Day: July 28, 2021

Categories : COVID Immune SystemTags :

T Cells Unnecessary for COVID Recovery

On By ModernMedia
Infected cell covered with SARS-CoV-2 viruses (yellow). Source: NIAID

New research with monkeys reveals that primates do not need T cells for the recovery of from acute COVID infections.

T cell depletion was also found not to induce severe disease, and T cells do not explain the natural resistance of rhesus macaques to severe COVID. Furthermore, it was found that strongly T cell-depleted macaques still develop potent memory responses to a second infection.

The findings, published in mBio, an open-access journal of the American Society for Microbiology, have implications for the development of second-generation vaccines and therapeutics.

Lead study author Kim Hasenkrug, PhD, senior investigator in the Laboratory of Persistent Viral Diseases, National Institutes of Health, explained: “We started this study early in the pandemic, trying to figure out how to make a good model to study the disease in humans using animals. The monkeys turned out to be more resistant to the disease than we expected, so we wanted to try to figure out why that was and try to gain some insights into the disease in humans as well. We now know that the antibody response is the most critical response for protection by vaccination, not the T cell response.”

In the new study, the researchers used classic reagents known to deplete CD4+ and CD8+ T cells in rhesus macaques. CD8+ T cells attack infected cells and kill them, and CD4+ T cells are helper T cells that set off the immune response by recognising pathogens and secreting cytokines, which signal other immune cells to act, including CD8+ T cells and antibody-producing B cells.

One week after depleting the macaques of CD4+ T cells, CD8+ T cells, or both at the same time, the researchers infected the animals with SARS-CoV-2. “We depleted, we infected them and then we continued the depletions during the first week of infection to make sure the animals were well depleted. Then we studied their blood to see how they were responding in terms of their T cells and B cells,” said Hasenkrug. Nasal swabs and bronchoalveolar lavages were performed over six weeks to measure virus in the nose, mouth and lungs, along with rectal swabs to check for virus shedding in the gut. After six weeks, the monkeys were re-challenged with SARS-CoV-2 and virus and blood samples collected, which let the researchers evaluate immune memory responses. “If there is a memory response, you get a much quicker immune response and control of the virus. That is how vaccinations work. Once your body has seen a viral pathogen, the next time it sees it, you can get a much faster and stronger immune response,” said Dr Hasenkrug.

Unexpected response

Even with T cell depletion, the monkeys were still able to mount a good memory response against the virus. “We found we got really good memory responses regardless of whether we depleted T cells or not. Basically, we found very strong virus neutralising antibodies, and they are the most important antibodies in controlling the infection. That was unexpected by most immunologists, virologists and vaccinologists,” said Dr Hasenkrug.

“The other thing that happens during a memory response is that antibodies mature, becoming stronger and more potent at binding the viral pathogen. We saw indications of this through what’s called ‘class switching’,” said Dr Hasenkrug.

‘Class switching’ was also not expected in these monkeys with depleted T cells. “We don’t have a firm explanation as to why that happened, but we think it involves some sort of compensatory response, which you can see in our study. For example, when we depleted CD8+ T cells, we saw stronger CD4+ T cell or B cells responses in some animals. When the animals are missing something, they will try to make up for it by making more of something else.”

Dr Hasenkrug doesn’t know why the T cells turned out to be not very important, but this may be a good thing, since people who fail to mount sufficient T cell responses still have opportunities to recover.

“This implies that the innate immune response is critical for initial control of the virus, rather than the adaptive immune responses we studied,” said Hasenkrug.

Source: American Society for Microbiology

Journal information: Hasenkrug, K.J., et al. (2021) Recovery from Acute SARS-CoV-2 Infection and Development of Anamnestic Immune Responses in T Cell-Depleted Rhesus Macaques. mBio. doi.org/10.1128/mBio.01503-21.

Categories : Cardiovascular DiseaseTags :

Weight Loss Not Prioritised in Heart Patient Care

On By ModernMedia
Image source: Neonbrand on Unsplash

Weight loss is given insufficient priority in the management of heart patients despite the benefits, according to a new study of over 10 000 European patients.

In overweight and obese patients with coronary heart disease, weight loss is strongly recommended to reduce the risk of another heart event by improving blood pressure and lipids levels and reducing diabetes risk. This study investigated the management of patients who were overweight or obese at the time of hospitalisation for a first or recurrent heart event such as heart attack. The researchers examined lifestyle advice received, actions taken, and the relationship between weight changes and health status.

