Tag: 16/9/21

Categories : Neurodegenerative Diseases New Compounds and TreatmentsTags :

New Drug Targets for Memory Loss

On By ModernMedia
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Researchers have identified specific drug targets within memory-encoding neural circuits, opening up possibilities for new treatments of a range of brain disorders.

Memory loss is a main feature of a number of neurological and psychiatric disorders including Alzheimer’s disease and schizophrenia. Presently, there are few, very limited memory loss treatments and the search for safe and effective drug therapies has, until now, borne little fruit.

The research was done in collaboration with colleagues at the international biopharmaceutical company Sosei Heptares. The findings, published in Nature Communications, identify specific receptors for the neurotransmitter acetylcholine that re-route information flowing through memory circuits in the hippocampus. Acetylcholine is released in the brain during learning and is critical for the acquisition of new memories. Until now, the only effective treatment for the symptoms of cognitive or memory impairment seen in diseases such as Alzheimer’s is using drugs that broadly boost acetylcholine. However, this leads to multiple adverse side effects. The discovery of specific receptor targets that have the potential to provide the positive effects whilst avoiding the negative ones is promising.

Lead author Professor Jack Mellor from the University of Bristol’s Center for Synaptic Plasticity, said: “These findings are about the fundamental processes that occur in the brain during the encoding of memory and how they may be regulated by brain state or drugs targeting specific receptor proteins. In the long-term, the discovery of these specific targets opens up avenues and opportunities for the development of new treatments for the symptoms of Alzheimer’s disease and other conditions with prominent cognitive impairments. The academic-industry partnership is important for these discoveries and we hope to continue working together on these projects.”

Dr Miles Congreve, Chief Scientific Officer at Sosei Heptares, added: “These important studies have helped us to design and select new, exquisitely targeted therapeutic agents that mimic the effects of acetylcholine at specific muscarinic receptors, without triggering the unwanted side effects of earlier and less-well targeted treatments. This approach has the exciting potential to improve memory and cognitive function in patients with Alzheimer’s and other neurological diseases.”

“It is fascinating how the brain prioritises different bits of information, working out what is important to encode in memory and what can be discarded. We know there must be mechanisms to pull out the things that are important to us but we know very little about how these processes work. Our future program of work aims to reveal how the brain does this using acetylcholine in tandem with other neurotransmitters such as dopamine, serotonin and noradrenaline,” said Professor Mellor.

Source: University of Bristol

Categories : COVID Obstetrics & GynaecologyTags :

Menstrual Changes After COVID Vaccinations

On By ModernMedia
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In an article in the BMJ, authors argue that menstrual changes after COVID vaccination are plausible and should be investigated. 

Listed common side effects of COVID vaccination include a sore arm, fever, fatigue, and myalgia. However, changes to periods and unexpected vaginal bleeding are not listed, and primary care clinicians and those in the reproductive health field are seeing more and more people who have experienced these events shortly after vaccination.

More than 30 000 reports of these events had been made to the UK;s surveillance scheme for adverse drug reactions by 2 September 2021, across all COVID vaccines currently offered.

Most post-vaccination changes to periods return to normal, and there is no evidence that COVID vaccination adversely affects fertility. In clinical trials, there were similar rates for unintended pregnancies in vaccinated and unvaccinated groups. In fertility clinics, fertility measures and pregnancy rates are similar in vaccinated and unvaccinated patients. The UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) says that there are few reported that 

Menstrual changes have been reported after both mRNA and adenovirus vectored COVID vaccines, suggesting that, if there is a connection, it is likely to be a result of the immune response to vaccination rather than a specific vaccine component. Human papillomavirus (HPV) vaccinations have also been associated with menstrual changes. Indeed, the menstrual cycle can be affected by immune activation from various stimuli, including viral infection: one study found about a quarter of menstruating women with COVID experienced menstrual disruption.

