#cftr

[v-albion]

Happy (late) Birthday Cass!! @somerandomdudelmao

Hope you have a wonderful birthday!

Closer look under the cut

[somerandomdudelmao]

i wanted to sketch them and i got no wifi to post anything so have a photo from the camera of my ipad jajajajaja

KfjdjPRKRNFBFJRJJTJTKTKTJTJ THIS IS SO GOOD HAVE I EVER TOLD YOU HOW MUCH I LOVE YOUR ART STYLE?? I LOVE YOUR ART STYLE THEY ARE SO PRECIOUS THIS IS AMAZING

[oldshowbiz]

1973.

Radio CFTR with Toronto disc jockey Rick Moranis.

[cfri]

TRIKAFTA FOUND TO IMPROVE INSULIN SECRETION, BODY WEIGHT IN CF

Researchers analyzed insulin and blood glucose data from more than 400 children and adults with CF from four CF centers. \

While one year of treatment with Trikafta improved insulin secretion and body weight in people with CF, there were no consistent treatment-related improvements in measures relating to CF-related diabetes.

The data highlights the need for future studies investigating the effects of treatments like Trikafta on weight gain and changes in insulin sensitivity and secretion.

[jcrmhscasereports]

Case Study: Trikafta and severe symptomatic hypoglycemia: cause or coincidence? by Samuel Kunz in Journal of Clinical Case Reports Medical Images and Health Sciences 

ABSTRACT

Background Trikafta (Ivacaftor / Elexacaftor / Tezacaftor) is a new combined

CFTR modulator and potentiator for the treatment of cystic fibrosis (CF), approved by Swissmedic since December 2020. It has shown to improve lung function in CFpatients. Trikafta also influences pancreatic function and glucose homeostasis, whereby hypoglycemic episodes have been described. The underlying mechanisms are not yet fully understood.

Case report We present a 16-year-old adolescent with CF with a first tonic-clonic seizure while being hypoglycemic approximately two weeks after therapy-onset with Trikafta. Diagnostic work-up found no other underlying cause for the seizureepisode.

Discussion Literature shows a complex influence of pancreatic CFTR channels on glucose homeostasis. CFTR channels have an important role in the first phase of insulin secretion as well as regulation of glucagon release. Hence, some effect on glucose homeostasis is expected from the treatment with CFTR modulators. Due to the timely connection in our patient the hypoglycemic state could have been provoked by a combination of changing eating habits and the direct influence of Trikafta on the regulatory mechanism of the pancreatic CFTR channels.

Conclusion Medical caregivers should be aware of potential hypoglycemia risk in CF-patients put on Trikafta.  Based on the literature CF-pathophysiology and the pharmacologic effect of Trikafta  we assume that the medication may have triggered this critical event. We thus conclude that before initiating therapy a) patients should be evaluated for prediabetic state; b) patients should be instructed regarding hypoglycemia-risk and c) the possibility of continuous-glucose-monitoring should be considered and discussed with the patients.

Keywords: Trikafta, Ivacaftor, Elexacaftor, Tezacaftor hypoglycemia, cystic fibrosis

INTRODUCTION

Cystic Fibrosis (CF) is caused by mutation in the cystic fibrosis transmembrane conductance regulator protein (CFTR) gene which leads to defects in the eponymous called protein.1 Because of these defects, the chloride conductance in and out of the cell is impaired in many organs, most importantly in lung and pancreas, which leads to building of thick mucus in these organs. In the last years there is a new way to treat CF-patients, namely with CFTR-potentiators/-modulators, Trikafta as an example. They have shown to be very potent with major lung improvements and seem to be safe concerning the adversary effects.

CASE PRESENTATION

A 16-year old adolescent with cystic fibrosis, who was under Trikafta-therapy was admitted to the emergency department following a generalized tonic-clonic seizure.

The event happened during moderate physical activity one hour after lunch.

Examination on site showed hypoglycemia (3.0mmol/L), 20 minutes after seizure onset. 10 minutes after spontaneous seizure termination glucose infusion was immediately started. Upon arrival at the hospital the patient was somnolent with GCS 8 but hemodynamically stable. Blood glucose was 4.6 mmol/l. Electrolytes and inflammation parameters were normal, lactate was 2.9 mmol/L. Critical sampling wasn’t performed because of normal glucose.

Head-CT and – MRI excluded intracranial hemorrhage and relevant ischemia as potential etiologies. ECG was normal.

After extubation, the patient remained drowsy but oriented when stimulated, complained about headache for the next 24 hours. Follow-up EEG performed after 36 hours showed an overall decelerated pattern, which 5 days later had disappeared.

