Exercise may help reduce side effects of chemotherapy

Colorado, Jul 24: A new study has found that physical stress in one's job may be associated with faster brain ageing and poorer memory.

Aga Burzynska, an assistant professor in the Department of Human Development and Family Studies, and her research team connected occupational survey responses with brain-imaging data from 99 cognitively normal older adults, age 60 to 79. They found that those who reported high levels of physical stress in their most recent job had smaller volumes in the hippocampus and performed poorer on memory tasks. The hippocampus is the part of the brain that is critical for memory and is affected in both normal ageing and in dementia.

Their findings were published this summer in Frontiers in Human Neuroscience under the research topic 'Work and Brain Health Across the Lifespan.'

"We know that stress can accelerate physical ageing and is the risk factor for many chronic illnesses," Burzynska said. "But this is the first evidence that occupational stress can accelerate brain and cognitive ageing."

She added that it is important to understand how occupational exposures affect the ageing of our brains.

"An average American worker spends more than eight hours at work per weekday, and most people remain in the workforce for over 40 years," Burzynska said. "By pure volume, occupational exposures outweigh the time we spend on leisure social, cognitive and physical activities, which protect our ageing minds and brains."

Physical demands at work

Burzynska explained that the association between "physical stress" and brain/memory were driven by physical demands at work. These included excessive reaching, or lifting boxes onto shelves, not necessarily aerobic activity. This is important because earlier work by Burzynska and her colleagues showed that leisure aerobic exercise is beneficial for brain health and cognition, from children to very old adults. Therefore, the researchers controlled for the effects of leisure physical activity and exercise.

As expected, leisure physical activity was associated with greater hippocampal volume, but the negative association with physical demands at work persisted.

"This finding suggests that physical demands at work may have parallel yet opposing associations with brain health," Burzynska explained. "Most interventions for postponing cognitive decline focus on leisure, not on your job. It's kind of unknown territory, but maybe future research can help us make some tweaks to our work environment for long-term cognitive health."

She added that the results could have important implications for society.

"Caring for people with cognitive impairment is so costly, on economic, emotional and societal levels," Burzynska said. "If we can support brain health earlier, in middle-aged workers, it could have an enormous impact."

The researchers considered and corrected for several other factors that could be related to work environment, memory and hippocampus, such as age, gender, brain size, educational level, job title, years in the occupation and general psychological stress.

One piece of the puzzle

"The research on this topic is so fragmented," Burzynska said. "One previous study linked mid-life managerial experience with greater hippocampus volume in older age. Another showed that taxi drivers had larger hippocampi than a city's bus drivers, presumably due to the need to navigate. In our study, job complexity and psychological stress at work were not related to hippocampal volume and cognition. Clearly, our study is just one piece of the puzzle, and further research is needed."

The magnetic resonance imaging (MRI) data used for the study was collected at the University of Illinois Urbana-Champaign between 2011 and 2014.

CSU researchers now can collect MRI data with the new 3T scanner at the University's Translational Medicine Institute.

With this new capability, Burzynska, along with Michael Thomas and Lorann Stallones of CSU's Department of Psychology, is launching a new project, "Impact of Occupational Exposures and Hazards on Brain and Cognitive Health Among Aging Agricultural Workers," which will involve collecting MRI brain scans and identifying risk and protective factors that could help the agricultural community age successfully. The project recently obtained funding as an Emerging Issues Short-Term Project from the High Plains Intermountain Center for Agricultural Health and Safety.

The Department of Human Development and Family Studies is part of CSU's College of Health and Human Sciences.

The American pharmaceutical giant Pfizer Inc. and the European biotechnology company BioNTech SE have conducted an experimental trial of a COVID-19 vaccine candidate and found it to be safe, well-tolerated, and capable of generating antibodies in the patients.

The study, which is yet to be peer-reviewed, describes the preliminary clinical data for the candidate vaccine -- nucleoside-modified messenger RNA (modRNA), BNT162b1.

It said the amount of antibodies produced in participants after they received two shots of the vaccine candidate was greater than that reported in patients receiving convalescent plasma from recovered COVID-19 patients.

"I was glad to see Pfizer put up their phase 1 trial data today. Virus neutralizing antibody titers achieved after two doses are greater than convalescent antibody titers," tweeted Peter Hotez, a vaccine scientist from Baylor College of Medicine in the US, who was unrelated to the study.

Researchers, including those from New York University in the US, who were involved in the study, said the candidate vaccine enables human cells to produce an optimised version of the receptor binding domain (RBD) antigen -- a part of the spike (S) protein of SARS-CoV-2 which it uses to gain entry into human cells.

"Robust immunogenicity was observed after vaccination with BNT162b1," the scientists noted in the study.

They said the program is evaluating at least four experimental vaccines, each of which represents a unique combination of mRNA format and target component of the novel coronavirus, SARS-CoV-2.

Based on the study's findings, they said BNT162b1 could be administered in a quantity that was well tolerated, potentially generating a dose dependent production of immune system molecules in the patients.

The research noted that patients treated with the vaccine candidate produced nearly 1.8 to 2.8 fold greater levels of RBD-binding antibodies that could neutralise SARS-CoV-2.

"We are encouraged by the clinical data of BNT162b1, one of four mRNA constructs we are evaluating clinically, and for which we have positive, preliminary, topline findings," said Kathrin U. Jansen, study co-author and Senior Vice President and Head of Vaccine Research & Development, Pfizer.

"We look forward to publishing our clinical data in a peer-reviewed journal as quickly as possible," Jansen said.

According to Ugur Sahin, CEO and Co-founder of BioNTech, and another co-author of the study, the preliminary data are encouraging as they provide an initial signal that BNT162b1 is able to produce neutralising antibody responses in humans.

