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According to research, the amygdala, a part of the brain that controls strong emotions like fear, may also be to blame for compulsive eating.

Professor Bo Li of Cold Spring Harbor Laboratory (CSHL) has found a set of neurons in the amygdala that cause mice to consume fatty or sweet foods even when they are not hungry. Therapeutics that target these neurons may result in novel, low-risk treatments for obesity. Mice, like the majority of us, favour diets that are heavy in fat and sugar. Instead of eating these foods to survive, they might do it for enjoyment.

This so-called hedonic feeding behaviour is triggered by the neurons Li and his colleagues researched. Li observes

“Though those neurons are still active, it can still push those animals to consume more, even if they are meant to stop eating since they are already full.”

Li asserts that almost no one who seeks to treat obesity is successful in long-term weight management. Any advancement is frequently undone by metabolic processes in the body. Therapeutics can enhance the likelihood that a treatment will be successful, however many medications have unfavourable side effects. “The drugs that are already on the market to help with weight management might have serious adverse effects. Therefore, a more focused strategy is required,” Li explains.

It’s critical to understand the brain circuitry that regulates eating in order to provide more effective treatments for those who have trouble managing their weight.

Mice were no longer lured to the fatty, sugary items that had previously tempted them after the research team turned off the particular neurons. Li explains, “They just joyfully ate and stayed healthy.” They stopped gaining weight and appeared to be generally much healthier. Turning off these neurons decreased binge eating and provided protection from obesity. It increased the animals’ physical activity as well, which helped them lose weight and improve their metabolic condition.

The neurons that cause hedonic eating are being studied by Li and his team for potential manipulation. The last stage, according to him, is to map out how these neurons react to various foods and determine what makes them so sensitive. He thinks that this partnership will result in fresh approaches to potent anti-obesity treatments.

It takes a while to determine the medication susceptibility profile of a bacterial illness. Researchers at the Nara Institute of Science and Technology and its collaborators have just released studies on a technology that, by greatly speeding up this currently laborious process, may be able to save lives.

According to the US CDC, antibiotic-resistant diseases kill more than a million people annually across the globe. Quickly determining a suitable medication to which the infective bacteria are amenable is essential to controlling resistant diseases. Senior author Yaxiaer Yalikun claims that “susceptibility data are frequently required much more quickly than conventional tests can provide them.” We created a technology that can suit this demand in order to address this.

The core of the group’s work is impedance cytometry, which examines the dielectric characteristics of individual cells with high throughput—more than a thousand cells per minute. Because the physical response of a bacterium to an antibiotic and its electrical readout coincide, it is simple to determine if an antibiotic kills the bacteria. Before calibrating the impedance of the two particles in a sample using conventional impedance cytometry, technical specialists must do substantial post-processing on the test (antibiotic-treated) and reference (untreated) particles. The team was adamant about getting through this significant obstacle.

In a work that appears in ACS Sensors, the team develops a novel impedance cytometry technique that simultaneously analyses the test and reference particles in various channels, resulting in readily analysed separate datasets.

The cytometry’s nanoscale sensitivity allowed it to identify even the tiniest physical changes in bacterial cells. In a similar study that was printed in Sensors and Actuators B, the team developed a machine learning method to analyse the impedance cytometry data. Because the novel cytometry method separates the test and reference datasets, the reference dataset may be automatically labelled as the “learning” dataset and used by the machine learning tool to learn the features of an untreated bacterium.

By comparing live data with cells that have received antibiotic treatment, the technology can identify whether the bacteria are susceptible to the drug and may even determine what proportion of bacterial cells are resistant in a population with mixed resistance.

Another senior author on the team, Yoichiroh Hosokawa, notes that despite the fact that their study had a misidentification error rate of less than 10%, they were still able to distinguish between susceptible and resistant cells two hours after antibiotic treatment.

Antiretroviral treatment (ART) that is initiated early in the course of HIV infection when the immune system is stronger has better long-term health outcomes than ART that is initiated later, according to research findings presented at the IDWeek Conference in Washington.

The findings are based on a thorough follow-up of participants in the National Institutes of Health-funded Strategic Timing of Antiretroviral Treatment (START) trial.