The patient had been diagnosed with CF - compound heterozygote type with F508deletion and 1717-1G>A. – 14 years ago.  His lung function had considerably declined resulting in nocturnal oxygen for the last 7 months. His last FEV1 was 38% with the lowest value of 21% during the latest exacerbation several months ago. Consecutively he was started off-label on Trikafta (Ivacaftor / Elexacaftor / Tezacaftor) additionally to his regular CF-treatment 18 days prior to the event. He noted an immediate substantial subjective improvement of lung function. Pulmonary secretion decreased and physical performance improved. His FEV1 almost doubled to 64% two weeks after treatment onset.

The adolescent had previously been diagnosed with exocrine pancreas insufficiency with failure to thrive and reduced bone mineral density despite pancreatic enzymes substitution. An oral glucose tolerance-test (oGTT) was normal nine months before the event. On Trikafta the patient developed increased appetite and a weight gain of 5kg in 18 days.

DISCUSSION

Trikafta  is a novel combined CFTR modulator and potentiator. Enhancing the quantity of correctly processed CFTR proteins and increasing their open-probability once integrated in the cell membrane, this medication has recently improved lung function in CF-patients by increasing the conductance of chloride across the epithelial cells.1 Whereas the primary target is improvement of epithelial lung cell function, the modulator therapy additionally influences the CFTR dependent function in other organs i.e., the pancreas.

CFTR channels are present in pancreatic islet cells. Animal and human studies show that CFTR deficiency leads to islet-intrinsic defects in insulin secretion. Kayani et al give an excellent overview of the role of the CFTR in insulin secretion focusing on the first-phase insulin response, which is depolarization-dependent and therefore possibly related to the CFTR function, whereas the second phase release is not.2 In addition to insulin secretion, CFTR presumably regulates glucagon release from the pancreatic alpha cell. Glucagon secretion was enhanced in response to glucose and forskolin following CFTR inhibition in human islets.  The exact impact of CFTR in pancreatic cells remain conflicting and further studies are needed. 3

Therefore, CF related diabetes (CFRD) could partially be explained by a reduction in early-phase insulin secretion, which is considered the initial marker of impaired insulin secretion.3

Hence, some effect on glucose homeostasis is expected from the treatment with CFTR modulators. Hypoglycemic events have been described with the administration of Ivacaftor in patients with a CFRD resulting in reduced insulin-requirements. Ivacaftor also improved the early phase insulin secretion in a relatively young CFpatient group with normal to mildly impaired glucose tolerance comparable to our patient. The extent to which this arises from b-cell-specific effects remains unclear; since CFTR protein expression has been identified also in pancreatic alpha-cells, Ivacaftor and with it Trikafta may have effect on both cell functions. 4; 5

The American FDA (Food and Drug Administration) reports a prevalence of 1% of hypoglycemic events with Trikafta as compared to placebo. The WHOpharmacovigilance database (www.vigylize.who-umc.org) has listed nine cases of hypoglycemia since 2019. According to the criteria of the Institute of Clinical

Pharmacology and Toxicology of the University Hospital of Zurich, a correlation of the hypoglycemic event and administration of Trikafta is possible, given the timely connection.

Our patient reported a sudden change of eating habits with the start of Trikafta, with larger meals and a weight-gain of 5kg in two weeks, which lead us to assume a change in glucose homeostasis. The aforementioned mechanisms in CFRD and documented reduction in early phase insulin secretion even in patients without CFRD, let us speculate on a prediabetic state in our patient. We suggested that the improved insulin secretion from beta cells after the start of Trikafta cumulating with the second phase release and simultaneously impaired glucagon release from alpha cells led to the hypoglycemic event. Christian et all. published a case with postprandial hypoglycemic events during the treatment with Ivacaftor hypothesizing a potentiation of the insulin-effect after meals.4  An additional potential risk factor is the changed eating habit in our patient with the possibility of faster gastric emptying and reduced insulin secretion 3; 5

While limitations lie in the thoroughly evaluation of hypoglycemia (C-peptide, Insulin, fasting-glucose-test), medication-induced hypoglycemia was the most possible solution. Knowing that a glucose of 3mmol/l doesn’t typically lead to general seizures we supposed a lower value during at the initiation, with counter-regulatory mechanisms already working until the first measurement, which we can’t prove

CONCLUSION

To our knowledge, this is the first reported case with a symptomatic hypoglycemic seizure event in a patient with CF under Trikafta. After exclusion of other potential causes, we hypothesize a combined effect of improved first phase insulin release together with a modifying effect on pancreatic glucagon secretion. This would be in line with the current literature on Trikafta and with data of CFTR-modulator pilotstudies suggesting an increased hypoglycemia risk.

