation to manpower and budget planning.

College of Physical Education and Sports Science was established in 2005. This college began its educational activities from 1996 by student recruitment before becoming an independent department in the Faculty of Humanities and Social Sciences. The same year, with the admission of 20 male students, they took their first steps towards scientific and educational development in this field. The College obtained the permission of the graduate in the fields of Physical Education and Sport Sciences (pure field) in 2002. And then in 2004 it was also successful in obtaining a license to establish the field of sports physiology in MA. The same year, the office of expansion of higher education in the Ministry of Science, Research and Technology, declared its agreement to establish a college, and on Mordad 2005 it officially began its activities by a new organizational structure. In addition, between 2007 and 1389, respectively, it was successful to establish the field of sport management and sport biomechanics in MA. Also in 2011, received a license to establish exercise physiology and sports management fields in PhD.

It is Essential that managers of the organizations have a view of major weaknesses of its system, and also accordingly be aware of the orientation of the developmental strategy, which is based on competitiveness and from outside the organization might have an impact, and through all of these they can resolve their defects. So that this view to be created by the organization itself and has organizational insights with itself, an assessment model is required [1].

The idea of qualifying the educational sectors has become a major concern of the educational systems. The importance of this matter is to the extent that it can be observed in the families'considerations. Bits and Glayn 2002 on the expression of intense sensitivity of public toward the quality of education system, says: "Nowadays parents before thinking about having a baby, think about this that at which university or school their children will be educated [2]. Evaluation is of the most important measures that could play an important role in qualifying the educational affairs. Evaluation by identifying the present situation, discovering strengths, weaknesses, opportunities and threats and led to the identification of the current situation, and under its shadow, managers can step more effectively in developing their programs.

There are several models for evaluation. One of the most widely used models that are used in educational settings as an evaluation model is CIPP model. This abbreviation stands for the four-word context, input, process and creators of this evaluation model are Daniel Stufflebeam 1971. This model with systemic approach evaluates the context, input, process and product as well as the decision to improve their performance. In the systemic approach, Final goals are not neglected, rather the goals are considered in a very complex set of criteria as a component. System emphasize on the criteria that will increase the long-term survival of the organization. Higher education is one of the most important educational systems, including the key elements of human development in any country in the world. Nowadays, in educational centers, evaluation because of its nature and function is one of the largest and most controversial topics of education that as a determinant of the usefulness and effectiveness of educational programs is used at all higher education institutions in the world. So the evaluation programs in the college of Physical Education Due to the need for training experienced and qualified human resources are of paramount importance [3]. Numerous studies have been conducted using CIPP evaluation model that in this section the most important ones are mentioned.

Qaderi Pasha [4] in a study entitled "Evaluation of Bachelor of Mathematics at the State University of Tehran (Based on CIPP model)" has been evaluated the three listed stages of the areas of input, process and product of the fields of Bachelor of Mathematics at the State universities in Tehran. In this research the universities of Tehran and teacher training (Hesarak unit) were selected as a non-industrial University and University of Amir Kabir and Khaje Nasir were selected as the University of Technology that the following results were obtained:

a) Tehran University: in the input field is at the desired level, and in the process field is rather desirable.

b) University Teacher training in the input field is rather desirable and in the process field is at the undesirable level.

c) University of Amir Kabir: in the input field is at the desired level, and in the process field is rather desirable.

d) Khaje Nasir University in the input and process field is rather desirable.

e) In total Sample universities: in the input field are at the desired level, and in the process field are rather desirable.

Shams, Golshiri [5] in a study titled "providing a model to improve children's nutrition and growth promotion based on cipp evaluation model in the city of Isfahan" found that the growth of children after implementation of the model was significantly improved (p <0. 005). Other factors such as mothers' recognition of the growth charts on the growth card, timely referral to health centers to care for the child and the average meals that were given to children, significantly increased after the intervention (in each case p <0. 001). Durrani, Salehi [2] in a study entitled "Evaluation of the students of Conservatories of working knowledge by using (CIPP) model to propose a framework for improving the quality ofvocational school: Case of Conservatories of District 2 in Tehran " evaluated this educational unit. The results showed that 17 out of the 19 factors were undesirable and 2 factors were rather desirable. Zandvaniyan [6] in a study entitled "comprehensive evaluation of teacher training centers of Khuzestan province based on the (CIPP) model of evaluation" evaluated these educational units. The results show that the goals of these centers that teacher training in associate degree and is funded by the Ministry of Education, compared to the side goals are completely desirable; geographic areas, socioeconomic and cultural development of teacher training centers are relatively desirable; the input of teacher training centers of the province and processes of structure / organization, teaching / learning, and service / support are relatively desirable; and finally, teacher training centers of the province are completely desirable.

Salehi 2006 for his thesis in the field of educational research evaluated the Conservatories of working knowledge by using the CIPP model, to propose a framework for improving the quality of Conservatories of working knowledge, and in this study, as a case study, he examined Tehran Conservatories of district 2, and found that the situation in three parts: input, process and product of the studied Conservatories are undesirable. Finally, to improve the Quality status, he provided recommendations at the level of each of the factors associated with the input, process and product. Akhlaghi and his colleagues [7] for implementing the research project for research deputy of Tehran University of Medical Sciences, evaluated the quality of educational programs in higher education by using the cipp model, and in the end they found that the highest level of total desirability, is related to the faculty members in the input area (the area of human resources), and the lowest total desirability is related to the budget in the input area (the area of Financial Resources). So it can be concluded that the continuous evaluation of medical records and MA medical records Education programs, helps to assess the strengths and weaknesses of programs and raise their quality. Pakdaman [8] in a study entitled "evaluation of the rate of achievement of educational objectives of the Educational Departments of Periodontics and Oral Health based on evaluation model of cipp" showed that in two areas of content and process, there was no significant statistical difference between the two groups. Reviewing of the subheads in the mentioned context, which its achieving was weak, is recommended to improve the educational program.

