Categories : Diseases, Syndromes and ConditionsTags :

Oil Exploration Software Reveals why Cystic Fibrosis Drugs Fail

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Scientists have harnessed a computational approach usually used in oil exploration to search for cures for rare genetic diseases such cystic fibrosis. By using the method to analyse the spatial relationships between different variants of a protein, instead of the relationships between test wells across an oil field, the researchers can obtain valuable information on how disease affects a protein’s underlying shape and how drugs can restore that shape to normal.

The new method, detailed in the journal Structure, runs with just a few gene sequences collected from people with disease. Then, it determines how the structure of each corresponding variant protein is associated with its function, and how this functional structure can affect pathology and be repaired by therapeutics. To test the techniques, the researchers showed why existing drugs for cystic fibrosis fall short of curing the disease.

“This is an important step forward for treating rare diseases,” said senior author William Balch, PhD, professor of Molecular Medicine at Scripps Research. “The fact that we can get so much information from a few gene sequences is really unprecedented.”

Studies on inherited diseases often rely on the precise three-dimensional shape of a protein affected by disease. But genetic diseases can be caused by thousands of gene variants, some of which destabilise or change the protein shape in ways that make isolating the protein for further investigation much more difficult than usual.

Prof Balch, with Scripps Research senior staff scientist Chao Wang and staff scientist Frédéric Anglés, instead wanted to use natural variation to their advantage. So the group developed a method called variation-capture (VarC) mapping to analyse the natural array of gene sequences which exist in the human population and determine the mechanism by which they each changed a protein’s structure to cause disease.

Among other statistical tools, Prof Balch’s group integrated the methods that oil companies use to draw inferences about the location of an oil reservoir using only a small number of test wells. With only a few gene sequences, this let the researchers determine the most likely structural mechanisms driving function for each variant leading to disease, as well as model how drugs impacted those structural functions.

In the case of cystic fibrosis, disease is caused by genetic variants in the cystic fibrosis transmembrane conductance regulator (CFTR), leading to a buildup of mucus in the lungs. More than 2000 variants of the CFTR gene have been identified, and many of these variants were known to have very different effects on the CFTR protein, but it has been difficult to compare and contrast these variants to guide how patients with different variants should be treated differently in the clinic.

“When you want to treat patients, you really have to appreciate that different therapeutics might target different variants in completely different ways, and that’s why our approach that looks at many different variants all at once is so powerful,” explained Wang. “Our approach not only reveals how these variants contribute to each patient’s biology, but also connects them in a way that each variant can inform how to manage the others.”

The researchers input about 60 genetic variants found in the cystic fibrosis population into their VarC program. The analysis captured how each amino acid residue talks to every other residue to generate function, and revealed that most of the cystic fibrosis patients had the same net effect on the protein: an unstable inner core.

When the program modelled how existing cystic fibrosis drugs impacted the structures, the researchers discovered that, despite the drugs’ effect on CFTR structure, none of them effectively stabilised the protein’s hidden inner core. This was like how the location of an oil reservoir in a complex landscape can be revealed by test wells.

Now that the researchers better understand the structural deficiencies in CFTR in cystic fibrosis patients, they say that the job of developing an effective drug to fix it is much easier. Potential compounds can be modelled in advance of lab experiments for their effect on the inner core of the CFTR protein.

“In most drug discovery, you throw thousands of compounds at a protein and see which ones change it, often without fully understanding the mechanism,” said Prof Balch. “To fix a thing, you must first understand the problem.”

Already, his team is applying the method to other rare genetic diseases, as well as pursuing new drugs to treat cystic fibrosis.

Source: Scripps Research Institute

Categories : Obstetrics & Gynaecology TransplantsTags :

Uterus Transplants are Safe and Effective, Study Finds

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Photo by Jonathan Borba on Unsplash

The world’s first complete study of living donor uterine transplantation, published in the journal Fertility and Sterility, has found that it is an effective, safe method to remedy infertility when a functioning uterus is lacking.

After seven of the study’s nine transplants, in vitro fertilisation (IVF) treatment ensued. In this group of seven women, six (86%) became pregnant and gave birth. Three had two children each, making the total number of babies nine.

In terms of what is known as the ‘clinical pregnancy rate’, the study also showed good IVF results. The probability of pregnancy per individual embryo returned to a transplanted uterus was 33%, about the same as for typical IVF.