Based on our patient's case we suggest evaluating patients carefully for pre-diabetic state before starting Trikafta, a good education regarding the potential for postprandial hypoglycemia and considering a continuous glucose monitoring in the first weeks of treatment.

Conflict of interest: None

For more information: https://jmedcasereportsimages.org/about-us/

For more submission : https://jmedcasereportsimages.org/

[cytgen]

Keywords: Cftr Nfkb1 Ocln gene expression full-thickness skin wounds purulonecrotic skin wounds melanin

[st4rguy]

For the character ask: the one and only peridot 💚😌

favorite thing about them: OH MY GOD SHE IS SO VCFTYUHGVFCTGYHB VGF SO SCRUNKY SO CUTE THE CHILD least favorite thing about them: NOTHING THEY ARE PERFECT IDC IDC favorite line: "NEVERMIND" this dequires context, this is in the q&a segment and she is talking about fanfic and the nightmare kniht asks her what fanfiction is brOTP i would be interested to see her and cuco interact, either they would be best friends, or bickering siblings OTP ALMODOT ALMODOT ALMODOT nOTP i have seen no one ship her with anyone else AND IT BETTER STAY VTHAT WAY OR FUCKING ELSE random headcanon: she likes vocaliod unpopular opinion: SHE IS PERFECT AND THE BEST AND CFTR^&YUHYGFTRGYHBGVFCDXFTGYHBVGCFXD song i associate with them fairytales by gabby sophia, its mostly general cucumber quest but still favorite picture of them

HEEEEEEEERRRRRRRR HEEEEEERRRRRRR

[rpmtrish]

THE JOHN MASSINGBERD MEMORIAL AWARD PRESENTED AT DRAG STRIP MEMORIES

Mount Hope, ONTARIO (April 14, 2024) – The John Massingberd Memorial Award has been presented by the Pro Modified Racing Association (PMRA) to a new, deserving individual, who represents the same commitment, dedication and passion that John Massingberd conveyed for the sport of auto racing. Massingberd, a long-time motorsports media personality, was instrumental in promoting Canadian motorsports until his passing in December of 2008, after a long and courageous battle with ALS, also known as Lou Gehrig's disease. This year’s award was presented on April 14, at the Drag Strip Memories show at the Canadian Warplane Heritage Museum in Mount Hope, Ontario to Erik Tomas. Erik caught the racing bug when his father took him to dirt tracks in the Niagara Region of Ontario, when he was seven years old and the sport has followed him everywhere since. While broadcasting news, sports and play-by-play hockey on Niagara radio stations CHSC, CKTB and CJRN in St. Catharines and Niagara Falls, “ET” started announcing the racing action at Merrittville Speedway, Ransomville Speedway and Cayuga Speedway through the 1970s. In the 1980s, Erik brought his broadcasting talents to the Toronto market, broadcasting news and sports for 680 CFTR (now 680 News) and CKFM/Mix 99.9 (now Virgin Radio 99.9).  He also had a stint as a play-by-play TV announcer for the NHL’s Toronto Maple Leafs on CHCH-TV and Global Television in the mid-1980s. Getting back to his auto racing roots while still working radio in Toronto, Erik took on the role of anchor, writer and co-producer for the Raceline Motorsport Television series on TSN, owned and produced by Bruce F. Mehlenbacher and the late John Massingberd’s Promark Motorsport International. Massingberd was inducted into the Canadian Drag Racing Hall of Fame posthumously in 2022 and was inducted into the Canadian Motorsport Hall of Fame posthumously in 2023. The Mehlenbacher family was inducted into the Canadian Motorsport Hall of Fame in 1998, and Bruce F. Mehlenbacher was inducted into the Canadian Drag Racing Hall of Fame in 2023. When the CART IndyCar Series came to the streets of Toronto, ET brought his track announcing experience to The Molson Indy from the first race in 1986, as track announcer. Erik’s auto racing passion turned into a full-time gig as anchor, producer, writer, and affiliate relations for the Raceline Radio Network, starting in 1992. Erik was Canada’s lone full-time auto racing broadcast journalist, and Raceline Radio remained Canada’s only nationally syndicated motorsport radio program until Erik retired from professional broadcasting in December 2023.  He dedicated 48 years to sports broadcasting and 31 years to the Raceline Radio Network. The Network comprised affiliates in Toronto, Montreal, Vancouver, Calgary, Halifax, Hamilton, and Niagara/Western New York State. Many affiliates aired Raceline Radio twice weekly, with an additional audience obtained through podcasts. Total weekly audiences exceeded 175,000 listeners.  2023 marked the 31st Anniversary of The Raceline Radio Network. During his career, Erik has interviewed some of the biggest and most influential stars in racing.  This includes Mario Andretti, Shirley Muldowney, John Force, Don Garlits, Rick Mears, Bobby Rahal, Tom Carnegie, Nigel Mansell, Al Unser Jr., Dale Earnhardt, Kenny Bernstein and Bob Jenkins. Raceline Radio has won numerous international motorsport journalism awards, with Erik at the helm.  Erik was a regular contributor to Inside Track Motorsport News. Erik Tomas was deservedly inducted into the Canadian Motorsport Hall of Fame in 2020. The John Massingberd Award honours a national ambassador of Canadian motorsport in all disciplines, through his keen insight and entrepreneurial creativity. In the late 1980s, John co-established Promark Motorsport International, which included Raceline Motorsport Television and SnowTrax Television with Bruce Mehlenbacher, two media ventures responsible for bringing Canadian motorsport to a greater audience and well-deserved prominence.  Along with coverage of drag racing, stock car racing, road racing, and tractor pulls with Promark Motorsport International and Raceline Television, he co-founded and co-anchored Raceline Radio in 1992. John was the executive producer of Canada’s first nationally syndicated motorsport radio program, the Raceline Radio Network, along with Erik Tomas.  Raceline Radio was Canada’s first and only nationally syndicated motorsport radio program that celebrated 31 years on the air in 2023 as Canada’s National Radio Motorsport Authority. All who knew John quickly recognized his larger-than-life stature. With his warm, friendly but firm handshake, quick wit and genuine charm, John had a fantastic ability to never be at a loss for words.  He pioneered his field, breaking new ground in radio and television coverage of Canadian motorsport. In keeping with the spirit of the Pro Modified Racing Association, it is appropriate and altogether fitting to recognize John Massingberd with this annual award. Past Recipients: Carl Spiering, Fred & Betsy Smith, R.W. (Bob) Slack, Vern Christy, John Waldie, Tim Miller, Bruce Biegler, Harvey Silverthorne and Rob Potter. #johnmassingberd #dragstripmemories #warplaneheritagemuseum #rpmmagazine #rpmmag #rpm25yrs Read the full article