Ali Mohammadi 2013 in a study entitled "Evaluation of Medical Science University of Rafsanjan, based on a theoretical model of CIPP," evaluated Medical Science University. The final results of the evaluation showed that, the university has a desirable situation. In order to achieve a highly desirable situation, officials of the colleges and universities should further consider the strengthening of the important factors such as revision of curriculum content, teaching methods of teaching, assessment and communication skills to the teachers. Okhovati and his colleagues [9] in a study titled "Evaluation of Health programs of the field of Bachelor of Health Services Management at the University of Medical Sciences Of Kerman based on the cipp model" found that Health programs of the field of Bachelor of Health Services Management In terms of context, input and product has some limitations and defects. Weaknesses in the curriculum and ambitious goals, which are considered for this field and are shown as Inefficiency of the graduates of this field, make it necessary to review the Bachelor curriculum. Zhang et al. [10] in a study entitled "Using the context, input, process and product (CIPP) as a comprehensive framework to guide the planning, implementation and evaluation of learning programs services" have used CIPP model. The results showed that Using CIPP method is useful in educational institutions. They also examined the impact of each component in the success of the project and discuss how the model will affect the quality of the project. Lin et al. [11] examined the impact of applying CIPP model on the learning process of student at the schools of Nepal, and in their study they examined the effect of each component of the mentioned model (context, input, process, and product).

Arsovski [12], in a study titled "Impact of quality in Business Excellence: A Case Study" that was conducted on 159 companies in Serbia, showed that; Business problem is its excellence. And improvement of business excellence through a relatively small investment in quality is possible. Kahn et al. [13] in a study entitled "A method for conducting the evaluation of longitudinal program of Health and Human Services of the National Action Plan for the Prevention of Infections", have used the evaluation model of CIPP. The results indicated that the evaluation model of CIPP provides a structure to track the components of a program. Relation examines the components, timing and method of implementation of each component. College of Physical Education of Mazandaran University began its educational activities in 2005 as a college. Over nearly a decade of activity of this college until now, it is not evaluated by a systematic model. What are the weaknesses and strengths of the educational system of the college? How can they be realized? To answer these questions, researchers are trying to use the CIPP model to evaluate this college.

    Methodology

Due to the research objectives; this study is a Descriptive survey and is of applied research and data collection method is of field survey. All the students and teachers of Physical Education College of Mazandaran University had formed the population of this research, of which there were 418 students and 17 teachers according to the statistics of the education center. All the students and teachers of Physical Education College of Mazandaran University had formed the samples of this research that based on Cochran sampling formula 200 students and 16 teachers (5 tuition teachers were among the 16 participants who responded to questions) answered the questions of the questionnaire. Students were selected by simple random sampling and 16 teachers were totally selected. In this research to collect the data on the four factors of context, input, process and product, and criteria for each of them, the questionnaire of the assessment of CIPP model by Ali Mohammadi 2010 was used. The questionnaire consists of 19 questions. 2 questions about the context factors, 6 questions related to Input factors, 5 questions related to the process factors, and 6 questions related to the product factors. Researcher has used Cronbach's alpha coefficient to assess the reliability of the questionnaire. In this research the questionnaire was given to a group of 30 samples, and its values were calculated by SPSS software and obtained as a =0/88 that this amount is statistically significant and is confirmed. For data analysis, descriptive and inferential statistical methods were used. In descriptive statistics, frequency, frequency percentage, mean, standard deviation, charts and tables are used. In inferential statistics Kolmogorov-Smirnov test was used to assess the normality of the data distribution, and one-sample t-test and binomial test were used to check the major and minor questions.

Findings of the research

Table 1 shows that, 43/5% of the samples are men and 56/5% of them are female. Table 2 shows the 80/5 percentage of respondents who are undergraduate student. Table 3 shows that the largest number of respondents is related to the undergraduate students of sport management. Table 4 shows the average age of students of 22/48 years and the average age of teachers of 39/94 years. According to the obtained results (Table 5) and significant levels that each research variable is larger than 0/05, the data of the variables are normal and parametric tests can be used and for each of the variables of the research that is less than 0/05, data distribution is abnormal and nonparametric tests can be used.

H0 =the data come from a normal population

H1 =the data does not come from a normal population

Table 6 shows that other than output variable, the average is less than moderate; other variables had the average above moderate, all variables were far from the desired point of 3/5. Table 7 indicates that from both students and professors perspective, there is a significant difference between the underlying factors of Mazandaran University of Physical Education with the ideal point of (3.5). Table 8 indicates that from both students and professors perspective, there is a significant difference between the input factors of Mazandaran University of Physical Education with the ideal point of (3.5). Table 9 indicates that from both students and professors perspective, there is a significant difference between the process factors of Mazandaran University of Physical Education with the ideal point of (3.5). Table 10 indicates that from both students and professors perspective, there is a significant difference between the output factors of Mazandaran University of Physical Education with the ideal point of (3.5).

    Discussion and Conclusion

Each organization has an urgent need to an evaluation system in order to determine the degree of acceptance and quality of their activities, especially in complex and dynamic environments [14].

