#Juniper Publishers Address

[spaceshipkat]

Well it took darn near 10 years but SJM finally addressed (if you can call it that) her appalling lack of diversity and her stereotypical diversity https://time.com/6590247/sarah-j-maas-interview-house-of-flame-and-shadow/

Brava, Janet.

yeah when i saw her claim of sensitivity readers, i just wanted to ask “are you listening to them??” bc like. where’s the proof? i didn’t finish hosab but i read a good chunk of it (and hoeab was just despicable with its colonizer and cop apologism, which i can’t see sjm improving on), and i read all of acosf, and i failed to see any improvement in any respect. even in hosab, with the two gay characters (Juniper and Fury—it took me a bit to actually remember their names when i was talking about it with @faithfire last night), they only ever talked about fucking. and in acosf, one of the most egregious things was how she wrote about Nesta’s addiction and recovery. if there was sensitivity reading done for that, she clearly didn’t listen to the readers (or the reads were never passed on by her editor, which—while i can’t say has happened w sjm given i doubt she’s had sensitivity reads before—happens often enough in publishing)

[livingfictionsystem]

Review for 'Yellowface' by R.F. Kuang

June Hayward, an aspiring author with only scarce flops to her name, best friends/frienemies/rivals with Athena Liu, successful Asian-American Indie darling, has a lot of possible reactions to witnessing Athena's sudden and accidental death. Stealing Athena's unpublished draft about Chinese labour camps and claiming it was her own was certainly a *choice.* This book was honestly a treasure. It's a blunt, biased, yet uniquely savage view into the world of cultural appropriation, media backlash, and publishing. It's also a treat for anyone who loves to follow petty cancellation deep-dives and general drama; I was reacting verbally like I was watching a football game for my entire listen-through.

I love how many infinite shades of grey there are in June Hayward's first person POV. On one hand, fellow struggling creatives could understand the bitterness at being overlooked and the temptation to launch oneself dishonestly into notoriety on a wave of trends. Fame-hungry creatives can be absolute sharks. Her sarcastic and exasperated take on everything is jarringly relatable and actually pretty witty. She wasn't completely irredeemable; she did write supposedly half of the book based on Athena's notes and 'unreadable draft,' did extensive research herself, and even donated money to related charities. On the other hand, you see June change her name to 'Juniper Song' ("Hey, it *is* my legal middle name!"), using phrases like "reverse racism", and thinking things like, "Oh, I think have some Cherokee genetics on my mom's side I could use for a new book idea."

It really has a Bojack Horseman-esque way of exploring how publicists twist things for 'the right spin.' How commodifying everything from diversity to drama is just part of the game, some sort of socio-political mental chess.

The POV followers the MC's reputation's endless rollercoaster rising and falling as her house of cards collapses. Multiple angles are addressed on both sides, anything from claiming that Asian trauma is being 'gatekept' from the poor misunderstood white writers, to digging up June's 5 year-old posts responding positively to a Wonder Woman film and saying it was 'proof of a white savior complex.' Then you have elderly Chinese immigrants thanking June with tears in their eyes about how much her book means to them, while the right wingers are defending her on Twitter.

It was all incredibly realistic and modern, to the point of my leaving a review of a book on Goodreads is feeling extremely meta. No one is likeable or sinless---only fascinating and multi-faceted. The POV leaves room for the reader to pivot from having anxiety about June getting caught, to looking forward to the truth being revealed.

June's racism is also extremely well-written and just as contemporary. You see her trying to unlearn, correct herself, pay her dues, even try to protect Athena's memory, but then she'll get desperate and go on an internal rant about how "Karen" is used to discriminate against white women. And the thing is, June's not written as a stereotypical bigot or right-winger. The book has her probably about left-of-centre. She's the kind that's on the side of the disenfranchised until it's time to get defensive about micro-aggressions. The kind who uses the term 'Cis-het' but gripes about how minority creators have this conspiratal advantage.

Definitely read this book. I loved it. An easy 10/10.

Also, with how intimately and accurately R.F. Kuang wrote about experiencing mass cancellation, I have to ask them---are you okay? Show me on this doll where Twitter hurt you.

One of my favourite parts was when June was being cancelled one time and someone stood up for her, calling the mass pile-on a 'lynch mob.' Then there was discourse about whether or not using 'Lynch mob" in this context was racially insensitive, and then there was discourse about race of the person who started the discourse---IT WAS SO REALISTIC.

There's also another really good scene where June sits down with film execs and tries to insist; "I need actual Asian people playing the Asian characters, though. Representation is important." And one of the producers makes a racist joke about Asian accents and the other one playfully scolds like "LOL you can't say that!! :)"

It really had a 'As long as we're all white here, we have a little racism, as a treat. Just to make you feel like you're part of the gang' vibe.

-Xanthe

[allthatisleftinthedark]

A letter is presented to Estranha, and once it's open, it has a familiar handwriting, that of one Nelia Zarin.

Hey, Es. It's been a while, I know, usually we have time to talk or we meet up a lot more often, but ever since the start of this journey, things have been going so fast it makes my head spin. From the moment I set out, I've been drugged, knocked out, got the boat i was traveling on smashed by a dragon...Caught in explosions, it's been a mess. Feels like I can't take a minute to catch my breath.

That's just the external stuff. I had a dream about an old friend and his little brother. I couldn't save the kid, he had a knife that cut holes into the elemental planes...At the end of the day, he was a scared kid with a shitty father. I should've been able to do more, should've saved him. Now he's scattered across the planes. Doesn't mean I'm gonna stop, I'll bring him back, no matter what it takes. You know me, I got a hard head that I'll keep banging against the wall until it breaks.

There's another dream I had. You were in it, and it was just us talking and hanging out while I worked out. And I...Gods, I'm so sorry I've been pulling you around for so long. I'm so afraid of losing you that I don't even know how to begin talking about how I feel about you. I've always been so damn uncertain, but now? After all of this? Nearly dying a few times, visions where you wind up dead...Or hell, even experiencing the feeling of seeing into other worlds and feeling my arm getting flayed to the point of uselessness...I know now.

Oh, and don't even get me started on meeting an ice dragon, or getting eaten by a Gibbering Maw, it's so fucking horrible on the inside of those things and I punched my way out with the help of my master, Ramona Hammerfist. I've seen things that people would only see in nightmares, and the cult...Let me tell you, I don't think I can take enough baths or showers to ever get the smell of rotting meat outta my clothes. I swear I can even smell the shit in my dreams.

I want to be with you. Every second of every day for the rest of my life. I'm supposed to be a wanderer, but I don't want to travel around for the rest of my life, and not have a home. Or at the very least, if I gotta travel for the rest of my life, I want it to be with you.

I want you to meet my friends, to meet Cassius when we get him back, he's such a good kid, and he just needs someone to encourage him. I want you to meet Junie, she's been the closest thing I've had to a mom, and Aika, she's a little serious sometimes, but she's got a curiosity about things that's pretty adorable. I don't know if you'd get to meet them, but the Crownswatch has been nice to know too, Dejin's kind of the serious type, but he knows good food and drink, Khiye, a little spooky, but she's good in a fight, I mean, she bashed a mound of flesh so hard the damn thing was knocked stupid. Garur, I think you'd look at them and then you'd understand why we get along so well. Nowhere...well, I might have to work to be her friend, I kinda can't translate her way of speech yet. I don't know when we'll meet again, but when we do...I'm gonna be a woman worthy of being your girlfriend. With love, Nelly

unprompted asks! | always accepting | @offrozenmemoirs

A/N's note: Any mentions of "Juniper" are replaced with "Ghost Whisker." Only Creed knows her private name and refers to her by that name one-on-one; everyone else knows her as Ghost Whisker and addresses her as such (Creed included when in public/group conversation).

