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TB vaccine may protect newborns against other infectious diseases

Infants who had been vaccinated with BCG at birth presented to doctors with any kind of infection 25% less often than infants who had not. Protection from BCG didn’t seem to be against one specific type of infection, but for all types, such as common colds, chest infections, and skin infections.

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The tuberculosis (TB) vaccine Bacillus Calmette-Guerin (BCG) could protect newborns against a variety of common infections, such as upper respiratory tract infections, chest infections and diarrhoea, according to a new study in The Lancet Infectious Diseases.

The research is the first of its kind to rigorously investigate the full range of illnesses BCG could protect infants against. It suggests that vaccinating all babies on the day of birth with BCG could reduce neonatal infections and death in areas with high infectious disease rates, potentially saving thousands of lives a year. The results also increase the possibility that the vaccine might be used to protect children and adults against COVID-19 and other new infectious diseases.

Led by the London School of Hygiene & Tropical Medicine (LSHTM) through the MRC/UVRI & LSHTM Uganda Research Unit, and funded by the Wellcome Trust, the study involved a randomized control trial of 560 newborns in Uganda, who were monitored for a range of illnesses.

After six weeks, infection rates from any disease were 25% lower in the group who received the vaccine at birth, compared to the group that had not yet received the vaccination. Particularly vulnerable groups such as low birth weight babies, and boys, seemed to be protected the most. Importantly, BCG appeared to protect against mild, moderate and severe types of infections.

Sarah Prentice, lead author from LSHTM, said: “Nearly a million babies die every year of common infections so we urgently need better ways to protect them. Our research suggests that ensuring that BCG is given at birth could make a big difference in low income countries, potentially saving many lives.”

In the study, healthy Ugandan infants were randomly assigned to receive BCG at birth or at six weeks of age. The infants were followed-up by doctors, blinded to the intervention, for 10 weeks to look for episodes of any type of illness or infection.

The research team then compared how often infants in the two groups presented to doctors with infections of any kind, except TB, to see whether having BCG made a difference. They also took blood samples from both groups, to look at differences in their innate immune system, the body’s first line of defence against infections.

Infants who had been vaccinated with BCG at birth presented to doctors with any kind of infection 25% less often than infants who had not. Protection from BCG didn’t seem to be against one specific type of infection, but for all types, such as common colds, chest infections, and skin infections.

After the group receiving BCG at six weeks had been vaccinated, there was no difference in the rates of infection between the two groups – the delayed group’s immunity ‘caught-up’ once they’d received BCG.

Hazel Dockrell, Professor of Immunology at LSHTM and one of the co-authors of the study, adds: “It’s very exciting to think that BCG vaccination might help keep newborns safe against other dangerous infections, in addition to providing protection against TB. Although BCG is recommended at birth in many countries, it is often delayed due to logistical difficulties. Ensuring that the vaccine is given on day one, in areas with high rates of infectious disease, could have a major impact on infections and deaths in the newborn period.”

The team can’t definitively say why BCG offered this additional non-specific protection, but the research showed evidence of changes in the innate immune system of vaccinated infants, which may suggest that BCG boosts the immune system to work better against any infection.

This has led the researchers to suggest that it could provide protection in the early stages of novel outbreaks, such as COVID-19 or Ebola, before specific vaccines have been developed.

Further studies are already underway to explore whether BCG could play a role in the response to COVID-19, with large trials involving health care workers and the elderly. The Director General of WHO Dr Tedros Ghebreyesus has co-authored an article expressing interest in the possible use of BCG for protection against COVID-19.

Dr Prentice said: “Since the findings show that BCG seems to offer wider protection against a range of infections, our study also raises hopes it might be useful in protecting the general population against COVID-19 and future pandemics – though we will need to see the results of other, more specific studies to know for sure.”

The researchers also believe it is worth investigating whether reintroduction of BCG in countries where it is no longer in routine use, such as the UK, is beneficial, not for its effects against TB, but to protect vulnerable infants in neonatal units against other infections.

The authors acknowledge limitations of their study. As it was relatively small, it was not possible to show an effect of BCG on numbers of deaths from infections in the study participants. Also, because the study was only conducted in Uganda, it cannot be certain that these extra, beneficial effects of BCG would be seen in other settings. However, previous studies conducted in West Africa have shown a reduction in neonatal deaths following BCG at birth, to a similar extent as the reduction in infection rates seen in this study.

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Heart disease risk may start in the womb, study finds

Young adults whose mothers had high blood pressure during pregnancy — either pregnancy-associated hypertension, pre-eclampsia or eclampsia — had more signs of early arterial injury, higher blood pressure, higher body mass index and higher blood sugar than peers.