Participants followed up

Few cases were studied, the researchers observed, but the material is the world best and included extensive, long-term follow-ups of participants’ physical and mental health.

None of the donors had pelvic symptoms but, in a few, the study describes mild, partially transient symptoms in the form of discomfort or minor swelling in the legs.

After four years, health-related quality of life in the recipient group as a whole was higher than in the general population. Neither members of the recipient group nor the donors had levels of anxiety or depression that required treatment.

Growth and development of the children were monitored as well, up to age two and is, accordingly, the longest child follow-up study conducted to date in this context. Further monitoring is planned to adulthood.

Good health in the long term

“This is the first complete study that’s been done, and the results exceed expectations in terms both of clinical pregnancy rate and of the cumulative live birth rate,” said study leader Mats Brännström, professor of obstetrics and gynaecology at Sahlgrenska Academy, University of Gothenburg.

“The study also shows positive health outcomes: The children born to date remain healthy and the long-term health of donors and recipients is generally good too.”

The first birth after uterine transplantation took place in Gothenburg in 2014. Another seven births followed, within the framework of the same research project, before anyone outside Sweden gave birth following uterine transplantation.

The research group has since passed on its methods and techniques through direct knowledge transfer to several research centres outside Sweden. By the end of 2021, there were an estimated 90 uterine transplants worldwide, of which 20 had been done in Sweden. Worldwide, some 50 children have been born after uterine transplantation.

Source: University of Gothenburg

Categories : Cardiovascular Disease Metabolic DisordersTags :

In Diabetes, Oestrogen Protects Against Cardiomyopathy

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Source: Pixabay CC0

Oestrogen may protect diabetes patients from cardiomyopathy, according to research published in Circulation: Heart Failure. The study showed that severe insulin resistance in the heart causes cardiomyopathy and death in male mice, but also showed that oestrogen protected female mice.

“Cardiovascular disease is the major cause of morbidity and mortality for diabetic patients,” explained Shaodong Guo, PhD, primary investigator for the study at Texas A&M.

“Previous studies have shown that while there’s a lower instance of both cardiovascular disease and Type 2 diabetes in premenopausal women than in their age-matched male counterparts, these incidences rise sharply after female menopause,” Prof Guo said.

This indicates that the ovaries and ovarian hormones, such as oestrogen, may protect from Type 2 diabetes and cardiovascular diseases, he said.

The study investigated the role of ovaries and oestrogen in cardiac function and energy metabolism with mice who had the the cardiac insulin receptor substrate, IRS, modified or suppressed to mimic cardiac insulin resistance.

“Our previous studies reported that impaired cardiac insulin signalling with loss of insulin receptor substrate IRS1 and IRS2 genes leads to death of male mice,” he said. “In this study, we wanted to know how the removal of the ovaries might affect cardiomyopathy in female mice and also what other impacts the loss of insulin receptors might have on energy metabolism and mitochondrial function.” 

Insulin resistance and signaling

About 90–95% of patients with Type 2 diabetes suffer from insulin resistance, a risk factor for heart failure. In healthy tissue, insulin binds to insulin receptors, activating a network of intracellular signalling pathways. Disruptions in these signalling pathways have been linked to mitochondrial dysfunction, cardiomyopathy, and impaired glucose and fatty acid metabolism, among other health issues.

In this study, mice lacking IRS developed dilated cardiomyopathy, and analysis showed lowered activity of genes important for mitochondrial function and energy metabolism.

“Type 2 diabetes patients and insulin-resistant patients exhibit mitochondrial dysfunction,” Prof Guo explained.

The study fills in some blanks in understanding the role of insulin and estrogen signaling in mitochondrial function.

Study findings

Guo said there were four important findings from the study:

  • All female mice that lacked insulin receptor substrates survived for more than a year.
  • Female mice without insulin receptor substrates were less likely to experience severe cardiac dysfunction and death if they had ovaries. If the mice also lacked ovaries but received oestrogen, it prolonged their lifespans. Doses of oestrogen also protected IRS-altered male mice from heart dysfunction. 

Guo said oestrogen also prevents cardiomyopathy induced by loss of cardiac insulin receptor substrates.

“And removal of the ovaries leads to the death of female cardiac IRS1 and IRS2 double genes knockout mice if there is no reintroduction of oestrogen,” he said.

