Publisher Health

In a pair of world firsts, UBC scientists have 3D printed human testicular cells and identified promising early signs of sperm-producing capabilities.
The researchers, led by UBC urology assistant professor Dr. Ryan Flannigan, hope the technique will one day offer a solution for people living with presently untreatable forms of male infertility.
“Infertility affects 15 per cent of couples and male factors are a contributing cause in at least half those cases,” said Dr. Flannigan, whose lab is based at the Vancouver Prostate Centre at Vancouver General Hospital.
“We’re 3D printing these cells into a very specific structure that mimics human anatomy, which we think is our best shot at stimulating sperm production. If successful, this could open the door to new fertility treatments for couples who currently have no other options.”
Within human testicles, sperm is produced by tiny tubes known as seminiferous tubules. In the most severe form of male infertility, known as non-obstructive azoospermia (NOA), no sperm is found in ejaculate due to diminished sperm production within these structures.
While in some cases doctors can help NOA patients by performing surgery to find extremely rare sperm, Dr. Flannigan says this procedure is only successful about half the time.

A retinal stem cell patch developed through a collaboration of researchers at UC Santa Barbara, University of Southern California and California Institute of Technology continues to make progress in its bid to secure approval from the Food and Drug Administration. The latest milestone? Results finding that after two years, not only can the implant survive, but also it does not elicit clinically detectable inflammation or signs of immune rejection, even without long-term immunosuppression.
“What really makes us excited is that there is some strong evidence to show that the cells are still there two years after implantation and they’re still functional,” said Mohamed Faynus, a graduate student researcher in the lab of stem cell biologist Dennis O. Clegg, and a co-author on a paper published in the journal Stem Cell Reports. “This is pretty important, because if the goal is to treat blindness, we want to make sure that the retinal pigment epithelium cells that we put in there are still doing the job they’re supposed to.”
A treatment in development since 2013, the California Project to Cure Blindness — Retinal Pigment Epithelium 1 (CPCB-RPE1) patch consists of a monolayer of human stem cell-derived RPE cells cultured on an ultrathin membrane of biologically inert parylene. The goal for this patch is to replace deteriorating cells in the retinas of those who have age-related macular degeneration, one of the leading causes of blindness worldwide for people over 50. The condition affects the macula — the part of the retina responsible for central vision. People with AMD experience distortions and loss of vision when looking straight ahead.
The researchers have made strides with the patch since its inception, guiding it through clinical trials for use with the dry form of AMD. If the implant works, the new cells should take up the functions of the old ones, and slow down or prevent further deterioration. In the best-case scenario, they could restore some lost vision.
The first sets of trials concentrated on establishing the safety of the patch and collecting any data on its effectiveness. The group, in a one-year follow-up published last year in the journal Translational Vision Science & Technology, concluded the outpatient procedure they were developing to implant the patch could be performed routinely and that the patch was well-tolerated in individuals with advanced dry AMD. Early results were promising: Of the 15 patients in the initial cohort, four demonstrated improved vision in the treated eye, while five experienced a stabilization of their vision. Visual acuity continued to decline in the remaining six, and the researchers are working to understand why.
Having implanted the patches in live volunteers, however, the researchers no longer had a direct means for assessing the patches’ function and any changes in the longer term.

Children who develop type 1 diabetes show epigenetic changes in the cells of their immune system already before the antibodies of the disease are detected in their blood. The findings of two new studies offer new opportunities to identify the children with the genetic risk for developing diabetes very early on.
Epigenetic changes can affect how our genes work. Environmental factors, such as viral infections, can cause epigenetic changes.
The findings in the epigenetic makeup linked to diabetes were discovered in two new studies led by researchers from Turku Bioscience at the University of Turku, Finland.
“We uncovered previously unknown, early-onset epigenetic changes. They offer us new opportunities to further develop ways to identify children who have a risk of developing type 1 diabetes even before they get sick,” says Professor Riitta Lahesmaa, Director of Turku Bioscience and a group leader in the InFLAMES research flagship initiative.