[helthcareheven]

Embryo Enhancement Strategies: Preimplantation Genetic Diagnosis

What is PGD?

PGD, or preimplantation genetic diagnosis, is a procedure performed on embryos prior to implantation in the womb. During in vitro fertilization (IVF), embryos are created through fertilization in a laboratory dish and are allowed to develop for a few days. At this early stage, one or two cells are gently removed from the embryo and tested for genetic abnormalities and conditions. Only healthy embryos, as determined by PGD, are selected for implantation. The History of PGD

The first baby born through PGD was in 1990 after testing for cystic fibrosis. In the years since, the technique has improved and can now test for hundreds of genetic disorders. Initially, PGD was used for serious hereditary conditions like cystic fibrosis, Tay-Sachs disease, sickle cell anemia, and muscular dystrophy. Today, it is also applied to detect chromosomal abnormalities like Down syndrome and gender selection for X-linked disorders. PGD has helped many couples avoid passing on serious genetic diseases to their children. The PGD Process

The general steps involved in PGD are:

1) IVF treatment is performed as normal to collect multiple eggs from the female patient. 2) Eggs are fertilized with sperm in the lab to create embryos. 3) Typically on day 3 of development, when the embryo contains 6-10 cells, one or two cells are gently removed for biopsy without harming embryonic development. 4) The biopsied cells are analyzed using techniques like fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR) to detect abnormalities. 5) Only healthy embryos, as confirmed by PGD results, are selected and implanted back into the woman's womb. Diseases Screened by PGD

Some of the more common genetic disorders for which PGD is often used include: - Cystic fibrosis: A lung disease caused by mutations in the CFTR gene. PGD can detect affected embryos. - Huntington's disease: A neurodegenerative condition caused by CAG repeat expansions. PGD finds embryos free of expansions. - Fragile X syndrome: The most common form of inherited intellectual disability caused by mutations in the FMR1 gene. Embryos can be tested. - Myotonic dystrophy: A muscular dystrophy caused by CTG repeat expansions that PGD can identify in embryos. - Beta thalassemia: An anemia caused by mutations in the HBB gene. PGD selects unaffected embryos. - Sickle cell anemia: Another anemia caused by a mutation in the HBB gene. PGD accurately diagnoses embryos. How Accurate is PGD?

