Day: December 2, 2022

Categories : GeneticsTags : Leave a comment

Down Syndrome Research Should Expand Focus to the Whole Cell

On By ModernMedia
Human chorosomes. Source: NIH

Researchers propose in The American Journal of Human Genetics a new way of looking at Down syndrome, suggesting that when an extra chromosome is present, the impact on the cell depends less on which chromosome is duplicated and more on the presence of extra DNA.

“Understanding the complexity and general nature of disease phenotypes allows us to see a bigger picture and not get stuck focusing on a single gene, due to its presence on the extra chromosome,” says lead author Maria Krivega, developmental biologist at Heidelberg University.

Every cell starts out with extra chromosomes during early embryogenesis; however, this DNA gets sorted into pairs after about a week of growth. When this process goes awry, it often leads to death of the embryo, with only a few being able to survive with the extra DNA, like in the case of Down syndrome.

By taking a step back and looking at the entire cell, researchers were able to create a new understanding of these syndromes. Krivega and her collaborators took a critical look at recent evidence suggesting that Down syndrome phenotypes arise not only because of increased dosage of genes on chromosome 21 but also because of global effects of chromosome gain.

The researchers sifted through published datasets of proteins and RNA of individuals with Down syndrome and compared these to laboratory made cells with trisomies of chromosomes 3, 5, 12, and 21. What they found from this comparison was that it didn’t matter which chromosome was in excess, the cells all had decreased ability to replicate, survive, and maintain their DNA.

“We were interested to find out why cells with imbalanced chromosomal content – in other words, aneuploid – are capable of surviving,” says Krivega. “It was particularly exciting to me to learn if viable aneuploid embryonic cells have similarities with aneuploid cancer cells or cell lines, derived in the laboratory.”

Additionally, they found that the adaptive T cell immune system was underdeveloped in all cells, while the innate immune system seemed to be overactive. The authors suggest that this is a consequence of general chromosome gain. This research can be expanded into autoimmune diseases, such as Alzheimer disease or acute leukemias in trisomy chr. 8 or 21, that also exist without any connection to aneuploidy.

“We hope that our work elucidating a complex trisomy phenotype should help to improve such kids’ development,” says Krivega.

Source: Cell Press

Categories : COVIDTags : 1 Comment

Study Pushes Back Date of Omicron’s Origin

On By ModernMedia
PCR device for detecting pathogens like SARS-CoV-2 (symbolic image) © Charité | Arne Sattler

Seemingly out of nowhere, the Omicron variant was first detected in South Africa and rapidly spread around the world. Now, a study published in the journal Science shows that Omicron’s predecessors existed on the African continent long before cases were first identified, suggesting that Omicron emerged gradually over several months in different countries across Africa.

Since the beginning of the pandemic, the coronavirus has been constantly changing. The biggest leap seen in the evolution of SARS-CoV-2 to date was observed by researchers a year ago, when a variant was discovered that differed from the genome of the original virus by more than 50 mutations. First detected in a patient in South Africa in mid-November 2021, the variant later named Omicron BA.1 spread to 87 countries around the world within just a few weeks. By the end of December, it had replaced the previously dominant Delta variant worldwide.

Since then, speculations about the origin of this highly transmissible variant have centred around two main theories: Either the coronavirus jumped from a human to an animal where it evolved before infecting a human again as Omicron, or the virus survived in a person with a compromised immune system for a longer period of time and that’s where the mutations occurred. A new analysis of COVID samples collected in Africa before the first detection of Omicron now casts doubt on both these hypotheses.

The analysis was carried out by an international research team led by Prof Jan Felix Drexler, a scientist at the Institute of Virology at Charité and the German Center for Infection Research (DZIF). Other key partners in the European-African network included Stellenbosch University in South Africa and the Laboratory of Viral Hemorrhagic Fever (LFHB) in Benin. The scientists started by developing a special PCR test to specifically detect the Omicron variant BA.1. They then tested more than 13 000 respiratory samples from COVID9 patients that had been taken in 22 African countries between mid-2021 and early 2022. In doing so, the research team found viruses with Omicron-specific mutations in 25 people from six different countries who contracted COVID in August and September 2021 – two months before the variant was first detected in South Africa.

To learn more about Omicron’s origins, the researchers also sequenced the viral genome of some 670 samples. Such sequencing makes it possible to detect new mutations and identify novel viral lineages. The team discovered several viruses that showed varying degrees of similarity to Omicron, but they were not identical.

“Our data show that Omicron had different ancestors that interacted with each other and circulated in Africa, sometimes concurrently, for months,” explains Prof Drexler. “This suggests that the BA.1 Omicron variant evolved gradually, during which time the virus increasingly adapted to existing human immunity.” In addition, the PCR data led the researchers to conclude that although Omicron did not originate solely in South Africa, it first dominated infection rates there before spreading from south to north across the African continent within only a few weeks.