Earlier studies have shown that certain antibodies detected in children’s blood samples indicate an increased risk of developing type 1 diabetes in the near future. So that medical professionals could intervene in the disease even sooner, earlier disease indicators than the antibodies are needed to detect the risk. This involves searching for biomarkers indicating type 1 diabetes, and epigenetic changes could be such a biomarker.
“Our observations on epigenetics are extremely important as our goal is to develop methods and tools to prevent the onset of type 1 diabetes in children who are at risk of developing the disease,” says Professor Laura Elo. Elo is the Director of the Medical Bioinformatics Centre at Turku Bioscience and a group leader in the InFLAMES research flagship.
Finnish children have an increased risk of developing type 1 diabetes
In Finland, children’s risk of developing type 1 diabetes is the highest in the world. In addition to the genetic susceptibility, environmental factors have a great significance for developing the disease. The environmental factors include, for example, excessive level of hygiene, biodiversity loss, and environmental toxins.
The newly published studies are based on long-term interdisciplinary research collaboration with international partners. The project has included doctors who are in charge of the patients and also conduct clinical research, researchers in molecular medicine and immunology, and experts in computational science. In the studies, researchers analysed longitudinal samples with deep sequencing covering the entire genome as well as with computational methods and artificial intelligence.
“Our research was enabled by close collaboration with Professor Mikael Knip from the University of Helsinki, who coordinates a study funded by the EU. He is also one of the key scientists in the national Type 1 Diabetes Prediction and Prevention (DIPP) project which was a partner in the other study,” highlights Professor Lahesmaa.
The studies were funded by the Academy of Finland, Juvenile Diabetes Research Foundation (USA), European Union, Business Finland, Novo Nordisk, and InFLAMES Flagship.
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Materials provided by University of Turku. Note: Content may be edited for style and length.

Alzheimer’s disease (AD) eventually leads to severe cognitive decline, but most affected individuals also develop distressing neuropsychiatric symptoms. These earlier effects may be more subtle and are not well understood; it remains unclear whether they arise directly from AD pathology or secondarily as psychological reactions due to the cognitive deficits. Now, a new study examines the connections between biomarkers of AD’s hallmark neuropathology, cognition, and other neuropsychiatric symptoms. The study appears in Biological Psychiatry, published by Elsevier.
The researchers, led by Oskar Hansson, MD, at Lund University in Sweden, tested cerebrospinal fluid or blood plasma from 356 cognitively unimpaired older adults for levels of the proteins amyloid-beta (Ab) and tau, which are thought to contribute to AD neurotoxicity, as well as markers of neurodegeneration.
Strikingly, the presence of Ab was associated with increased anxiety and apathy. Higher levels of apathy were also related to a more rapid cognitive decline.
“Most importantly, this study signals that certain neuropsychiatric symptoms such as apathy and anxiety develop predominantly due to underlying AD-related pathology and not due to the concomitant cognitive impairment,” said Maurits Johansson, MD, lead author of the study. “It seems reasonable that neuropsychiatric symptoms would arise from neuropathology just as cognitive deficits do, especially because AD ultimately affects large areas of the brain,” he added.
The study did not exclude a role for cognitive impairment altogether. For example, in one of the statistical analyses, cognitive decline slightly but significantly mediated the effect of amyloid pathology on the development of apathy.
“Combined with earlier studies, our findings strengthen the proposed idea that cognitive deficits and neuropsychiatric symptoms can develop independently, yet in parallel to one another. They have a common underlying neuropathology, but to some extent they can also reinforce one another,” said Professor Hansson.
“These findings could ultimately lead to more efficient study design of clinical trials for AD in that they point to neuropsychiatric symptoms as potential alternative outcome measures,” concluded Professor Hansson.
John Krystal, MD, Editor of Biological Psychiatry, said of the new findings, “We are used to thinking about Alzheimer’s disease from the perspective of memory impairments. This new study highlights that the earliest signs of amyloid-related pathology may be changes in mood and behavior, particularly apathy and anxiety.”
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Three-quarters of kitchens in low-income homes across 12 major global cities are heavily polluted by cooking emissions, according to research from the University of Surrey and its global partners.
