In a new study published in the American Journal of Transplantation, researchers report that they successfully transplanted two kidneys from a genetically modified pig into a human recipient who had suffered brain death.
The use of pig organs, genetically modified to enable transplantation into humans, could ease the shortage of available donor organs for transplantation and prevent thousands of deaths that result each year due to a shortage of organs. Recently, a US man became the first human recipient of a genetically modified pig heart.
This study used a novel preclinical human model to answer numerous critical safety questions. No hyperacute rejection was seen for the 74 hours until termination. No chimerism or transmission of porcine retroviruses was detected. Longitudinal biopsies revealed thrombotic microangiopathy that did not progress in severity, without evidence of cellular rejection or deposition of antibody or complement proteins. Although the xenografts produced variable amounts of urine, creatinine clearance did not recover. Whether renal recovery was impacted by the milieu of brain death and/or microvascular injury remains unknown.
The study provides important insights and identifies several areas where additional research is needed before xenotransplantation can be used to help address the current organ shortage.
“This study provides knowledge that could not be generated in animal models and moves us closer to a future where organ supply meets the tremendous need,” said senior author Jayme E. Locke, MD, MPH, of the University of Alabama at Birmingham.
Among 25 183 women aged 50 to 79 years, there were 1455 cases of hospitalisation for heart failure during a median follow-up of 16.9 years. Compared with women who walked at a casual pace, those who walked at an average pace or fast pace had 27% and 34% lower risks of heart failure, respectively.
Fast walking for less than 1 hour per week was associated with the same risk reduction of heart failure as average or casual walking for more than 2 hours per week.
“This study confirms other studies demonstrating the importance of walking speed on mortality and other cardiovascular outcomes,” said senior author Charles B. Eaton, MD, MS, of the Warren Alpert Medical School of Brown University. “Given that limited time for exercise is frequently given as a barrier to regular physical activity, walking faster but for less time might provide similar health benefits as the recommended 150 minutes per week of moderate physical activity.”
Further study is warranted to determine whether interventions to increase the walking pace in older adults will reduce heart failure risk and whether fast pace will compensate for the short duration of walking.
A five year-long randomised, placebo-controlled study found that in older adults taking vitamin D supplements, alone or with omega-3 fatty acids, the risk of developing autoimmune disease was reduced.
Autoimmune diseases (AD) such as rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease and psoriasis, are a leading cause of morbidity and mortality as people age. Few effective treatments are available for AD, but some research has hinted that supplements, including vitamin D and omega-3 fatty acids, could have beneficial effects.
In a new study published in the BMJ, investigators from Brigham and Women’s Hospital evaluated whether taking vitamin D and/or omega fatty acid supplements could affect rates of AD. The large-scale vitamin D and Omega-3 Trial (VITAL), a randomised study which followed participants for approximately five years. Taking vitamin D, or vitamin D and omega-3 fatty acids had a significantly lower rate of AD than placebo.
“It is exciting to have these new and positive results for non-toxic vitamins and supplements preventing potentially highly morbid diseases,” said senior author Karen Costenbader, MD, MPH. “This is the first direct evidence we have that daily supplementation may reduce AD incidence, and what looks like a more pronounced effect after two years of supplementation for vitamin D.”
“Now, when my patients, colleagues, or friends ask me which vitamins or supplements I’d recommend they take to reduce risk of autoimmune disease, I have new evidence-based recommendations for women aged 55 years and older and men 50 years and older,” said Dr Costenbader. “I suggest vitamin D 2000 IU a day and marine omega-3 fatty acids (fish oil), 1000 mg a day – the doses used in VITAL.”
VITAL included 25 871 participants, with men aged 50 and older and women aged 55 and older, conducted to investigate whether taking vitamin D3 and/or omega-3 supplements could reduce the risk for developing cancer, heart disease and stroke in people who do not have a prior history of these illnesses. Prior to the launch of VITAL, investigators determined that they would also look at rates of AD among participants, as part of an ancillary study.
Participants answered questionnaires about new diagnoses of diseases, including rheumatoid arthritis, polymyalgia rheumatica, autoimmune thyroid disease, psoriasis and inflammatory bowel disease, with space to write in all other new onset ADs. Medical records were reviewed to confirm reported diagnoses.
“Autoimmune diseases are common in older adults and negatively affect health and life expectancy. Until now, we have had no proven way of preventing them, and now, for the first time, we do,” said first author Jill Hahn, ScD, post-doctoral fellow at the Brigham.
Among patients randomised to vitamin D, 123 participants in the treatment group and 155 in the placebo group were diagnosed with confirmed AD (22 percent reduction). Among those in the fatty acid arm, confirmed AD occurred in 130 participants in the treatment group and 148 in the placebo group. Omega-3 fatty acids alone did not significantly lower incidence of AD, but there was some evidence of a decrease over long periods.
Using a mix of drugs and a regenerative seal, scientists were able to successfully regrow frog legs, as reported in Science Advances. This represents an eventual step towards possibly regrowing limbs in humans.