START discovered in 2015 that individuals who began antiretroviral therapy (ART) when their CD4+ T-cell counts—a crucial indicator of immune system health—were higher than 500 cells per cubic millimetre (mm3) had a 57% lower risk of developing AIDS and serious non-AIDS health outcomes than those who waited until either their CD4+ counts fell below 350 cells/mm3 or they contracted AIDS. After these results were published in 2015, the patients in the postponed treatment arm were advised to begin ART.

The Centers for Disease Control and Prevention estimate that 1.2 million Americans are HIV +, with 13% of them being uninformed of their status. If treatment and diagnosis are postponed, HIV continues to reproduce.

As a result, there may be negative effects on the infected person’s health as well as an increased likelihood of the virus spreading to other people.

A longer-term follow-up of 4,446 participants was conducted to determine whether the health benefits of early ART compared to deferred ART increased, remained the same, or decreased after the participants in the deferred arm were advised to start ART. The international START study had already established the value of early ART initiation.

The primary objectives of the trial were the number of people who developed AIDS, those who developed severe non-AIDS illnesses like significant cardiovascular disease, kidney failure, liver disease, and cancer, as well as those who died.

Participants who began ART before the end of 2015 had median CD4+ cell counts of 648 cells/mm3 for the immediate arm and 460 cells/mm3 for the postponed arm. The key research endpoints that occurred before the end of 2015 were compared to those that occurred during the extended follow-up period, which lasted from January 1, 2016, to December 31, 2021, in the analysis that was presented today. The majority of individuals in the deferred-arm group were taking ART at this point.

During the second phase, those beginning ART in the postponed group saw rapid and sustained decreases in HIV viral load (less than or equal to 200 copies/mL), but their CD4+ cell counts stayed, on average, 155 cells lower than those of those beginning ART immediately.

Although the risk of adverse health consequences was much lower in the deferred treatment group than it was in the immediate treatment group shortly after ART was initiated, some excess risk persisted.

In comparison to the group receiving urgent treatment, the deferred ART group continued to have a slightly higher chance (21%) of experiencing major health issues or passing away. In the deferred treatment group, there were 27 instances of AIDS throughout the five-year follow-up period, compared to 15 cases in the early treatment group.

The deferred treatment arm saw 88 significant non-AIDS health concerns, compared to 76 in the urgent treatment arm. The deferred treatment group saw 57 deaths, compared to 47 in the immediate treatment group.

These findings support the notion that ART dramatically enhances the health of HIV-positive people and reduces their risk of developing AIDS and other life-threatening diseases. To maximise these benefits and reduce risk, the presenters contend that early identification and treatment are crucial.

updated guidelines for bariatric surgery

Expanding patient eligibility for weight-loss surgery and supporting metabolic surgery for people with type 2 diabetes starting at a body mass index (BMI) of 30, two of the top experts in the world on bariatric and metabolic surgery have released new evidence-based clinical guidelines that, among a slew of other recommendations, expand patient eligibility.

Most insurers and doctors still use a consensus statement from the National Institutes of Health (NIH) that was created more than 30 years ago to assess who needs weight-loss surgery, what kind of surgery they need, and when they need it.

This consensus statement will be replaced by the ASMBS/IFSO Guidelines on Indications for Metabolic and Bariatric Surgery – 2022. The American Society for Metabolic and Bariatric Surgery (ASMBS) is the largest organisation of bariatric surgeons and integrated health professionals in the United States, and the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) represents 72 national associations and societies globally.

According to Teresa LaMasters, MD, President of the ASMBS, “The 1991 NIH Consensus Statement on Bariatric Surgery served a valuable purpose for a while, but after more than three decades and hundreds of high-quality studies, including randomised clinical trials, it no longer reflects best practises and lacks relevance to today’s modern procedures and patient population.”

“For the benefit of patients, it is time for a shift in both theory and practise. It’s far past due.”

Only those with a BMI of at least 40 or a BMI of 35 or more with at least one obesity-related ailment, such as hypertension or heart disease, were considered candidates for bariatric surgery, according to the 1991 consensus statement. There were no allusions to metabolic surgery for diabetes, nor to the burgeoning laparoscopic techniques and procedures that would become conventional and make weight-loss surgery as safe as or safer than common operations like gallbladder surgery, appendectomy, and knee replacement. The statement discouraged surgery because it had not been properly examined, even for patients with BMIs over 40.

