Tag: 3/12/21

Categories : Mental HealthTags :

Can Seven Questions Measure Wisdom and Resilience?

On By ModernMedia
Photo by Natasha Brazil on Unsplash

In a new study published in International Psychogeriatrics, researchers report that a shortened, seven-item scale can help determine a person’s level of wisdom, a potentially modifiable personality trait shown to be strongly associated with well-being.

Previously, the researchers had developed the 28-item San Diego Wisdom Scale (SD-WISE-28), which has been used in large national and international studies, biological research and clinical trials to evaluate wisdom.

But researchers found that an abbreviated seven-item version (SD-WISE-7 or Jeste-Thomas Wisdom Index), was comparable and reliable.

“Wisdom measures are increasingly being used to study factors that impact mental health and optimal aging. We wanted to test if a list of only seven items could provide valuable information to test wisdom,” said senior author Dilip V. Jeste, MD.

Past studies have shown that wisdom is comprised of seven components: self-reflection, pro-social behaviours (such as empathy, compassion and altruism), emotional regulation, acceptance of diverse perspectives, decisiveness, social advising (such as giving rational and helpful advice to others) and spirituality.

The latest study surveyed 2093 participants online, ages 20 to 82. The seven statements, selected from SD-WISE-28, relate to the seven components of wisdom and are rated on a 1 to 5 scale, from strongly disagree to strongly agree. Examples of the statements include “I remain calm under pressure” and “I avoid situations where I know my help will be needed.”

“Shorter doesn’t mean less valid,” said Dr Jeste. “We selected the right type of questions to get important information that not only contributes to the advancement of science but also supports our previous data that wisdom correlates with health and longevity.”  

In addition, the SD-WISE-7 was found to strongly and positively correlate with resilience, happiness and mental well-being and strongly and negatively correlate with loneliness, depression and anxiety.

“There are evidence-based interventions to increase levels of specific components of wisdom, which would help reduce loneliness and promote overall well-being,” said Dr Jeste.

“Like the COVID vaccine protects us from the novel coronavirus, wisdom can aid in protecting us from loneliness. Thus, we can potentially help end a behavioural pandemic of loneliness, suicides and opioid abuse that has been going on for the last 20 years.”

Next steps include genetic, biological, psychosocial and cultural studies of large numbers of diverse populations to assess wisdom, as well as various factors related to mental, physical and cognitive health in people across the lifespan.

“We need wisdom for surviving and thriving in life. Now, we have a list of questions that take less than a couple of minutes to answer that can be put into clinical practice to try to help individuals,” said Dr Jeste. 

Source: University of California San Diego School of Medicine

Categories : Mental Health NeurologyTags :

Why Antidepressants Take Weeks to Provide Relief

On By ModernMedia
A healthy neuron.
A healthy neuron. Credit: NIH

The findings of a study published in Science Translational Medicine paint a new picture of how current antidepressant drugs work and suggest a new drug target in depression. As with most drugs, antidepressants were developed through trial and observation. Some 40% of patients with the disorder don’t respond adequately to the drugs, and when they do work, antidepressants take weeks to provide relief. Why this is has remained largely a mystery.

To figure out why these drugs have a delayed onset, the team examined a mouse model of chronic stress that leads to changes in behaviours controlled by the hippocampus. The hippocampus is vulnerable to stress and atrophies in people with major depression or schizophrenia. Mice exposed to chronic stress show cognitive deficits, a hallmark of impaired hippocampal function.

“Cognitive impairment is a key feature of major depressive disorder, and patients often report that difficulties at school and work are some of the most challenging parts of living with depression. Our ability to model cognitive impairment in lab mice gives us the chance to try and understand how to treat these kinds of symptoms,” said Professor Dane Chetkovich, MD, PhD, who led the study.

The study focussed on an ion transporter channel in nerve cell membranes known as the HCN channel. Previous work has shown HCN channels have a role in depression and separately to have a role in regulation of cognition. According to the authors, this was the first study to explicitly link the two observations.

Examination of postmortem hippocampal samples led the team to establish that HCN channels are more highly expressed in people with depression. HCN channel activity is modulated by a small signaling molecule called cAMP, which is increased by antidepressants. The team used protein receptor engineering to increase cAMP signaling in mice and establish in detail the effects this has on hippocampal HCN channel activity and, through that connection, on cognition.

Turning up cAMP was found to initially increase HCN channel activity, limit the intended effects of antidepressants and negatively impact cognition (as measured in standard lab tests).

However, a total reversal took place over a period of some weeks. Previous work by the researchers had established that an auxiliary subunit of the HCN channel, TRIP8b, is essential for the channel’s role in regulating animal behaviour. The new study shows that, over weeks, a sustained increase in cAMP starts to interfere with TRIP8b’s ability to bind to the HCN channel, thereby quieting the channel and restoring cognitive abilities.