The researchers pooled data from the EUROASPIRE IV (2012 to 2013) and EUROASPIRE V (2016 to 2017) studies, which included 10 507 patients with coronary heart disease. Patients were visited 6 to 24 months after hospitalisation for their heart event (the average gap was 16 months). The visit consisted of an interview, questionnaires and a clinical examination including weight, height and blood tests.

The study found that less than 20% had a healthy body mass index (BMI) at the time of hospitalisation for a heart event. Some 16 months later, 86% of patients who were obese during hospitalisation were still obese while 14% of overweight patients had become obese. Young women were particularly affected, with nearly half of those under 55 years being obese. Yet more than a third of obese patients reported they had not received advice on physical activity or nutrition and nearly one in five said they had not been informed that they were overweight. Half of all patients reported not receiving such advice.

Weight management proved effective, with overweight or obese patients who lost 5% or more of their body weight having significantly lower levels of hypertension, dyslipidaemia, and previously unrecognised diabetes compared to those who gained 5% or more of their body weight. However, quitting smoking was observed to result in a 1.8kg average weight gain compared to an 0.4kg average weight gain in persistent smokers.

Study author Professor Catriona Jennings of the National University of Ireland – Galway said cardiac rehabilitation programmes, which typically emphasise exercise, should give equal priority to dietary management. She said: “Weight loss is best achieved by adopting healthy eating patterns and increasing levels of physical activity and exercise. Whilst actively trying to lose weight at the same time as trying to quit smoking is not advised, adopting a cardio-protective diet and becoming more physically active has the potential to mitigate the effects of smoking cessation on weight gain in patients trying to quit. Their aim is to maintain their weight and to avoid gaining even more weight following their quit.”

“Uptake and access to cardiac rehabilitation programmes is poor with less than half of patients across Europe reporting that they completed a programme,” added Professor Jennings. “Such programmes would provide a good opportunity to support patients in addressing overweight and obesity, especially for female patients who were found to have the biggest problem with overweight and obesity in the study. Uptake and access could be improved with the use of digital technology, especially for women, who possibly are less likely to attend a programme because they have many other competing priorities, such as caring for others. There are good reasons for people to address their weight after a cardiac event – but it’s not easy and they do need help.”

The study was published in European Heart Journal – Quality of Care and Clinical Outcomes, a journal of the European Society of Cardiology (ESC).

Source: European Society of Cardiology (ESC)

Journal information: Harrison, S.L., et al. (2021) Cardiovascular risk factors, cardiovascular disease, and COVID-19: an umbrella review of systematic reviews. European Heart Journal – Quality of Care and Clinical Outcomes. doi.org/10.1093/ehjqcco/qcab029.

Categories : GeneticsTags :

Mice Born From Stem Cell-derived Gametes

On By ModernMedia
Photo by Kanashi on Unsplash
Photo by Kanashi on Unsplash

For the first time, mice have been born from gametes that have been created entirely from stem cells, marking the beginning of a revolutionary new reproductive option.

The experiment is the brainchild of Dr Katsuhiko Hayashi of Kyushu University, who has led the pursuit of making gametes outside of a living body. If adapted for humans, these wild reproductive pursuits are bound to shake up our entire conception of the beginning of life, similar to the way “test-tube” babies did when in vitro fertilisation (IVF) was first introduced.

Dr Hayashi dreams of even bigger possibilities; since stem cells can be rapidly created from skin or other cells, they are an endless source of raw material to make sperm and egg cells. These gametes, if fully functional, can merge into a zygote inside a test tube, be transplanted into a surrogate, and birth a new generation without ever seeing testes or ovaries.

Though still far off for humans, in vitro gametogenesis, or IVG, has great potential. Researchers can use these lab-grown models to better understand how reproductive cells form and mature. For couples struggling to conceive, or people who’ve lost reproductive function due to diseases like cancer, IVG would offer a new route towards pregnancy. Same-sex couples could also potentially conceive children with their own genetic makeup. There are many possibilities, and a wide range of ethical problems.

The basis of the technology uses induced pluripotent stem cells (iPSCs), which can be nudged in any direction, including sperm and egg. Back in 2011, Dr Hayashi showed that by bathing stem cells in a particular chemical soup, his team was able to produce sperm cell precursors, with the capacity to turn into functional sperm.

In 2016, the team achieved the same with eggs in mice, mimicking the entire process of how ovaries make eggs – which were used to produce healthy pups. However, eggs made in a test tube couldn’t develop naturally outside the ovary. Fresh ovarian tissue from mice was needed, creating an obvious challenge for fertility treatments in humans.

In the current study, the team focused on the support cells that normally encapsulate a developing egg. These support cells thrive inside the ovary, secreting hormones and nutrients that help support the metabolic needs of an egg  – a crucial step, which includes forming ovarian follicles for the eggs to mature in.

