Month: September 2021

Categories : Medical Research & TechnologyTags :

Thrombin’s Involvement with Coagulation Reconsidered

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Source: NIH

After 20 years of research, an established truth of how thrombin interacts with coagulation has been overturned.

“It has been said that an established truth in medicine lasts for about 10 years. It is probably the case that many truths last longer, but on the other hand, the time that different truths stand is constantly shrinking. This is because our perception of reality is changing rapidly, in step with new research,” said Tom Eirik Mollnes, Professor at the University of Oslo and Oslo University Hospital.

Based on more than 20 years of work to develop a whole blood model, Mollnes and colleagues have recently disproved an established truth about the immune system.

“There was an established truth in the literature for many years that a protein in the coagulation system called thrombin could activate a protein called C5 in the complement system,” Prof Mollnes said.

However, Prof Mollnes and his colleagues doubted whether the methods used in the studies were reliable.

“The notion that the protein thrombin could activate the protein C5 was only shown in so-called purified systems. That is, the proteins were taken out of their natural context,” he explained.

The researchers thought that the results would possibly be different if you looked at how the proteins work in their natural environment in the blood.

“The modified model made it possible to study the connection between the various proteins and defence systems as close to reality as possible,” Prof Mollnes explained. “Using the new model, we clearly showed that the previous findings were incorrect. We showed that the proteins changed structure and function during the purification, and that this was the reason for the former findings.”

When the proteins were in their natural environment in the blood, thrombin did not activate the protein in the complement system. Thus, the researchers had disproved the established truth.

“Many findings have been published in purified systems that are not representative of reality,” he said. “You can say that Gro Harlem Brundtland’s statement that “everything is connected to everything” is a very good description of how biology and the human body work. Therefore, it is important to use methods that make it possible to look at how different systems in the body interact and cooperate.”

The whole blood model makes such methods possible, and the model can be used widely. The whole blood model can, by and large, be used to study all the substances and biological systems in the blood.

Professor Mollnes therefore considers the model to have great potential.

“With the whole blood model, we have contributed to something that we will not only benefit from in our own laboratory, but that can be an asset to research groups in a number of fields,” he said.

It takes time to develop new models, and it was a long uphill battle for Prof Mollnes and his research group. Even so, the researchers have now received recognition for their work from the research community. The article got a recommendation by the editors of The Journal of Immunology, [PDF] in which it was published, as a ‘Top Reads Selection’.

“Changing so-called established truths is not easy, and we had to go through many rounds, with a number of experiments, to gain acceptance for our findings. That is why our work was especially recognised,” he concluded.

Source: University of Oslo

Categories : Immune SystemTags :

Degree of Platelet Drop, Not Count, Important in Sepsis Mortality

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Photo by National Cancer Institute on Unsplash

Mortality risk in sepsis is linked to the degree of platelet reduction, rather than absolute platelet count, according to new Japanese research.

Sepsis, a potentially life-threatening condition, arises from tissue and organ damage from an overactive infection response. Sepsis is commonly characterised by abnormally low platelet counts, which is believed to be associated with its high mortality rate.

Recently, Nagoya University researchers and colleagues have shown that a high degree of platelet reduction, rather than an abnormally low platelet count, raises mortality risks in sepsis. The findings, recently presented in the journal Scientific Reports, could lead to the development of precise and preventive treatments for sepsis-associated coagulopathy.

It is known that during sepsis, disseminated intravascular coagulation (DIC) forms tiny blood clots throughout the bloodstream, depleting platelets. Based on this, the international criterion for the diagnosis of sepsis-associated DIC uses platelet count and trials have been done using this criterion. However, very few trials have led to the development of effective treatments for sepsis-associated DIC.

There is however a different theory, that degree of platelet depletion (a rapid drop), rather than the absolute platelet count, accounts for much mortality risk in sepsis-associated DIC. But since there is little evidence for this theory, it has not been considered an international criterion for the disease prognosis.

With this in mind, researchers conducted a study to examine the significance of the degree of platelet reduction on sepsis mortality rate, using data from 200 859 sepsis patients staying in intensive care units of 208 US hospitals.

Corresponding author Dr Daisuke Kasugai of the Nagoya University Hospital, said: “To our knowledge, it was the largest study to evaluate the prognostic impact of both the degree of platelet depletion and absolute platelet counts in patients with sepsis.”