Performance Evaluation of Physical Education Faculty of the University of Mazandaran will be the first step toward excellence in the quality and quantity ofthe activities ofteachers and students of the Physical Education Faculty ofthe University of Mazandaran. In a general category Verten and Sanders 1987 have categorized evaluation models into six categories of evaluation approaches: goal-oriented evaluation, management-oriented model, and consumer-based model, a model based on experts' opinion, the model based on advocacy, Naturalistic and participatory model [15]. But some of the most important evaluation models that have been used more in higher education include: Tyler evaluation model, Hammond assessment model, and portfolio evaluation model, CIPP evaluation model, evaluation model of the University of California-Los Angles and the validation model and Heywood 2001. The researchers have applied the CIPP model in this research, due to its comprehensiveness. This model has four criteria. The CIPP model has provided a comprehensive framework for the evaluation of different areas including curriculum. The most important evaluation purpose of the CIPP model is the performance improvement of the program. This model helps the people involved in the curriculum to correct their curriculum during the program and after the program, to collect data. This model is designed to recognize the success of the program in achieving the objectives, in addition to the three stages mentioned above, it refers to 2 types of descriptive and judgment information and 4 key elements of the program which should be assessed and evaluated. Therefore, in this research, the evaluation of Mazandaran University of Physical Education has been based on the CIPP model.

The results of the study indicated that the Faculty of Physical Education is not in a good condition regarding the underlying variable (school environment for the education of the students and their interest to learn science). Therefore, the Faculty of Physical Education has had a modest performance in creating environmental conditions for education and is distant from the ideal point. It seems that if the course material is taught in a social and cultural environment, the intellectual development of learners will be decisive. Therefore, social participation is one of the important conditions for learning. A targeted education environment is an environment that creates different opportunities to interact with a variety of thoughts and ideas. Such an environment allows the student to discover his surroundings in his own way, and these conditions can of course create opportunities for the faculty to find different ways to deal with the students.

The issue of students’ interest to learn science, has been a very important issue in recent years, but according to the researcher, these researches should be conducted from the time of selecting fields in high school; where the students make decisions for their academic future, which group and field to choose in order to meets his educational needs. Therefore the researcher suggests that in order to find more accurate results, he must start before the university and expand the range of assumptions as well, because this subject and such human subjects are of those topics that are not restricted to one or more variables. So you should strive to achieve a higher status. The results of the study indicated that the Faculty of Physical Education is not in a good condition regarding the input variable (students’ abilities, professors’ abilities, educational content, educational facilities, educational goals and curriculum).

Universities and institutions of higher education as the highest centers of deliberation and the scientific community with an established presence of thoughtful thinkers, researchers, scholars and students in academic promotion and to accelerate the movement of thought, belief, political and cultural community has a major role. In this regard, we should try to find college students with good abilities to send to the universities, employ skilled and talented teachers, and continuously update educational content, educational facilities, educational goals and curriculum. The results of the study indicated that the Faculty of Physical Education is not in a good condition regarding the process variable (students’ activities, professors’ activities, academic performance, activities of the personnel and authorities). Mazandaran University of Physical Education should help students who have difficulty in learning to promote learning through conducting education programs and provide a special program for the students who are in a proper level.

Regarding the employees, the main objective of the performance evaluation is the access to accurate information about the performance of employees and the more accurate is this information, the more benefits it has, including:

a) Acceleration in the decision-making process by showing the strengths and weaknesses of various Operations

b) Accountability of the officials,

c) Increasing the feeling of solidarity and loyalty

d) Increasing the leadership power of the managers

e) Better communication between managers and employees

f) Identifying corrective views

g) Orientation of the educational programs.

Although the professors’ activities are distant from the ideal point, it is recommended that the financial mechanism be applied as important tools in policies and codification of education policies. With the allocation of funds to educational departments and delegating the authority in order to use the funds, has created a high incentive in the faculty members to work and try.

The results of the study indicated that the Faculty of Physical Education is not in a good condition regarding the output variable (employment, continuing education, entrepreneurship, scientific production, realization of educational goals and social goals). Most of the world countries deal with the problems of employment, but the multiplicity of factors and anonymity of some factors in third world countries has led to more complex issue. Now, the overall management of the country followed by the application of scientific methods is to identify and control the problematic factors in the field of employment and turning the challenges into opportunities to accelerate the momentum of development. Universities and centers of higher education are charged with the mission such as the production of knowledge, training of experts needed in society, technology development, innovation and creativity, and nowadays, the experts believe that achieving sustainable development can be realized in the light of applying modern knowledge and technology.

Therefore, in order to be on the road of development and avoiding the underdevelopment, some circumstances should be provided that university could train students to apply new technology and foster acceptance of different responsibilities in the organization and the community. In order to discuss about the challenges and opportunities of the higher education in providing needs of skilled manpower required in the labor market, the effective factors are divided into two groups of internal and external groups and then each group is described in detail.

The entrepreneurship characteristics have also been known as the factors affecting the education performance in colleges. Hence, the allocation of a part of the promotion points and the promotion of the faculty members to the entrepreneurship characteristic through considering coefficients to create a relationship between industry and university, relationship with the alumni office, doing projects in order to solve the problems of the country, creation of entrepreneurship unit in each college, supporting the knowledge-based companies of the faculty members which are predicted in the Fifth Development Plan projected bill, are among the approaches that have been proposed. The findings of the present study are inconsistent with the findings of Zendoaniyan [6], Qaderi Pasha [4], Ali Mohammadi et al. 2010 and Pakdaman [8], and are consistent with the findings of Smith 2013. The results of the study indicated that Mazandaran University of Physical Education has a proper distance with the ideal point in all the four criteria of CIPP model. It is recommended that the authority of the university propose revisions to these processes in order to improve their utility [16,17].

