Day: November 16, 2022

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Delivery Method Affects Babies’ Vaccine Responses

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Photo by Christian Bowen on Unsplash

The method by which a baby was delivered is associated with how its immune system will respond to pneumococcal and meningococcal vaccinations, according to a study in Nature Communications. After vaccination, babies born naturally had higher antibody levels than those born via Caesarian section.

Experts say the findings could help to inform conversations about C-sections between expectant mothers and their doctors, and shape the design of more tailored vaccination programmes.

Researchers studied the relationship between gut microbes and antibody levels after vaccination in a cohort of 120 babies, who were vaccinated at 8 and 12 weeks against lung infections and meningitis.

The researchers tracked the development of the gut microbiome in the child’s first year of life and their immune response to the vaccines by testing saliva samples at 12 and 18 months.

Research was carried out by a team from the University of Edinburgh, Spaarne Hospital and University Medical Centre in Utrecht and the National Institute for Public Health and the Environment in The Netherlands.

In the 101 babies tested for antibodies as a result of the vaccine that protects against lung infections, the investigators found double the antibody levels in babies delivered naturally compared with those delivered by C-section.

Breastfeeding was linked with 3.5 times higher antibody levels compared with formula-fed children who had been delivered naturally.

Levels of antibodies as a result of the vaccine that protects against meningitis were tested in 66 babies. Experts found the levels of antibodies were 1.7 times higher for naturally delivered babies, regardless of breastfeeding, compared with those delivered via C-section.

The gut microbiome is seeded at birth, developing rapidly over the first few months of life, and is influenced mostly by delivery mode, breastfeeding, and antibiotic use.

The team found a clear relationship between microbes in the gut of those babies and levels of antibodies.

For example, among a host of bacteria in the gut, high levels of two in particular — Bifidobacterium and E. Coli — were associated with a high antibody response to the vaccine that protects against lung infections.

High levels of E. Coli were also linked with a high antibody response to the vaccine that protects against meningitis.

The baby acquires the Bifidobacterium and E.coli bacteria through natural birth and human milk is needed to provide the sugars for these bacteria to thrive on.

The team concludes that the babies’ microbiome in early life contributes the immune system’s response to the vaccines and sets the level of protection against certain infections in childhood.

Vaccination schedules could also be adjusted based on mode of delivery or an analysis of the baby’s microbiome in the future, experts say.

Dr Emma de Koff, first author and microbiology trainee at the Amsterdam University Medical Center, said: “We expected to find a link between the gut microbiome and the babies’ vaccine responses, however we never thought to find the strongest effects in the first weeks of life.”

Professor Debby Bogaert study lead and Chair of Paediatric Medicine at the University of Edinburgh said “I think it is especially interesting that we identified several beneficial microbes to be the link between mode of delivery and vaccine responses. In the future, we may be able to supplement those bacteria to children born by C-section shortly after birth through, for example, mother-to-baby ‘faecal transplants’ or the use of specifically designed probiotics.”

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European Medicines Agency Moves to Minimise JAK Inhibitor Risks

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Photo by Myriam Zilles on Unsplash

The European Medicines Agency’s safety committee (PRAC) has recommended measures to minimise the risk of serious side effects associated with Janus kinase (JAK) inhibitors used to treat several chronic inflammatory disorders. These side effects include cardiovascular conditions, blood clots, cancer and serious infections.

The Committee recommended that these medicines should be used in the following patients only if no suitable treatment alternatives are available: those aged 65 years or above, those at increased risk of major cardiovascular problems (such as heart attack or stroke), those who smoke or have done so for a long time in the past and those at increased risk of cancer.

The Committee also recommended using JAK inhibitors with caution in patients with risk factors for blood clots in the lungs and in deep veins (venous thromboembolism, VTE) other than those listed above. Further, the doses should be reduced in some patient groups who may be at risk of VTE, cancer or major cardiovascular problems.

The recommendations follow a review of available data, including the final results from a clinical trial of the JAK inhibitor tofacitinib and preliminary findings from an observational study involving baricitinib, another JAK inhibitor. During the review, the PRAC sought advice from an expert group of rheumatologists, dermatologists, gastroenterologists and patient representatives.