=========

Sheltered by the canopy of a weather-worn canvas tent, Estranha peruses speculative fiction of the to-be future during the 4000s from a tome published circa 3200 PC. Their roosting spot is on a sturdy wooden crate adorned with crimson-painted words. As alien as the language on the box is, its definition is meaningless. 

With weighty volume, they perch upon a sturdy wooden crate with painted crimson words on one side. Alien is the language to them, but its definition is meaningless. In this instance, this serves as a "seat" and nothing more. 

As their gaze skims across the printed character, a slender finger idly twirls a plum-purple stray lock. A sudden snort, reminiscent of crackling flames, disrupts the silence. Aimless exploration constitutes a significant portion of Estranha's scholarly pursuits. Uncovering peculiarities and pockets of amusements are commonplace amidst their research. Of course, these are abrupt conclusions in their currently fruitless endeavors. But not every dead end heralds a soured conclusion. Rather, they often encounter unexpected delights along the winding search of inquiry, each revelation saccharine in an otherwise dried pool. 

Upon the page from Grand Magister Salazar Silverwinds's The Revolution of Magicracy, Estranha's soft green irises race over the words, over and over, "Under the harmonious collection of the magically inclined and gifted, the natural world and humanity unite. The future order may see that those bestowed with gifts of casting would be better attuned to granting and guiding individuals into an enlightened society that bolsters and salvages the new world." They place their thumb on the tome's pages and ponder the publication details. Interestingly, it was not produced by any Graneyean territory or ally of the era. 

Besides the thinly veiled hierarchal oppression in the text, exciting sections recount the prestige of the fabled ancient era. Without a doubt, there are continuous odes to the times before from this book published over a thousand years ago. Still, the modern-day sees toward the future and ignores the possible reaches of civilization before the "Dark Days." Advancing past the point of where society was once at? That query died on the tongues of philosophers hundreds of years ago. 

As Estranha reads further into Grand Magister Salazar Silverwinds's work, an unforeseen event suddenly interrupts their scholarly pursuit.

A russet-haired man with lengthy curls tied into a neat ponytail peers into the tent. His hazel eyes twinkle in quite an ensemble of clothes—a uniform fitting any Four Seasons United Postal Service worker. The heat on the Nihiranian deserts must have had his sleeves rolling and hat slightly disheveled as if he were fanning himself with it before.

"Telegram for a Miss Extraña?" He calls out, looking around the barren tent before his eyes finally land on Estranha. 

The recipient closed the book and cast it aside when the man poked his head in. They approached, giving a dull nod before plucking the missive from his hands. They turned the envelope over. "I never realized you reached this far."

"Well," he speaks as his chest swells with pride, "it is a recognized global service." He removes his hat, placing it over his heart. "From the head of Rivera to the feet of Nihiran, we can be found anywhere across the world, through sleet, storm, sand--"

Estranha turns on their heel, squinting at the crimson seal. Two bare arms cross over the other; it is definitely Nelia's seal. "Mhm," they nod as their hand reaches out, grabs one fold of the tent's canvas, and closes it back up. 

Unfolding the letter, a several-month estrangement between "friends," as colloquially as Estranha can define, meets its end. All they recall was the tiefling mentioning a journey overseas on a boat to another continent like Tahrea. Creed never considered setting a hoof outside of Nihiran; her thirty and more years were spent in the red dunes. Though, anyone can change. Il'Surrish is the Wanderer; paths treaded, and new is how her worshippers go. 

Estranha's thumb guides their reading and marking of the paragraph. Returning to their perch on the crate top, they criss-crossed their legs. The twinkling mischief in their eyes fades further down as they read the letter. Hesitation draws the corners of their ever-smiling expression lower and lower. Two years after that conversation, Estranha still could not ascertain its intention.

A letter was drafted and sent within a few days of the initial telegram's receipt. It would only take some weeks before Nelia received a letter back. 

Hi Nel,

It is wonderful to know you are in one piece despite the destroyed ship, the hungry, hungry Gibbering Maw, and a suspicious number of assumedly extinct dragons on your latest travels. For someone who always enjoyed a surprise and a show, that was a lot, even for you. 

Tahrea brought on much more than I anticipated in a letter; I expected much more debauchery and other rendezvous with other women at the encampments along the dirt roads. As I reread each line before getting to the climax of my thoughts, everything is happening or has happened in a compressed and narrow time frame. Now, you are at the apex of it. From what I hope, you just survived another scrap on the long road and plan on continuing. 

On my side of this expansive pond, what remains true of the sands is that it brings me excitement and new ideas, but nothing that progresses my ongoing research. The tracks behind me will soon meet their end. The civilizations beneath the dunes and what came before the city that was a black speckle in the sun serve nothing to me. But are they fascinating tales? Of course. But the sea salt gales shall take me elsewhere after three years. Where they may take me, I have mapped out some alternatives and continents, but I cannot return to the university without any proper advancement in my thesis.  

Foregoing the timeline of when this chapter will come to a close is something I cannot bring myself to do. For as long as I have been at this, there is nothing else I can do until I accomplish this entirely. One may compliment my tenacity for conclusions rather than jeering it as aimless stubbornness or pride. 

It is at least a concrete resolve, no matter which direction I may go. 

Sifting between what I share and what you've shared, you now have a new conclusion, a revelation, about us coming together and going somewhere. But a question continuously spurs me as much as it has you. Your answer leaves only further queries on my end and our relationship. What else springs from this drive to be together besides the glaring external variables that are beyond stressing you out? 

Nelia, you remain seeking yet are convinced in this letter that you have something in mind. I entrust your goals to be well-meaning, and I ask what is there in the long run beyond doing things on account of other relationships? 

How much will you risk for the boy you dream of saving? Is guilt rooting you down to attempt to reverse a mistake you feel can be undone? As far as I understand from this letter, that is your current goal. That has been the clearest I have understood of what you have wanted to do. This is past starting a career in labor law and your past training in the Mduara Kuona. 

Become the woman you want to be, which will steady your future's compass. The arrow keeps turning and turning, unnecessarily working like a poor-functioning clock and needs calibration. You will soon find the direction you need to take. 

There, you can see who you want to become. There, you can figure out what you want and why. 

Time will only make us lose opportunities, but it will not lose us. I will still be here, as you will, accomplishing what we want to do. As you discover what you wish to do, I still have my fair share of goals. That remains something I still have to accomplish, but I at least know my calling. 

The duress you are under, with these new obligations and the people you are around, complicates many things. Do not abandon it, but remember that under such stress, one cannot ascertain what one wants. The mind focuses on the present and current fixes to a problem; the life of another, or your own, is not considered when solving things. 

When we meet again, it may not be at the right time and place, but we will be in another person's company again. When we meet after that, some things may even be wrong, but there are still us. So on and so forth, our paths will cross repeatedly because we desire it. 

Maybe then, we will both have the answers we want. 

Give yourself a break, Nel, and don't get in over your head. 

Until we meet again, Estranha Extrana 

[requiesticat]

Life update: drama, job, new pets

Back from hiatus

I took a break from social media for awhile. This was due to mental health, as well as other reasons

Drama/unemployment

A few months ago, I made a character analysis to support a user who was getting harassed for making one. This lead to me getting targeted instead. OP didn't respond to my post, or address that targeting, so I decided to private it.

This isn't the first time I've experienced harassment. Different instances have occurred over the years, with the most prominent one happening on Furvilla. Updated my about page to address it in general:

In March, a few weeks before publishing the post, I quit my job. The position was retail, but it proved to be too demanding. Now I'm unemployed, and unsure if I'll be able to find fulltime work. May start taking commissions.