The degree of platelet reductions was found to be associated with the mortality risk associated with sepsis, regardless of absolute platelet count, indicating higher mortality risk with a fast decrease in platelet count. Dr Kasugai said:  “Surprisingly, we also found that if the platelet count decreases by 11% or more, the risks of bleeding, as well as thrombosis development (a serious condition caused by the formation of blood clots in blood vessels or the heart), increases.”

The researchers therefore concluded that, compared to the absolute platelet count, the degree of platelet reduction could be a more plausible criterion for assessing the mortality risk of the sepsis-associated DIC. They hope that this study will lead to effective treatments for sepsis-associated DIC.

Source: Nagoya University

Categories : Diet and Nutrition Metabolic DisordersTags :

Body Clock Disruption on High-fat Diet Leads to Obesity

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Photo by Ilya Mashkov on Unsplash

According to a new study, when rats are fed a high fat diet, this disturbs the body clock in their brain that normally controls satiety, leading to over-eating and obesity. 

This new research, published in the Journal of Physiology, may be a cornerstone for future clinical studies that could restore the proper functioning of the body clock in the brain, to avoid overeating.

It was believed that the body clock resided only in the hypothalamus, but research over the years has clarified that some control of our body’s daily rhythms (hormone levels, appetite etc) lies in several other parts of the brain and body, including a group of neurons in the evolutionary ancient brainstem, called the dorsal vagal complex (DVC).

Specifically, the DVC has been shown to moderate food intake by inducing satiety. In obesity, research has shown that daily rhythms in food intake and the release of hormones related to eating, are blunted or eliminated. It is unclear if the malfunctioning of brain centres controlling appetite is a cause or the result of obesity.

This new study found that rats on a high-fat diet, before they started to gain weight, showed changes in the DVC’s daily neuronal rhythms and its response to appetite hormones. Thus, the researchers proposed that DVC disruption causes obesity.

Two groups of rats were used: those fed a well-balanced control diet (10% kcal from fat) and a high-fat diet (70% kcal from fat). To mimic the impact of unhealthy diet on humans, the researchers introduced the new diet to adolescent rats and monitored their food intake over 24h for four weeks.

Using multi-electrode arrays, the researchers measured DVC changes over 24h, simultaneously monitoring around a hundred DVC neurons from each brainstem slice. With this, circadian changes of neuronal activity could be assessed as well as neuronal responses to metabolically-relevant hormones in each of the diet groups.

Rats being nocturnal animals is a limitation of the study. The DVC activity peaked at the end of day, the rest phase for rodents, but an active phase for humans. Thus, it remains to be established if the phase of the brainstem clock is set to day and night, or whether it depends on patterns of rest and activity. These findings however could lead to understanding how to reset the body clock and tackle obesity.

First author Dr Lukasz Chrobok said:

“I’m really excited about this research because of the possibilities it opens up to tackle the growing health issue of obesity. We still do not know what are the time cues which are able to reset or synchronise the brainstem clock. Hopefully, the restoration of daily rhythms in this satiety centre before or after the onset of obesity may provide new therapeutic opportunities.”

Source: The Physiological Society

Categories : Diseases, Syndromes and Conditions General InterestTags :

September 7 is the First World Field Epidemiology Day

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Photo by Kyle Glenn on Unsplash

In honour of field epidemiologists across the globe, the Training Programs in Epidemiology and Public Health Interventions Network (TEPHINET) has declared 7 September 2021 #WorldFieldEpidemiologyDay.

This day, the first of its kind, is aimed at recognising and raising awareness of the invaluable role Field Epidemiologists play.

As health systems face increasingly complex threats, training workers in field epidemiology is even more important.. The NICD, a division of the National Health Laboratory Service, embarked on a joint collaboration more than 15-years ago in establishing the South African Field Epidemiology Training Programme (SAFETP).  To date the program has trained 98 epidemiologists with the majority located in the public service in South Africa.

Field Epidemiologists, or ‘disease detectives’ are considered the cornerstone of public health preparedness and response. They undertake arduous, time-consuming tasks that include contact tracing, case investigations, community engagement, data collection and analysis.

One such ‘disease detective’ is Alain Musaka Abera, whose team was deployed to Equateur province in the DRC in response to an outbreak of Ebola virus disease (EVD). “The health zone of Ingende had already reported seven confirmed cases, including two deaths in the community,” said Abera, describing his work. “I had to set up the different pillars of epidemiological surveillance (management of alerts, active research, investigation, follow-up of contacts) and, at the same time, support coordination of the response in the health zone.