The review confirmed tofacitinib increases the risk of major cardiovascular problems, cancer, VTE, serious infections and death due to any cause when compared with TNF-alpha inhibitors. The PRAC has now concluded that these safety findings apply to all approved uses of JAK inhibitors in chronic inflammatory disorders (rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis, axial spondyloarthritis, ulcerative colitis, atopic dermatitis and alopecia areata).

The product information for JAK inhibitors used to treat chronic inflammatory disorders will be updated with the new recommendations and warnings. In addition, the educational material for patients and healthcare professionals will be revised accordingly. Patients who have questions about their treatment or their risk of serious side effects should contact their doctor.

More about the medicines

The Janus kinase inhibitors subject to this review are abrocitinib, filgotinib, baricitinib, upadacitinib and tofacitinib. These medicines are used to treat several chronic inflammatory disorders (rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis, axial spondyloarthritis, ulcerative colitis, atopic dermatitis and alopecia areata). The active substances in these medicines work by blocking the action of enzymes known as Janus kinases. These enzymes play an important role in the process of inflammation that occurs in these disorders. By blocking the enzymes’ action, the medicines help reduce the inflammation and other symptoms of these disorders.

Some JAK inhibitors are used to treat myeloproliferative disorders; the review did not include these medicines. The review also did not cover the use of baricitinib in the short-term treatment of COVID, which is under assessment by EMA.

Source: European Medicines Agency

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Hormonal Contraceptives’ Impacts on the Adolescent Brain

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Photo by Reproductive Health Supplies Coalition on Unsplash

Hormonal contraceptives are safe and highly effective at preventing pregnancy, but their impact on the developing bodies of teenage girls, especially their brains, is not well understood.

New research in young rats links the synthetic hormones found in birth control pills, patches and injections with disordered signal transmission between cells in the prefrontal cortex, which is still developing during adolescence. Compared to control rats, the animals receiving hormonal contraceptives also produced higher levels of the stress hormone corticosterone, which is similar to cortisol in humans.

The Ohio State University scientists began investigating the prefrontal cortex, where mood is regulated, because some previous research has associated early adolescent use of hormonal contraceptives with adulthood depression risk. But the most important thing, the researchers said, is learning how birth control affects the developing brain so individuals can weigh the risks and benefits of their reproductive health choices.

“Birth control has had a major positive impact for women’s health and autonomy – so it’s not that we’re suggesting adolescents should not take hormonal contraceptives,” said senior study author Benedetta Leuner, associate professor of psychology at Ohio State.

“What we need is to be informed about what synthetic hormones are doing in the brain so we can make informed decisions – and if there are any risks, then that’s something that needs to be monitored. Then if you decide to use hormonal birth control, you would pay more attention to warning signs if you knew of any possible mood-related side effects.”

The research poster was presented to at Neuroscience 2022, the annual meeting of the Society for Neuroscience.

An estimated 2 in 5 teenage girls in the US have sexual intercourse between age 15 and 19, and the vast majority use a contraceptive, mostly condoms. Of those using birth control, almost 5% use hormonal contraceptives, also known as long-acting reversible contraceptives. These products are also prescribed to treat acne and heavy periods.

Despite their popularity, “there isn’t a lot known about how hormonal birth control influences the teen brain and behaviour,” said co-author Kathryn Lenz, associate professor of psychology at Ohio State. “Adolescence is a crucially under-investigated period of dramatic brain change and dramatic hormonal change that we really haven’t understood.”

The researchers gave a combination of synthetic estrogen and progesterone typically found in hormonal contraceptives to female rats for three weeks beginning about a month after they were born, an age equivalent to early adolescence in humans. Researchers confirmed the drugs disrupted the animals’ reproductive cycling — these birth control products work by stopping ovaries from producing hormones at levels necessary to generate eggs and making the uterine lining inhospitable for an egg to implant.