Things sort of went downhill from there. The aa drama happened. A falling out with a friend lead to our relationship deteriorating. For awhile, it was like I had the worst luck imaginable, and I've been spending more time alone, isolating myself as a result.

So I might leave twitter. The only reasons I've stayed is because all my mutuals use it. Elon Musk's ownership as well as anti/proship discourse has put me off the site entirely; honestly feel more comfortable using mastodon. I'll probably be more active on tumblr as well.

Pets

Some good news: my cats are doing fine. I haven't posted about them much, but their names are Sophie and Milo. They're siblings that come from the same litter

Since 2019 I started taking care of fish, mainly bettas. Right now I own a female koi betta (Pippa), a male platy (Nougat), and an ivory mystery snail (Perry).

Last week, I adopted a jumping spider who kept showing up on my back porch. Not sure about the gender yet, but it's a bold jumper/phidippus audax. I got them a terrarium as well as some crickets for live food.

Its name is Juniper. Jumpy for short, after the protagonist of 999. They're wary of me, but curious and spend a lot of time making webs at the top of the terrarium. I've always wanted a tarantula, so this is sort of the next best thing.

(Sorry for blurry photo)

[thesecrettimes]

Central Bank Digital Currency Transactions to Reach $213 Billion Annually by 2030, Research Shows

A new study shows that payments via central bank digital currencies (CBDCs) are expected to reach $213 billion annually by 2030. Furthermore, 92% of the total value transacted via CBDCs will be paid domestically, the research found.

$213 Billion Annually

Research and market intelligence firm Juniper Research published a report on central bank digital currencies (CBDCs) Monday. The firm wrote: The value of payments via CBDCs (central bank digital currencies) will reach $213 billion annually by 2030; up from just $100 million in 2023. This radical growth of over 260,000% reflects the early stage of the sector; currently limited to pilot projects. “Adoption will be driven by governments leveraging CBDCs to boost financial inclusion and increase control over how digital payments are made,” the firm added. “CBDCs will improve access to digital payments, particularly in emerging economies; where mobile penetration is significantly higher than banking penetration.” Furthermore, Juniper Research detailed: The research found by 2030, 92% of the total value transacted via CBDCs will be paid domestically. This reflects a change from almost 100% during current pilot stages, as of 2023. Initially, central bank digital currencies (CBDCs) will be primarily focused on addressing domestic payment challenges due to their issuance by central banks, while cross-border payments are expected to follow subsequently “as systems become established and links made between CBDCs used by individual countries,” the study shows. “While cross-border payments currently have high costs and slow transaction speeds, this area is not the focus of CBDC development,” report author Nick Maynard said, elaborating: As CBDC adoption will be very country specific, it will be incumbent on cross-border payment networks to link schemes together; allowing the wider payments industry to benefit from CBDCs. The research firm also noted that the absence of commercial product development for CBDCs is a primary constraint for the current market, adding that there are few well-defined platforms for central banks to utilize. According to the Atlantic Council’s central bank digital currency tracker, 114 countries, representing over 95% of global GDP, are currently exploring a CBDC. In addition, 11 countries have fully launched a digital currency. Do you think CBDCs will dominate digital payments? Let us know in the comments section below. Read the full article

[annieboltonworld]

City Scale Vs. Regional Scale Co-Benefits of Climate and Sustainability Policy: An Institutional Collective Action Analysis

Short Communication

Multiple levels of government must play complementary roles in mitigating climate changes (Francis and Feiock 2009; Ostrom 201#), but city level engagement and action are particularly critical for two reasons. First, urban areas are the primary source of GHG emissions worldwide. For example, in the US urban areas hold over three-fourths of the population and account for about 80% of global primary energy use and greenhouse gas (GHG) emissions [1]. Second, cities have the potential to significantly influence environmental and problems since they have primary responsibility for the local land use and building decisions that are critical to sustainability efforts. In many countries’ cities have stepped up to address climate and GHG mitigation issues. City leadership in climate protection is especially visible in the US due to the absence of action by the national level government, but cities have been leaders in nations across the globe (Krause et al. 2019).

Read More about this Article: https://juniperpublishers.com/ijesnr/IJESNR.MS.ID.556185.php

Read More Juniper Publishers Google Scholar: https://scholar.google.com/citations?view_op=view_citation&hl=en&user=4WXzQFMAAAAJ&citation_for_view=4WXzQFMAAAAJ:ldfaerwXgEUC

[juniperpublishers-agriculture]

Winter Collection of the Underutilized Berry Corema Album (l.): New Insights on its Maturation Progression

Abstract

Increasing interest in Corema album L. is raising due to the appealing white colour and potential health benefits related to its bioactive composition. White fruits production culminates in late August on coastal dunes, but fruits of various colours are present almost till flowering (late February). We undertook a preliminary physical-chemical characterisation (biometric, CIELab colour, pH, soluble solids content and titrable acidity) of a late fruit collection to disentangle maturity progression and to reveal latent qualities for future utilisation. Irrespective of fruit perceived colouration (white, translucent, brown, brown with black spots and black), the characterized high acidity (1-3 g.100 mL-1) is suggestive that over-mature fruits can still be further explored as food additives. Moreover, using a multivariate exploratory technique, we found a clear fruit’s maturation progression from white/translucent to black, a so-far unreported maturity stage. Addressing gaps in plant phenology and fruit’s maturity behaviour is needed before undertaking cultivation.

Read more about this article: https://juniperpublishers.com/artoaj/ARTOAJ.MS.ID.556274.php

Read more Juniper Publishers Google Scholar articles: https://scholar.google.com/citations?view_op=view_citation&hl=en&user=Zt1YgWcAAAAJ&citation_for_view=Zt1YgWcAAAAJ:R3hNpaxXUhUC

[juniperpublishersoceanography]

Uncertainty Quantification of Sea Waves - An Improved Approach

Abstract

Sea waves are important dynamic loadings for the design of offshore structures. Casual observations will indicate that the sea waves are very unpredictable and may not be modeled deterministically. To capture the unpredictable nature of the sea waves, they are generally expressed in terms of a joint probability density function of mean zero crossing period Tz and the significant wave height Hs. Estimation of parameters of the joint distribution can be very challenging, particularly considering the scarcity of data. The joint probability density function (PDF) of Tz and Hs is generally represented as the multiplication of a conditional distribution for Tz given Hs and the marginal distribution of Hs. The estimation of parameters of the joint PDF is addressed in this paper. The available information on North Atlantic, as reported by Det Norske Veritas (DNV), is considered to document its applicability. DNV reported values for all the required parameters. They are considered as the reference values. Using the Maximum Likelihood Method (MLM), the three parameters of the Weibull distribution for the marginal distribution of Hs are estimated. Assuming Hs can be represented by a two-parameter Weibull distribution, they are also estimated. To compare different alternatives, their Root-Mean-Square-Error values are also estimated. It can be observed that the proposed MLM to estimate the parameters of Hs is superior to that of proposed by DNV.

Read more about this article: https://juniperpublishers.com/ofoaj/OFOAJ.MS.ID.555775.php

Read more Juniper Publishers Google Scholar articles https://scholar.google.com/citations?view_op=view_citation&hl=en&user=V6JxtrUAAAAJ&citation_for_view=V6JxtrUAAAAJ:l7t_Zn2s7bgC

[danuellebennet-blog]

Controlling Informative Features for Improved Accuracy and Faster Predictions in Omentum Cancer Models

Abstract

Identification of suitable biomarkers for accurate prediction of phenotypic outcomes is a goal for personalized medicine. However, current machine learning approaches are either too complex or perform poorly. Here, a novel feature detection and engineering machine-learning framework is presented to address this need. First, the Rip Curl process is applied which generates a set of 10 additional features. Second, we rank all features including the Rip Curl features from which the top-ranked will most likely contain the most informative features for prediction of the underlying biological classes. The top-ranked features are used in model building. This process creates for more expressive features which are captured in models with an eye towards the model learning from increasing sample amount and the accuracy/time results. The performance of the proposed Rip Curl classification framework was tested on omentum cancer data. Rip Curl outperformed other more sophisticated classification methods in terms of prediction accuracy, minimum number of classification markers, and computational time.