New Criteria for Patient Selection — The Times Have Changed

The ASMBS/IFSO Guidelines now advise considering metabolic and bariatric surgery for people with a BMI of 35 or higher “regardless of the presence, absence, or severity of obesity-related conditions,” as well as in “appropriately selected children and adolescents,” and for people with a BMI of 30-34.9 and metabolic disease.

However, even in those who do not have metabolic disorder, the guidelines state that if nonsurgical approaches do not result in a significant or long-lasting weight loss or alleviation of obesity-related conditions, weight-loss surgery should be considered starting at a BMI of 30. Additionally, it was suggested that Asian people start thinking about weight-loss surgery at a BMI of 27.5 and that population-based adjustments be made to the traditional BMI thresholds for defining obesity.

Greater Safety and Efficacy of Contemporary Weight-Loss Surgery

The new guidelines also state that “studies with long-term follow-up, published in the decades following the 1991 NIH Consensus Statement, have consistently demonstrated that metabolic and bariatric surgery produces superior weight loss outcomes compared with non-operative treatments” and that “metabolic and bariatric surgery is currently the most effective evidence-based treatment for obesity across all BMI classes.”

It is also said that “previous surgical operations have been replaced with safer and more successful operations,” with numerous studies demonstrating a considerable improvement in metabolic disease and a drop in overall mortality following surgery. Sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB), two laparoscopic procedures, now make up nearly 90% of all operations carried out globally.

In any given year, between 1 and 2 percent of all eligible patients worldwide undergo weight-loss surgery. According to experts, the limited usage of such a treatment that has been shown to be safe and effective is a result of the unduly restrictive consensus statement from 1991. In 2016, 13% of the adult population worldwide, or more than 650 million persons, were obese. According to the CDC, over 42% of Americans are obese, which is a record high.

According to Scott Shikora, MD, President of IFSO, “The ASMBS/IFSO Guidelines give a critical reset when it comes to the treatment of obesity.”

“Insurers, governments, healthcare professionals, and patients should pay close attention and endeavour to dismantle the obstacles and antiquated assumptions that obstruct access to one of the safest, most efficient, and well researched procedures in medicine.”

The discovery of a genetic variant that is relatively common among people of Polynesian ancestry but incredibly rare in most other populations is providing hints to the genetic underpinnings of high cholesterol in all people, according to new research led by geneticists at the University of Pittsburgh School of Public Health in collaboration with several other organisations, including the University of Otago and the Samoan health research community.

The unexpected finding, which was just released this week in the journal Human Genetics and Genomics Advances, emphasises the need of ensuring diversity in genetic databases.

“We might have completely missed this discovery if we had just been looking in populations with European heritage,” said the study’s primary author, Jenna Carlson, PhD, an assistant professor of human genetics and biostatistics at Pitt Public Health. We were able to uncover this mutation thanks to the kindness of thousands of Polynesians, and it’s a smoking gun that will inspire further investigation into the biology of cholesterol.

The World Health Organization estimates that high cholesterol causes 2.6 million deaths yearly worldwide, is a major contribution to disease burden in countries of all income levels, and is a risk factor for heart disease and stroke.

Carlson and her team constructed their study to examine a signal that showed up in a thorough genome-wide search for genes associated with lipids or fats in the body. A chromosome 5 gene variation was thought to be related to cholesterol. The scientists set out to “fine map” the region using the genetic data from 2,851 Samoan individuals who participated in the Obesity, Lifestyle, and Genetic Adaptations (OLAGA) Study Group and who also submitted health information, including lipid panels. 3,276 more Polynesians from Samoa, American Samoa, and Aotearoa New Zealand were discovered to have the variation and cholesterol connection. This was carried out to validate the initial discovery.

“We don’t know a lot about this variant,” Carlson said. “It’s virtually nonexistent in European ancestry populations, has a very low frequency in South Asians, and isn’t even particularly common in eastern Polynesian people, such as Maori living in Aotearoa New Zealand. Published genome references, which overrepresent European ancestry individuals.” “We didn’t realise this gene was significant for cholesterol before, but the way it’s connected to lipid panels in Samoan people tells us as much. We may one day find new approaches to assist everyone in maintaining healthy cholesterol levels by further investigating BTNL9.”