Biologically plausible mechanisms linking immune stimulation with menstrual changes include immunological influences on the hormones driving the menstrual cycle or effects mediated by immune cells in the lining of the uterus, which are involved in the cyclical build-up and breakdown of this tissue. Research may also help understand the mechanism.

Though the period changes are short lived, there is need for adequate research. Vaccine hesitancy among young women is largely driven by false claims that COVID vaccines could harm their chances of future pregnancy. Failing to thoroughly investigate reports of menstrual changes after vaccination is likely to fuel these fears. If a link between vaccination and menstrual changes is confirmed, this information will allow people to plan for potentially altered cycles. Clear and trusted information is particularly important for those who rely on being able to predict their menstrual cycles to either achieve or avoid pregnancy.

In terms of management, the Royal College of Obstetricians and Gynaecologists and the MHRA recommend that anyone reporting a change in periods persisting over several cycles, or new vaginal bleeding after the menopause, should be managed according to the usual clinical guidelines for these conditions.

The authors conclude by stating there is an important lesson in that the effects of medical interventions on menstruation should not be an afterthought in future research. In clinical trials, participants are unlikely to report changes to periods unless specifically asked, so in future trials, information about menstrual cycles and other vaginal bleeding should be actively solicited.

Source: The BMJ

Categories : VaccinesTags :

Attenuated Virus Confers Broader Flu Protection

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A mouse study using both attenuated and inactivated forms of influenza has helped explain why people vaccinated with the inactivated virus still occasionally end up contracting the illness. The finding should help researchers develop vaccines that offer broad protection against viruses.

Influenza is a major global health burden, with the World Health Organization estimating that it causes one billion cases annually. Each year, vaccines are developed that offer some protection against infection. But the influenza virus is a moving target that is constantly mutating, and so vaccines can lose their effectiveness as a season progresses.

Influenza vaccines commonly come in two forms: inactivated vaccines (including component vaccines) and live attenuated vaccines. Live vaccines confer broader protection against variants than inactivated vaccines, but side effects such as fevers and headaches are more common. A result they have yet to be approved in some countries. Live vaccines induce the production of broadly reactive antibodies, but until now, scientists didn’t know why.

In a recent study, Masato Kubo of the RIKEN Center for Integrative Medical Sciences and his co-workers have discovered two processes that live vaccines induce in mice that together account for their broader protection.

They found that, like the virus itself, the live vaccine virus causes the virus to replicate deep in the lungs, which in turn induces a structural change in the virus haemagglutinin, a mushroom-shaped protein on the surface of the virus involved in infecting cells. This structural change exposes previously hidden regions of antigens that the immune system can recognise.

Next, germinal cells are activated by interleukin 4 (IL-4), a cytokine heavily involved in regulating antibody production. IL-4 is derived from special T cells known as follicular helper T cells. This activation causes a minor population of B cells to proliferate and it is these B cells that are responsible for generating broadly protective antibodies.

The role of IL-4 in inducing the broad immune response came as a surprise. “Until now there had been no direct evidence to show the importance of IL-4,” says Kubo. “That was one of the surprises of this study for me.”

“We believe both processes are needed for generating broadly active antibodies: viral duplication in the lungs and expansion of the minor population of B cells,” says Kubo. “These two processes mostly likely occur when a person is infected by the influenza virus itself.”

The team now plans to see if there are similar mechanisms for other viruses such as SARS-CoV-2.

Source: RIKEN

Categories : UncategorizedTags :

Nelson Mandela Bay Area Hit by Rabies Outbreak

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An outbreak of rabies has hit the Nelson Mandela Bay metro, with a nine-year-old Gqeberha boy being its first victim so far.

The Nelson Mandela Bay Metropolitan Municipality (NMBMM) issued a warning calling on residents to be vigilant and to take their domestic pets for rabies vaccinations, following the death of a boy last weekend who was bitten by a dog. Health-e News received confirmation from NMBMM that the nine-year-old boy died at the Dora Nginza Hospital on Friday last week.