The first-of-its-kind study found that poor ventilation and fuel choices were the most significant contributors to poor air quality in people’s kitchens, but the size of the kitchen and the way food was cooked also mattered. Frying food led to particularly high levels of indoor pollution.
Professor Prashant Kumar, Founding Director of the University of Surrey’s Global Centre for Clean Air Research (GCARE), who led the research published in Environment International, said:
“There’s a notable wealth divide when it comes to indoor air quality and also a gender divide, as women are typically disproportionately impacted by pollution caused by cooking, especially in the developing world. This problem must be addressed to improve health and equality.”
The highest average levels of pollution were found in Dhaka, Bangladesh, where kitchens were typically small and people cooked for prolonged periods, often frying food. The cleanest air was found in Medellín, Colombia, due to more space in their kitchens and the use of cleaner cooking fuels.
The way different cuisines are typically cooked also made a difference to air quality in kitchens. The study found that occupants in Dhaka, Nanjing, Dar-es-Salaam and Nairobi spent more than 40 per cent of their cooking time frying, the cooking activity which emits most polluting particles. However, in Cairo, Sulaymaniyah and Akure, roughly two-thirds of cooking time was spent boiling or stewing, which results in fewer particles emitted.
Cooking on charcoal caused the highest levels of kitchen pollution — more than three times the levels when using liquefied petroleum gas (LPG). However, the levels of pollution caused by cooking on natural gas were just thirty per cent lower than that of charcoal.
A combination of natural ventilation and mechanical (for example, extractor fans) in Chennai, Cairo and Sulaymaniyah helped halve kitchen pollution, compared with the use of natural ventilation alone in Addis Ababa, Dar-es-Salam and Nairobi.
Professor Kumar said: “Improving airflow, using cleaner fuels, filtering efficiency of cooking hoods, and frying less are all ways to reduce the pollution people breathe from cooking. Around the world, kitchens are often where people congregate, but these findings suggest that cooks should discourage family and friends from being around when they’re cooking.”
The World Health Organisation estimates that approximately four million people die prematurely from illnesses attributed to indoor air pollution caused by polluting stoves operating on solid fuels and kerosene. Exposure to high levels of particulate matter, including that from cooking, has been linked to health conditions including heart disease, pneumonia, stroke, lung cancer, and chronic obstructive pulmonary disease.
Next, the research team will further analyse their findings and will develop guidance for reducing exposure to kitchen pollution.
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Materials provided by University of Surrey. Note: Content may be edited for style and length.

Imagine if the real cost to society of the food you buy at the grocery store was built right into each product’s price. Everything with added sugar would cost a whole lot more, according to University of Alberta researchers in a new study in The Canadian Journal of Public Health.
They peg the economic burden of excessive sugar consumption in Canada at $5 billion a year, thanks to the direct and indirect costs related to 16 chronic diseases. The researchers call on governments to use taxation, subsidies, education and other measures to encourage healthier eating habits, saying it is “an area of urgent need for action” in the post-COVID-19 pandemic era.
“This pandemic has brought us more unhealthy lifestyles — on the nutrition side, on the physical activity side and on screen time for kids. If we do not act now, we should expect more chronic diseases such as Type 2 diabetes in the years ahead,” said principal investigator Paul Veugelers, professor in the U of A’s School of Public Health.
“Health care costs for chronic diseases are ballooning,” Veugelers said. “We not only need to make our health-care system more efficient, we should also act on the demand side by investing in primary prevention to ensure we have fewer patients with chronic diseases. Addressing sugar consumption is one strategy to achieve that.”
Both Canada’s Food Guide and the World Health Organization recommend we consume less than 10 per cent of our daily energy intake as “free sugar” from foods made with added sugar and naturally sweet juices, honey and syrup. For additional health benefits, less than five per cent is recommended.
Using data reported in the 2015 Canadian Community Health Survey on nutrition, the researchers found that two out of three Canadians eat more sugar than recommended. They then established risk estimates for 16 diet-related chronic conditions, including diabetes, cardiovascular diseases, cancer, kidney disease and low back pain. They calculated avoidable direct health-care costs such as doctors, hospitals and drugs, along with indirect costs like productivity losses due to illness and disability.
