Day: September 7, 2021

Body Clock Disruption on High-fat Diet Leads to Obesity

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

September 7 is the First World Field Epidemiology Day

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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

Circadian Rhythm Contributes to Asthma Severity

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

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

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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

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

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

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