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A child’s future heart health may be partially shaped before they are born, reports a new Northwestern Medicine study that found pregnancy complications are linked to poorer cardiovascular health in offspring more than 20 years later.

The study found that young adults whose mothers had high blood pressure during pregnancy — either pregnancy-associated hypertension, pre-eclampsia or eclampsia — had more signs of early arterial injury, higher blood pressure, higher body mass index and higher blood sugar than peers.

The authors said the study adds to growing evidence that cardiovascular risk may be transmitted across generations through a combination of biological, environmental and behavioral factors.

“That means we must make sure people maintain good health from childhood into young adulthood, so that if or when someone becomes a parent, they pass on the best opportunity for good health to their children,” said study senior author Dr. Nilay Shah, assistant professor of medicine in the division of cardiology at Northwestern University Feinberg School of Medicine.

How the study was conducted

Shah and colleagues evaluated nearly 1,350 mother-child pairs from the Future of Families and Child Well-Being Study, which enrolled mothers and children at birth between 1998 and 2000 across 20 U.S. cities. The children were then followed into adulthood.

Using delivery hospitalization records, the Northwestern scientists first identified whether mothers experienced pregnancy complications, including high blood pressure during pregnancy, gestational diabetes (high blood sugar during pregnancy) or preterm birth (before 37 weeks of pregnancy).

The three pregnancy complications are on the rise, and affect almost one in four pregnancies in the U.S.

The research team then analyzed cardiovascular health of offspring at age 22, using blood pressure measurements, blood testing, body mass index assessments and carotid artery ultrasounds to look for signs of artery injury.

Finally, the scientists compared participants with and without exposure to each pregnancy complication and adjusted for factors like income, education, difference in birth weight and smoking during pregnancy.

Key findings

At around age 22, participants whose mothers had high blood pressure during pregnancy had:

  • Higher body mass index (+2.8 BMI points)
  • Higher diastolic blood pressure (+2.3 mm Hg)
  • Higher blood sugar levels (+0.2% HbA1c)
  • Thicker artery walls (~0.02 mm)

While the difference in artery wall thickness may seem small, the study authors said it corresponds to roughly three to five years of additional vascular aging. That means arteries looked older and less healthy than expected, which raises the risk of future heart disease.

Other pregnancy complications also showed some long-term effect:

  • Exposure to gestational diabetes was linked to worse blood pressure and some evidence of artery thickening
  • Being born preterm was associated with higher blood sugar levels

‘Most heart disease is preventable’

With pregnancy complications on the rise in the U.S., Shah said the study provides compelling evidence that improving health before and during pregnancy could help reduce heart disease risk in the next generation.

“There is evidence that both parents’ health at the time of conception and during pregnancy influences a child’s health,” he said. “So, promoting health from an early age, like exercising regularly, eating healthfully, never smoking and getting enough sleep, is not just meant for an individual, but doing so may help future generations be healthier, too.”

Shah also emphasizes that risk is not destiny.

“The good news is that most heart disease is preventable,” he said. “If you experienced high blood pressure or high blood sugar during pregnancy, or your child was born early, it does not absolutely mean that your child will have worse health as adults. But I would encourage you to pay attention now to your child’s health behaviors.

“What children learn in childhood sets the stage for their health across their lives. If you are wondering whether your children’s behaviors are healthy, or are considering making a change, please speak with your child’s pediatrician for advice and guidance.”

Other Northwestern co-authors include Emily Lam, Abigail Gauen, Dr. Sadiya Khan, Alexa Freedman and Norrina Allen.

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Viagra could hold key to halting Peyronie’s disease

Combining two widely prescribed drug classes could provide the first effective treatment for early-stage Peyronie’s disease.

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Combining two widely prescribed drug classes could provide the first effective treatment for early-stage Peyronie’s disease, according to a study published in The Journal of Sexual Medicine.

Peyronie’s disease (PD) is caused by the development of fibrotic scar tissue within the penis, leading to pain, curvature, sexual dysfunction and, in many cases, significant psychological distress. It affects an estimated 10 per cent of men during their lifetime, but despite its prevalence, treatment options are limited, particularly in the early phase of the condition.

The study, carried out by Anglia Ruskin University (ARU) and University College London Hospital (UCLH), found that combining phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil (Viagra) and tadalafil (Cialis) with selective oestrogen receptor modulators (SERMs), including tamoxifen, may slow or even stop disease progression when given early.

The clinical study, carried out by Professor David Ralph of UCLH, evaluated outcomes in 133 men diagnosed with acute Peyronie’s disease who were treated with the drug combination for three months. Their results were compared with a smaller group of patients receiving standard care, which included giving vitamin E or no treatment at all. Standard care did not include surgery.