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Use of Moringa (Moringa Stenopetala) Seed Extract for Removal of Some Anionic Dyes (Direct and Reactive Dyes) in Textile Wastewater - Juniper Publishers

Abstract

With textile wastewater being one of the most sources of pollution containing higher value of colour, BOD, COD and several pollutants, brings serious problem to the ecological environment. This study is particularly focused on evaluating the efficacy of removal of dyes such as reactive dyes, direct dyes, mixture of dye wastes and mixture of industrial and dye wastewaters by the natural absorbent Moringa. The seeds of the Moringa tree contain a coagulant protein that can be used in the treatment of industrial wastewater. The extracts of seeds (coagulant) obtained by two methods viz. simple extraction with distilled water and with saline water have been used for the study. The effect of some operating parameters on coagulation namely pH, coagulant dosage, mixing time, colour removal and turbidity was studied. It was observed that the colour removals in direct red and reactive red dyes are 94.45 and 98.4% respectively with simple extract of seeds done with distilled water and it was in the order of 96.6 and 97.3% respectively with saline extracts of the seed. These values of colour removal of dyes are optimized at 70ml/L of coagulant and pH 10. The mixture of industrial wastewater and dye wastes, colour removal and turbidity removal was 85.8% with simple extract and 53% with saline extract respectively at optimized point. Moringa stenopetala seed has demonstrated to have high removal ability for anionic dyes.

Keywords: Moringa stenopetala; Natural coagulant;Colour removal; Wastewater; Treatment; Coagulation; Flocculation

Introduction

In textile waste water, dyes are considered the most important pollutants. High volume of waste water that is produced by the textile industry causes water pollution. Generally, dyes in waste water from textile and dyestuff industries are difficult to remove. This is because dyes are usually synthetic and have complex aromatic structures which make them more stable consequently they are difficult to biodegrade [1]. The removal of dyes from textile waste water is one of the most environmental challenge [2]. For many years, researchers have been working on ways of removing dyes from wastewater and different procedures have been developed; for example, physical and chemical degradation and adsorption onto materials such activated carbon and, in addition to a large number of other techniques such as Fenton’s oxidation, electrochemical degradation, ozonisation, etc [3]. The most commonly used in the textile industry are chemical methods that use oxidizing agents such as, peroxide of hydrogen, ozone and purification by physicochemical process of coagulation-flocculation, in which chemical compounds are used, the most employed are iron and aluminum salts [4]. This physicochemical process is widely used both in developed countries as in developing, for it easy operation and low cost. Nevertheless, when applied in textile wastewater, it generates large volumes of sewage sludge and the ineffective decoloration of some soluble dyes.

Moringa tree belongs to the family Moringaceae which is shrubs trees cultivated across the whole of the tropical belt including Ethiopia, used for a variety of purposes such as food, medicinal, and others [5]. The seeds of the Moringa tree contain a coagulant protein that can be used in the treatment of industrial wastewater. For drinking water clarification, Moringa seeds is also used as coagulant/flocculent agent due to its high content of a water-soluble cationic protein which able to reduce turbidity. Oil extracted from Moringa can be used for water treatment, for drinking water clarification and it is also used for textile wastewater treatment [6]. The use of natural coagulant is followed in developing countries, as substitution of external chemical coagulants such as aluminum sulfate and ferric chloride. The water -soluble extract of the dry seeds of Moringa is one of the natural coagulants. Moringa is used for water treatment in two different methods, one as a primary source of activated carbon and the second method through seed extraction, and produce a product working as a coagulant/flocculant agent [2].

At low temperature working conditions, the performance of these customary chemical coagulants is dubious and on-going developments have resulted in the introduction of polymerized aluminium coagulants. Owing to its higher superiority and lower consumption of alkalinity, Polyaluminium chloride (PACl) has garnered a growing market. Flocculants such as the more common polyacrylamide, which are organic synthetic polymer available in the market, offers a wider selection of chemical coagulants to cater for the diverse requirements of the individual water treatment plants [7]. Currently, there is an increased interest in the decolorization and decontamination of industrial textile wastewater. Different treatment technologies have been studied in order to solve the problems caused by the toxic substances contained in industrial textile wastewater, such as electrocoagulation, adsorption, photocatalytic process, ozonation, membrane bioreactor and anaerobic/aerobic biological treatment [8]. However, these methods are neither economically nor technologically suitable for large scale use and normally require the combination of two or three methods to achieve an appropriate level of colour removal [9-11]. The various coagulants attempted for colour removal and their efficiencies are listed in Table 1. To overcome the drawbacks of inorganic coagulants and synthetic polymers associated with growing environmental concerns worldwide, there is a need to consider other potential alternatives for textile wastewater treatment in order to minimize environmental damage and improve the wellbeing of human populations. Therefore, researchers have shown considerable interest in the development of natural polymers as coagulants in the recent past [7,12-14].

RTW: Real Textile Wastewater; SS: Suspended Solids; SSP: Surjana Seed Powder; MSP: Maize Seed Powder; TW, Cr: Tannery Waste, Chromium

Plant materials as coagulants offer several advantages over conventional coagulants such as aluminium sulphate as stated below [8].

1. Activity is maintained over a wide range of influent pH values - no pH correction required

2. Natural alkalinity of the raw water is unchanged following coagulation-no addition of alkalinity required

3. Sludge production is greatly reduced and is essentially organic in nature with no aluminium residuals – sludge volumes are reduced by a factor of up to 5.