Loss of IRS1 and IRS2 genes in heart tissue disrupts cardiac energy metabolism, gene activity involved in mitochondrial function, and whole-body energy metabolism. However, oestrogen partially reverses these effects.

Oestrogen is important for healthy cellular signalling pathways and promotes mitochondrial function.

Prof Guo said the study shows that oestrogen enhances cardiac function, promotes energy metabolism, prevents cardiomyopathy and prolongs survival in both male and ovariectomy female mice lacking the insulin receptor substrates.  

“This study provides evidence for the gender difference for the incidence of cardiovascular disease and implies that oestrogen replacement therapy is feasible for the treatment of diabetic cardiomyopathy through enhancement of mitochondrial function and energy metabolism,” he said. “It also reveals some of the signalling pathways that may be potential therapeutic targets for the prevention or treatment of cardiovascular diseases in patients with Type 2 diabetes.” 

Guo also noted that diet could also play a role with oestrogens in foods.

“The study implies that food-derived oestrogens or phytoestrogens may play similar roles to oestrogen, as observed in mice,” he said. “This may help us reshape our knowledge of nutrient and food sciences related to plant hormones that can modulate chronic metabolic diseases such as Type 2 diabetes and associated cardiovascular complications.”

Source: Texas A&M University

Categories : Ethics and Law TransplantsTags :

Experimental Surgeon Convicted for Tracheal Implant Death

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A Swedish court has convicted Paolo Macchiarini, a formerly lauded trachea surgeon, of causing bodily harm to a patient through negligence during a highly experimental stem-cell trachea transplant. For this, the court handed down a two-year probational sentence. He was acquitted of assault charges on two other patients; all three died in the months and years after the surgeries.

In 2010, Macchiarini was hired by the Karolinska Institute (KI) and the Karolinska University Hospital to support Sweden’s regenerative medicine innovation. His specialty was replacing damaged tracheae with artificial ones that combined stem cells with polymer scaffolds or decellularised donor tracheae. Starting in 2011, he began operating on patients as an experimental life-saving measure but his work at at KI was suspended in 2013 after the second of his three patients died. However, he continued performing surgeries in Russia.

Yet there were already hints that something was amiss even before the first surgeries. In 2011, another academic, Pierre Delaere of UZ Leuven in Belgium accused Macchiarini of misrepresenting research findings in published articles. In 2012, Macchiarini was arrested in Italy and charged with fraud and attempted extortion. 

By 2014, after the death of his first patient, three separate allegations were raised of scientific misconduct in reporting the cases. He would later be cleared of these, but in 2016 a TV documentary called ‘The Experiment’ described the suffering and deaths patients of failed artificial tracheas transplants, and raised many issues concerning care and research ethics. The severe public backlash caused KI to launch another investigation into Macchiarini, amid an upheaval which saw a string of resignations and an overhaul of hiring and ethics. He was found to have falsified his CV, and published papers with false or misleading data that were subsequently retracted. By March, he had been fired and criminal charges filed against him.

BBC News reported that at least seven people had died following the surgeries. In 2018, KI found seven researchers guilty of academic misconduct. Swedish authorities decided to reopen investigations into the three deaths.

Matthias Corbascio, a cardiac surgeon at KI who testified in the trial, told SVT Nyheter that he doesn’t believe justice has been done. “My reaction is that it is very meager. It is a terrible scandal and terrible for the patients’ families that he could get away so easily,” he said.

Chief judge Bjoern Skaensberg said the court had agreed with prosecutors that the surgery had not been consistent with “science and proven experience”. However, he told public broadcaster SVT that it had concluded that “two of the interventions were justifiable, but not the third”.

The court had found that all three patients had suffered serious bodily injury, Judge Skaensberg said. But Macchiarini was cleared of assault as no intent to harm had been proven.

Macchiarini had always denied any wrongdoing, arguing that the transplants were aimed at saving the patients’ lives.

However, whistleblower Dr Matthias Corbascio told SVT that the verdict was a scandal and there had never been any chance of the operations succeeding.

The suspended sentence means he will be on probation for the next two years.

Source: BBC News

Categories : Diet and NutritionTags :

A Way to Prepare Potatoes for a Lower Glycaemic Index

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Researchers have tested a new potato processing technique designed to slow down the digestion of potato starch. Their experiments show that the approach prevents certain digestive enzymes from reaching the potato starch as quickly, leading to a more controlled release of dietary glucose.