“The task was tough; the means of transport insufficient; communication almost non-existent. It was necessary to travel long distances in the forest on motorcycles that sometimes broke down and to cross the river in a canoe to search for and investigate suspects. It took courage, determination, and will to face these constraints.”

Source: NICD

Categories : Respiratory DiseasesTags :

Circadian Rhythm Contributes to Asthma Severity

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Source: Pixabay/CC0

By pinning down the influence of the circadian system on nocturnal asthma, researchers have uncovered a key role for the biological clock in asthma.

Asthma severity has long been observed to worsen in the nighttime. Lung function is highest at around 4pm and worst around 4am. One longstanding question has been to what degree the body’s internal circadian clock contributes to worsening of asthma severity, as opposed to behaviours such as sleep. Using two circadian protocols, researchers have delineated the influence of the circadian system. Understanding the mechanisms behind asthma severity could have important implications for both studying and treating asthma. 

“This is one of the first studies to carefully isolate the influence of the circadian system from the other factors that are behavioral and environmental, including sleep,” said co-corresponding author Frank AJL Scheer, PhD, director of the Medical Chronobiology Program in the Division of Sleep and Circadian Disorders at the Brigham.

As many as 75 percent of people with asthma report experiencing worsening asthma severity at night. Asthma severity is influenced by behavioural and environmental factors, such as exercise, air temperature, posture, and sleep environment. The researcher sought to understand the internal circadian system’s contributions to this problem. The circadian system is composed of a central pacemaker in the brain (the suprachiasmatic nucleus) and “clocks” throughout the body and is critical for the coordination of bodily functions and to anticipate the daily cycling environmental and behavioral demands.

To isolate the influence of the circadian system from that of sleep and other behavioural and environmental factors, the researchers enrolled 17 participants with asthma into two complementary laboratory protocols where lung function, asthma symptoms and bronchodilator use were continuously assessed. In the “constant routine” protocol, participants spent 38 hours continuously awake, in a constant posture, and under dim light conditions, with identical snacks every two hours. In the “forced desynchrony” protocol, participants were placed on a recurring 28-hour sleep/wake cycle for a week under dim light conditions, with all behaviours scheduled evenly across the cycle.

Co-corresponding author Steven A. Shea, Ph.D., professor and director at Oregon Institute of Occupational Health Sciences said, “We observed that those people who have the worst asthma in general are the ones who suffer from the greatest circadian-induced drops in pulmonary function at night, and also had the greatest changes induced by behaviours, including sleep. We also found that these results are clinically important because, when studied in the laboratory, symptom-driven bronchodilator inhaler use was as much as four times more often during the circadian night than during the day.”  

The study was published in Proceedings of the National Academy of Sciences.

Source: Medical Xpress

Categories : Diet and Nutrition Neurodegenerative DiseasesTags :

Small Study Hints at Omega-3 Protection of Memory in Alzheimer’s

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Photo by Kindel Media on Pexels

A first-of-its-kind study on Alzheimer’s disease found an indication that omega-3 fatty acids taken early on protect against Alzheimer’s disease, despite not finding biomarkers in patients’ cerebrospinal fluid.

The researchers published their findings in Journal of Alzheimer’s Disease.

“We are careful not to draw any wider conclusions, but we can see a difference in the results of the memory tests. Patients who were taking omega-3 supplements at an early stage of the disease scored better,” cautioned Yvonne Freund-Levi, researcher in neuroscience at Örebro University.

The small study enrolled 33 patients, 18 of which were given omega-3 supplements morning and evening, and15 were in the control group. Spinal fluid samples were collected, and patients performed a memory test at the start of the study and after six months.

“We can see that the memory function of the patients in the group that had taken omega-3 is stable, whereas the patients in the control group have deteriorated. That’s what the memory tests show,” said Yvonne Freund-Levi.

“But we can’t see any differences between the groups when we look at the various biomarkers in the spinal fluid samples.”

However there are differences within the group given omega-3: an increase of two of the markers that are linked to damaged nerve cells. There is no clinical link to the memory tests, however.

“Even if this data isn’t enough for us to change our recommendations to patients at this time, it is an interesting material for researchers to build on.”

This study is based on a larger study with over 200 patients with mild to moderate Alzheimer’s disease, initiated by Yvonne Freund-Levi and her research team 15 years ago. In that previous study, the researchers found that omega-3 transfers from the supplements to the brain.

