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High blood pressure, often known as hypertension, is a major risk factor for heart disease and stroke, two of the top causes of mortality in the United States. It’s also one of the most common chronic illnesses in the United States, with over half of all individuals in the country classified as hypertensive according to current standards.

An estimated 20% of persons with high blood pressure have resistant hypertension, which means their blood pressure stays high despite vigorous therapy. According to recent research, gut bacteria can limit the efficiency of certain blood pressure medications, possibly opening the door to creating new approaches to manage treatment-resistant hypertension.

The study, which was published this month in the journal Hypertension, provides the first answers to a long-standing mystery: why do some people not respond effectively to treatment.

“High blood pressure is often called a silent killer because it doesn’t usually cause symptoms. However, there is a big population of individuals who know they have hypertension but still cannot get it under control, even though they’re taking blood pressure drugs,” said Dr. Tao Yang, an assistant professor in the Department of Physiology and Pharmacology and the study’s first and lead author. “Addressing this is of huge clinical importance.”

High blood pressure, often known as hypertension, is a major risk factor for heart disease and stroke, two of the top causes of mortality in the United States. It’s also one of the most common chronic illnesses in the United States, with over half of all individuals in the country classified as hypertensive according to current standards.

An estimated 20% of persons with high blood pressure have resistant hypertension, which means their blood pressure stays high despite vigorous therapy.

“The only thing doctors can really do in these patients is adding or switching medications and increasing the dose with the hope they can find something that works,” Yang said. “Until now, we haven’t had any clear indication what the mechanism is for resistant hypertension. Our research could provide a first step toward identifying new ways to effectively overcome treatment-resistant hypertension.”

In recent years researchers have more intently examined the link between an individual’s blood pressure readings and the unique collection of bacteria that lives in their gut.

That work — significant portions of which has been done at UToledo — has helped to unravel potential causes of hypertension that extend beyond diet and exercise. However, Yang’s research is the first to examine the impact of gut bacteria on blood pressure medication itself.

Dr. Bina Joe, Distinguished University Professor and chair of the UToledo Department of Physiology and Pharmacology, and the study’s senior author, said the research is a significant extension of UToledo’s work to better understand the causes of hypertension and find new ways to treat it.

“Yang pioneered this important, highly translational idea during his training as a postdoctoral fellow in my laboratory,” she said. “This is now a major research theme in his own laboratory at The University of Toledo.”

In the study, UToledo scientists compared the effectiveness of the antihypertensive drug quinapril in rats with normal gut bacteria against those whose gut microbiota had been depleted by high doses of antibiotics.

Researchers found a clear difference between the two, with animals that were given antibiotics first responding much better to quinapril.

Analysis of the gut bacteria composition in the animals identified the bacteria Coprococcus as the culprit. Laboratory experiments proved that Coprococcus comes, a dominant bacteria species in this genus, can break down quinapril and ramipril, resulting in the compromised blood pressure-lowering effects.

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While the UToledo study was limited to animal models and lab experiments, researchers identified at least one intriguing case study that seems to bolster the argument that this finding could be applicable to humans.

That 2015 report, published in the International Journal of Cardiology, described a woman with a long history of treatment-resistant hypertension whose blood pressure was controlled without any antihypertensive medication for the two weeks she was taking antibiotics for a post-surgical infection. Her blood pressure was able to be controlled with only one medication for six months after stopping antibiotics before again becoming treatment-resistant.

“This is just one report and more research is needed. However, this suggests that gut bacteria can play a very real and very important role in regulating the efficacy of blood pressure medication,” Yang said.

The research group plans to continue its work by studying the interaction between additional blood pressure medications and other common types of gut bacteria.

Though long-term use of antibiotics isn’t a realistic strategy for addressing treatment-resistant hypertension, Yang said it should be possible for someone to alter their microbiota through probiotics, prebiotics and changes in diet.
“The ultimate goal of my research is to identify ways we can specifically target the bacteria in an individual’s gut to improve drug efficacy,” he said. “This has the potential to benefit a lot of people.”