Foods with lower glycaemic index have a variety of health benefits, such as reducing the risk of cardiovascular disease.

“There is a perception that potato foods are unhealthy because eating a large amount of some potato foods can cause a rapid increase in blood sugar, which is a risk for people with diabetes or those who want to control body weight,” said Amy Lin, PhD, the study’s principal investigator at A*STAR. “Our team revealed that toggling the accessibility of two digestion enzymes – α-amylase and mucosal α-glucosidase – in the small intestine is a successful strategy to make dietary glucose slowly and continuously release from potatoes.”

The findings are being presented online at NUTRITION 2022 LIVE ONLINE, the flagship annual meeting of the American Society for Nutrition.

The researchers cut potatoes into cubes and blanched them in hot water with a food grade ingredient for 30 minutes., though they did not disclose what the ingredient was.

An enzyme barrier of pectin

This process causes a reaction with pectin, a water-soluble fibre in potatoes, creating a gelling structure which makes a porous barrier between starch granules and digestive enzymes. The size of the barrier’s pores can can be determined by the processing method to moderate how quickly α-amylase is able to penetrate the potato parenchyma cells and degrade starch to small molecules. Converting starch molecules to glucose relies on mucosal α-glucosidase, which is too big to penetrate those pores. Therefore, the elevation of dietary glucose of processed potatoes depends on the how quickly small starch molecules leach out of parenchyma cells and are digested by mucosal α-glucosidase.

“Without our treatment, enzymes move freely in and out of cells, and starch is quickly degraded by both enzymes and rapidly converted to glucose,” said Dr Lin. “The treatment allows the starch to be slowly degraded to prevent a spike in glycemia and then fully converted to glucose to meet our energy and nutritional needs.”

The technique is not designed to prevent the potato from being digested, but rather to slow digestion to avoid a rapid increase in blood sugar. Researchers say the modification could also help consumers feel full for a longer period after eating the treated potatoes, helping to avoid overeating.

Researchers report that the method performed well in tests with a simulated digestion process in the laboratory. Treatment increased the fraction of the starch that is considered slowly digestible from 10% to 35% and significantly reduced the ability for the enzyme a-amylase to access starch within the cell walls.

But how do they taste?

Since the process essentially pre-cooks the potatoes, treated potatoes are not shelf-stable but could be frozen and then cooked or further processed for dishes such as roasted potatoes, hash browns, soups or stir-fry, researchers say. Initial taste tests had good results in terms of digestibility and texture.

As a next step, the researchers are preparing to further test impacts on digestibility in a clinical trial. They also plan to study whether a similar approach could be used to improve other staple foods.

Source: American Society for Nutrition

Categories : COVIDTags :

Substantially Lower Long COVID Risk from Omicron Infection

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SARS-CoV-2 infecting a human cell
Infected cell covered with SARS-CoV-2 viruses. Source: NIAID

Findings from a new study reported in The Lancet has found the risks of developing long COVID are greatly reduced (by ~50% to 75%) as a result of Omicron infection compared to Delta infection.

The study, the first of its kind to report on long COVID risk associated with Omicron, highlights the speed with which app-based health surveillance can provide insights. These have further been shown to be consistent and replicable.

A major strength of the study was the ability to log a wide range of symptoms with the app. Limitations of the self-reported data include no direct testing of infectious variants (here assumed from national data) and no objective measures of illness duration. There was insufficient data to estimate the odds of long COVID in unvaccinated individuals. Finally, to enable swift reporting, the period of assessment of omicron cases was slightly shorter than for the delta variant, and assessment of longer durations of long COVID (eg, >12 weeks) was not possible.

In this case-control observational study, the researchers took self-reported data from the COVID Symptom Study app.

Participants were selected on a positive COVID test after SARS-CoV-2 after vaccination, at least one log per week in the app for at least 28 days after testing positive, and no previous SARS-CoV-2 infections before vaccination. The researchers identified 56 003 UK adults first testing positive between Dec 20, 2021, and March 9, 2022, when the Omicron variant became dominant. Similarly, researchers identified 41 361 UK adult cases first testing positive between June 1, 2021, and Nov 27, 2021, during the period of Delta dominance.