4. Minimal coagulant dosage requirement

5. Efficiency at low temperature

6. Chemical coagulants are generally more expensive, toxic and with low biodegradability.

Many researchers carried out studies using Moringa seed for water and wastewater treatment on the seed itself and as cake powder. As the studies reported, the Moringa seeds have content of protein (26.50% - 32.00%), fiber (5.80% - 9.29%), ash (5.60% -7.50%), fat (42% - 45%) and moisture contents (8.7% - 9.1%) [15]. It is also stated that Moringa seeds as one of the most effective natural coagulants, applied to transform water constituents into forms that can be separated out physically. Significant quantities of high molecular weight water-soluble proteins present in the seed of Moringa carry a positive charge [16]. When the crushed seeds added to raw water, the protein produces positive charges acting like magnets and attracting the predominantly negatively charged particles (such as clay, silt, bacteria, and other pollutants). Under proper agitation, these bound particulates then grow in size to form the flocs, which may be removed by filtration or left to settle by gravity [17-19]. In developing countries, Moringa seed is considered favorably in terms to reduce the costs of wastewater treatment in comparison with chemical coagulants [17,20-22]. In addition, the sludge produced by Moringa seed as a coagulant is stated to be innocuous and 4-6 times less in volume than the chemical coagulants produced. In the present attempt, a study has been carried out systematically to assess the efficacy of colour removal in textile waste water containing some anionic dyes such as direct and reactive dyes which are most widely used for coloration of cotton, using Moringa stenopetala seed extracts as coagulant.

Materials and Method

Materials

Domestic mill for grinding the seeds in to powder, nylon sieve filter, Whatman filter paper 4, digital pH meter, UV spectrophotometer (Perkin Elmer, Model Lambda 2500), and Moringa seed were used during the experiment work. The HI93703 Turbidity meter was used to measure turbidity as per ISO 7027 Method. The dyes used in this study were Direct Blue/ Red, Reactive Red/ Blue and a mixture of both dyes; such as C.I Direct Red 81 (λmax 497nm), C.I Direct Blue 86 (λmax 346nm), C.I Reactive Blue 19 (λmax 315nm) and C.I Reactive Red 195 (λmax 532 nm)). Finally, all dyes are mixed together simultaneously with themselves (λmax 362nm) and with industrial wastewaters obtained from Bahir Dar Textile Share Company, Bahir Dar, Ethiopia (λmax 333nm). Various chemicals as presented in Table 2 for making the buffer solutions of different pH, Sodium chloride and ethanol for Moringa seed extraction, were used.

Methods

Moringa (M. Stenopetala) seed collection: Moringa seed were collected manually from the dried pods of trees. The seeds were dried in sun light for three dyes. The hull was removed from the seed surface and wings from the kernels after drying. The kernels were ground in to medium fine powder with a domestic mill to achieve solubilization of active ingredients in the seed.

Coagulant extracts: It is possible to use the Moringa seed as coagulant either as seed or extracting the oil from the seed (defatted cake). To enhance effectiveness on wastewater treatment, some studies have recommended the importance of using defatted Moringa seed[23,24]. In line with this recommendation, defatted Moringa seed was prepared for the purpose of this study.Extracts were prepared by two methods such as a simple extract with distilled water and a saline extract with sodium chloride, as explained below.

1. Simple extract

Production process of simple extract coagulant: Grinding of dry seed without shell→Aqueous dissolution of seed in distilled water→stirring→filtration To prepare 1 L of simple extract coagulant in aqueous solution, 50 g of seed powder was dissolved on 1 L of distilled water by mixing vigorously for 45 min in a magnetic stirrer at room temperature. Then, the mixture was filtered twice: once through commercial filter paper on a funnel and once again through a finefiltering system (Whatman filter paper). The result was clear, milklike liquid and was used as coagulant without further purification.

2. Saline extract

Production process of saline extract coagulant: Grinding of dry seed without shell → Dissolution of seed in a solution of 0.5M NaCl → Stirring → Filtration

To prepare 1L of saline extract coagulant in aqueous solution, 50g of powder were dissolved on 1L of NaCl 0.5M solution by mixing vigorously at pH 7 for 45min in a magnetic stirrer at room temperature. Then, the mixture was filtered twice: once through commercial filter paper on a funnel and once again through a finefiltering system (Whatman filter paper). The result was clear, milklike liquid and was used as coagulant without further purification. After, the seeds kernel dried, a domestic mill was used to grind in to fine powder to achieve solubilization of active ingredients in the seed. The extract oil was soaked in 95% ethanol, 100g of the powder in 500ml of ethanol for 45 minutes at room temperature while mixed with the help of stirrer from time to time. To obtain the defatted cake, it was required to filter the solution using filter paper. The remaining solids (pressed cakes) in the filter were then dissolved in water followed by stirring and filtration in the same way. Then the cake was allowed to dry in oven at 40 °C for 24 hours. In that process ethonal got removed from the seed cake powder. Finally, the dried seed powder is stored under room temperature until it is used for coagulation experiments (Figure 1).

a. Yield of Moringa seed in coagulant preparation

The yield is calculated as given in equation (1).

Yield of moringa=

Where Mi is the original weight of Moringa powder; Mf is the Final weight of Moringa powder after filtration (undissolved solids in the solution).

b. Preparation of synthetic Effluent samples

In order to test the coagulants extracts, in a first stage, synthetic samples were prepared in the laboratory using two types of dyes, all are azo type but with a classification of different class; direct and reactive dye; tested individually and as mixtures and with industrial wastewater, and mixture of dyes added to industrial waste water. The dye stock solutions were prepared by dissolving accurately weighed dyes in water to the concentration of 100-300mg/L, then dyeing with 100% cotton fabric sample following the standard procedures was carried out and dye waste water was collected after dyeing. Different concentrations were prepared from collected dye waste (250, 500, 1000ml in beakers) for treating with coagulant.

c. Effluent analysis

Total solids, dissolved solids, suspended solids, BOD5, COD were measured following standard procedure (AMHA, 1995 and Standard methods, 1995) and SPSS Statistical Data Analysis Software was used for analyzing the data.

d. Optimisation of process parameters

In order to optimize the various process parameters, coagulant dosage range of 10-80ml/L, mixing time of 30-45 minutes, pH in the range of 2-12 were used.

e. Colour Measurements

The difference in absorbance before and after treatment measured in UV-VIS spectrophotometer was used for measurements of colour removal. The results are presented as graphs with respect to various process parameters. The percentage removal efficiency of the parameters was calculated using following formula (2).