According to a study, one-fourth of recurring oestrogen receptor-positive (ER+) breast tumours do not express the ER, are unresponsive to endocrine therapy, and have the potential to spread uncontrollably.

A team of researchers from Baylor College of Medicine has published a study that discloses a mechanism that not only explains the process but also offers workarounds in the Proceedings of the National Academy of Sciences. According to corresponding author Dr. Weei-Chin Lin, professor of medicine-haematology and oncology and of molecular and cellular biology, “For years, our goal has been to tease out the complex puzzle of breast cancer progression to understand how the players interact with one another to confer resistance to therapy and persistent growth.”

ER loss in breast cancer cells

Two cellular proteins called 14-3-3 and ER-36 have previously been associated to breast cancer resistance to endocrine therapy.

Working with a mouse model of human ER+ breast cancer, Lin of the Dan L Duncan Comprehensive Cancer Center said, “We were shocked to find that over-expressing 14-3-3t in these tumours led to all the cancer cells becoming ER-negative (ER-). “I can still clearly recall the day I saw the figures. The transformation was striking—all of the tumours had lost their ER!”

The researchers created an alternate model because they realised that studying the mechanism in animal models would be labor-intensive, expensive, and time-consuming.

Lidija A. Wilhelms Garan, first author, is a graduate student in the Baylor Cancer and Cell Biology Program who works in the Lin lab. She created a spheroid model of human breast cancer cells that replicates the transformation from ER+ to ER- and offers a useful experimental tool for future research.

In a patient, a breast tumor’s progression from ER+ to ER- can take years; in our animal model, it takes several months; but, in our spheroid model, it does so in just one to two weeks, according to Garan.

The scientists discovered that when 14-3-3t is overexpressed in cancer cells in the lab spheroid model, under the correct circumstances, the cells will raise their levels of ERa36, which is followed by ER loss.

Other molecular players, such AKT and GATA3, are also necessary, according to Garan. Importantly, we discovered that the transition from ER+ to ER-is aided by substances produced by the tumour microenvironment, which includes fibroblasts and immune cells that are present in the tumour mass and communicate with the cancer cells.

We were aware that the major agents in converting ER+ breast cancer cells into ER- cells were 14-3-3t, ERa36, AKT, and GATA3. Here, we’ve established their functional relationships with one another, putting up a road map for ER loss,” Lin added.

“I am thrilled that we now have a useful tool with our spheroid breast cancer model to examine not just the cellular alterations involved in breast cancer progression but also to test medications for their capacity to stop the process that leads to ER loss,” the researcher said.

“About 60% of breast tumours have an overexpression of the protein 14-3-3t. Not all patients with high 14-3-3t will lose the ER, but for those who do, our findings may one day aid in bringing their tumours back to a state where they are therapy-sensitive “said Garan. The ability to translate research findings into clinical practise and enhance people’s lives has always been a priority for me.

Soumya Swaminathan, chief scientist of the World Health Organization, stated on Friday that there were over 300 sub-variants and the fact that XBB is a recombinant virus is cause for alarm in light of India’s announcement of a highly contagious new COVID-19 variant.

She also emphasised how immune evasive the new variant is. “Omicron has more than 300 sub-varieties. The recombinant virus XBB, in my opinion, is the one that needs to be worried about right now. Recombinant viruses were something we had seen previously. Because it is very immunological evasive, it can get past the antibodies. As a result of XBB, we could conceivably witness another wave of illnesses in some nations “Swaminathan stated.

She made her comments during a media briefing in Pune.

We are also following derivatives of BA.5 and BA.1, which are likewise more transmissible and immune evasive, she added, putting emphasis on the tracking of other XBB compounds. The virus will continue to develop and grow more transmissible as it does so. There is currently no evidence from any nation that these new sub-variants are more clinically severe. The intensity seems to be similar even if the virus is infecting more people in some nations.

We need to keep monitoring and tracking, she added, highlighting the significance of it.

We have observed a decrease in testing across all nations, and a decrease in genetic surveillance during the past few months. In order to continue tracking the variations as we have been doing and investigating, we must at the very least maintain a strategic sampling genomic surveillance.”