Both symptomatic and asymptomatic infections were considered, and, for the Omicron period, only participants testing positive before Feb 10, 2022, were included, to ensure all participants had at least 28 days for symptom reporting after testing positive. The researchers adjusted for socioeconomic deprivation and other factors.

In both periods, female participation was higher than male participation (55% for Omicron and 59% for Delta cases). Delta and Omicron cases had similar age (mean age 53 years) and prevalence of comorbidities (around 19%). Among Omicron cases, 2501 (4.5%) of 56 003 people experienced long COVID and, among Delta cases, 4469 (10.8%) of 41 361 people experienced long COVID. Cases were stratified by time from vaccination to first infection. They found that, for all vaccine timings, Omicron cases were less likely to experience long COVID, with an odds ratio ranging from 0.24 to 0.50.

However, the researchers noted that the the absolute number of people with long COVID at a certain time depends on the pandemic curve. Considering the UK Omicron peak of more than 350 000 new symptomatic COVID cases per day estimated on March 26, 2022, by the ZOE app model, with 4% of cases being long COVID, future numbers with long COVID will inevitably rise.

Source: The Lancet

Categories : AddictionTags :

Fentanyl Induces Autism-like Behaviours in Young Mice

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Mouse
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Fentanyl is one of the most commonly used analgesics in the hospital and, in rodents, may have lasting sensorimotor and behavioural impacts. A study published in the British Journal of Anaesthesia has shown that fentanyl can induce changes similar to autism-like behaviours in young mice.

Fentanyl, a mu-opioid receptor agonist, is a potent synthetic opioid, which, similar to morphine, produces analgesia but is 50 to 100 times more potent. A dose of only 100 micrograms can produce equivalent analgesia to approximately 10mg of morphine. However, fentanyl exhibits vastly different properties and pharmacokinetics. Clinically, its most common use is as a sedative in intubated patients and severe cases of pain in patients with renal failure due to its primarily hepatic elimination. Fentanyl’s side effects are similar to those of heroin.

However, whether the use of fentanyl is associated with the development of autism is not known. An animal study led by investigators at Massachusetts General Hospital (MGH), Shanghai 10th People’s Hospital, and the University of Pennsylvania e. The findings are

Research by other groups has shown that N-methyl-D-aspartate receptor dysfunction contributes to autism. Variations in Grin2a and Grin2b, the genes encoding GluN2A and GluN2B subunits of N-methyl-D-aspartate receptor, are associated with autism. In addition, the anterior cingulate cortex of the brain is affected in autism.

In this current study, the research team reported that fentanyl induces autism-like behaviors in young male and female mice via activating the mu-opioid receptor in the anterior cingulate cortex. Further, these fentanyl-induced autism-like behaviors appear partially due to the hypermethylation-mediated reduction of Grin2b expression in the anterior cingulate cortex of mice.

“Because the anterior cingulate cortex is a hub for mediating social information, we focused on the expression of Grin2b in that area,” says Yuan Shen, MD, PhD, the paper’s senior author and a professor of Psychiatry at Shanghai 10th People’s Hospital. “We found fentanyl decreased expression of Grin2b in the anterior cingulate cortex. The overexpression of Grin2b prevents fentanyl-induced autism-like behavior in the mice. These findings suggest a potential mechanism to prevent or treat the autism-like behavior,” says Shen.

The group used an open field test (in which a mouse can walk inside a box) and an elevated plus-maze (in which a mouse can walk on an elevated platform) to observe the anxiety and stereotyped behaviours of mice. Using a three-chamber social preference test (where a mouse can interact with another mouse), they also assessed potential social deficits. “We used these tests because impaired social interaction, stereotyped behaviours, and anxiety are the key feature of autism-like behaviours in mice,” said Zhihao Sheng, co-first author of the paper. Sheng is a graduate student at Shanghai 10th People’s Hospital.

“However, the changes of mice in these behavioral tests do not equal autism in humans. These behavioral tests are only used to study the autism-like behaviors in mice because they can demonstrate certain features of behavior changes similar to the manifestation of autism,” said co-first author Qidong Liu, PhD, assistant professor at Shanghai 10th People’s Hospital.

Co-senior author Zhongcong Xie, MD, PhD, added: “There is no current evidence that fentanyl is associated with a similar effect in humans and the outcome of the animal study is not an indication to avoid fentanyl in clinical anesthesia. However, the outcome will promote further research, including clinical investigations, to determine the potential neurobehavioral influence of opioids on brain development.” 