Colour Removal efficiency=

Where Ao is the Absorbance value before treatment and A is the Absorbance value after treatment.

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Results and Discussion

Yield of extracts

It has been observed that the yield of moringa seed powder dissolved in the solution is 93.4% and 92.5% for simple and saline extracts respectively. There was no significant difference between the extraction methods in terms of yield and it is evident that maximum percentage of Moringa powder is going to be consumed by the water and used wastewater treatment in the studies by dissolution.

Characteristics of Raw Textile Effluent

An initial experiment was carried out to determine the preliminary characteristics of textile effluent for examining the effectiveness of the M. stenopetala as a coagulant. The pH of the effluent was found to be in the range of pH 9 and 11.5 for all dye effluents and industrial wastewater having dyes Table 3. This indicated that the effluent/dye waste from the textile industry has more alkaline in nature. As the measurement shows, the total solids were found at maximum level of 9000ppm and 8000ppm for the two direct dyes Red 81 and Blue 86 respectively. It was decreased to 3575ppm and 3830ppm after treatment with simple extract and 3500 and 2200 in saline extract as shown in Table 4. In addition, the experiment also confirmed that the particles of TDS are higher than TSS in the textile wastewater samples. Furthermore, the experimental result of wastewater sample show COD higher than BOD5 values. This value indicates, textile wastewater contains high amount of non-biodegradables, 3 to 4 times than degradable organic matters. For instance, direct red 81 abd blue 86 have higher value of COD which is decreased to 750 and 190 respectively in simple extract. In the same way, the highest value of BOD5 was found at reactive 195 and blu 19 which was reduced to 180 and 205 respectively in simple extract. The reduction of COD and BOD5 was also observed in saline extract treatment. The treated effluent was characterized and the values of various parameters (pH, Total Dissolved Solids, turbidity, BOD5 and COD) are compared with the raw effluent. The characteristics of raw textile effluent and after treatment with simple and saline extracts are summarized in (Table 3 & 4). One liter of wastewater was used for the treatment from the total solution. All samples have been mixed for 30-45minutes. From the table, it is also clear that less removal of Turbidity, TS, COD and BOD5 for Industrial wastes and the one mixed with dye solutions waste water due to plenty of other components of wastes in industrial wastewater.

The Effects of processing parameters on Coagulation

Effect of coagulant dose

Coagulant dosage is one of the most important parameters that have been considered to determine the optimum condition for the performance of coagulants in coagulation and flocculation. The coagulant dosage indicates the concentration of M. stenopetala seed extract in the water. This difference is important to note since a lot of the seed mass was separated during the filtration step when preparing the extract. Essentially, insufficient dosage or overdosing would result in the poor performance in flocculation. Therefore, it is significant to determine the optimum dosage in order to minimize the dosing cost and sludge formation and also to obtain the optimum performance in treatment. The effect of coagulant doses (10-80ml/L) on the removal of reactive and direct dyes using Moringa stenopetala coagulant and flocculation time is 30-45min is shown in Figure 2-5. This shows that there was continuous removal of these dye colours with increasing coagulant doses up to 70ml/L as shown in (Figure 2 & 3). After 70ml/L, the colour removal decrease that confirms the optimal concentration as 70ml/L. This may be as a result of re-suspension of solids at this concentration. Furthermore, the high concentrations (>25.0mg/L) of the coagulant confer positive charges on the particle surface (a positive zeta potential), thus redispersing the particles.

It is also an assumption that an increase in the coagulant dose may cause a decrease in pH of system. The decrease in pH may be as a result of the hydrolysis of the coagulants. Low pH values of the coagulated system usually may be attributed to the neutralization of the negatively charged surfaces of wastewater colloids, leading to their destabilization by H+ ions. However, acidification of coagulated wastewater may disturb sorption or could increase the solubility of freshly formed sludge. The highest percentage colour removal of these dyes was found to be 98.4, 86, 94.45, 89.3, 90.5 and 85.8% and 97.3, 84.45, 96.6, 84.8, 87.73 and 84.6% for Reactive red 195, Blue19, Direct Red 81, Blue 86, Industrial waste water and the mixture for both simple and saline extract respectively. This confirms that Moringa seeds to have absorbent properties and effective for removal of colour.

Colour removal

After the characterization of the effluent, the prepared coagulants from the Moringa stenopetala seeds were added to the effluent in the form of coagulant to determine the effectiveness of the extract over the textile effluent. The result shows that the extract removes the turbidity and colour from the textile effluent. Removal efficiency of up to 98.4%, for colour, was reached using 70ml Moringa Stenopetala coagulant extract. The use of Moringa seeds has an added advantage over the chemical treatment of water because it is biological and has been reported as edible [25]. All dyes selected for this study, was prepared in the laboratory for treatments and also mixed with industrial wastewater. A dye solution was prepared as required and its pH was measured by using pH meter. One liter of the initial solution was put into two beakers, and various doses of coagulant were added (10, 20, 30, 40, 50, 60, 70 and 80 in ml/L). The beakers were put one by one onto a standard magnetic stirrer. The solution was stirred for 10 min at high speed and then slowly mixed at 60rpm for 30-35min. After that, the solution was left for 45-60min for settling. The supernatant after settling was filtered through a Whatman filter paper (pore size 20–25μm). The reduction in colour concentration was measured at maximum absorbency visible wavelength of each dye solution was measured by using a UV-VIS spectrophotometer. The result of colour removal is shown in (Figure 2 & 3). In industrial wastewater colour removal is less because the effluent contains high content of dyestuff, surfactants and other additives that are generally made up of organic compounds with a complex structure. These wastewaters are collected from different sections having such different compounds and collected in wastewater plant for treatment.