The study found 43 per cent of patients on the combination experienced an improvement in penile curvature, almost three times higher than in the standard‑care group (15 per cent).

At the start of treatment, 65 per cent of patients in the combination group reported pain during erections. After three months, that figure had fallen to just 1.5 per cent. By comparison, pain prevalence in the standard‑care group fell from 50 per cent to 27 per cent.

The clinical findings build on earlier laboratory work led by Professor Selim Cellek at ARU’s Fibrosis Research Group. Over the course of several years, Professor Cellek’s team screened 1,953 FDA‑approved drugs to identify compounds capable of blocking the transformation of fibroblasts into myofibroblasts, the key cells responsible for fibrosis. PDE5 inhibitors and SERMs emerged as particularly effective, and when used together demonstrated an effect greater than either drug alone.

Currently, there are no approved oral therapies proven to prevent early disease progression, forcing patients in the acute phase to wait until the condition stabilises before they can be offered treatments including injections or surgery.

Professor Cellek said: “Positive findings from this pilot clinical study validate our drug‑screening approach in the lab. It shows how repurposing well‑known medicines can accelerate progress in areas of unmet clinical need.

“Because both PDE5 inhibitors and SERMs are already widely used in clinical practice and have established safety profiles, the approach could be readily adoptable if confirmed in larger studies.

“These results suggest that early intervention targeting fibrosis could change how we treat Peyronie’s disease. Repurposing existing drugs may allow us to move from managing symptoms to modifying the disease itself.”

Professor David Ralph, Professor of Urology at UCLH, said: “This paper confirms the basic science research with regards to halting the progression of Peyronie’s disease. In previous papers we have noted that tamoxifen and PDE5 inhibitors inhibit the transformation of fibroblasts into myofibroblasts and therefore contraction of the plaque.

“This has now been put into clinical practice where this paper shows that when tamoxifen and a PDE5 inhibitor are combined, there is statistically less progression of the disease and improvement in curvature compared to the control arm. This is where from bench to clinical practice prevails and hopefully now a prospective clinical trial can be initiated.”

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Healthier brains may be more resilient to early Alzheimer’s disease

Maintaining good overall brain health may help reduce the impact of Alzheimer’s‑related changes on cognitive function.

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A healthy brain may help protect thinking and memory skills from the early effects of Alzheimer’s disease, a new study has found.

Dementia is currently the leading cause of death in Australia and Alzheimer’s disease is its most common form — accounting for more than 70% of cases.

Alzheimer’s is a progressive brain disease in which cognitive abilities gradually decline, leading to impaired memory and thinking skills.

However, some people maintain high levels of cognitive function even though their brains show early signs of the disease. Specifically, some older adults have Alzheimer’s‑related brain pathology, but no noticeable cognitive problems.

The study, Cognitive and Brain Reserve as Modifiers of Early Alzheimer Disease–Related Cognitive Vulnerability, was a collaboration between Murdoch University and AdventHealth, and investigated why some people remain cognitively healthy despite early Alzheimer’s‑related brain changes.

“Our study looked at why some brains were more resilient than others, and whether factors such as peoples’ education, socioeconomic status and health of their brain made a difference,” said lead author Dr Kelsey Sewell, from Murdoch University’s School of Allied Health.

“Understanding these protective factors could help us develop earlier and more targeted strategies to minimise the effects of the disease on memory and thinking skills,” she said.

The research team analysed data from more than 600 older adults in the United States aged 65 to 80, who were living independently and had no signs of dementia or memory impairment.

They used blood tests and MRI scans to assess early Alzheimer’s‑related changes and overall brain health, examined life and social factors such as years of education, income, savings and financial security, and conducted cognitive tests measuring memory, attention, processing speed, working memory and executive function.

“Our main finding was that maintaining good overall brain health may help reduce the impact of Alzheimer’s‑related changes on cognitive function,” Dr Sewell said.

“We also observed early evidence that people with a higher socioeconomic status may be less affected by Alzheimer’s-related changes when it comes to memory, although more research is needed to confirm this relationship.”

Dr Sewell said the main takeaway for the public was to do everything you can to maintain a healthy brain.

“Things like exercise, maintaining a healthy diet, sleeping well, and finding new cognitive challenges can help to maintain a healthy brain. It is never too late, or too early to start,” she said .

“These results underscore the need for coordinated action across research, policy, and industry to design environments that support healthier choices and promote brain health at a population level.”

The data collection for this study was led by researchers at AdventHealth in Orlando, Florida.

The paper, Cognitive and Brain Reserve as Modifiers of Early Alzheimer Disease–Related Cognitive Vulnerability, was published in the journal Neurology.

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