They concluded that if Canadians had followed the 10 per cent recommendation in 2019, an estimated $2.5 billion could have been saved, and $5 billion in costs could have been avoided by following the stricter five per cent recommendation.
Treatment and management of chronic diseases accounts for 67 per cent of all health-care costs in Canada, they reported, with an annual price tag of up to $190 billion.
The researchers estimated that limiting free sugar consumption to less than 10 per cent of energy intake could reduce the prevalence of diabetes by 27 per cent, and that benefit could reach 44.8 per cent if Canadians limited their sugar consumption to less than five per cent.
“Diabetes is just a very expensive condition to manage and to treat. It can occur at an early age, and you can live with it for a long, long time. Kidney issues, dialysis, amputation, those are just a few gruesome examples of where that disease trajectory can go,” said Veugelers. “Patients require lots of health-care interactions that drive the costs of chronic diseases.”
Forty countries and cities around the world have already introduced a special tax on sugar-sweetened beverages such as pop as a disincentive to consumption, building on lessons from tobacco control measures. Newfoundland and Labrador recently introduced Canada’s first such tax and similar policies have been suggested elsewhere, but in this study the researchers push for a broader approach, because they found that only 17 per cent of the costs related to sugar consumption could be traced back to sugary drinks.
Instead, they advocate for higher taxes on all sugar-added products, and to put the tax revenues towards subsidies for healthful foods, education programs, limits on advertising to children, and better product labeling.
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Materials provided by University of Alberta. Original written by Gillian Rutherford. Note: Content may be edited for style and length.

Life expectancy for individuals with Down syndrome has grown in recent decades, thanks in large part to progress in patient care and treatment. But with survival into the fifth and sixth decades of life now possible, increasing numbers of these individuals are affected by conditions linked to aging, among them impairments in thinking that are associated with the accumulation in the brain of atypical proteins better known for their involvement in Alzheimer’s disease.
Precisely why Alzheimer-like changes — marked by the build-up of harmful amyloid and tau proteins — occur in the brain in Down syndrome has been unclear. But now, in new research, scientists at the Lewis Katz School of Medicine at Temple University show that reduced efficiency of a key protein transport system is partly to blame. In analyses of human brain tissue collected post-mortem, the researchers found that the so-called retromer complex system, which plays a critical role in clearing damaged and degraded proteins from neurons in the brain, operates at only about 50 percent of its usual efficiency in Down syndrome patients. The reduction was linked specifically to the accumulation of pathogenic tau protein.
“The decline in protein transport via the retromer system is a lot like a traffic jam, with the transporter stalling out and causing a major back-up in the clearance of pathologic tau proteins, leaving them to accumulate over time,” explained Domenico Praticò, MD, Scott Richards North Star Foundation Chair for Alzheimer’s Research, Professor in the Department of Neural Sciences, Director of the Alzheimer’s Center at Temple, and senior investigator on the new study.
“We also found that a major factor underlying tau accumulation is diminished activity of the cathepsin-D enzyme, which resides within the retromer complex,” Dr. Praticò added. Cathepsin-D normally acts like a pair of scissors, cutting up tau to facilitate its digestion and removal.
The study, published online in the journal Annals of Neurology, is the first to connect reductions in retromer system efficiency and cathepsin-D activity to the accumulation of pathogenic tau in Down syndrome. The findings are significant because they suggest that Alzheimer-like changes are not strictly modulated by the extra copy of human chromosome 21 that is characteristic of Down syndrome. Even though the extra chromosome provides an additional copy of a gene known as amyloid precursor protein (APP), which increases the risk of amyloid plaque formation, not all Down syndrome patients develop dementia, implicating the involvement of factors beyond genetics.
Dr. Praticò and colleagues first measured the extent of tau pathology in brain tissue from patients with Down syndrome and then assessed the relationship between the retromer core protein levels and the amount of pathologic tau protein in young and aged individuals with Down syndrome. They further compared the activity of cathepsin-D with the amount of tau pathology in the same individuals.