“This leaves us with acute and chronic changes in cAMP, of the sort seen in antidepressant drug therapy, seen here for the first time to be regulating the HCN channel in the hippocampus in two distinct ways, with opposing effects on behaviour,” Prof Chetkovich said. “This appears to carry promising implications for new drug development, and targeting TRIP8b’s role in the hippocampus more directly could help to more quickly address cognitive deficits related to chronic stress and depression.”

Source: Vanderbilt University

Categories : COVIDTags :

Moderna Narrowly Beats Pfizer in Effectiveness

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

In the first head-to-head comparison of the effectiveness of the Pfizer-BioNTech and Moderna COVID vaccines, researchers examined the electronic health records of veterans who had received each vaccine and found Moderna to be slightly more effective.

The Moderna vaccine’s increased level of protection included a 21% lower risk of documented infection and 41% lower risk of hospitalisation, according to the research team, whose findings were published in the New England Journal of Medicine.

“Both vaccines are incredibly effective, with only rare breakthrough cases,” said Dr J.P. Casas, a member of the research team. “But regardless of the predominant strain – Alpha earlier and then Delta later – Moderna was shown to be slightly more effective.”

Researchers designed their comparative effectiveness study to address the previously unanswered question of which of the two mRNA vaccines is more effective. Effectiveness outcomes were: documented COVID, symptomatic disease, hospitalisation, ICU admission, and death. The investigators drew on the database of US veterans who received one of the two COVID vaccines between early January 2021 and mid-May 2021.

As initially designed, the research focused on the Alpha variant that predominated at the time. The study matched 219 842 recipients of the Pfizer vaccine to the same number of recipients of the Moderna vaccine. The two groups were matched based on a variety of clinical and demographic factors that could affect outcomes.

Over the study’s 24-week follow-up period, the estimated risk of documented infection was 4.52 events per 1000 people in the Moderna vaccine group and 5.75 per 1000 in the Pfizer group, an excess of 1.23 cases per 1000. The investigators also observed smaller excesses of symptomatic COVID (0.44 events), hospitalisation (0.55 events), ICU admission (0.10 events), and death (0.02 events) per 1000 people in the Pfizer group relative to the Moderna group.

This pattern of a lower risk for Moderna held up when Delta was the main strain. In this comparison, excess risk of documented infection over 12 weeks was 6.54 events per 1000 people for the Pfizer vaccine, compared to Moderna. Given the shorter time frame available for this supplementary research, infection was the only outcome researchers analyzed. Also, the estimates were considered less precise because a smaller number of individuals were eligible for this analysis.

Randomised trials comparing the mRNA vaccines against placebos had previously shown both vaccines to be very effective against symptomatic COVID infection (95% effectiveness for Pfizer-BioNTech, 94% for Moderna), borne out by real-world vaccine use.

“Given the high effectiveness of both the Moderna and Pfizer vaccines, confirmed by our study, either one is recommended to any individual offered a choice between the two,” said first author Dr Barbra A. Dickerman. “However, while the estimated differences in effectiveness were small on an absolute scale, they may be meaningful when considering the large population scale at which these vaccines are deployed. This information may be helpful for larger decision-making bodies.”

The massive Veteran Association records system supported a very large sample size. This, in turn, allowed the study to identify even small differences in effectiveness between the Pfizer and Moderna vaccines. The researchers used a methodology known as causal inference to mirror a gold standard randomised trial as closely as possible. Causal inference is a type of data analysis that helps researchers draw firm conclusions about cause and effect.

Using the VA database, vaccine recipients were closely matched on age, sex, race, geographic location, and other attributes that could affect COVID-related outcomes.

“After this careful matching, we found that the two vaccine groups were extremely similar in terms of variables with respect to an extensive set of demographic, geographic, and health-related attributes,” Dr Dickerman said. “This allowed our observational analysis to produce exceptionally credible results during a global emergency, when answers are needed fast and randomised trials can be impractical.”

As the global pandemic continues to unfold, the research team is working on answers relating to the comparative safety, versus effectiveness, of the Pfizer and Moderna vaccines. Dr Dickerman characterises comparative safety as an “additional piece of the puzzle to support vaccine decision-making.”

Even beyond this analysis, further evaluation of the vaccines’ comparative effectiveness and safety is needed, the authors concluded. Meanwhile, given the evidence at hand, the authors concluded about the Pfizer and Moderna vaccines considered in their study, “Given the high effectiveness and safety profile of both mRNA vaccines, either one is strongly recommended.”

Source: EurekAlert!

Categories : COVIDTags :

Six Different Booster Vaccines Found to be Safe and Effective

On By ModernMedia
Image by Ivan Diaz on Unsplash

The first randomised trial of COVID boosters, published in The Lancet, has shown that six are safe and provoke strong immune responses. Participants have previously received a two-dose course of ChAdOx1-nCov19 (Oxford–AstraZeneca [ChAd]) or BNT162b2 (Pfizer-BioNTech [BNT]). The announcement comes just as the Omicron variant is beginning to spread around the world.