Dr. Young Oh, a program officer with the National Heart, Lung, and Blood Institute, agrees that this study represents an important piece of the puzzle in understanding resistant hypertension. The study was supported in part by the NHLBI, part of the National Institutes of Health.

“The gut microbiome has been understudied as it relates to hypertension,” said Oh, who was not a member of the study team. “While this study fills an important knowledge gap, more studies are needed, particularly in humans, to confirm the findings.”

University of Calgary researchers have developed a potentially successful new way for treating bacterial skin infections.

The study’s findings were published in the journal ‘Nature.’

“While translating our research from bench to bedside will require many more experiments and involve a model more closely related to human disease, it is exciting that we have made a fundamental discovery that could improve infections and tissue repair in humans, especially hard-to-treat cases,” said Kratofil.

Previously, experts believed that neutrophils and monocytes (white blood cells) were both recruited to eliminate germs from an infected spot on the skin. When these cells function together, they serve as our bodies’ initial line of defence against the immune system.

However, current study shows that monocytes alone are capable of encouraging quicker wound healing. Monocytes contribute to wound healing by controlling leptin levels and blood vessel development. They also generate ghrelin, a hormone that aids in wound healing.

Ghrelin is produced by the stomach when you are hungry, and leptin — also a hormone — is produced by fat cells after you eat a meal and feel full. This balance between ghrelin and leptin has long been understood as critical to metabolism and diet, but until now, has not been known for its connection to immune mechanisms and tissue repair.

Using intravital microscopy, which allows observation of live cells and is a specialization of the Kubes Lab, Kratofil was able to visualize the immune response to Staphylococcus aureus (S. aureus) bacteria in an animal model.

S. aureus is a germ commonly found on the skin or in the nose of a healthy body. It can be a catalyst for a wide variety of diseases related to skin and tissue infections such as abscesses or boils. In some cases, the bacteria can lead to severe infections like pneumonia and endocarditis, a life-threatening inflammation of the inner lining of the heart’s chambers and valves.

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After an S. aureus infection, the body recruits those helpful immune cells, neutrophils and monocytes. Neutrophils clear bacteria, while monocytes help repair tissue. In the absence of monocytes, there is increased leptin production, leading to blood vessel growth in the infection. The result can be delayed healing and scarring. In contrast, monocytes produce ghrelin at the injection site, which blocks the formation of excess blood vessel growth driven by leptin, leading to tissue repair.

“This research is important because it indicates a paradigm shift challenging the current thinking that neutrophils and monocytes clear bacteria. Our study elevates the role of monocytes in wound repair,” explains Kratofil.

Principal investigator Kubes and his research team believe this study opens the door to introducing metabolic hormones (ghrelin and leptin) in the fields of immunology and microbiology.

“It will be interesting, for example, to see how ghrelin and leptin respond in other disease models such as sterile injury or cancer, and to learn how these processes are altered when a patient has multiple simultaneous diseases or conditions such as obesity and diabetes,” said Kubes.

A recent study establishes a direct relationship between Piezo1, an ion channel that is mechanically activated, and intracellular cholesterol levels during neural development in neural stem cells. This study also reveals how mechanical forces and tissue mechanics affect the morphology of the developing brain.

The research was published today in the Journal of General Physiology under the headline, “Piezo1 controls cholesterol biosynthesis to alter neural stem cell destiny throughout brain development.” The results of the study show that Piezo1 is involved in the neurodevelopmental process that controls cellular cholesterol metabolism to modify the number, quality, and arrangement of cells.

According to Medha Pathak, PhD, an assistant professor in the Department of Physiology & Biophysics at the UCI School of Medicine, “Our unexpected finding linking Piezo1 and cholesterol also motivates investigations for Piezo1 in neurodegenerative diseases linked to cholesterol homeostasis, such as Alzheimer’s Disease.” “We may be able to create innovative therapy for some of these disorders by modulating Piezo1 activity through medicines,” said the researcher.

The orchestration of several complicated processes during a number of stages of neural development results in the formation of the brain and spinal cord. Cells replicate, form structures, and interact with other cells as the brain grows. These processes generate mechanical forces that further mould brain architecture, but it is unclear how cells pick up on these mechanical signals.