“We are cautious about giving recommendations, but we know that starting early is by far the best thing – it is difficult to influence the disease at a later stage. The best piece of advice we have to offer at the moment is to be physically active and to include omega-3 in your diet – in the form of oily fish or as supplements.”

In future, researchers will be able to measure biomarkers in blood samples rather than having to perform spinal tap procedures.

“We have already tested this approach at Sahlgrenska University Hospital. Without a doubt, it is so much better for the patients.”

Source: Örebro University

Categories : COVIDTags :

C.1.2 Variant Slows in SA; Colombian Variant Named Mu

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Computer image of SARS-CoV-2. From CDC at Pexels
Source: CDC on Pexels

The Network for Genomic Surveillance in South Africa (NGS-SA) has reported that the C.1.2 variant is spreading less slowly than in July, from 2.2% of all sequenced COVID cases to 1.5% in August, and is therefore unlikely to become a dominant variant.

Meanwhile, B.1.621,  another variant that first emerged in Colombia in January has been recently classified by the World Health Organization (WHO) as a variant of interest (VOI), receiving the Greek letter “Mu”. Since its first detection, it has spread across North America, South America and Europe, and has also been detected in Asia. The majority of the Mu sequences (5123) have been detected in North America (55%, n=2841) followed by South America (23%, n=1328), Europe (18%, n=948) and Asia (0.1%, n=6). As of 3 September 2021, Mu has not been detected in Africa. Thus far, it makes up less than 1% of the globally circulating viruses with Delta accounting for 88%.

NGS-SA, which includes the National Institute for Communicable Diseases (NICD), continuously and rigorously monitors SARS-CoV-2 sequences circulating in South Africa. This work is crucial in the early detection of SARS-CoV-2 variants, including Mu.

Many of the mutations within the spike protein which define the Mu variant (T95I, E484K, N501Y, D614G, P681H and D950) have been seen before in other VOIs or variants of concern (VOCs) including Beta and Delta. Some of these mutations have previously been associated with decreased antibody responses and increased transmissibility. Therefore it is likely that Mu will have similar properties to other variants with increased transmissibility and reduced sensitivity to antibodies in vaccines and those who have recovered from COVID.

The NICD advises that both COVID vaccines being used in South Africa have high levels of protection against severe disease requiring hospitalisation and death even against VOI/VOCs such as Beta and Delta and therefore will likely also protect against Mu. 

Source: NICD

Categories : PaediatricsTags :

Female Blood Donors Better for Very-low-birthweight Transfusions

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The sex of adult blood donors may affect the risk of common complications in transfusions of red blood cells (RBCs) to premature or very-low-birthweight infants while in the neonatal intensive care unit (NICU), according to new research.

Anaemia is common in premature or very-low-birthweight infants, often requiring an RBC transfusion. Common negative outcomes that can occur with very low birth weight infants include necrotising enterocolitis, lung damage or retinopathy of prematurity. Studies provided conflicting evidence of transfusions being a risk factor.

The study was led by Dr Ravi Patel is director of neonatal research in the Department of Pediatrics at Emory University School of Medicine and Children’s Healthcare of Atlanta. Dr Patel and colleagues followed 181 very-low-birth-weight infants at three hospitals from 2010 to 2014. The infants were selected who received RBC transfusions from only male donors or only female donors.\

The study, published in JAMA Network Open, found that a typical very-low-birth-weight infant who received red blood cell transfusion from only female donors had a three times lower risk of negative outcomes than one who received red blood cells from only male donors.

Increasing donor age increased the protective effect of female donors. Some potential explanations for the protective effect could be reduced breakdown during storage of RBCs from female donors, along with less inflammation and more antioxidant capacity, the authors wrote.

RBC transfusion is common, according to Dr Patel, with about half of very low birth infants receiving at least one RBC transfusion while in the NICU. RBC transfusion is necessary to treat anaemia related to prematurity. In rare circumstances, this can lead to an infection or transfusion reaction. It is uncertain whether RBC transfusion increases the risks of some adverse clinical outcomes.
  Is it correct to say that the suspected mechanism for the difference in risk has to do with the characteristics of the RBCs, rather than immune differences, the suspected reason for the reverse effect in adults?