Read More About This Article: https://juniperpublishers.com/ctbeb/CTBEB.MS.ID.555559.php

Read More Juniper Publishers Google Scholar Articles: https://scholar.google.com/citations?view_op=view_citation&hl=en&user=nWCnyqYAAAAJ&citation_for_view=nWCnyqYAAAAJ:YsMSGLbcyi4C

[ictandmediavynzresearch]

Global Security Policy Management Market Size, Share, Demand and Growth Forecast to 2027

The Global Security Policy Management Market Research Report published by VynZ Research offers first-hand data, qualitative and quantitative analysis by industry analysts, and inputs from industry experts and stakeholders across the entire chain. The research examines current market trends, macroeconomic factors, regional analysis in-depth, as well as market attractiveness by segment.

The Global Security Policy Management Market is anticipated to be valued at USD 3.2 billion by 2027, registering a market growth rate 10.5% CAGR during the 2021-2027. The Market research offers SWOT analysis of competitors including external environment analysis and PEST analysis. Furthermore, the Market study provides business methods for dealing with COVID-19 impact on the Market.

Get a sample copy of the market report: https://www.vynzresearch.com/ict-media/security-policy-management-market/request-sample

Segmentation Analysis:

The study report examines significant market characteristics and latest developments, as well as research about relevant market segments and sub-segments, in-depth.

Segmentation of the Global Security Policy Management Market

By Component

Solution

Services

By Organization Size

Large Enterprises

Small & Medium Enterprises

By Application

Network Policy Management

Compliance and Auditing

Change Management

Vulnerability Assessment

By Industry

IT & Telecom

Healthcare

BFSI

Manufacturing

Energy & Power

Government

Other

Prominent Leading Companies and Regional Outlook of Global Security Policy Management Market Share Analysis

The report also covers the market's major strategic developments, such as R&D, M&A, agreements, novel product launches, collaborations, partnerships, joint ventures, and regional growth of the market's competing firms on a global and regional scale.

Furthermore, the study includes Porter's five forces analysis of the industry to understand the impact of various factors on the growth of the market, such as bargaining power of suppliers, rivalry among competitors, the threat of new entrants, threat of substitutes products or service, and bargaining power of supplier.

The major industry players across the value chain for Global Security Policy Management Market include:

Cisco Systems

Check Point Software Technologies Ltd

Palo Alto Networks

Micro Focus International plc

McAfee

HelpSystems

AlgoSec

Juniper Networks

FireMon

Tufin

Some of the frequently asked questions addressed in the report include:

- What are the trends and drivers impacting the Global Security Policy Management Market?

-Preparation of SWOT and PESTLE analysis of competitors in the market.

-What are the regions covered in the report and the opportunities prevalent in the region leading to the growth of the market?

-What are the segments covered in the report and the strategies adopted by Industry Players in the Report?

-What are the innovative technologies in the market that are covered and their outlook?

-What are the regulations initiated by the government so as to expand the market?

- What are some recent trends that may have an impact on the product/service and return on investment (ROI)?

More Reports by VynZ Research:

Global Advanced Analytics Market – Analysis and Forecast (2021-2027)

Global RegTech Market – Analysis and Forecast (2021-2027)

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Global Cyber Security Market – Analysis and Forecast (2021-2027)

About Company:

VynZ Research is a global market research firm offering research, analytics, and consulting services on business strategies. VynZ Research has a recognized trajectory record and our research database is used by many renowned companies and institutions in the world to strategize and revolutionize business opportunities. The company focuses on providing valuable insights on various technology verticals such as Chemicals, Automotive, Transportation, Energy, Consumer Durables, Healthcare, ICT and other emerging technologies.

[someshd95]

Edge Computing Market Analysis, Growth, Outlook and Forecast by 2029

The study and estimations of an excellent Edge Computing Market report helps to figure out types of consumers, their views about the product, their buying intentions and their ideas for the step up of a product. With the market data of this report, emerging trends along with major drivers, challenges, and opportunities in the market for this industry can be identified and analysed. For the clear and better understanding of facts and figures, the data is represented in the form of graphs and charts. With the studies, insights, and analysis mentioned in the finest Edge Computing market report; get comprehensible idea about the marketplace with which business decisions can be taken quickly and easily.

Download Sample Copy of the Report to understand the structure of the complete report (Including Full TOC, Table & Figures) @ https://www.databridgemarketresearch.com/request-a-sample/?dbmr=global-edge-computing-market

Edge computing market is expected to grow by USD 38.65 billion at CAGR of 33.75% in the forecast period of 2021 to 2028. Data Bridge Market Research report on edge computing market provides analysis and insights regarding the various factors expected to be prevalent throughout the forecasted period while providing their impacts on the market’s growth. The growing adoption of IoT and overload on cloud infrastructure has been directly impacting the growth of edge computing market.

Edge Computing Market Key Trends Analysis

The important factors influencing the growth of the Edge Computing market have been examined in this report. The driving factors that are boosting demand for Edge Computings and the restraining factors that are slowing growth of the Edge Computing industry are addressed in depth, as well as their implications for the worldwide Edge Computing market. In addition, the published analysis identifies and discusses in detail the trends that are driving the market and impacting its growth. In addition, other qualitative variables such as risks connected with operations and key problems faced by market players are covered in the report.

Edge Computing Market Strategic Analysis

The market was studied using several marketing methodologies such as Porter’s Five Forces Analysis, player positioning analysis, SWOT analysis, market share analysis, and value chain analysis in the Edge Computing market study. The market dynamics and factors such as the threat of a Edge Computing substitute, the threat of new entrants into the Edge Computing market, buyer bargaining power, supplier bargaining power to Edge Computing providing companies, and internal rivalry among Edge Computing providers are analysed in Porter’s Five Forces analysis to provide the report’s readers with a detailed view of the current market dynamics.

This analysis assists report users in evaluating the Edge Computing market based on various parameters such as economies of scale, switching costs, brand loyalty, existing distribution channels, capital investments, manufacturing rights & patents, government regulations, advertising impact, and consumer preference impact. This simplified data is expected to aid the industry’s key decision-makers in their decision-making process. Furthermore, this study answers the crucial question of whether or not new entrants should enter the Edge Computing industry.

View Full Report@ https://www.databridgemarketresearch.com/reports/global-edge-computing-market

Leading Key Players Operating in the Edge Computing Market Includes:

The major players covered in the edge computing market report are Nokia, Huawei Technologies Co. Ltd., Juniper Networks Inc., Dell, Cisco, Hewlett Packard Enterprise Development LP, SixSq Sàrl, FogHorn Systems, Vasona Networks Inc., MachineShop Inc., Saguna Networks Ltd., Vapor IO, Violin Systems LLC, Aricent Inc., ADLINK Technology Inc., Amazon Web Services Inc., GENERAL ELECTRIC, IBM Corporation, Intel Corporation, Microsoft, SAP SE. among other domestic and global players. Market share data is available for global, North America, Europe, Asia-Pacific (APAC), Middle East and Africa (MEA) and South America separately. DBMR analysts understand competitive strengths and provide competitive analysis for each competitor separately.

Key Market Segments:

Based on component, the edge computing market has been segmented into hardware, gateways, micro data centers, platform, solution and services.

Edge computing market on the basis of technology has been segmented as mobile edge computing and fog computing.