These ovary-supporting cells can also be made from stem cells if the right chemical keys are used, and so after five years Dr Hayashi figured out those keys. Many of them sport fanciful names like ‘sonic hedgehog‘ (SHH), but most of these proteins belong to the morphogen family, in that they can morph the physical structure and identity of a tissue.

After dousing stem cells with this soup, the cells differentiated into foetal ovary supporting cells, with a gene expression profile closely mimicking that of their natural counterparts.

Next, the researchers added precursor immature egg cells, also made from stem cells. Together, the cells coalesced into tiny ovarian follicles, with support cells forming a bubble wrapping the developing egg. The eggs were then fertilised with sperm, transplanted into surrogate mouse mothers, and after normal pregnancies, resulted in about a dozen healthy pups. Those mice eventually gave birth to babies of their own.

The artificial ovary produces mature eggs less effectively than its natural counterpart, suggesting there’s still much to be learned about this stage of reproduction.

Application of this technology to assisted reproduction in humans is still decades away: human reproductive cells take far longer to mature than those in mice, and likely require different supporting nutrients for the sperm, egg, and surrounding tissue.

The team is now testing their chemical soup in marmosets, to be followed by primates.

Currently no laws or ethical frameworks deal with IVG, since the technology is so new.

Dr Hayashi is taking it step by step, and welcoming public discourse before even considering any clinical use. The first step, he said, is verifying the quality of the stem-cell derived eggs, adding, “That could take a long, long time.”

Source: SingularityHub

Categories : COVID General InterestTags :

COVID Crowdfunding Entrenches Health Inequalities

On By ModernMedia
Photo by Carlos Muza on Unsplash
Photo by Carlos Muza on Unsplash

A study set to be published in the August issue of Social Science & Medicine found that Americans created over 175 000 COVID-related crowdfunding (CCF) campaigns in the first half of 2020, with many receiving no funding at all and campaigns in the most privileged areas receiving the most funding.

During the first year of the COVID crisis, many Americans turned to charitable crowdfunding for help with medical bills, funeral expenses, lost wages, small business support, food assistance, and other needs. CCF increased exponentially after March 2020 on platforms such as GoFundMe. Europe saw CCF focusing largely on support for medical facilities and workers, while the majority of US CCF aimed to support individuals, raising money for food, rent, funerals, and other expenses. In India, which only spends 1.2% of its GDP on healthcare, huge numbers of people are turning to crowdfunding in an attempt to cover costs caused by patchy medical insurance which often does not cover COVID-related illness, nor the significant outpatient costs.

According to GoFundMe CEO Tim Cadogan, the platform saw “unprecedented use,” in the first few months of the COVID pandemic, and crowdfunding “activity has persisted at an alarming rate” since then. Unlike most disasters, which generally have an acute phase of destruction followed by a recovery phase, the economic and health impacts of the pandemic are long-lasting, a trend reflected in the prolonged growth of CCF campaigns. Between March and August of 2020, GoFundMe reported that more than 150 000 CCF campaigns had been started.

Drawing on a large dataset of geo-tagged CCF campaigns started on GoFundMe between January 1 and July 31, 2020, researchers found a number of surprising results in their analysis.
They found that the median campaign raised only $65 out of a $5000 goal, with a median of 2 donations. A striking 43.2% of CCFs received zero donations, with more than 90% not reaching their campaign goal. This is worse than reported in prior research; a 2017 study of medical campaigns found only 3.5% had no donations.
Medical fundraising made up 18.3% of all CCF campaigns, and those indicating severe medical needs, with terms like “ICU”, received an average of 96 donations, and an average donation size of $197, while campaigns mentioning “rent” or “eviction” received an average of 23 donations, with an average size of $84. Campaigns seeking money for businesses or PPE fell between these extremes.

The researchers also noted that CCF campaigns are created most often in the highest-income areas, not those hardest hit by COVID. Previous research on charitable crowdfunding has shown that it exacerbates social inequities by providing financial relief primarily to privileged recipients. Previous economic and ecological crises have also been used by powerful individuals and institutions to serve their own interests, deepening inequities and health disparities during recovery.

“We find a significant disconnect between COVID- related needs, and the ability to adequately and equitably address them with crowdfunding. CCF campaigns face heightened competition, and steep inequalities between winners and losers,” the authors wrote. “Campaign success increasingly accrues among those with more social and economic capital.”

Link to journal article

Journal information: Igra, M., Kenworthy, N., Luchsinger, C. and Jung, J., 2021. Crowdfunding as a response to COVID-19: Increasing inequities at a time of crisis. Social Science & Medicine, 282, p.114105.