“This means Omicron’s sudden rise cannot be attributed to a jump from the animal kingdom or the emergence in a single immunocompromised person, although these two scenarios may have also played a role in the evolution of the virus,” says Prof Drexler.

“The fact that Omicron caught us by surprise is instead due to the diagnostic blind spot that exists in large parts of Africa, where presumably only a small fraction of SARS-CoV-2 infections are even recorded. Omicron’s gradual evolution was therefore simply overlooked. So it is important that we now significantly strengthen diagnostic surveillance systems on the African continent and in comparable regions of the Global South, while also facilitating global data sharing. Only good data can prevent policymakers from implementing potentially effective containment measures, such as travel restrictions, at the wrong time, which can end up causing more economic and social harm than good.”

Source: Charité – Universitätsmedizin Berlin

Categories : HIVTags : Leave a comment

First HIV Prevention Injection Approved in SA

On By ModernMedia
Image of a syring for vaccination
Photo by Mika Baumeister on Unsplash

By Marcus Low

The South African Health Products Regulatory Authority (SAHPRA) has authorised an injection containing the antiretroviral cabotegravir for use to prevent HIV infection, according to drugmaker ViiV Healthcare.

“We are very pleased that this week, SAHPRA granted regulatory approval of Apretude or cabotegravir long-acting injectable,” ViiV Healthcare spokesperson Catherine Hartley told Spotlight. “It brings a much-needed innovative HIV prevention option to the communities that need it most, including women and adolescent girls where challenges with adherence, limited efficacy, and stigma have hindered the impact of current PrEP options.”

At the time of publication, SAHPRA had not yet confirmed the registration, although Spotlight understands a media statement on the issue is imminent. The regulator received ViiV Healthcare’s initial application for approval in November 2021.

ViiV Healthcare has not disclosed at what price it will offer the shot in South Africa or other African countries. The company has, through a deal with the Geneva-based Medicines Patent Pool, agreed to grant voluntary licenses to at least three generic producers that could potentially supply the injection to South Africa. It is however expected to take three to five years before any of the generics will be ready.

Executive Director of the HIV prevention organisation AVAC confirmed news of the authorisation late Wednesday in a social media post, calling it a critical step in making the injection available to millions that could benefit from the shot.

Thursday’s announcement makes South Africa at least the third African country to approve the shot for use, following similar approvals in Zimbabwe, Uganda, and Botswana. A duo of large clinical trials led in part by South African researchers found that people who were given an injection of the antiretroviral cabotegravir every other month were about 80% less likely to contract HIV than those on the HIV prevention pill.

The bi-monthly shot likely outperformed the pill, the World Health Organization explains in new guidelines, mainly because it was easier for people to get an injection every two months than to take the pills every day.

Previously, Spotlight reported that pilot projects are slated to begin providing access to the HIV prevention shot early next year. Demonstration projects run in partnership with the national health department and research organisations the Wits Reproductive Health and HIV Institute and Ezintsha are expected to offer patients a choice of the HIV prevention shot, pill, or monthly vaginal ring.

The pilot projects, sometimes called “demonstration” projects, will be looking to help answer major questions about an eventual national rollout, including how to create national awareness campaigns about the HIV prevention injection and how to provide it outside of hospitals and clinics and closer to communities.

SAHPRA authorisation marks the first step toward an eventual national rollout, according to national health department HIV prevention technical advisor Hasina Subedar. Subedar spoke to Spotlight in July at the International AIDS Conference. In particular, the finer details of the registration – which are still not public – will guide who can and can’t receive the shot, for instance.

Many will be watching to see whether the injection will be made available to pregnant and breastfeeding people, who remain at high risk for contracting HIV in South Africa. Early data presented at the International AIDS Conference in July suggests that the injection is safe to use during pregnancy, although research is ongoing.

Republished from Spotlight under a Creative Commons 4.0 Licence.

Source: Spotlight

Categories : Neurodegenerative Diseases New Compounds and TreatmentsTags : 1 Comment

Alzheimer’s Drug Breakthrough Hailed as ‘Momentous’

On By ModernMedia
Photo by Matteo Vistocco on Unsplash

An 18-month randomised controlled trial of the new Alzheimer’s drug lecanemab has been hailed as “momentous” after encouraging Phase III trial results. The effects, while moderate, stand in contrast to virtually all other Alzheimer’s drug development efforts which have ended in failure.

According to the trial results published in the New England Journal of Medicine, lecanemab slows the rate of progression of Alzheimer’s by about 25%, though it is only really effective if the disease is caught early. Cognitive assessment scores as well as positron-emission tomography (PET) imaging of amyloid showed benefits.

This may be of great benefit to those who already know that they are already at risk of the disease, such as actor Chris Hemsworth who, at age 39, is taking a break from acting after he discovered that he has a high genetic risk of Alzheimer’s.