Based on application, the edge computing market has been segmented into smart cities, location services, analytics, environmental monitoring, optimized local content, data caching, augmented reality and others.

Based on organization size, the edge computing market has been segmented into small & medium-sized enterprises and large enterprises.

Based on vertical, the edge computing market has been segmented into manufacturing, healthcare, transportation, government & public, media & entertainment, energy & utilities, telecom & IT, retail and others.

Edge Computing Market, By Region:

North America (USA, Canada and Mexico)

Europe (Germany, France, the United Kingdom, Netherlands, Russia, Italy and Rest of Europe)

Asia-Pacific (China, Japan, Australia, New Zealand, South Korea, India and Southeast Asia)

South America (Brazil, Argentina, Colombia, rest of countries etc.)

Middle East and Africa (Saudi Arabia, United Arab Emirates, Israel, Egypt, Nigeria and South Africa)

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Dead or Alive? A New Dilemma of Probiotic Skin Care for Healthier Skin

Abstract

Our microbiota, a collection of micro-organisms is a living ecosystem inside (gut) and outside (skin) of our body. As a part of the inner and outer barrier of the body, it plays an important role in maintaining health. One attractive approach to enhance health and combat certain gut and skin inflammatory diseases is to modulate our microbiome using probiotics (live bacteria). Probiotics benefits on gut health is widely accepted, but we just started to understand health benefits of their use in skin care formulations. The formats already adopted in topical applications are live bacteria (probiotic) and dead bacteria, either inactivated or homogenized or ferments (postbiotics, or also called lysates or ferments). It is still a dilemma which format is the most suitable for skin care inventions but considering challenges in formulation design, development, manufacturing, and life cycle management of live bacteria in topical formulation, the focus is now shifted more toward postbiotic research to obtain similar claims as their alive counter partners. But still, the question remains, what are these additional benefits of having live bacteria in skin health care and if this is something worth the extra effort? Our first comparative study on both dead and live L. reuteri DSM 17938 indicated that probiotic in both formats could be used in management of skin inflammation related to photoaging and skin barrier claims like dry/sensitive skin. Additionally, the live format could be suitable for the management of pathogenic bacterial overgrowth such as in acne/sensitive skin conditions.

Keywords: Skin Microbiome Probiotics Postbiotic Ferment UV Inflammation Skin Barrie Lysate Health Aging Bacteria

Abbrevations: S.A: Staphylococcus Aureus; C.A: Cutibacterium Acnes; L Reuteri: Lactobacillus Reuteri; UV: Ultraviolet; UVB: Ultraviolet B

Introduction

Our microbiota, a collection of micro-organisms such as bacteria, viruses and fungi are a living ecosystem inside (gut) and outside (skin) of our body. As a part of the inner and outer barrier of the body, it plays an important role in maintaining health [1,2]. Microbiota impact in gut health and disease is widely accepted, but we are just starting to understand the role of cutaneous microbiota and its influence on skin health and aging. Clearly, there is a strong tête-à-tête between our gut and the skin, where healthy gut contributes to beautiful skin appearance too [3]. A recent study showed interesting inverse relation, where skin exposure to external stressor, such as Narrow Band Ultraviolet B (NB-UVB) light impacted the human intestinal microbiome [4]. This novel study opens a new vision between two barrier organ bidirectional interactions. How does the microbiota influence our skin health? As an outermost layer of the skin barrier, our microbiota is involved in regulating host inflammation, skin barrier, wound healing and premature skin aging process [5-8]. There are many skin concerns associated with dysbiotic (imbalanced) microbiota such as psoriasis, rosacea, atopic dermatitis, acne [9,7]. Thus, keeping the microbiota diverse and in a good balance is crucial for maintaining healthy skin. One attractive approach to enhance health and combat certain gut and skin inflammatory diseases is the use of probiotics [10], defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host” [11].

Probiotics, when taken orally, can transiently colonize the human gut mucosa, influence the intestinal microbiota and exert their effects not only in the gut [12], but also impact on overall skin health [13]. Based on recent in vivo studies, oral probiotics could be considered for the management of acne, rosacea, and as a protection against photodamage/premature skin aging [10, 14,15]. Due to these effects, it was reasonable to consider that the same/similar probiotics could also benefit skin when administered topically. The formats already adopted in topical applications are live bacteria (probiotic) and dead bacteria either inactivated or homogenized or ferments of probiotics (postbiotic, or also called lysates or ferments). It is still a dilemma which format is the mostsuitable for skin care inventions, but considering challenges in formulation design, development, manufacturing, and life cycle management of live bacteria in topical formulation, the focus is now shifted more toward postbiotic research to obtain similar claims as their live counter partners. To date, many skincare brands have started to incorporate lysates and ferments in their formulations with skin health claims such as strengthening skin barrier, boosting skin´s natural defense, support healthy microbiome growth, photo/ pollution protection, soothe the skin and etc. But still, the question remains, what are these additional benefits of having live bacteria in skin care and if this is something worth extra effort? To tackle the dilemma, we have performed the first comparative study of dead and live bacterias´ of L. reuteri DSM 17938 using skin equivalent ex vivo models [16]. This specific strain of L. reuteri is widely studied for gut health improvement [17-19], but there are limited studies in topical applications for cutaneous health. Interestingly, our results showed that live both forms of L. reuteri, dead and live, possessed anti-inflammatory effects toward UV induced inflammatory cytokines (IL-6 and IL-8) at protein level and a positive impact on skin barrier. Additionally, and differently from lysate, live L. reuteri had an inhibitory action against pathogenic skin bacteria such as Staphylococcus aureus (S.A) and Cutibacterium acnes (C.A) [16]. In conclusion, both dead and live formats of L. reuteri DSM 17938 could be used in management of skin inflammation related to photoaging and skin barrier claims like dry/sensitive skin. Additionally, the live format or probiotic ferments could be suitable for the management of pathogenic bacterial overgrowth such as in acne/sensitive skin conditions due to the anti-microbial activity of such formats [16].

Conclusion

Based on consumer’s growing interest in having natural, probiotic derived active ingredients in skin care formulation, we performed the first comparative study on a dead and alive bacterial strain of L. reuteri DSM 17938 and propose the use of dead (lysate, postbiotics) bacteria of L. reuteri in topical applications when UVB protection and skin barrier improvements are desired. However, live bacteria, probiotics, exert additional anti-microbial effect toward pathogenic/opportunistic bacterias´ on the skin, compared to postbiotics. Our findings open for more exploration to consider probiotics for enhanced skin health to mitigate or treat diverse skin inflammatory conditions and/or dysbiosis.

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Spermidine for a Long, Dementia-Free Life?

Authored by Tsikas D

Abstract

Spermidine, N-(3-aminopropyl) butane-1,4-diamine, is an endogenous basic compound known for more than 90 years. The biosynthesis of spermidine, its pharmacological properties including distribution, metabolism and excretion have been thoroughly investigated. Spermidine and other polyamines have been early associated with growth and aging, and were found to stabilize various cellular and subcellular components including nucleic acids due to their polyvalent cationic structures. Polyamines including spermidine have been found at elevated circulating and urinary concentrations in a variety of diseases including cancer and psoriasis. Thus, decreasing the concentration of polyamines mainly by inhibiting their biosynthesis is regarded as a realistic therapeutical strategy. Yet, more recent studies suggest that exogenous spermidine exerts beneficial effects on the brain where it protects from age-induced memory impairment, protects the heart and extents lifespan.