“We previously discovered that human foetal brain-derived neural stem/progenitor cells activate Piezo1 channels in response to both externally applied and cell-generated mechanical forces, and we now show in our current study thatPiezo1 is important for proper brain development,” said Jamison Nourse, PhD, assistant project scientist in the Department of Physiology & Biophysics and study’s first author. “Through our research, we identified a unique relationship between Piezo1 and cholesterol production, opening up new directions for research into how mechanical forces affect lipid metabolism in the brain,” the authors write.

In many physiological systems, including vascular development, cardiovascular homeostasis, lymphatic development, red blood cell volume regulation, the baroreceptor response in neurons, cartilage mechanics, bone formation, macrophage polarisation responses, keratinocyte migration in wound healing, and neural stem cell fate, the Piezo family of mechanically-activated ion channels has been shown to play a role in mechanotransduction. For his ground-breaking discovery of the Piezo channels, Dr. Ardem Patapoutian of The Scripps Research Institute in San Diego was given the Nobel Prize in Physiology or Medicine in 2021.

According to Pathak, improper brain development can result in deformities and functional problems that last a lifetime. Furthermore, “our study offers fresh ways for understanding how brain problems may originate,” despite the fact that “we still do not understand the cause behind many brain developmental disorders.”

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Piezo1 and its impact on cholesterol metabolism in both early human brain development and adult-onset neurodegenerative disorders are still being studied by Pathak and her research team.

The National Institutes of Health provided funding for this endeavour.

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Researchers at the National Center for Advancing Translational Sciences (NCATS), Mount Sinai’s Icahn School of Medicine, and other organisations have successfully reversed the effects of several lethal inherited neurodegenerative diseases known as lysosomal storage disorders (LSDs) in patient cells and mice.

The group at NCATS, a division of the National Institutes of Health, led by translational scientist Juan Marugan, PhD, and Mount Sinai’s Yiannis Ioannou, PhD, restored the proper operation of the mitochondria and lysosomes by using novel compounds they discovered that increased the activity of TRAP1. This protein aids in the normal operation of the mitochondria, which generate energy within cells. The study’s results were released in the iScience publication.

At Mount Sinai’s Icahn School of Medicine, Dr. Ioannou teaches genetics and genomic sciences.

Genetic flaws in LSDs prohibit the cell’s lysosomes from digesting and recycling fats, carbohydrates, and proteins. As a result, these substances build up in various organs, such as the liver and brain. This may result in the mitochondria malfunctioning, further harming these organs.

To combat lysosomal storage disorders, researchers have long searched for medications that could have an influence on the lysosomes. This is a novel method of treating various illnesses. Increasing TRAP1 activity aided in the appropriate balance of the cell and improved mitochondrial protein folding. These novel compounds inhibit storage in lysosomal storage disorders by activating TRAP1 in the mitochondria.

The studies show that mitochondrial TRAP1 is a potentially new therapeutic target for a variety of central nervous system illnesses. In order to restore the internal equilibrium of the cell, the researchers found that TRAP1-initiated a “crosstalk” between mitochondria and lysosomes. The researchers found it interesting that in lysosomal storage disorders, activating TRAP1 triggers a cascade that results in the restoration of regular lysosomal function. Each lysosomal disease’s underlying genetic flaw is still present, but this interaction gets around it.

The researchers demonstrated that treating cells from individuals with Niemann-Pick disease type C1, a form of LSD, with an increase in TRAP1 activity might resolve the lipid storage problem and return cholesterol levels to normal.

Additionally, improving TRAP1 activity reversed the lipid accumulation in patient cells from different LSDs such Fabry, Farber, and Wolman illnesses. The uncommon genetic condition Niemann-Pick disease type C1 impairs the body’s capacity to digest fat in cells.

The findings, according to the researchers, may have ramifications for other neurodegenerative illnesses with comparable underlying causes, such Parkinson’s, amyotrophic lateral sclerosis, and Alzheimer’s.

Dr. Ioannou and his associates created a technique to gauge a substance’s impact on Niemann-Pick type C1. They worked together with Dr. Marugan and NCATS scientists who quickly sorted through hundreds of chemicals using the test and NCATS’ high-throughput screening capabilities.