The senior scientist emphasised the benefits and recommended for the use of the tools at hand.

“The good news is that we have a variety of tools at our disposal, with vaccines being the most crucial. Our objectives for vaccination coverage are 100% of those over 60 and 100% of healthcare and frontline employees.

We have a target of achieving 70 per cent of the country but subgroups are more essential since they are the groups that are most prone to face morbidity and mortality,” she added.

Earlier on Tuesday, Maharashtra saw a 17.7 per cent jump in coronavirus cases compared to last week, according to a state health department bulletin.

New CoVid cases have been reported by the state, including those caused by the XBB sub-variant of the SARS-CoV-2 virus, which has been found in Kerala and other regions of India.

In addition, Maharashtra has reported incidences of Omicron sub-variants BA.2.3.20 and BQ.1, which were discovered for the first time in India on Monday in a patient’s sample from Pune.

A recent spike was observed in the fast-spreading variation XBB, which is a recombinant lineage between the Omicron sublineages BJ.1 and BA.2.75.

Tuesday’s high-level discussion about the appearance of new subvariants of Omicron between senior health officials and Union Health Minister Mansukh Mandaviya resulted in the decision to continue mask use and COVID19-appropriate behaviour nationwide.

Additionally, expanding surveillance and genome sequencing have been suggested by the group of scientists, physicians, and top administrators.

Additionally, the health professionals advocated mission mode acceleration of the COVID-19 cautionary dose to the eligible population.

According to official sources, VK Paul, a member of the Niti Aayog, NK Arora, the chair of the COVID-19 working group, representatives from NTAGI, NEGVAC, and other senior health authorities were there.

The first induced pluripotent stem cell model of PTSD provides insights into underlying genetics and novel therapeutic prospects.

The study, published on October 20 in Nature Neuroscience, is the first to investigate PTSD using induced pluripotent stem cell models. It was carried out by a group of scientists from Mount Sinai’s Icahn School of Medicine, the James J. Peters Veterans Affairs Medical Center, Yale School of Medicine, and The New York Stem Cell Foundation Research Institute (NYSCF). Post-traumatic stress disorder (PTSD) can develop in the aftermath of extreme trauma and is a major public health issue for both veterans and civilians.

However, it is unknown how much hereditary and environmental factors influence individual clinical outcomes. To fill this knowledge vacuum, the researchers evaluated a group of 39 combat veterans with and without PTSD from the James J Peters Veterans Affairs Medical Center in the Bronx. Skin biopsies were performed on veterans, and their skin cells were transformed to become induced pluripotent stem cells.

“Reprogramming cells to become induced pluripotent stem cells is like virtually transporting cells back in time to when they were embryonic and had the ability to generate all the cells of the body,” said Rachel Yehuda, PhD, Professor of Psychiatry and Neuroscience at Icahn Mount Sinai and Director of Mental Health for the James J.

Peters Veterans Affairs Medical Center, and the paper’s senior author. “These cells can then be differentiated into neurons with the same qualities as that person’s brain cells had before trauma happened, allowing them to operate differently.” These neurons’ gene expression networks show early gene activity originating from genetic and very early developmental contributions, hence they depict the ‘pre-combat’ or ‘pre-trauma’ gene expression state.”

“Two people can suffer the same event, but they won’t necessarily both acquire PTSD,” said co-author Kristen Brennand, PhD, Elizabeth Mears and House Jameson Professor of Psychiatry at Yale School of Medicine and a NYSCF — Robertson Stem Cell Investigator Alumna.

“This form of modelling in brain cells from people with and without PTSD helps explain how heredity can predispose someone to PTSD.”

The scientists subjected the induced pluripotent stem cell-derived neurons to the stress hormone hydrocortisone, a synthetic counterpart of the body’s own cortisol that is employed as part of the “fight-or-flight” response, to imitate the stress reaction that causes PTSD.

“Adding stress hormones to these cells simulates biological impacts of warfare, allowing us to understand how distinct gene networks mobilise in response to stress exposure in brain cells,” Dr. Yehuda added.

Using gene expression profiling and imaging, the researchers discovered that neurons from PTSD patients were hypersensitive to this pharmacological trigger.

The researchers were also able to identify distinct gene networks that responded differently after being exposed to stress chemicals.