Effect of flocculation time

The time of macrofloc formation (flocculation time) is one of the operating parameters that is given great consideration in any water treatment plant that involves coagulation–flocculation operations (Figure 4 & 5). Presents the effect of flocculation time using different dose of coagulants for removal of reactive dyes, direct dyes and mixture of industrial wastewater and dyes of textile effluents. The consistence increment of removals has been revealed with increasing flocculation time up to 60min, and then it decreased. The optimum flocculation time was found to be 60min. The highest removal of selected dye colours was found to be 98.4, 86, 94.45, 89.3, 90.5 and 81.5% in reactive red, reactive blue, direct red, direct blue mixed dyes and mixture of dyes/and industrial wastewater respectively in simple extract at 60 minute. As well as, for saline extract the maximum colour removal was 97.3, 84.41, 96.6, 84.8 87.73 and 80.3% in reactive red, reactive blue, direct red, direct blue, mixed dyes and mixture of dyes/and industrial wastewater respectively.

Ebeling et al studied that the removal of Turbidity and Soluble Reactive Phosphorus (SRP, orthophosphate) was increasing as settling time increased from 5 to 45min [26]. A series of jar tests were conducted to fetch the effect of settling time (0, 5, 10, 15, 20, 25 and 30min) on the removal efficiencies of BOD5, COD and TSS using low alkalinity wastewater and the results show that the small particles settle out quickly within the first 5min, with little change in the values up to 15min. The differences in BOD5, COD and TSS removal were not significant after 20min of settling as indicated by other studies [27,28]. The result of settling time is given below in (Figure 4 & 5).

Effect of mixing time

Studies were made to find out the effect of variation of the mixing time on the colour removal efficiency. Various mixing time ranging from 15 minutes to 60 minutes were maintained and the results were reported in (Figure 6 & 7). The experimental result shows that there was a continuous removal of colour, turbidity, TDS and TSS while increasing the mixing time from 15 to 45 minutes. Similar results are observed by Patel and Vashi for some other dyes [29]. When the mixing time is short (<45 minutes), the collisions between the coagulants and colloids are not efficient to precipitate suspended solids in wastewater. On the other hand, if mixing time is longer (>45 min) it would lead to an increase in flocs breakage & limit the size of the floc formed. As a result, small size flocs which are not dense to settle down & finally cause the sample to be turbid again. In sum, it is also found that the longer or shorter mixing time would result in the poor performance of the coagulant seed for binding and bridging. There were similar results in experiments made by other researchers [16]. Initially at less contact time (≤15min.) the maximum colour removal efficiency was achieved to only 63.6 and 63.7% for mixed dyes and reactive red respectively in both simple and saline extract methods respectively. But results show that when the reaction time was increased to 45 minutes, the efficiency was nearly 95% and it decreased when time increased was beyond 45minutes [30- 35].

Effect of pH

The aqueous solution of dye wastes was treated by constant concentrations of dose at 70ml/L in dye wastewater of adsorbent for half a day with varying pH (2 -12). The pH was maintained with the help of buffer solutions. (Figure 8 & 9) show the effect of pH of the dye solution on the decolorization percent within the range of (2-12) for both simple and saline extract methods. The results showed that the decolorization reached maximum between pH 8-10 for both the selected dyes waste and industrial wastewater for all dosages. The effect of pH was one of the crucial parameters to determine the optimum leveling order to minimize the dosing cost and to obtain the optimum performance in treatment. pH variation in comparison had a significant effect on the decolorization of reactive dye, direct dye and mixture of them with textile wastewaters by Moringa stenopetala seed extract.

From these figures, we can understand that the highest colour removal was at pH 10 for all dye wastes. As pH increases from 2-10 the colour removal from textile wastewater increases and reach the highest point at pH 10. The removal of dyes are more at higher pH, because the surface of activated coagulants are negatively charged, the decrease in adsorption capacity at the low pH values would be expected as the acidic medium would lead to an increase in hydrogen ion concentration which would then neutralize the negatively charged coagulant surface thereby decreasing the adsorption of the positively charged ions because of reduction in the force of attraction between adsorbate and adsorbent [36-40].

Removal of Turbidity

Varying doses of the seed extract were added to the effluent followed by mixing at optimum time. The mixture was then filtered through filter paper, finally measure the turbidity value by turbidity meter. The result shows that the higher turbidity removal efficiency was obtained in simple extract method in the order of 84.6% and 83.7% in Saline extract methods for reactive blue dye (Reactive Blue 19) with the dosage of 70ml/L as shown in (Figure10 & 11).

Effect of Dye types

Comparative efficiency of colour removal between reactive, direct dyes and mixture of them with industrial wastewater for both the dyes is shown as bar chart in Figure 12. The average colour removal efficiency of reactive dyes is higher than direct dyes because of the fact that the reactive dyes are a colour that can be water dissolved due to the negative charge of the sulphonate group (SO3-) and direct dyes are the molecular structure with planar positive charges that are more than the negative charges and is water soluble. Direct dyes also have sulphonate (SO3-) functionality, but in this case, it is only to improve solubility, as the negative charges on dye and fibre will repel each other. The colour shade affects the efficiency of reactive colour removal natural coagulant. On the other hand, for the mixed dye, the average colour removal is found between reactive and direct dyes, because all reactive and direct dyes are mixed together and to have interchanging of all charges which affect colour removal [41-43].