Categories : Cardiovascular DiseaseTags :

Nine in Ten Hypertension Cases Need More Treatment

On By ModernMedia
Image by Hush Naidoo from Unsplash
Image by Hush Naidoo from Unsplash

A series of studies has shown that in most cases, hypertension is not being adequately treated.

Hypertension is the leading treatable cause of illness and death worldwide. More than a billion people are hypertensive, defined as having diastolic blood pressure (BP) with 140mmHg or higher, or diastolic blood pressure (DBP) 90 mmHg or higher. Fewer than half of people with hypertension are aware of their condition.

This condition increases the risk of several dangerous illnesses, such as myocardial infarction (MI) and stroke, and of dying prematurely. For some patient categories, the most advantageous BP levels in terms of avoiding MI and stroke are uncertain.

In one of the studies in his thesis at Sahlgrenska Academy, University of Gothenburg, specialist doctor Johan-Emil Bager investigated the link between BP levels and the risk of MI or stroke in 5041 older patients.with hypertension but no history of heart attacks or strokes.
Risk for MI or stroke was found to be some 40 percent lower for the patients with systolic blood pressure (SBP) below 130 mmHg, compared with those in the SBP 130–139 range. In the latter group, 5.2 percent of the patients experienced a heart attack or stroke during the follow-up period, compared with 3.4 percent of those in the lower SBP group.

This pattern was repeated in another study, which investigated the risk of haemorrhagic stroke at different levels of BP in 3972 patients with atrial fibrillation (AF). These patients were receiving treatment with blood-thinning drugs, such as Warfarin or Eliquis.

The study showed that patients with SBP ranging from 140 to 179 mmHg had a haemorrhagic stroke risk roughly double that of patients with SBP of 130–139 mmHg. In the patient group with higher SBP, 1.4 percent suffered a hemorrhagic stroke during the follow-up period, compared with 0.7 percent of patients in the group with lower SBP.

A separate study with data on 259 753 patients also demonstrated insufficiency of hypertension treatment. Nine out of ten patients had either insufficient BP control or high blood lipids (cholesterol), or were smokers.

Johan-Emil Bager at the University of Gothenburg, said: “This means that an overwhelming majority of the patients with high blood pressure are exposed to at least one important, modifiable risk factor for cardiovascular disease and premature death.”

He concluded that an unnecessarily high number of people in Sweden suffer MI or stroke, or die prematurely, because of insufficiently treated hypertension.

“Health professionals and patients with hypertension alike need to aim higher when it comes to treating high blood pressure. The vast majority of patients with hypertension could reduce their MI and stroke risk by lowering their BP and blood lipids with more drugs, or through lifestyle changes.”

Source: University of Gothenburg

Categories : Cardiovascular Disease HospitalsTags :

Heart Failure Diagnoses Being Missed in Primary Care Settings

On By ModernMedia
Image by StockSnap from Pixabay
Image by StockSnap from Pixabay

A considerable number of heart failure diagnoses may be missed in primary care settings, a new Stanford University study suggests, with gender, racial and income disparities.

Black adults, women and individuals with lower net worth are significantly more likely to be diagnosed with heart failure in an acute care setting such as the emergency room or during a hospitalisation, according to a new study. This is true even if they reported symptoms of heart failure in a routine, outpatient health care appointment within the previous six months. The study was published in Circulation: Heart Failure, an American Heart Association journal.

“This national study raises concerns that many heart failure diagnoses may be missed in a primary care setting,” said Rebecca Tisdale, MD, MPA, co-first author and health services research and development fellow at the US Department of Veterans Affairs and Stanford University. “Our results suggest acute care diagnosis rates for heart failure may be reduced if signs and symptoms of heart failure are more closely assessed in a primary care setting, particularly among women and Black adults.”

According to the American Heart Association 2021 Statistical Update, an estimated 6 million Americans ages 20 and older have been diagnosed with heart failure, with mortality rates of over 20% within the first year after diagnosis. Previous studies have found that heart failure is frequently first diagnosed in an acute care setting.

“Patients diagnosed with heart failure in the emergency room or during inpatient hospitalisation often have more advanced heart failure and complications with worse prognoses than individuals diagnosed with heart failure in a primary care setting,” said Alexander Sandhu, MD, MS, lead author of the study, an instructor of medicine in advanced heart failure in the division of cardiovascular medicine and the Stanford Cardiovascular Institute at Stanford University. “Since earlier recognition and treatment may prevent some of the serious complications and costs of heart failure, our analysis focused on evaluating whether heart failure is identified before the patient is in the emergency room or the hospital.”