They observed that substances that triggered TRAP1 restored appropriate mitochondrial function and began the recycling of lysosomes, aiding in the reduction of lipids in lysosomes and cells. The best-performing compounds were refined chemically and put through additional testing by the researchers.

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In order to create possible pharmacological therapies, the scientists are interested in learning more about how the chemicals might reverse the symptoms of the lysosomal storage disorders. Additionally, they intend to keep developing these substances and studying their results in numerous models, including how well they can treat more prevalent neurological conditions like Alzheimer’s and Parkinson’s illnesses.

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Restricting calories has long been associated with fewer seizures in epileptics. The effects of fasting on brain neurons are now better understood according to recent study from Boston Children’s Hospital, which may also open the way for novel therapies that don’t include fasting or stringent diets.

The journal Cell Reports reported the study’s findings. According to first author Christopher J. Yuskaitis, MD, PhD, a neurologist from the Epilepsy Center and Epilepsy Genetics Program at Boston Children’s Hospital, “this study represents the first step in understanding how dietary therapy for epilepsy work.” “The mechanics are absolutely unknown as of right moment.”

Fasting, DEPDC5 and mTOR

The researchers started with the body of evidence that already existed to link food and seizures. They were aware that many neurological illnesses include the well-known mTOR cellular pathway, and they had previously demonstrated that over-activating this system in neurons makes them more susceptible to seizures. While these investigations didn’t focus on the brain, they did demonstrate that acute fasting inhibits mTORC function.

Finally, Yuskaitis and associates became aware that the DEPDC5 protein’s signalling inhibits the mTOR pathway. That was noteworthy because a lot of epileptics have lately had mutations in the DEPDC5 gene. Children’s abrupt death, infantile spasms, and focal epilepsy have all been connected to DEPDC5 mutations.

We discovered that employing a mTOR inhibitor helped lower seizures when we employed an animal model that precisely wipes off DEPDC5 in the brain, says Yuskaitis. That inspired us to investigate the relationship between DEPDC5, mTOR, and fasting.

Sensing of amino acids

In the recent work, it was demonstrated that mTOR signalling was decreased in the brain after fasting using a mouse seizure model. Additional research on rat neurons grown in culture suggests that the absence of three amino acids is what causes this fasting effect (leucine, arginine, and glutamine).

Further, the group showed that the DEPDC5 protein can detect the presence of these nutrients. When DEPDC5 was removed from the brain, mTOR activity was unaffected, and fasting no longer prevented seizures in the mice.

According to Yuskaitis, amino acid sensing appears to be essential for the positive benefits of fasting on seizures. “This shows that individuals with DEPDC5 mutations may not benefit from dietary modification because they are unable to feel the loss of amino acids. However, individuals without DEPDC5 mutations could gain from a focused nutritional approach.”

According to him, this may be accomplished by consuming meals that are lower in the three amino acids or by using drugs or supplements that prevent the absorption of those amino acids.

Following a ketogenic diet

This research is simply the beginning. Yuskaitis and associates are currently interested in testing certain amino acid-free diets on animal models to see how they affect seizure frequency. They also aim to investigate how the ketogenic diet, a well-known method of treating epilepsy, reduces seizure frequency. Nobody now understands why this high-fat, low-carb diet is effective.

According to Yuskaitis, “We’re hoping this will help us identify new dietary-based treatments other than the ketogenic diet, which may be challenging to maintain for a long time owing to side effects.”

Such research could potentially offer a fresh perspective on all neurologic illnesses.

According to prominent researcher Mustafa Sahin, MD, PhD, executive director of the Rosamund Stone Zander Translational Neuroscience Center at Boston Children’s, “We are starting to get basic insights into the role of nutrition in brain function using these uncommon genetic illnesses.” Findings from these uncommon illnesses may pave the way for more effective therapies for epilepsy generally.

Also Read: Years prior to onset of symptoms, schizophrenia may be detected!

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New research suggests that bipolar disorder and schizophrenia risk can be detected years before symptoms appear.