Conclusion

Seeds of Moringa stenopetala contain materials that are effective as coagulant. Coagulant dose and coagulation pH are important factors influencing the mechanism of coagulation. Depending up on the type of dye, the coagulation process varies. The optimized parameters for the coagulation of textile wastewater using M. stenopetala were pH 10 and dosage of 70ml/L that can result in removal of 98.4 and 94.45% of colour in simple extract and 97.3 and 96.6% in saline extract in both reactive and direct red dyes respectively. Moringa seed can also remove the maximum turbidity of textile dye wastes to the tune of 85%. It could be concluded that natural coagulant aid created a significant impact on the physical treatment of textile wastewater. The colour removal of mixture of industrial wastewater having reactive and direct dye solution was 85.8 and 84.6% in both simple and saline extract respectively because industrial effluent contains high content of dyestuff, surfactants and other additives that are generally made up of organic compounds with a complex structure while it is collected from different sections which use different compounds.

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Secrets of Mammary Stem Cells Secretome- Juniper Publishers

Abstract

The role of mammary stem/progenitor cells and its secreted proteins in therapeutic application has not been evaluated yet. Here, author reviewed information pertaining to secreted proteins of mammary epithelial cells and mammary stem/progenitor cells and supported their ideas that secretome could potentially be explored for natural antimicrobials against supportive therapy of bovine mastitis.

Keywords: Mammary stem cell; Secretome; Mastitis; Bovine; Spectrophometer; Proteins; Laboratory; Lactoferrin; Receptors; Biomarkers; Pacific; Population; Antibiotics; Progenitor cells

Abbrevations: HMEC: Human Mammary Epithelial Cells; CM: Conditioned Medium; EGFR: Epidermal Growth Factor Receptor; AFDC: Adherent Fraction Derived Cells; MDC: Mammosphere Derived Cells; TGFβ: Transforming Growth Factor Beta; MDBK: Madin Darby Bovine Kidney Epithelial; LPS: Lipopolysaccharides

Opinion

Secretome are the cell secreted proteins released in the cell extracellular space. Groups of proteins present in the secretome are involved in signalling and cell communications. Study of such proteins, thus would be helpful in understanding the niche of the cell. Researchers of Pacific Northwest National Laboratory, Washington probably was the first group which demonstrated secretome of human mammary epithelial cells (HMEC) in 2008 [1]. They identified secretome of human mammary epithelial cells (HMEC)-conditioned medium (CM) cell lysates and showed regulation of matrix metalloproteases through epidermal growth factor receptor (EGFR). In 2009, Simpson and co-investigators have profiled three different secretome of basal MaSC, luminal progenitors and mature luminal cell lines. In this study, in addition to enriched expression of ephrin receptors and integrins, the activity of Wnt signalling pathway was uniquely detected in the MaSC [2]. In a recent publication of Scientific Reports journal, researchers from Cornell University, Ithaca, NY has defined secretome of mammosphere derived MaSC and opened up new doors for the possible treatment of bovine mammary gland infections [3].

For their studies, the team isolated cultured two different populations of bovine mammary cells- adherent fraction- derived cells (AFDC) and suspension mammosphere-derived cells (MDC). These two cell population were immunopheno typically different as analyzed by various cell surface markers. However, the expression of CD44 and CD49f was higher in MDC CM than the AFDC CM. Level of CD29 was high in CM of both these cells. Proteome analyses of AFDC and MDC CM, using mass spectrophometer, revealed 347 and 537 matched proteins and peptides functionally related to defense and immunity and tissue regeneration like angiogenesis and cell migration. Furthermore, two antimicrobial proteins namely lactoferrin and cathelicidine have been validated and quantified using Western blot (Figure 1) and observed differential expression of the proteins in CM of MDC versus AFDC. Two angiogenesis factors namely, angiopoetin 1 and vascular endothelial growth factor alpha, angiopoetin 1 showed high expression level in MDC CM. Likewise, levels of proteins involved in cell migration (transforming growth factor beta (TGFβ), Insulin-like growth factor-1 and hepatocyte growth factor) were estimated in the CM and found that the concentration of TGFβ was high in CM of MDC. TGFβ induces epithelial cell to mesenchymal type and promotes cell migration. Taken together, this study showed CM of AFDC and MDC contains various proteins which have roles in tissue regeneration and immune defence of the host.

Interestingly, proteins of AFMC and MDC also contained factors which protects bacterial toxin-induced MEC death. Loss of MEC damage is an important consequence of mastitis and it is induced by the toxins of Gram-positive bacteria and lipopolysaccharides (LPS) of Gram-negative bacteria. A significant reduction in growth of bacteria (measured by optical density) was observed when Madin-Darby Bovine Kidney Epithelial (MDBK) cells were grown in presence of Klebsiella (a Gram-negative bacteria) and Staphylococcus aureus (a Grampositive bacteria) in presence of MDC CM. The researchers also evaluated shelf-life of MDC CM for one week and found that frozen CM is biologically effective on MDBK cell migration. The storing of CM for long time would be advantageous for future clinical use in mastitis management even at remote places.

In summary, these studies providing rationale for the potential use of MDC secretome as supportive or adjunct therapy in bovine mastitis. Secretome could be an ideal biological source for naturally occurring anti-microbial and potentially beallogenically safe like antibiotics. In future, an important follow-on studies should include evaluation of novel proteins as biomarkers and identification of newly identified proteins with no to little annotations. In vivo application of MDC secretome in management of naturally occurring bovine mastitis, also warranted future investigations.

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