Supplementation of the natural compound spermidine has emerged as an autophagy and mitophagy inducer in a mice model of aging and hypertension and lowered high blood pressure. In humans, high dietary spermidine intake was found to correlate with reduced blood pressure and decreased risk of cardiovascular disease and related death. Scientists in this area of research suggest that integration of spermidine in common diets may represent a cardio- and vascular-protective autophagy inducer in humans. The present article provides a brief review of the recent literature reporting on spermidine and takes the chance to make a first evaluation of the pharmacological potential of spermidine to reverse age-induced memory impairment, to protect the heart and to extent lifespan.

Keywords: Aging; Autophagy; Cancer; Dementia; Helicobacter pylori; Memory, to Mitophagy; Polyamines; Supplementation

Abbreviations: DMFO: α-difluoromethylornithine; GABR: Global Arginine Bioavailability Ratio; NOS: Nitric Oxide Synthase

    Introduction

Spermidine, N-(3-aminopropyl) butane-1,4-diamine, is a low-molecular-mass organic base (C7H19N3, CAS 124-20-9) and belongs to the polyamine family which includes spermine and putrescine, the direct precursor of spermidine (Figure 1).At ambient temperature (22-25 °C) spermidine is a colorless liquid or a white powder. In biological samples, the two primary amine groups and the secondary amine group of spermidine are protonated so that the spermidine molecule is a polyvalent cation. Spermidine is a natural compound and widely distributed in plants, animals and humans. Scientific reports on spermidine and putrescine exist for more than 90 years, whereas articles on spermine appeared 25 years earlier (Table 1).

Spermidine is biosynthesized by microorganisms, plants and animals including humans [1-3]. Two possible biosynthetic pathways are illustrated in a simplified form in Figure 1. Hydrolysis of L-arginine by arginase yields L-ornithine which is decarboxylated by ornithine decarboxylase to form putrescine (butane-1,4-diamine or 1,4-diaminobutane). Putrescine can also be formed by hydrolysis of agmatine which is produced from L-arginine by the action of arginine decarboxylase. Putrescine is alkylated by the decarboxylated S-adenosyl-methionine which regularly serves as the major methyl (CH3) group donor for methyl transferases. Spermidine and other polyamines have been and are still subject of continuous scientific research from many different disciplines (Table 1). Spermidine's pharmacological properties including distribution, metabolism and excretion have been thoroughly investigated. A major fraction of injected spermidine is excreted in the urine [4]. Spermidine and other polyamines have been early and widely associated with growth (Table 1) and aging. They were found more than 50 years ago to stabilize various cellular and subcellular components including nucleic acids due to their polyvalent cationic structures.

Several analytical methods have been reported for the simultaneous measurement of spermidine, spermine and putrescine in human biological samples, including HPLC and GC-MS [5,6] and LC-MS/MS [7]. Polyamines including spermidine have been found at elevated circulating and urinary concentrations in a variety of diseases including cancer and psoriasis (Table 1). In plasma spermidine concentration was found to be 220 nM in healthy humans and 200-800 nM in cancer patients. Mean spermidine concentrations in urine were found to be also in the nM-range, e.g., 130 nM in healthy subjects, 186 nM in diabetic patients and 680 nM in patients with severe complications [7].

Measurement of elevated spermidine concentrations in subjects suffering from various diseases has early prompted research on developing drugs to inhibit polyamine biosynthesis. One of these drugs is α-difluoromethylornithine (DMFO) [2]. More recent studies suggest that spermidine supplementation may exert beneficial effects on the brain and the heart, and can even extent lifespan. A selection of these studies is provided in Table 2 [8-31] and is briefly reviewed and discussed in the section that follows. Escherichia coli (E. coli) has been very often associated with polyamines (Table 1). The pathogenic Helicobacter pylori (H. pylori) from subjects infected with the bacterium produces large amounts of spermidine and histamine in culture [32]. The potential implication of H. pylori-derived spermidine in diseases remains to be investigated. Spermidine is considered an inducer of autophagy. For recent reviews and commentaries to autophagy and longevity and underlying mechanisms see References [33-42]. For the polyamine content of food see the recent review by Kalač [43].

    Discussion

Spermidine and other polyamines are biologically active compounds and have numerous biological activities in humans. More recent non-human studies suggest polyamines as potential candidates for diseases associated with autophagy or impairment of memory due to advanced age. Due to their pharmacological potential, their toxicity and health risks have been thoroughly investigated twenty years ago. Oral acute toxicity of spermidine was determined to be 600mg (4.1mmol)/kg body weight in Wistar rats, with the no-observed-adverse-effect being 83mg (0.57mmol)/kg body weight [43]. Pharmacokinetic data for spermidine and other polyamines in humans are very scarce and need to be generated in carefully performed studies. The toxicity and health risks data observed in animals and the polyamine concentrations measured in healthy and diseased subjects provide an approximate idea of the dose regimen for spermidine supplementation in humans.

Despite the long interest in polyamines, reference values and intervals have not been established thus far. Moreover, reported circulating and urinary polyamine concentrations vary considerably. As an example, plasma spermidine concentration lies between 0.2μM (healthy subjects) and 0.8μM (cancer patients) [6]. Spermidine concentration seems to be ten times higher in packed red blood cells (5-8μM) [43-45] compared to plasma, suggesting accumulation of spermidine in human erythrocytes. To our knowledge, there is only a single paper reporting on circulating spermidine concentration in healthy humans of both genders aging between 31 and 106 years. In the Group 1 (age range, 31-56 years) the spermidine median [95%CI interval] concentration was approximately 63 [48-100] pmol/mg whole blood proteins. In the Group 2 (age range, 60-80 years) the spermidine concentration was approximately 23 [20-30] pmol/mg protein, i.e., about three times lower than in Group 1. In the Group 3 (age range, 90-106 years) the spermidine concentration was approximately 70 [48-81] pmol/mg protein, i.e., even higher than in Group 1 [18]. This is a very important but also surprising observation and needs evaluation in forthcoming studies.

Eisenberg et al. [31] reported that "In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease."

As the authors acknowledged in their paper, estimation of dietary spermidine intake on the basis of food-frequency questionnaires is an indirect method. In our opinion, this estimation is not eligible to draw far reaching conclusions that spermidine is the elixir for cardioprotection and lifespan extension. This must yet be demonstrated in further studies. In this context, we should remember that the mean daily dietary intake of spermidine in Western countries ranges between 7.9mg (54μmol) and 12.6 mg (87μmol) [43]. Even if these dietary spermidine amounts would be completely absorbed, the spermidine concentrations that would occur in blood and tissue would be not high enough to exert the reported effects in the majority of the studies in which spermidine was used mostly in the lower mM-range (Table 2). Eisenberg et al. [31] assumed that the blood pressure lowering effect of polyamines is presumably due to an increase of the bioavailability of L-arginine, but not data were reported about the nitric oxide (NO) synthesis from L-arginine. Based on the same thoughts and estimations stated above, dietary spermidine, and most likely other dietary polyamines, cannot considerably contribute to the global arginine bioavailability ratio (GABR), especially in regard to the about 1000 times higher dietary intake of L-arginine. Thus, food is likely to contribute to polyamines via bactericidal metabolism of exogenous L-arginine.

Therefore, if spermidine and other polyamines can indeed lower the blood pressure in humans, the underlying mechanisms are unlikely to be enhancement of the GABR. In mice, spermidine supplementation (3mM spermidine in drinking water for 4 weeks; 3mM in vitro in cultured aortic rings) has been reported to improve arterial aging in terms of a normalization aortic pulse waive velocity, endothelium-dependent dilation, autophagy, and even to reduce oxidative stress (based on nitrotyrosine measurement) in the older animals [46]. Unfortunately, in this paper no circulating concentrations were reported for spermidine and for the NO metabolites nitrite and nitrate. Very recently, the L-arginine metabolism has been investigated in rat vestibular nucleus and cerebellum. Measured biomarkers included arginine, citrulline, ornithine, glutamine, glutamate, GABA, spermidine, spermine, putrescine and agmatine and NOS activity by measuring the 3H-L-arginine to 3H-L-citrulline conversion rate [47].