He said the immune response observed in the patients treated with the experimental vaccine are at, or above, the levels observed from convalescent sera, adding that it does so at "relatively low dose levels."

"We look forward to providing further data updates on BNT162b1," Sahin said.

According to a statement from Pfizer, the initial part of the study included 45 healthy adults 18 to 55 years of age.

It said the priliminary data for BNT162b1 was evaluated in 24 subjects who received two injections of 10 microgrammes ( g) and 30 g -- 12 subjects who received a single injection of 100 g, and 9 subjects who received two doses of a dummy vaccine.

The study noted that participants received two doses, 21 days apart, of placebo, 10 g or 30 g of BNT162b1, or received a single dose of 100 g of the vaccine candidate.

According to the scientists, the highest neutralising concentrations of antibodies were observed seven days after the second dose of 10 g, or 30 g on day 28 after vaccination.

They said the neutralising concentrations were 1.8- and 2.8-times that observed in a panel of 38 blood samples from people who had contracted the virus.

In all 24 subjects who received two vaccinations at 10 g and 30 g dose levels, elevation of RBD-binding antibody concentrations was observed after the second injection, the study noted.

It said these concentrations are 8- and 46.3-times the concentration seen in a panel of 38 blood samples from those infected with the novel coronavirus.

At the 10 g or 30 g dose levels, the scientists said adverse reactions, including low grade fever, were more common after the second dose than the first dose.

According to Pfizer, local reactions and systemic events after injection with 10 g and 30 g of BNT162b1 were "dose-dependent, generally mild to moderate, and transient."

It said the most commonly reported local reaction was injection site pain, which was mild to moderate, except in one of 12 subjects who received a 100 g dose, which was severe.

The study noted that there was no serious adverse events reported by the patients.

Citing the limitations of the research, the scientists said the immunity generated in the participants in the form of the T cells and B cells of their immune system, and the level of immunity needed to protect one from COVID-19 are unknown.

With these preliminary data, along with additional data being generated, Pfizer noted in the statement that the two companies will determine a dose level, and select among multiple vaccine candidates to seek to progress to a large, global safety and efficacy trial, which may involve up to 30,000 healthy participants if regulatory approval to proceed is received.

China, where the novel coronavirus originated, has reported 111 cases since beginning of May, which shows the infection rate has dipped, and 3 deaths since April 27, according to the WHO. A Shanghai-based Noida doctor says China is close to winning the battle against COVID-19, and the combination of zinc, hydroxychloroquine (HCQ) and antibiotic azithromycin has been able to save the lives of coronavirus patients.

Speaking to media persons, Dr Sanjeev Choubey, Medical Director Internal Medicine at St. Michael Hospital said this combination has been adopted as a line of treatment for patients infected with coronavirus, and as a result patients are recovering, decreasing their need for intensive care.

What is the line of treatment for COVID-19 patients, which also include asymptomatic patients?

The combination of zinc, hydroxychloroquine and antibiotic azithromycin has produced positive results, and it helped in the recovery of many COVID-19 patients. The combination -- Ascorbic Acid, B-complex, Zinc, Selenium, L-carnitine, Vitamin B-12 and Glutathione normal saline should be administered on patients twice a week for at least 6 weeks. This is COVID-19 treatment protocol for prophylaxis, and it implies both asymptomatic and symptomatic along with other medicine support.

Based on your experience on COVID-19 in China, after how many tests, is it safe to call a person coronavirus free?

The coronavirus should be performed at least 9 times, before terming a patient COVID-19 free. It is a standard in China. This procedure has worked in China and it will also work in India. Minimum five tests should be mandatory through RT-PCR.

Does coronavirus majorly attack the respiratory system or it could lead to organ failure too?

Line of treatment should not be just looking at the respiratory system, as the problem lies somewhere else. COVID-19 attacks many vital organs in the body. In China, a coronavirus patient died from a stroke. In the autopsy it was found that the innermost layer in the arteries was swollen. It was concluded that coronavirus had inflamed the layer of the arteries leading to clotting, which was a factor in generating a heart attack. Therefore, COVID-19 is not just a respiratory problem.

Amid the coronavirus pandemic, should autopsy be made mandatory in the case of unpredictable death or where reasons for death are not unknown?

Patients below 50 years, who die suddenly and the reasons are not known, then it should be mandatory to conduct the autopsy. After death, coronavirus is active in the body for five days, and it fades away on day 6. Therefore, if an autopsy is done then it will help in understanding this disease. In China, we have seen young COVID-19 patients, aged 22 and 28, succumbed to strokes.

Since the beginning of May, India has recorded more than 2,000 cases everyday in the first week, then it jumped past 3,000 mark in the second week. Finally, the tally is 4,987 on May 17. At 90,927 cases, has India progressed into community transmission or Stage3?

Yes, India has moved into Stage 3. The data suggests that 3,000 to 4,000 active COVID-19 cases, who are asymptomatic, are moving around and spreading the infection. The research has indicated that COVID-19 from an infected person spreads in 30 minutes to non-infected persons. The relaxation on the lockdown will certainly contribute to a high infection rate.

Do you think India has reached its peak in COVID-19 cases, or the sharp rise will continue till July end?

It seems India has already reached its peak and cases will begin to come down from June end or beginning of July first week. If social distancing norms are followed then certainly things can improve, but if not followed then it may get worse. High population density is a major contributor for the increase in cases. The government should continue to focus on finding hotspots, and urge people to follow the rules, eventually it is for people’s own benefit.

Has China won the battle against COVID-19?

It seems China has won the battle by not opening up Wuhan. The Chinese are following a COVID-19 patient’s engagement program, where the authorities continuously interact with people infected with the disease. The Government of India should reward people who follow the guidelines; it will help in setting up a positive trend in the society.