Specialized Child and Adolescent Mental Health Services were accessed by 50% of individuals who acquired these mental health disorders, according to a Health Research Board-funded study done by University College Dublin (CAMHS). The multinational study was directed by Professor Ian Kelleher from the UCD School of Medicine and collaborated with the Finnish Institute for Health and Welfare. The findings were published in the journal World Psychiatry. The results, in Professor Kelleher’s opinion, suggest that earlier intervention and perhaps prevention may be possible (THL).

Schizophrenia and Bipolar disease

The doctor said, “Schizophrenia and bipolar disease typically present in early adulthood and may be quite detrimental to both the affected individuals and their families.

“Our data show that half of people with these illnesses sought care from CAMHS at some time in their childhood, typically years before developing schizophrenia or bipolar disorder, according to the researchers.

We know that developing specialised early intervention services within existing child and adolescent mental health services will be crucial to improving outcomes for those with serious mental illness, and these findings show the enormous opportunities to provide far earlier intervention, even while still in childhood.

Using unique patient IDs, the researchers were subsequently able to follow all of these individuals up to the age of 28 and identify those who later received a diagnosis of schizophrenia or bipolar illness.

They observed that 1.8% of those who had not attended CAMHS by the age of 28 were likely to have psychosis or bipolar disorder. However, the risk was 37% for those who were admitted to an inpatient adolescent CAMHS facility and 15% for those who had visited teenage outpatient CAMHS.

“This research highlights the capacity of electronic healthcare records to solve key questions surrounding human health and illness,” said Professor Mika Gissler, THL.

The study’s authors state that its findings “demonstrate how healthcare registry data may be utilised to better understand routes to significant mental illness, from infancy into adulthood, and to identify vital possibilities for early intervention.”

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In order to completely avoid sickness, Professor Ian Kelleher emphasised the need of early intervention and said, “Ideally, we would like to be able to act even before the commencement of illness. We are aware that early intervention is essential to preventing some of these disorders’ severe side effects. These results suggest the possibility of acting far earlier than we now do, even infancy and adolescence, to prevent the formation of these serious mental illnesses.

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A recent research found that lowering the target blood sugar level for women with gestational diabetes did not reduce the likelihood of having big neonates but did lower the possibility of the baby dying or suffering harm during birth.

The results of research conducted by Caroline Crowther and a group from the University of Auckland in New Zealand were published in the journal PLOS Medicine. Gestational diabetes is a serious and spreading health issue that frequently results in the birth of exceptionally big newborns who have a high chance of developing type 2 diabetes and obesity as adults.

To manage their blood sugar, women can alter their diets and use medications, but it is still uncertain how closely those levels should be kept in check to reduce hazards to the mother and unborn child.

Pregnancy and Gestational Diabetes

Researchers studied 1,100 pregnant women with gestational diabetes who were examined at 10 hospitals in New Zealand to ascertain if stronger management is preferable. The study involved switching each hospital’s blood sugar objectives from higher to lower, and the results for the mothers and their offspring in each group were compared.

Tighter blood sugar management did not result in larger-than-expected newborns, but it did cut the risk of baby mortality, injury, and shoulder dystocia in half after delivery.

However, tighter management nearly quadrupled the chance of catastrophic health consequences for the mother, including issues like a big postpartum haemorrhage. The new findings can assist physicians in determining the target blood sugar level that each patient should work toward while controlling their gestational diabetes.

The study is the biggest randomised comparison of two blood sugar level objectives in a varied population that has been documented to date. The researchers do note that further randomised trials in other healthcare settings are still required to corroborate their findings.

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“This unique experiment allowed for the progressive deployment of the newly suggested stricter treatment objectives for women with gestational diabetes and investigated if there are real advantages, without harm, to usage of tighter treatment targets,” Crowther continues.

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The Election Commission of India (ECI) was ordered by the Delhi High Court on Thursday to ensure strict adherence to its instructions regarding the COVID regulations to be observed by political parties and leaders organising public gatherings and election campaigning.