This assay is associated with remarkable pitfalls, most notably with unspecificity, in tissue homogenates because of their capacity to produce and utilize L-citrulline by alternative pathways [48]. The study revealed that brain L-arginine metabolism is influenced by age. With regard to spermidine, age-related differences were found in the cerebellum but not in the vestibular nucleus complex of the rats (age, 4 v. 24 months), and not between middle-aged and aged rats (12 vs. 24 months). With minor exceptions [11,15], reported effects of exogenous spermidine have been observed at very high concentrations, mostly at 3mM (435mg/L) to 5mM (725mg/L). These concentrations are three and four orders of magnitude higher than spermidine concentrations found in plasma and red blood cells of humans, respectively. Although supplementation of high amounts of spermidine, putrescine or spermine is feasible from a pharmaceutical point of view, it has first to be demonstrated that supplementation of polyamines to reach concentrations that were turned out to be effective in flies, worms and small animals (mice and rats), is safe in humans.

Unfortunately, in the majority of the studies reported in the last decade, drug safety has not been implemented. Also, the potential formation of catabolic and metabolic reaction products of polyamines has not been considered at all. However, catabolism of polyamines produces many toxic compounds including H2O2 and aldehydes [43,49]. And last but not least important, spermidine can be nitrosated to N-nitrosospermidine which is further converted by cyclisation to N-nitrosopyrrolidine [50] which is classified as a possible carcinogen. Formation of nitrosopolyamines from polyamines and inorganic nitrite, that is abundantly present in human saliva, is favored under acidic conditions as they prevail in the stomach. In this context, a possible involvement of H. pylori which produces spermidine in large amounts [8] is worthy of investigation

A first research paper on spermidine and spermine in tissues of rats of increasing age revealed that the spermidine content decreased in all tissues with increasing age, with the fall being most marked during the first month of life [51]. The spermidine/ spermine molar ratio in the tissues was highest immediately after birth. In contrast to other tissues, in rat brain the spermidine/ spermine increased from 1.3 to 2.1 during the first 9 months. Similar results were found in liver and kidney of rats aged 1, 3, 6, 13 and 22 months [52].

In human brain, polyamines are heterogeneously distributed [53,54]. The highest spermidine levels were measured in white matter (20nmol/mg protein) and thalamus (9.3nmol/ mg protein) [29]. In contrast to rodents, spermidine levels in occipital cortex of neurologically normal human brain were found to increase markedly from birth, to reach maximal tissue content at the age of about 40 years and not to decrease up to senescence [53]. Spermidine tissue content was found to correlate positively with age from birth to adulthood (p=0.71, P<0.01, for day 1 to 50 years; p=0.40, P<0.01, for day 1 to 103 years). In contrast to spermidine, putrescine and spermine tissue concentrations were found to be independent of age. In older adults (mean age, 58-85 years), spermidine content in several brain regions was found to decrease with age [54]. Among the degenerative movement disorders investigated (Parkinson's disease, Huntington's disease to Progressive supra nuclear palsy), only spermidine putamen content was lower compared to healthy controls.

H. pylori has been declared as a definite gastric carcinogen [55]. The prevalence for H. pylori is about 50% around the world. This bacterium is considered to be responsible for about 90% of noncardia gastric cancer. The precise molecular and cellular mechanisms of gastric cancer development associated with H. pylori infection are still elusive. One possible mechanism could involve misregulation of p27 expression by H. pylori [55]. In cultures of this bacterium isolated from subjects infected with the H. pylori we measured large amounts of spermidine and histamine [8]. High circulating and urinary concentrations of polyamines are found in cancer patients [6]. One may therefore ask the question whether spermidine produced by H. pylori might be involved in gastric cancer. The potential implication of H. pylori-derived spermidine in diseases remains to be investigated. A very recent study revealed that spermidine, spermine and putrescine at very low concentrations (range, 8nM to 10|iM) induced proliferation and migration of certain cancer cells by up regulating among others ornithine decarboxylase and by down regulating p27 [56].

    Conclusion

Since the fall of mankind, human beings strive for longevity in good physical and mental health. Can Science, the modern Prometheus, disclose us the secret of the Gods? Are natural polyamines the elixir for long life and against dementia? Might spermidine be the core-polyamine for a long and dementiafree life? Many sophisticated studies published in the last decade suggest that spermidine exerts beneficial effects in the cardiovascular system and in the brain, at least in yeast, flies, worms and small animals. Yet, in many respects human biology differs from that of rodents behave. With exception of isolated cells, where spermidine exerted remarkable effects at concentrations of the order of 20nM, too high spermidine concentrations have been supplied to achieve measurable biological effects.

Within a few years, there is already a general belief that spermidine is an inducer of autophagy and that this prolongs life. Spermidine, being an L-arginine metabolite, seems to be associated with NO which plays multiple roles in the renal, cardiovascular and central nervous systems. Yet, can the results observed in microorganisms and small animals be translated to man? Is high dietary spermidine intake a risk-free option for good physical and mental health? Data from human studies on spermidine are very rare, contradictory and not convincing for example with respect to the inverse correlation between spermidine and blood pressure or risk of cardiovascular disease and related death. In the past, observations from the use of many antioxidants at high concentrations in vitro and in vivo animal experiments raised the expectations for health-promotion in humans, but large clinical studies were very disappointing [57]. For the same reasons, most notably use of irrelevantly high concentrations/doses and disregard of health-risk effects, this may also happen to the use of spermidine and/or other polyamines as supplements. It’s a long way to Longevity!

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Late Infectious Complications after Liver Transplantation in Children- Juniper Publishers

Late Infectious Complications after Liver Transplantation in Children- Juniper Publishers

Authored by Anita Verma

Introduction

Infectious complications in children after liver transplantation are a major cause of morbidity and mortality. Most of the life-threatening infections are seen in the first few months after the operation and are related to their stay in the intensive care unit, invasive monitoring, anastomotic leaks and higher levels of immunosuppressive medications. Infections that happen after six months of liver transplant operation are considered as late infections. True incidence of the type of infections is difficult to establish as most of these patients are usually not managed in the liver transplant centre and the data may not be always provided to the transplant centre by local hospitals. Hence this subject has been only a matter of few research publications [1].

After 6 month we can divide liver transplant recipients into three groups, in term of their risk to acquire infections: Group 1: patients with good allograft function and low immunosuppression (comprising about 80% of the patient population). This group usually have very low risk of infections. Most common infections in this group of patients are community-acquired and include respiratory viruses: e.g., influenza, para-influenza, respiratory syncytial virus, human metapneumovirus, swine flu virus, coronaviruses. The common bacterial infections are Streptococcus pneumoniae (drug resistant), Haemophilus influenzae, MRSA, Mycobacterium tuberculosis. Gastrointestinal pathogens - Noravirus, Rotavirus, Compylobacter, Salmonella. Rarely atypical organisms such as Mycoplasma and Legionella. Paediatirc liver transplant recipients particularly young children who are unable to receive live vaccines before transplant are also prone to vaccine-preventable diseases- variciella, measles and mumps. Second category of patients (Group 2, about 10-15% of patient population), who have on going biliary complications secondary to anastomotic strictures or cholangiopathies secondary vascular problems are more likely to get infections due to endogenous flora coliforms, enterococci and emerging carbapenem resistant enterobacteraceae (CRE). Invasive procedures like cholangiography, percutaneous or endoscopic predispose further these patients to environmental pathogens like Pseudomonas hence it is important to consider the antibiotic cover for this type of organisms when using empiric antimicrobial therapies. Patients with recurrent cholangitis are exposed to repeated courses of antibiotics which make them prone to fungal infections. Hence antifungal cover depending on local epidemiology should be considered when response to standard antimicrobials is less than optimal. Third category of patients (Group 3, about 2-5% of patient population) who have difficult to treat allograft rejection requiring higher levels of immunosuppresion and or use of biological agents like mono or polyclonal antibodies. This group can present with severe opportunistic infections involving- P jiroveci, Cryptococcus neoformans, Nocardia and invasive fungi such as Aspergillus, Mucor and other molds. Reactivation of viruses- Herpes group: CMV, HSV encephalitis, EBV and Herpes zoster.