Drawing on a national database of health care claims from 2003-2019, the investigators evaluated if patients with new incidence of heart failure were diagnosed in an outpatient (primary care) or acute care (emergency room or urgent care) setting. The analysis included nearly one million adults ages 18 or older with a first-time heart failure diagnosis.

A large proportion of new heart failure diagnoses were found to have occurred in the emergency room or during hospitalisation, particularly among women and Black adults, yet many had potential heart failure symptoms in the months before their acute care visits. Delving further, the investigators found that:

  • Among patients with newly diagnosed heart failure, 38% were diagnosed in acute care settings.
  • Of patients diagnosed in the acute care setting, 46% had potential heart failure symptoms during primary care clinic visits in the previous six months, including oedema (15%), cough (12%), shortness of breath (11%), and chest pain (11%).
  • Heart failure diagnosis in an acute care setting was higher for women than men, and also higher for Black adults than white adults.
  • People with a net worth of under $25 000 had 39% higher odds of receiving heart failure diagnoses in an acute care setting compared to people with a net worth of over $500 000.

Disparities in heart failure diagnosis within clinical practices persisted nationally across race, gender and economic status, suggesting potential differences in either quality of care or local resource availability. In addition, acute care heart failure diagnoses increased by 3.2% annually during the 16-year study period.

Timely heart failure diagnosis can lead to earlier care with the slowing of heart failure progression and improved patient outcomes. However, previous research has shown that both women and Black adults are less likely to be referred to a cardiologist or to promptly receive advanced heart failure treatment.

“Further research is needed to better understand the factors influencing these disparities,” Dr Sandhu concluded. “It is important to note that we only analysed patients with health insurance, raising concerns that inequities may be even larger among people who are uninsured, marginally insured or those who have less access to care.”

Source: American Heart Association

Journal information: Sandhu, A.T., et al. (2021) Disparity in the Setting of Incident Heart Failure Diagnosis. Circulation: Heart Failure. doi.org/10.1161/CIRCHEARTFAILURE.121.008538.

Categories : Cancer Immune SystemTags :

Unleashing the Immune System to Attack Cancers

On By ModernMedia
Shown here is a pseudo-colored scanning electron micrograph of an oral squamous cancer cell (white) being attacked by two cytotoxic T cells (red), part of a natural immune response. Photo by National Cancer Institute on Unsplash

A potential treatment has been identified, that could boost the immune system’s ability to find and destroy cancer cells, by impeding certain cells which regulate the immune system, which in turn can unleash other immune cells to attack tumours in cancer patients.

“A patient’s immune system is more than able to detect and remove cancer cells and immunotherapy has recently emerged as a novel therapy for many different types of cancers,” explained study leader Nullin Divecha, Professor of Cell Signalling at the University of Southampton. “However, cancer cells can generate a microenvironment within the tumour that stops the immune system from working thereby limiting the general use and success of immunotherapy,” he continued.

One of a number of types of T cells, Teffector cells (Teffs) carry out the task of detection and removal of cancer cells . How well Teff cells work in detecting and removing cancer cells is partly governed by other T cells called T-regulatory cells, or Tregs for short. Tregs physically interact with the Teff cells, producing molecules which dampen the functioning of the Teff cells.

Prof Divecha added, “Tregs carry out an important function in the human body because without them, the immune system can run out of control and attack normal cells of the body. However, in cancer patients we need to give the Teff cells more freedom to carry out their job.”

Molecules released by tumour cells exacerbate the problem by attracting and gathering Tregs, reducing the activity and function of Teff cells even further. Though there are mechanisms to inhibit Treg cells, since Treg and Teff cells are very similar, Teff cells are also generally inhibited.

In this new study, published in PNAS, scientists from the University of Southampton and the National Institute of Molecular Genetics in Milan showed that inhibition of a family of enzymes in cells called PIP4K could be the answer to how to restrict Tregs without affecting Teffs.

The research team isolated Tregs from healthy donors and used genetic technology to suppress the production of the PIP4K proteins. They saw that loss of PIP4Ks from Treg cells stopped their growth and response to immune signals, in turn stopping them from impeding Teff cell growth and function.

Importantly, the loss of the same enzymes in Teff cells did not limit their activity.

“This was surprising because PIP4Ks are in both types of T cells in similar concentrations but our study shows that they seem to have a more important function for Tregs than Teffectors,” said Dr. Alessandro Poli who carried out the experimental research.

Scientists must next develop molecules in order to inhibition of PIP4K as a potential therapy for patients. “Towards this end we show that treatment with a drug like inhibitor of PIP4K could enable the immune system to function more strongly and be better equipped to destroy tumour cells.”

Source: EurekAlert!