The team’s analyses uncovered an inverse relationship between the emergence of tau pathology in Down syndrome and the levels of retromer proteins and activity of cathepsin-D. Moreover, the team’s observations suggest that reduced levels of retromer proteins in young Down syndrome subjects sets the stage for the development of tau pathology later in life.
“Overall, our data identify the retromer complex as a key regulator of pathogenic tau in Down syndrome, with evidence for the development of tau pathology at a relatively young age,” Dr. Praticò said.
The results also identify the retromer system as a promising new target for the treatment of Alzheimer’s disease pathology in Down syndrome patients. Drugs that target the retromer system, such as small chaperones, have already been developed. In future work, Dr. Praticò and colleagues plan to explore these potential treatments in animal models that reproduce most of the aspects of Down syndrome observed in humans.
“Using these existing therapeutics, we want to see if it is possible to reverse amyloid plaque and pathological tau accumulation in animal models,” Dr. Praticò added. “If we are successful, we will have created an exciting opportunity to explore treatments in human patients with Down syndrome.”
Other investigators who contributed to the new study include Mary Elizabeth Curtis and Tiffany Smith, Alzheimer’s Center at Temple, Lewis Katz School of Medicine; and Daohai Yu, Department of Clinical Sciences, Lewis Katz School of Medicine.
The study was funded in part by grants from the National Institutes of Health (AG055707 and AG056689).

Scientists from Nanyang Technological University, Singapore (NTU Singapore) have developed a novel method of delivering drugs into human cells using large biological molecules, by first encasing them in a protein-based microdroplet.
This discovery promises to be faster, safer, more effective, and better suited for gene therapy, cancer treatment, and vaccine delivery, including mRNA-based vaccines such as those currently used for Covid-19 vaccinations by Pfizer and Moderna.
These microdroplets, made up of small proteins named peptides, can encase large biomacromolecules that carry drugs inside them. In doing so, they allow these biological molecules to enter cells, something the molecules cannot do by themselves.
Biomacromolecules are large biological molecules such as nucleic acids (DNA, mRNA), proteins and carbohydrates. They are of great research interest as drug carriers, as they can carry a large amount of drugs, are nontoxic, able to target specific sites, and do not trigger the body’s immune response. This makes them preferable and advantageous over synthetic carriers currently used in the market.
However, their large size and inability to pass through the cell membrane have held them back from widespread clinical use.
Now, the NTU research team, led by Professor Ali Miserez from the School of Materials Science & Engineering and the School of Biological Sciences, showed in lab experiments that their method of first encasing drug-carrying biomacromolecules in protein-based microdroplets lets them reliably and effectively enter cells, overcoming the main challenge of cell entry.

Genomic sequencing of tumors from pediatric cancer patients experiencing a relapse enabled 107 patients to receive an appropriate matched therapy that is not the standard of care, according to data from the international clinical trial MAPPYACTS.
Pediatric cancers have a high rate of remission, with 85 percent of patients surviving five years or longer after diagnosis. However, if the cancer returns, treatment options are limited.
“The main purpose was to genetically profile the patients’ tumors and use that to suggest a treatment,” said Birgit Geoerger, MD, PhD, a professor of pediatric clinical research at Gustave Roussy Cancer Center in France. “Are there molecular alterations that we can target with these newer drugs?”
In many cases, pediatric cancers are subjected to gene panel sequencing, in which common cancer driver genes are sequenced to look for mutations. While this information can provide valuable insights about how the tumor operates, it is not often used to guide treatment decisions. “There are not a lot of trials testing targeted therapies in children,” Geoerger said.
Geoerger and colleagues initiated the MAPPYACTS clinical trial to prospectively recruit pediatric patients with relapsed cancers and perform comprehensive whole exome sequencing (WES) and/or RNA sequencing in order to recommend a therapy tailored to each patient. They collected tissue samples from 774 patients, 632 of which were successfully sequenced. A clinical molecular tumor board then reviewed the sequencing data from each patient.
Mutations were considered “ready for routine use” if there was significant clinical evidence that a drug could effectively treat tumors harboring the mutation. Mutations were considered “potentially actionable” if any evidence existed that an approved or investigational drug — a drug being tested in clinical trials — could target the mutated protein or another member of the affected signaling pathway.