Categories : Surgeries & ProceduresTags :

AI-enabled Kidney Surgery Makes it Easier for Novice Surgeons

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Anatomic model of a kidney
Photo by Robina Weermeijer on Unsplash

Percutaneous nephrolithotomy (PCNL) is an efficient surgical intervention for removing large kidney stones. However, it is a challenging procedure that requires years of training to perform. To address this, a group of scientists from the Nagoya City University, developed and trialled an artificial intelligence (AI)-enabled robotic device for assisting surgeons in PCNL.

Creating a renal access from the skin on the back to the kidney is a crucial yet challenging step in PCNL. A poorly performed renal access can lead to severe complications including massive bleeding, thoracis and bowel injuries, renal pelvis perforation, or even sepsis. This procedure takes years of training to master. The two main renal access methods for PCNL – X-ray guidance and ultrasound (US) guidance deliver similar postoperative outcomes but require experience-based expertise.

Many technologies are being developed to bridge this skill gap. This inspired a Nagoya University research team to question if artificial intelligence (AI)-powered robotic devices could be used for improved guidance compared with conventional US guidance. Specifically, they wanted to see if the AI-powered device called the Automated Needle Targeting with X-ray (ANT-X), which was developed by the Singaporean medical start-up, NDR Medical Technology, offers better precision in percutaneous renal access along with automated needle trajectory.

The team performed a randomised, single-blind, controlled trial comparing their robotic-assisted fluoroscopic-guided (RAF) method with US-guided PCNL. The results of this trial were detailed in the The Journal of Urology. “This was the first human study comparing RAF with conventional ultrasound guidance for renal access during PCNL, and the first clinical application of the ANT-X ,” said Dr Kazumi Taguchi, Assistant Professor at NCU.

The trial was conducted with 71 patients—36 in the RAF group and 35 in the US group. The primary outcome of the study was single puncture success, with stone-free rate (SFR), complication rate, parameters measured during renal access, and fluoroscopy time as secondary outcomes.

The single puncture success rate was ~34 and 50% in the US and RAF groups, respectively. Fewer needle punctures were needed in the RAF group (1.82 times) as opposed to the US group (2.51 times). In 14.3% of US-guided cases, the resident was unable to obtain renal access due to procedural difficulty, prompting a surgeon change. However, none of the RAF cases faced this issue. The median needle puncture duration was also significantly shorter in the RAF group (5.5 minutes vs 8.0 minutes). No significant differences in the other secondary outcomes was found.

Multiple renal accesses during PCNL are directly linked to postoperative complications including, decreased renal function. Therefore, the low needle puncture frequency and shorter puncture duration, as demonstrated by the ANT-X, may provide better long-term outcome for patients. While the actual PCNL was performed by residents in both RAF and US groups, the renal access was created by a single, novice surgeon in the RAF group, using ANT-X. This demonstrates the safety and convenience of the novel robotic device, which could possibly reduce surgeons’ training load and allow more hospitals to offer PCNL procedures.

Dr Taguchi commented, “The ANT-X simplifies a complex procedure, like PCNL, making it easier for more doctors to perform it and help more number of patients in the process. Being an AI-powered robotic technology, this technique may pave the way for automating similar interventional surgeries that could shorten the procedure time, relieve the burden off of senior doctors, and perhaps reduce the occurrence of complications.”

Source: Nagoya City University

Categories : Diet and NutritionTags :

Humans Naturally Moderate their Intake of Energy-rich Meals

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A hamburger
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A new study has shown that, instead of overeating, humans moderate the size of energy-rich meals they consume, suggesting people are smarter eaters than previously thought.

The findings, published in The American Journal of Clinical Nutrition, revisit the long-held belief that humans don’t notice the energy content of the foods they consume, making them prone to eating the same quantity of food by weight, regardless of it being energy-rich or energy-poor.

The study, led by the University of Bristol, challenges a common view among researchers that people tend to overconsume high-energy foods.

Previous studies manipulated the energy content of foods or meals to create low- and high-energy versions. In those studies, people were not informed of which version they ate, and findings showed they tended to eat meals of the same weight, resulting in greater calorie intake with the high-energy version.

