Tag: 17/6/22

Categories : Obstetrics & Gynaecology TransplantsTags :

Uterus Transplants are Safe and Effective, Study Finds

On By ModernMedia
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

On By ModernMedia
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

On By ModernMedia
Photo by Tingey Injury Law Firm on Unsplash

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

On By ModernMedia
Photo by Clark Douglas on Unsplash

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

On By ModernMedia
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