Blood samples showed the treated rats were producing more corticosterone than untreated animals, a sign that they were stressed. And after being subjected to and recovering from an experimental stressor, the treated rats’ corticosterone level remained high. Their adrenal glands were also larger, suggesting their stress hormone production was consistently higher than that of control animals.

An analysis of gene activation markers in the animals’ prefrontal cortex showed a decrease in excitatory synapses in that region of treated rats’ brains compared to controls, but no change to inhibitory synapses — a phenomenon that could set up an imbalance of normal signaling patterns and result in altered behavior. The loss of only excitatory synapses in the prefrontal cortex has been linked to exposure to chronic stress and depression in previous research.

“What this means for the function of particular circuits, we don’t know yet. But this gives us a clue of where to look next in terms of what the functional outcomes might be,” Lenz said.

The researchers are moving forward with additional studies targeting hormonal contraceptive effects on the brain between puberty and late adolescence – a tricky time to study the developing brain because it is undergoing constant change, Leuner said. The reasons behind the drugs’ effects are an open question, as well.

“These are synthetic hormones, so are they affecting the brain because of their synthetic properties, or are they affecting the brain because they’re blocking the naturally produced hormones?” she said. “It’s a difficult question to answer, but an important one.”

Source: Ohio State University

Categories : Regenerative MedicineTags : Leave a comment

Scientists Discover that Leprosy has an Organ Regeneration Secret

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Photo by Aldo Hernandez on Unsplash

Researchers say that leprosy may hold to the key to safe and effective organ regeneration, after discovering that leprosy can double the size of livers in armadillos by stimulating normal, healthy growth.

Their findings, published in the journal Cell Reports, reveal a previously unknown interaction of the leprosy bacterium with its host, in this study, an armadillo – the only one known one besides humans that the disease may manifest in.

The researchers found that leprosy appears to rewind the developmental clock of liver cells, effectively reprogramming them to be in an ‘adolescent’ state.

Regenerative medicine aims for ‘grown to order’ organs to replace those damaged by disease or age, but organ development is an extremely complex process which takes place in vivo and so far only limited progress has been made using in vitro models. The liver, a highly resilient organ, stops regenerating once it reaches its original size, making it difficult to study regeneration pathways.

Leprosy, also referred to as Hansen disease, is a chronic granulomatous infection generally caused by Mycobacterium leprae and Mycobacterium lepromatosis, both of which primarily affect the skin and peripheral nerves. It also has the ability to convert body tissues from one type to another.

Researchers infected four cloned armadillos with the bacteria, and observed the growth of their livers. The bacteria enlarged the liver, basically give themselves more room – and this was accomplished in a way that left the livers perfectly functional and healthy.

The researchers suggest that, as with other body tissues, the bacteria-induced partial reprogramming also works in adult liver in vivo, turning hepatocytes into liver progenitor-like cells leading to proliferation and subsequent re-differentiation in the microenvironment created by the bacteria.

Prof Anura Rambukkana, from the University of Edinburgh’s centre for regenerative medicine described the discover as “completely unexpected”.

“It is kind of mind-blowing,” Prof Rambukkana told the BBC. “How do they do that? There is no cell therapy that can do that.”

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HIV Uses Immune Response as a Way to Hide

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HIV Infecting a T9 Cell. Credit: NIH

An immune response that likely evolved to help fight infections appears to be the mechanism that drives human immunodeficiency virus (HIV) into a latent state, lurking in cells only to erupt anew, according to research published in the journal Nature Microbiology. The findings help explain why HIV particularly stealthy, but could also apply to other viral infections.

“HIV has proven to be incurable because of a small number of latently HIV-infected T-cells that are untouched by both antiviral drugs and the immune response,” said senior author Bryan R. Cullen, PhD, professor at Duke University School of Medicine.

“These cells, which are very long lived, can spontaneously emerge from latency and start producing HIV even years after infection, thus necessitating the life-long use of antiretrovirals,” Cullen said. “The origin of these latently infected cells has remained unknown despite considerable effort.”

The findings offer important insights, pointing to a protein complex called SMC5/6, which is involved in a host cell’s chromosome function and repair.