Treating physicians should also keep in mind travel associated pathogens, specific exposures to uncommon pathogens related to work, recreational activities and pets. We evaluated the incidence, risk factors and pathogens for late IC in 181 paediatric LTR between 2004 to 2008 at King’s College Hospital, London. Follow-up end points were 2-year, death or re-transplantation. Overall incidence of late infections was 21.4% (39/181); predominant infections were due to viruses 19%, most common viral infection was due to cytomegalovirus (CMV) 10.4%, followed by respiratory tract viruses i.e. influenza, Swine flu, rhinovirus, adenovirus & gastrointestinal virus- noravirus. One patient each had cholangitis due to Candida albicans, bacteraemia (E.faecium), conjunctivitis (S aueus) and diarrhoea (Compylobacter).

    Late Cytomegalovirus (CMV) Infection in Liver Transplant Recipients

Although late CMV infection is well studied in adult LTR but there is paucity of data in paediatric patients. The risk factors for late CMV infection described are prolonged antiviral prophylaxis, recurrent rejection while on antiviral prophylaxis and increased immunosuppression especially use of antilymphocyte products [2]. Late CMV presentation can manifest as non-specific viral syndrome (fever, leukopenia, atypical lymphocytosis & thrombocytopenia) or involvement of visceral organ (common sites include the gastrointestinal tract, liver, and lungs) and the site of involvement varies according to the type of transplant. This is the first centre we analysed highest number of pedaitric LTR for late CMV complications. The overall 1st CMV infection after transplant was in 51%, 67%, 66% 10% in D-R+, D+R-, D+R+ & D-R- respectively. The overall incidence of late CMV infection in three high risk group (D-R+, D+R-, D+R+ excluding low risk patients D-R-) was 18/131 (13.7%). Most of these patients were young and had late post-transplant complications. Late rejection was seen in 25% of patients mainly in D+R- & D-R+ group. The most important finding was, D-R+ group showed very high rate of hepatitis (36%) on liver biopsies in comparison to 15 % in other two groups.

The anti CMV prophylaxis protocol included IV ganciclovir 5mg/kg twice daily for 2 weeks for D+R- starting at day 7 posttransplant, followed by CMV DNA monitoring till patient is discharged or when symptomatic for other groups. Late CMV disease was present in 5/131 (3.8%) patients. Less than 2% patients required the second line treatment with foscarnet. Late CMV infection was associated with increased morbidity but no mortality. Antiviral prophylaxis only delays the onset of viral replication, and therefore, it does not prevent the development of a primary infection, which is relatively common after prophylactic therapy has been completed [3]. In a study of 67 high-risk CMV liver transplant recipients (9 patients on oral ganciclovir, 58 patients on valganciclovir for 92 days), primary CMV disease was observed in 2%, 25%, 27%, 27%, and 29% of patients at 1, 3, 6, 12, and 24 months, respectively, after antiviral prophylactic therapy was stopped with similar incidences between the two treatment groups [2].

Patient who develop allograft rejection during prophylaxis are at an increased risk for developing delayed-onset CMV disease after cessation of prophylaxis, which has led to increased mortality [4-6]. Risk of delayed onset CMV disease could be prevented by minimization of immunosuppression or by prolonging CMV prophylaxis i.e., 6 months instead of 3 months. However, these measures are associated with risk of; graft rejection, drug toxicity, increased cost, emergence of drug resistance [7]. In adult patient’s antiviral prophylaxis has been proven to be of benefit as without antiviral therapyrisk of CMV infection was reported to be 44-65%, in high risk CMV LT-recipients during first 12 month [8,9]. Meta-analysis on prophylaxis with ganciclovir or valganciclovir vs placebo showed significant reduction of - CMV infection, CMV disease & mortality in solid organ transplant recipients. Few other studies have reported improved survival and reduction of biopsy proven rejection [10,11].

However, there is no consensus on duration of antiviral prophylaxis. Prolonged duration of treatment could result in ganciclovir resistance. Resistance should be suspected if viral load persists while on antivirals, this could be confirmed by testing for genotypic mutations within the viral genes UL97 and/or UL54. Ganciclovir-resistant CMV disease was reported in up to 7% of high risk CMV recipients while none in CMVseropositive recipients in a group of solid organ transplant recipients [12]. Ganciclovir resistant patients could be treated with foscarnet or cidofovir with or without immunoglobulin and reducing immunosuppression [13]. Other antiviral agents that could become available are oral maribavir, CMX-001, artesunate, and everolimus [14]. Increased understanding, as well as the use of newer diagnostic tests, antiviral therapy, and preventative strategies, have led to marked improvements in the prevention and management of many of the complications associated with post-transplant CMV infections in children.

    Influenza Infection

The 2nd most common late viral infection was respiratory virus influenza. Reported incidence in SOT recipients is 2- 4%. In our data of 181 LTR 3% were admitted to hospital because of influenza infection. It is mainly upper respiratory tract (RT) disease, lower RT disease is estimated to occur in 1-5% of LTR. Parainfluenza & influenza were associated with high morbidity and mortality in very young LTR [15]. Oseltamivir is an effective agent with protective efficacy of 75% [16]. It is very important to consider early diagnosis and treatment for influenza infection in SOT recipients as it reduces the severity of influenza, shorten duration of viral shedding, reduce the frequency of lower RT complications e.g. bronchiolitis and pneumonia. Prevention is the most important strategy for influenza management-all LTR should have annual vaccine, 6 months after transplant surgery, if used before that immune response to vaccination could be suboptimal [17,18].

    Carbapenem resistant Enterobacteriaceae (CRE)

Excessive use of antibiotics has led to emergence of multidrug resistant gram-negative bacteria. The emerging problems with the CRE is becoming an issue in LTR, because of not only it is harboured in gut for long but can spread rapidly to other patients if stringent infection control precautions are not followed. We encountered an outbreak of infection with Carbapenem resistant Enterobacteriaceae (CRE) in our unit lately. A very stringent infection control protocol including; quarantine of all new admission from other hospitals in to single rooms till results of screening swabs (rectal swabs) are negative for CRE [19-21] hand hygiene, environmental cleaning, and antibiotic stewardship helped to control the outbreak. Further continuation of active surveillance prevented the silent dissemination of these superbugs in this immunosuppressed population.

    Conclusion

In conclusion the late infections after transplantation requiring hospital admission are not uncommon. Most severe infections occur in patients with biliary complications and during periods of increased immunosuppression. Careful monitoring and treatment could limit morbidity and avoid mortality.

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Protecting Biodiversity through Forest Management: Lessons Learned and Strategies for Success

Abstract

The strong links among biodiversity, forests, and climate change require that forces affecting them be addressed simultaneously. Here we summarize findings and lessons learned from decades of field work exploring ways to balance conservation with development, while effectively addressing drivers of deforestation and biodiversity loss. Examples are provided for approaches to forest management that support both biodiversity conservation and greenhouse gas mitigation. Causes of deforestation are reviewed and recommendations provided for    specific steps that would slow the loss of high conservation-value forests.

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