Future research should investigate inflammation or antioxidant capacity of red blood cells since these mechanisms may differ from adults, Dr Patel suggested.
Should their findings that age and sex have an effect on transfusion outcomes be confirmed, the next step would be transfusing blood from only males or only females, which could inform changes in practice.
Source: Emory University

Categories : Diseases, Syndromes and ConditionsTags :

Use of Nicotine-containing E-cigarettes Increases Blood Clot Formation

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Photo by Toan Nguyen on Unsplash

A new study found the use of e-cigarettes containing nicotine has a number of immediate effects, which include increased blood clot formation, blood vessel dysfunction, as well as raised heart rate and blood pressure.

These effects are similar to smoking traditional cigarettes with heart attack or stroke risk with long-term use, according to researchers. The study was presented at the ERS International Congress by Gustaf Lyytinen, a clinician at Helsingborg Hospital and researcher at the Karolinska Institute in Stockholm, Sweden. 

Each of the 22 occasional smoker volunteers was tested before and after taking 30 puffs from an e-cigarette with nicotine, and before and after 30 puffs from an e-cigarette without nicotine. These two sets of tests were conducted on separate occasions, at least one week apart.

On each occasion, the researchers measured volunteers’ heart rate and blood pressure and took a blood sample before they used the e-cigarettes, then 15 minutes after use and again 60 minutes after use. A laser was used to measure dilation of skin blood vessels before volunteers used e-cigarettes and 30 minutes afterwards.
E-cigarettes with nicotine caused an immediate short-term change: a 23% average increase in blood clots after 15 minutes, that returned to normal levels after 60 minutes. Average heart rates also increased from 66bpm to 73bpm. as did blood pressure from 108mmHg to 117mmHg. Researchers observed temporary narrowing of blood vessels after nicotine-containing e-cigarettes use.

These effects were not observed after volunteers used e-cigarettes without nicotine. Nicotine is known to raise levels of hormones including adrenaline, which can increase blood clot formation.

Dr Lyytinen said: “Our results suggest that using e-cigarettes that contain nicotine have similar impacts on the body as smoking traditional cigarettes. This effect on blood clots is important because we know that in the long-term this can lead to clogged up and narrower blood vessels, and that of course puts people at risk of heart attacks and strokes.”

Source: European Respiratory Society

Categories : COVID Immune SystemTags :

Metabolic Changes in Plasma, Immune Cells Linked to COVID Severity

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Analysing plasma from patients infected with SARS-CoV-2, researchers have uncovered underlying metabolic changes that regulate how immune cells react to COVID, these are associated with disease severity and could be used to predict patient survival. The findings were published in the journal Nature Biotechnology.

“We know that there are a range of immune responses to COVID, and the biological processes underlying those responses are not well understood,” said co-first author Jihoon Lee, a graduate student at Fred Hutchinson Cancer Research Center. “We analyzed thousands of biological markers linked to metabolic pathways that underlie the immune system and found some clues as to what immune-metabolic changes may be pivotal in severe disease. Our hope is that these observations of immune function will help others piece together the body’s response to COVID. The deeper understanding gained here may eventually lead to better therapies that can more precisely target the most problematic immune or metabolic changes.”

The researchers performed two draws on each of nearly 200 patients during the first week after being diagnosed with SARS-CoV-2 infection, and analysed their plasma and single immune cells. The analysis included 1387 genes involved in metabolic pathways and 1050 plasma metabolites.

Increased COVID severity was found to be associated with metabolite alterations, which suggests increased immune-related activity. In addition, each major immune cell type was found to have a distinct metabolic signature.

“We have found metabolic reprogramming that is highly specific to individual immune cell classes (eg “killer” CD8+ T cells, “helper” CD4+ T cells, antibody-secreting B cells, etc.) and even cell subtypes, and the complex metabolic reprogramming of the immune system is associated with the plasma global metabolome and are predictive of disease severity and even patient death,” said co-first and co-corresponding author Dr. Yapeng Su, a research scientist at Institute for Systems Biology. “Such deep and clinically relevant insights on sophisticated metabolic reprogramming within our heterogeneous immune systems are otherwise impossible to gain without advanced single-cell multi-omic analysis.”

“This work provides significant insights for developing more effective treatments against COVID. It also represents a major technological hurdle,” said Dr. Jim Heath, president and professor of ISB and co-corresponding author on the paper. “Many of the data sets that are collected from these patients tend to measure very different aspects of the disease, and are analysed in isolation. Of course, one would like these different views to contribute to an overall picture of the patient. The approach described here allows for the sum of the different data sets to be much greater than the parts, and provides for a much richer interpretation of the disease.”

Source: Max Planck Institute