As the techniques used for PGD continue to improve, the tests have become highly accurate. FISH analysis has an accuracy rate of about 95-99% while PCR-based methods detect abnormalities with over 99% accuracy. However, there is still a small chance of diagnostic errors. PGD is not currently able to test for all known genetic disorders and conditions either. While it has helped many couples, PGD is not perfect and misdiagnosis is still possible in a small number of cases. Continued clinical testing and experience will help further enhance the accuracy and reliability of PGD. Overall, when performed by experienced centers, PGD provides an effective method for screening embryos. Limitations and Ethical Considerations

While PGD addresses the desire to have healthy, genetically related children, it is not without limitations and ethical concerns. Aside from occasional misdiagnosis risks, PGD is not accessible or affordable for all couples and families affected by genetic disorders. The procedure is also limited to testing only those disorders with a known genetic cause and diagnostic test. There are ongoing debates around the widening scope of what conditions PGD is used for, including gender selection for social reasons alone. Some argue this could eventually lead to selecting embryos for traits like intelligence or athletic ability. Most experts agree PGD should only be offered for preventing medical disease or conditions. Overall, PGD is an advancing technology that provides benefit but also responsibility in its application. In conclusion, through the advances of preimplantation genetic diagnosis, modern science now offers new hope for couples at high risk of passing on life-altering genetic disorders. When performed carefully by trained professionals, PGD has proven an effective tool for pre-implantation diagnosis of embryos. Continued progress is still needed to further increase accuracy, expand testing options, and ensure judicious application in line with ethical standards. Looking ahead, PGD promises more couples the ability to have healthy children free of devastating genetic diseases.

[v-albion]

History repeats itself @somerandomdudelmao

[somerandomdudelmao]

This is probably a slly question but what does the cftm tag in some of your posts stand for?

It's my little tagging system hehe

So

Cft - Cas Fanart Tag

And then I add the name of the revived turtle

Cftm - Mikey

CftR - Raph

CftL - Leo

CftD - Donnie

Then I have Cftmnt - for the big reunion~

______

And since I'm already explaining my tags, here's the all others

Cass apocalyptic series - for my comic only.

Cas fanart tag - for the comic fanart in general

Cas edit - ...for edits..obviously haha

Fic tag - your fics (I forgot to add Cas ._. )

Helpful - for when I need a help or inspiration with creating.

[oldshowbiz]

Late Night Radio: CFTR Radio AM 680

[ptmasterguide]

CFTR gene (Function)

CFTR gene (Function) Function: The CFTR protein is a chloride channel that regulates the flow of chloride ions across cell membranes. It plays a crucial role in maintaining the balance of salt and water in various tissues and organs of the body, including the lungs, pancreas, liver, intestines, and sweat glands.

[nitasonwane]

Cystic Fibrosis Market Size, Share and Growth during Forecast Period

The cystic fibrosis (CF) market has been an area of significant focus for pharmaceutical companies and research institutions due to the unmet medical needs of individuals affected by this genetic disorder. CF is a lifelong condition that affects the lungs and digestive system, causing difficulties in breathing and digestion.

The CF market has seen advancements in treatment options, focusing on managing symptoms, improving quality of life, and targeting the underlying genetic causes of the disease. Some of the key aspects of the CF market include:

Drug Therapies: Pharmaceutical companies have developed and continue to develop various drugs targeting specific mutations of the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene, which is responsible for CF. These drugs aim to correct the dysfunctional CFTR protein or improve its function. Examples include modulator therapies like ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor, elexacaftor/tezacaftor/ivacaftor, and others.

Gene Editing and Gene Therapy: Research is ongoing in the field of gene editing and gene therapy to address the root cause of CF by repairing or replacing the defective CFTR gene. Techniques such as CRISPR/Cas9 and viral vectors for gene delivery hold promise in this area.

Market Dynamics: The CF market is competitive, with several pharmaceutical companies investing in research and development to introduce new therapies. Pricing, access to medications, and reimbursement policies are factors influencing market dynamics.

Patient Care and Support: Beyond medications, there's a growing emphasis on holistic care for CF patients, including nutritional support, physiotherapy, and mental health services, to improve overall well-being and life expectancy.

Clinical Trials: Ongoing clinical trials assess the safety and efficacy of new drugs, combinations, and treatment modalities, aiming to further enhance CF management and outcomes.