On adult frogs, which are naturally unable to regenerate limbs, the researchers were able to trigger regrowth of a lost leg using a five-drug cocktail applied in a silicone wearable bioreactor dome that seals in the treatment over the stump for just 24 hours. That brief treatment sets in motion an 18-month period of regrowth that restores a functional, near-complete leg.
In humans and mammals loss of a large and structurally complex limb cannot be restored by any natural process of regeneration in humans or mammals. In fact, we tend to cover major injuries with an amorphous mass of scar tissue, protecting it from further blood loss and infection and preventing further growth.
The Tufts University researchers triggered the regenerative process in African clawed frogs by enclosing the wound in a silicone cap, which they call a BioDome, containing a silk protein gel loaded with the five-drug cocktail.
Each drug fulfilled a different purpose, including tamping down inflammation, inhibiting collagen production which would lead to scarring, and encouraging the new growth of nerve fibres, blood vessels, and muscle. The combination and the bioreactor provided a local environment and signals that tipped the scales away from the natural tendency to close off the stump, and toward the regenerative process.
A dramatic growth of tissue was observed in many of the treated frogs, re-creating an almost fully functional leg which was able to respond to stimuli, though the “toes” grown had no bones.
“It’s exciting to see that the drugs we selected were helping to create an almost complete limb,” said Nirosha Murugan, research affiliate at the Allen Discovery Center at Tufts and first author of the paper. “The fact that it required only a brief exposure to the drugs to set in motion a months-long regeneration process suggests that frogs and perhaps other animals may have dormant regenerative capabilities that can be triggered into action.”
Within the first few days after treatment, they detected the activation of known molecular pathways that are normally used in a developing embryo. Activation of these pathways could allow the burden of growth and organisation of tissue to be handled by the limb itself, similar to that in an embryo, rather than require ongoing therapeutic intervention over the many months it takes to grow the limb.
Animals naturally capable of regeneration live mostly in an aquatic environment. The first stage of growth after loss of a limb is the formation of a blastema, a mass of stem cells at the end of the stump, which is used to gradually reconstruct the lost body part. The wound is rapidly covered by skin cells within the first 24 hours after the injury, protecting the reconstructing tissue underneath.
“Mammals and other regenerating animals will usually have their injuries exposed to air or making contact with the ground, and they can take days to weeks to close up with scar tissue,” said Tufts University Professor David Kaplan, co-author of the study. “Using the BioDome cap in the first 24 hours helps mimic an amniotic-like environment which, along with the right drugs, allows the rebuilding process to proceed without the interference of scar tissue.”
Previous work using just progesterone with the BioDome resulted in a spike-like limb.
The five-drug cocktail is a major step toward the restoration of fully functional frog limbs and suggests further exploration of drug and growth factor combinations could lead to regrown limbs that are even more functionally complete.
“We’ll be testing how this treatment could apply to mammals next,” said corresponding author Professor Michael Levin at Tufts University.
“Covering the open wound with a liquid environment under the BioDome, with the right drug cocktail, could provide the necessary first signals to set the regenerative process in motion,” he said. “It’s a strategy focused on triggering dormant, inherent anatomical patterning programs, not micromanaging complex growth, since adult animals still have the information needed to make their body structures.”
A new meta-analysis has established an association between alcohol and epilepsy, in contrast to previous studies which reported conflicting results on the relationship.
Epilepsy is one of the most common neurological conditions, with an annual incidence of 40–70 per 100 000 people in industrialised countries. It is also a disease that is highly stigmatised.
A number of studies have focused on how alcohol consumption leads to provoked seizures, commonly resulting from alcohol withdrawal, or heavy intoxication. Very few of these however focused on the link between alcohol consumption and unprovoked seizures. A 2010 meta-analysis found that alcohol users were more prone to developing unprovoked seizures – but data from recent cohort studies contradict these findings. A 2018 meta-analysis suggested that the relationship may only hold true for heavy drinkers.
Now, using more accurate diagnostic methods and recent data, a team of scientists from Pusan National University, South Korea, conducted an updated meta-analysis to conclusively clarify the relationship between alcohol consumption and unprovoked seizures and epilepsy.
For this meta-analysis, appearing in Drug and Alcohol Dependence, the researchers included a total of eight studies, of which five were case-control studies and three were cohort studies. They analysed the data to assess the dose-response relationship between alcohol intake and epilepsy. The results suggested that overall, compared to non-drinkers, alcohol drinkers were at a significantly higher risk of developing epilepsy, which increased with alcohol intake. These findings are consistent with previous meta-analyses.
An important finding was that cohort studies did not show a positive association between alcohol intake and epilepsy. In fact, 2 out of 3 cohort studies suggested that alcohol intake reduces the risk of epilepsy.
More large cohort studies are needed to prove a causal relationship between alcohol drinking and epilepsy, as well as a threshold of onset, said second author Professor Yun Hak Kim.