“We have learnt with sadness of the passing of the boy from Motherwell, who died due to rabies. We have the family in our prayers,” said Acting Mayor Luxolo Namette.

The municipality’s health services directorate deputy director Dr Patrick Nodwele said vaccinating domestic pets can be the most effective way of preventing rabies transmission to humans.

“The boy passed at Dora Nginza Hospital where it was established that he had been bitten by a dog. Our health officials, together with the Department of Agrarian Reform, have been busy these last couple months vaccinating dogs and cats in an effort to curb the virus as we know that rabies is a vaccine-preventable disease and post-bite vaccinations save lives,” Dr Nodwele told Health-e News.

Rabies causes viral encephalitis which kills up to 70 000 people a year around the world. Infected animal saliva transmits viral encephalitis to humans. Rabies is one of the oldest known diseases in history with cases dating back to 4000 years ago. For most of human history, a bite from a rabid animal was uniformly fatal. In the past, people were so scared of rabies that after being bitten by a potentially rabid animal, many would commit suicide. 

Rabies cases rose significantly over August and September, he added, which is why they are calling on residents to take their domestic pets for vaccinations. The outbreak is spread throughout the entire Nelson Mandela metro region and Nodwele said that 61 rabies specimens submitted for testing all came back positive.

So far 5254 dogs and 438 cats have been vaccinated across the metro. The municipality from time to time issues a domestic pets vaccination schedule, and is calling on residents to observe the schedule so that they bring their animals for vaccination. A vaccination and community education programme is also being run.

Dr Nodwele said the incubation period of rabies is two to three months, though with factors such as bite location and viral load, it can also vary from one week to a year.

“Initial symptoms include a fever and pain, and unusual or unexplained tingling, pricking or burning sensations at the wound site. As the virus spreads through the body to the central nervous system, progressive and fatal inflammation of the brain and spinal cord develops,” Dr Nodwele explained.

Source: Health-e News

Categories : COVID VaccinesTags :

Nasal COVID Vaccines Will Greatly Reduce Transmission

On By ModernMedia
Source: CDC on Unsplash

Though great progress has been made in developing intramuscular COVID vaccines, as yet nothing provides mucosal immunity in the nose, the first barrier against the virus encounters before it travels down to the lungs.

In terms of both immune cell deployment and immunoglobulin production, the mucosal immune system is by far the largest component of the entire immune system, having evolved to provide protection at the main sites of infectious threat: the mucosae.

In iScience, Navin Varadarajan, Professor of Chemical and Biomolecular Engineering, and colleagues, report the development of an intranasal subunit vaccine that provides durable local immunity against inhaled pathogens.

“Mucosal vaccination can stimulate both systemic and mucosal immunity and has the advantage of being a non-invasive procedure suitable for immunization of large populations,” explained Prof Varadarajan. “However, mucosal vaccination has been hampered by the lack of efficient delivery of the antigen and the need for appropriate adjuvants that can stimulate a robust immune response without toxicity.”

To get around this, Prof Varadarajan worked with Xinli Liu, associate professor of pharmaceutics, and an expert in nanoparticle delivery. Prof Liu’s team packaged the agonist of the stimulator of interferon genes (STING) inside liposomal particles to create an adjuvant called NanoSTING. 

“NanoSTING has a small particle size around 100 nanometres, which exhibits significantly different physical and chemical properties to the conventional adjuvant,” said Prof Liu.

“We used NanoSTING as the adjuvant for intranasal vaccination and single-cell RNA-sequencing to confirm the nasal-associated lymphoid tissue as an inductive site upon vaccination. Our results show that the candidate vaccine formulation is safe, produces rapid immune responses—within seven days—and elicits comprehensive immunity against SARS-CoV-2,” said Prof Varadarajan.

Intramuscular vaccines have a fundamental limitation in that they are not designed to elicit mucosal immunity. As shown in previous work with respiratory pathogens like influenza, sterilising immunity to virus reinfection requires adaptive immune responses in the respiratory system.