The court demanded punishment against the leaders of several political parties for breaking the COVID norms of mask and social distance during demonstrations when dealing with public interest litigation (PIL). The petition was resolved by the Justice Satish Chander Sharma and Justice Subramonium Prasad Bench, who ruled that the Election Commission must follow the rules that were released on April 16, 2021, one year prior.

The bench also took note of the arguments made by Attorney Sidhant Kumar, who represented ECI, who said that the organisation had taken stringent action in this matter and had stuck closely to the aforementioned rules.

The current COVID crisis is under control, the bench added.

Earlier, ECI had vigorously refuted the argument and said that the topic of the elections held in five distinct states fell under territorial authority. Additionally, ECI claimed that the petition was false and urged its rejection.

Dr. Vikram Singh, a former DGP and the chairman of the think tank CASC, filed a PIL in March 2021 requesting that the COVID Guidelines of Mask and Social Distancing be enforced against the leaders of various political parties. The case was currently being heard by the Delhi High Court.

The petition also requested that the Election Commission display prominently the “Election Commission Guidelines for the Conduct of General Elections/Bye-Elections During Covid-19” released in August 2020 on its website, mobile applications, election materials, and other platforms.

The petitioner’s attorney, Virag Gupta, also requested instructions to recover the fine from all political parties based on the number of crowds allegedly present at roadshows and rallies that violated COVID-19 rules of the Election Commission.

Additionally, it requested permission to file formal complaints (FIRs) against prominent political figures and party leaders who had flagrantly disregarded the Election Commission’s rules regarding social distance and masking.

The petition also asked for the punishment of Election Commission personnel who disregarded the petitioner’s legal advice and failed to follow their own mandated COVID rules.

The request demanded the confiscation of every electronic record of political party rallies and road shows that was kept by the Election Commission.

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In response to a request to guarantee that masks be worn during election campaigns during ongoing elections in various regions, the Delhi High Court had sent notice to the Centre and the Election commission of India.

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According to a recent study, the bulk of the long-term effects patients experienced months after obtaining COVID-19 are greatly reduced by receiving at least two doses of Pfizer vaccines.

Among this study, eight of the ten most frequently reported symptoms were reported between 50% and 80% less frequently in individuals who got at least two doses of the COVID-19 immunisation as opposed to those who did not. The study, which was just published in the Nature journal npj Vaccines, was headed by Professor Michael Edelstein of the Azrieli Faculty of Medicine at Bar-Ilan University. At three of the Faculty’s associated hospitals in northern Israel, Baruch Padeh Medical Center, Ziv Medical Center, and Galilee Medical Center, he collaborated with the IT and infectious disease teams.

Of the 2,447 individuals who reported having no past illnesses, 21 (0.9%) had only had one dose, 1,195 (48.8%) had received two doses, 744 (30.4%) had received three doses, and 19.9% had not received any immunizations.

Comparisons were made between those who had gotten vaccines and those who had not regarding post-acute self-reported symptoms. They found that having two or more doses of the Pfizer vaccine was associated with a decreased likelihood of reporting the most common post-COVID symptoms after accounting for age and the interval between infection and survey participation. Participants in the current trial saw reductions in the most frequently reported symptoms, including fatigue, headaches, limb weakness, and persistent muscle pain, by 62%, 50%, 62%, and 66%, respectively. Breathlessness decreased by 80% and chronic muscular pain by 70%.

The study expands on the scant information currently known about how vaccinations affect long-term COVID. Prof. Michael Edelstein of the Azrieli Faculty at Bar-Ilan University, the study’s lead investigator, adds that “we don’t fully understand what occurs in the months and years following COVID-19 in terms of physical and mental health and welfare.” “We felt it was vital to investigate whether vaccinations could help treat the symptoms of extended COVID because it seems to afflict so many people. It is becoming more and more obvious that vaccinations offer defence not only against infectious diseases, but also against other diseases.

Also Read: Two antibodies found in Israel may fight all known Covid strains

The degree of protection offered by immunizations against prolonged COVID is less well understood. In order to determine how vaccinations impact long-term quality of life, various COVID variants, and long-COVID symptoms, Edelstein has begun a series of studies that will follow a substantial cohort of individuals from all elements of Israel’s varied population.

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