At present, the only FDA-approved drug to slow the progression of Alzheimer’s, Aduhelm, is of questionable benefit at best, is exorbitantly expensive and there has been an official probe into alleged irregularities in its approval process.

The 1975 trial participants were 50–90 years old with early Alzheimer’s disease (mild cognitive impairment or mild dementia due to Alzheimer’s disease) with evidence of amyloid on PET or by cerebrospinal fluid testing. Participants were randomised to receive intravenous lecanemab (10mg/kg of body weight every 2 weeks) or placebo.

The primary end point was the change from baseline at 18 months in the score on the Clinical Dementia Rating–Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater impairment). Key secondary end points included change in amyloid burden on PET, and on other cognitive impairment assessment scores.

 The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.21 with lecanemab and 1.66 with placebo. In a substudy involving 698 participants, there were greater reductions in brain amyloid burden with lecanemab than with placebo. Other cognitive assessments favoured lecanemab as well. Lecanemab resulted in infusion-related reactions in 26.4% of the participants and amyloid-related imaging abnormalities with oedema or effusions in 12.6%.

Categories : Cardiovascular DiseaseTags : Leave a comment

Protecting Patients with Automatic External Defibrillators (AEDs)

On By ModernMedia

Automated external defibrillators (AEDs) are an important lifesaving technology and may have a role to play in treating workplace cardiac arrest. Most sudden cardiac deaths occur outside of the hospital, and many patients visiting doctors’ practices are already at risk for cardiovascular events, many going there because they are already feeling unwell as a precursor to a cardiac arrest.

It is estimated that 5% or less of victims of sudden cardiac deaths are successfully resuscitated and discharged alive from the hospital. 

In a study on public access defibrillation (PAD), communities with volunteers trained in CPR and the use of AEDs had twice as many victims survive compared to communities with volunteers trained only in CPR.

There are potential risks that come with the improper use of these devices. It is therefore essential to do thorough research before purchasing a specific product.

Why install an AED in my practice?

The primary purpose of an AED is to assist in the detection of heart arrhythmias. When an arrhythmia is identified with the use of an AED, a shock can be delivered to the heart to help normalise the function and rhythm of the patient’s heart.

In addition to being a tool used in the treatment of heart arrhythmia, another critical purpose that an AED device serves is to help restore a heartbeat in cases where a patient had suffered a sudden cardiac arrest (SCA), where patients may be saved if a shock is delivered inside a three minute window.

A 2021 study of out-of-hospital cardiac arrests in Cape Town found a rate of 23.2 per 100 000 population – likely an underestimate. Less than one in 10 cases had resuscitation attempts, and the average time for arrival of emergency services was 26 minutes. Thus, placing automated external defibrillators (AEDs) in the workplace can mean the difference between life and death.

AED use within the first three minutes after a patient experiences a cardiac arrest has an efficacy rate of about 80%. Performing CPR together with an AED is proven to be a significant improvement of efficacy rate compared to the CPR method alone. Therefore, it is necessary to install AEDs in the workplace, which will likely be granted the highest level of protection and make employees rest assured.

When does an AED shock?

The most common abnormal rhythm that causes cardiac arrest is ventricular fibrillation (VF). Electric shock can prevent ventricular fibrillation and restore the heart to its natural rhythm. An AED is applied to the casualty using two chest pads. The machine delivers electrical shocks to the heart muscle through the chest pad, which double as sensors to detect electrical activity. If the machine senses electrical activity with a heartbeat, it will not give an electric shock. Therefore, AEDs are very safe because they do not produce shock unless required. Products such as the AED7000 also feature locks preventing unintentional defibrillation.

Is it safe to use an AED?

Many associate AEDs with their specialised in-hospital equivalents, which require specialist training for safe use. Use of an AED device is usually considered exceptionally safe: the mechanism underlying the procedure is designed to ensure the patient will not be harmed when the device is use appropriately. Many newer models, such as the AED7000 series or the i-PAD NF1200, come with a smart system, which guides the rescuers through the procedure, ensuring the safety of both the patient and the person conducting the defibrillation.

Is it legal to use an AED on a patient?

There have been some concerns about the use of an AED device on patients of cardiac arrest. The concerns are primarily related to the fear of being sued by the patient when these devices are used. While South Africa lacks a Good Samaritan law to protect bystanders when assisting a patient, there is also no legal obligation for a member of the public to assist. However, doctors are legally required to render assistance in an emergency if they are able to do so.

Generally speaking, an AED is considered a safe device. Nevertheless, there are cases where the use of these devices could be considered inappropriate, for example, when the patient’s heart stops due to problems other than ventricular fibrillation, and thus cannot be saved by defibrillation. In these cases, there may be certain legalities involved when someone does decide to use an AED on such a patient.

The good news is that most AEDs will tell you whether or when it is appropriate to give a shock when you apply the pads on the patient’s chest. However, it’s always best to provide non-medically trained staff with AED knowledge and CPR training.