The nasal vaccine will also help the equitable global distribution of vaccines, according to the researchers. Many smaller countries have only vaccinated a small percentage of their population, and outbreaks continue. These outbreaks and viral spread are known to facilitate viral evolution, ultimately leading to decreased efficacy of all vaccines.

“Equitable distribution requires vaccines that are stable and that can be shipped easily. As we have shown, each of our components, the protein (lyophilised) and the adjuvant (NanoSTING) are stable for over 11 months and can be stored and shipped without the need for freezing,” said Prof Varadarajan.

Source: University of Houston

Categories : COVIDTags :

COVID Hit South Africa Harder Than Expected Despite Preparedness

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New research finds African countries, assessed as being least vulnerable to an epidemic were the worst affected by COVID, particularly South Africa.

A team of researchers from the NIHR Global Health Research Unit Tackling Infections to Benefit Africa (TIBA) worked with the World Health Organization (WHO) African Region to identify factors affecting mortality rates during Africa’s first two COVID waves and the timing of the first reported cases. The study, published in the journal Nature Medicine, found that countries with greater urban populations and strong international travel links were worst affected by the pandemic. Mortality rates and levels of restrictions, such as lockdowns and travel bans, were found to be lowest in countries previously thought to be at greatest risk from COVID.

Professor Mark Woolhouse, TIBA Director, who co-led the study, said, “Our study shows very clearly that multiple factors influence the extent to which African countries are affected by COVID. These findings challenge our understanding of vulnerability to pandemics.

“Our results show that we should not equate high levels of preparedness and resilience with low vulnerability.

“That seemingly well-prepared, resilient countries have fared worst during the pandemic is not only true in Africa; the result is consistent with a global trend that more developed countries have often been particularly hard hit by COVID.”

Among 44 countries of the WHO African Region with available data, South Africa had the highest mortality rate during the first wave between May and August 2020, at 33.3 deaths recorded per 100k population. Cape Verde and Eswatini had the next highest rates at 17.5 and 8.6 deaths per 100k, respectively. At 0.26 deaths recorded per 100,000, the lowest mortality rate was in Uganda.

South Africa also recorded the highest mortality rate during the second wave between December 2020 and February 2021, at 55.4 deaths per 100,000. Eswatini and Botswana recorded rates of 39.8 and 17.7 deaths per 100,000, respectively. The lowest rate was in Mauritius, which recorded no deaths during the second wave.

“The early models which predicted how COVID would lead to a massive number of cases in Africa were largely the work of institutions not from our continent. This collaboration between researchers in Africa and Europe underlines the importance of anchoring analysis on Africa’s epidemics firmly here,” said Dr. Matshidiso Moeti, WHO Regional Director for Africa and co-author. “We can no longer focus our understanding of disease transmission purely on the characteristics of a virus—COVID operates within a social context which has a major impact on its spread.”

Countries with high rates of HIV were also more likely to have higher mortality rates. This may be because people with HIV often have other health conditions that put them at greater risk from COVID, the team suggests.

The weak association between mortality rate and the timing or severity of government-imposed social restrictions shows the varied impact and enforcement across the region, making a consistent impact pattern difficult to discern. Restrictions during peaks of infection are well documented to have interrupted transmission in the region.

The findings show that the earliest recorded cases of COVID were in countries where most people live in urban areas, with strong international travel links and greater testing capacity. Algeria was the first of 47 African countries to report a case, on 25 February 2020. Most countries had recorded cases by late March 2020, with Lesotho the last to report one, on 14 May 2020.

Higher death rates were observed during the second wave, compared with the first. The infection peak during the second wave was also higher, with 675 deaths across the continent on 18 January 2021 compared with 323 during the first wave peak on 5 August 2020. Potential under-reporting was accounted for in the analysis.

Source: University of Edinburgh