“For years we’ve believed that humans mindlessly overeat energy-rich meals. Remarkably, this study indicates a degree of nutritional intelligence whereby humans manage to adjust the amount they consume of high-energy density options,” said lead author Annika Flynn, Doctoral Researcher in Nutrition and Behaviour at the University of Bristol.

Rather than artificially manipulating the calories in single foods, this study looked at data from a trial using a normal, everyday meals with different energy densities, such as a chicken salad sandwich with fig roll biscuits or porridge with blueberries and almonds. The trial involved 20 healthy adults who temporarily lived in a hospital ward where they were served a variety of meals for four weeks.

The international team of researchers calculated the calories, grams, and energy density (calories per gram) for every meal each participant consumed. They found that meal calorie intake increased with energy density in energy-poor meals as previous observations with artificially manipulated foods also found. Surprisingly, with greater energy density a turning point was observed whereby people start to respond to increases in calories by reducing the size of the meals they consume. This suggests a previously unrecognised sensitivity to the energy content of the meals people were eating.

As this finding was based on data from a small, highly-controlled trial, the researchers next investigated whether the general population followed this pattern eating freely. Using data from the UK National Diet and Nutrition Survey, researchers again found meal calorie intake increased with energy density in meals which were energy-poor and then decreased in energy-rich meals. Importantly, for this turning point pattern to occur, participants would have needed to consume smaller meals, by weight, of the more energy-rich meals.

Annika said: “For instance, people ate smaller portions of a creamy cheese pasta dish, which is an energy-rich meal, than a salad with lots of different vegetables which is relatively energy-poor.”

This research sheds new light on human eating behaviour, specifically an apparent subtle sensitivity to calories in energy-rich meals.

Co-author Jeff Brunstrom, Professor of Experimental Psychology, said: “This research gives added weight to the idea humans aren’t passive overeaters after all, but show the discerning ability to moderate how much of an energy-rich meal they consume.

“This work is particularly exciting as it reveals a hidden complexity to how humans interact with modern energy-rich foods, something we’ve been referring to as ‘nutritional intelligence’. What this tells us is we don’t seem to passively overconsume these foods and so the reason why they are associated with obesity is more nuanced than previously thought. For now, at least this offers a new perspective on a longstanding issue and it opens the door to a range of important new questions and avenues for future research.”

Source: University of Bristol

Categories : COVIDTags :

Few Patients get ‘Rebound COVID’ after Paxlovid Treatment

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Image from Pixabay

Mayo Clinic researchers studied the outcomes of 483 high-risk patients  treated for COVID with a five-day oral regimen of Paxlovid, a combination of nirmatrelvir and ritonavir. Only a handful developed COVID rebound symptoms, something which the researchers say needs further investigation. Their findings appear in the journal Clinical Infectious Diseases.

All of the patients benefited from Paxlovid and recovered, including the patients who developed rebound symptoms, which were generally mild.

“We found that rebound phenomenon was uncommon in this group of patients,” says senior author Aditya Shah, MBBS, an infectious diseases physician and researcher at Mayo Clinic. “The four individuals who experienced rebound [symptoms] represent only 0.8% of the group, and all of them recovered quickly without additional COVID-directed therapy.”

Most of the patients had been vaccinated, and many had received booster vaccinations. The median age was 63. While these patients were high-risk for COVID, none was immunocompromised. Only two patients were admitted to the hospital, and it was for reasons other than COVID.

The study focussed on four patients with rebound symptoms:

  • A 75-year-old man with coronary artery disease who had increased cough and muscle aches 19 days after treatment.
  • A 40-year-old woman with obesity, hypertension and kidney disease who developed fatigue and sore throat six days after treatment.
  • A 69-year-old man with hypertension and obesity who exhibited nasal discharge and cough 10 days following therapy.
  • A 70-year-old man with a history of prostate cancer, obesity, hypertension and high cholesterol, who developed significant sinus congestion 10 days after treatment.

Why did some rebound?

Researchers think one explanation could be that a replication of SARS-CoV-2 could have triggered a secondary immune response, which showed up as mild COVID symptoms. This question could be answered by prospective studies could answer the question. They also note that all four patients with rebound symptoms had many serious health problems known as comorbidities — a factor shown to complicate recoveries. And all four patients had been vaccinated more than 90 days before becoming infected with COVI.

Source: Mayo Clinic