HIV enters the body, infects the immune system’s CD4+ T-cells, then makes a genome-length DNA molecule that it integrates into a host cell chromosome where it is then copied to generate viral RNAs and proteins.

If this so-called DNA provirus is prevented from integrating into the host cell DNA, for example by a drug that blocks this process, then it fails to make any viral RNAs and proteins and becomes inert. In contrast, DNA proviruses that are able to integrate are normally able to drive a productive HIV infection.

Cullen and his team found that, in a small number of infected cells, the SMC5/6 protein complex initiates a process that silences the DNA provirus before it integrates into a host cell chromosome. These proviruses remain inert even after integration and result in latent infections, lying low until prompted to erupt into an active infection.

“Our research suggests that latency results not from any intrinsic properties of the infecting HIV but rather from an unfortunate side effect of a cellular innate immune response that probably evolved to silence invasive foreign DNA,” Cullen said.

The researchers found that a molecule that shuts down SMC5/6’s silencing action showed promising results as a potential therapeutic strategy as it inhibited the establishment of latent HIV infections. Reactivated proviruses are vulnerable to natural immune system responses and anti-retroviral drugs.

“Although antiretroviral therapies can reduce the viral load in AIDS patients to below the level of detection, these drugs fail to eradicate HIV-1,” Cullen said. “While there has been considerable effort expended on trying to develop therapies that can activate latent HIV-1 and help antiretroviral therapies clear the body of infectious virus, this effort has so far failed to identify drugs that are both effective and non-toxic. Our study represents a potentially important step toward achieving this goal.”

“Clearly, understanding the mechanism that results in HIV-1 latency may provide insights into how latent HIV-1 proviruses can be reactivated and then destroyed,” Cullen said.

Source: Duke University Medical Center

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Bariatric Surgery Slashes Risk of Cardiovascular Events

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Obesity
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A study of obese adults with nonalcoholic fatty liver disease (NAFLD) and morbid obesity has shown that those who underwent bariatric surgery suffered far fewer extreme cardiovascular events subsequently.

Reporting their results in JAMA Network Open, the researchers, reported that these obese patients (BMI > 40) undergoing bariatric surgery had a 49% lower risk of developing adverse cardiovascular events.

“The findings provide evidence in support of bariatric surgery as an effective therapeutic tool to lower elevated risk of cardiovascular disease for select individuals with obesity and NAFLD,” said Vinod K. Rustgi, profesor at Rutgers Robert Wood Johnson Medical School. “These finding are tremendously impactful for many reasons.”

NAFLD, and a more advanced form known as NASH, are rapidly increasing causes of liver disease which occur because of excessive fat storage in the liver. As such it is common in obesity and type 2 diabetes.

In the study, researchers analysed outcomes data, using a medical insurance database, from 2007 to 2017. Of 230 million covered individuals, 86 964 adults between the ages of 18 and 64 who had obesity and NAFLD were identified. Of those, 68% were female, 35% underwent bariatric surgery and 65% received nonsurgical care.

Bariatric surgery patients experienced a 49% decrease in the risk of developing major cardiovascular events such as heart attacks, heart failure or ischemic strokes. They were also far less likely to experience angina, atherosclerotic events or arterial blood clots.

The association between bariatric surgery and risk reduction of developing cardiovascular disease has not been studied to this level of detail before, the researchers said.

There is growing evidence that bariatric surgery, because of the weight reduction it brings about in patients, offers definitive health benefits. A study conducted by Rustgi and colleagues, published in the journal Gastroenterology in March 2021, showed that bariatric surgery can also significantly reduce the risk of cancer, especially obesity-related, in obese individuals with NAFLD. Importantly, these cancers included colorectal, pancreatic, endometrial, thyroid cancer, multiple myeloma and hepatocellular carcinoma.

“Although bariatric surgery is a more aggressive approach than lifestyle modifications, it may be associated with other benefits, such as improved quality of life and decreased long-term health care burden,” Rustgi said.

Source: Rutgers University