ChAd has now been deployed in more than 180 countries and BNT in more than 145 countries. Several studies show that two doses of ChAd and BNT confer 79% and 90% protection, respectively, against hospitalisation and death after six months. However, protection against COVID infection wanes in time, which has led to the consideration of boosters. However, there are currently little data on the comparative safety of COVID vaccines, and the immune responses they stimulate, when given as a third dose.

The COV-BOOST study looked at safety, immune response (immunogenicity) and side-effects (reactogenicity) of seven vaccines when used as a third booster jab. The vaccines studied were ChAd, BNT, NVX-CoV2373 (Novavax [NVX]), Ad26.COV2.S (Janssen [Ad26]), Moderna [mRNA1273], VLA2001 (Valneva [VLA]), and CVnCov (Curevac [CVn]).

“The side effect data show all seven vaccines are safe to use as third doses, with acceptable levels of inflammatory side effects like injection site pain, muscle soreness, fatigue. Whilst all boosted spike protein immunogenicity after two doses of AstraZeneca, only AstraZeneca, Pfizer-BioNTech, Moderna, Novavax, Janssen and Curevac did so after two doses of Pfizer-BioNTech”, commented Professor Saul Faust, trial lead.

“It’s really encouraging that a wide range of vaccines, using different technologies, show benefits as a third dose to either AstraZeneca or Pfizer-BioNTech. That gives confidence and flexibility in developing booster programmes here in the UK and globally, with other factors like supply chain and logistics also in play”, added Prof Faust.

“It’s important to note that these results relate only to these vaccines as boosters to the two primary vaccinations, and to the immune response they drive at 28 days. Further work will generate data at three months and one year after people have received their boosters, which will provide insights into their impact on long-term protection and immunological memory. We are also studying two of the vaccines in people who had a later third dose after 7-8 months although results will not be available until the new year.”

A randomised, phase 2 trial of seven booster vaccines was conducted, with the third doses given 10-12 weeks after initial two-dose courses of ChAd or BNT. The trial involved 2878 healthy participants between June 1st and June 30th 2021. Participants had received their first doses of ChAd or BNT in December 2020, January or February 2021, and second doses at least 70 days before enrolment for ChAd and at least 84 days for BNT. About half of participants received two doses of ChAd and half two doses of BNT. The control vaccine used was a meningococcal conjugate vaccine (MenACWY).

Participants were aged 30 or older, roughly half of whom were 70 or older. The average age of participants who received ChAd was 53 years in the younger age group and 76 years in the older age group. Average ages for BNT were 51 and 78 years, respectively.

Thirteen experimental and control arms of the trial (seven vaccines plus three at half dose and three control arms) were split into three participant groups. Group A received NVX, half dose NVX, ChAd, or a control. Group B received BNT, VLA, half dose VLA, Ad26 or a control. Group C received Moderna, CVn (development of which was halted in October 2021), half dose BNT, or a control.

Primary outcomes were adverse effects seven days after receiving a booster, and levels of antibodies targeting the SARS-CoV-2 Spike protein after 28 days, compared to controls. Secondary outcomes included the response of T cells to wild type, Alpha, Beta, and Delta variants. 

Increases in anti-spike protein antibody levels after 28 days varied across the vaccines. After two doses of ChAd these ranged from 1.8 times higher to 32.3 times higher according to the booster vaccine used. Following two doses of BNT, the range was 1.3 times higher to 11.5 times higher. Significant T-cell responses were reported in several combinations.

At 28 days, all booster results were similar for participants aged 30-69 years and those aged 70 years or older. Boost ratios should be interpreted with caution, the authors caution, since they relate to immunogenicity rather than protection against disease, and the relationship between antibody levels at day 28 and long-term protection and immunological memory is unknown.

Reactions to all seven vaccines were similar, with fatigue, headache, and injection site pain most often reported. These were more commonly reported by those aged 30-69. 912 of the 2878 participants experienced a total of 1036 adverse events, 24 of which were severe.

Source: EurekAlert!

Categories : Cardiovascular DiseaseTags :

Neuromodulation Could Help Heart Muscle Regeneration

On By ModernMedia
Photo by Robina Weermeijer on Unsplash

Human heart muscle cells stop multiplying after birth, making any heart injury later in life a permanent one, reducing function and leading to heart failure. Now, however, researchers have new evidence that manipulating certain nerve cells or their controlling genes might trigger the formation of new heart muscle cells and restore heart function after heart attacks and other cardiac disorders.

The study, published in Science Advances, sheds new light on how some neurons regulate the number of heart muscle cells. While nerve cells have long been known to regulate heart function, their role and impact during heart development and their effect on muscle cell growth has been unclear.

“Our study sought to examine the role of so-called sympathetic neurons on heart development after birth, and what we found is that by manipulating them, there could be tremendous potential for regulating the total number of muscle cells in the heart even after birth,” said lead author Emmanouil Tampakakis, MD, assistant professor of medicine at the Johns Hopkins University School of Medicine.

The nerve cells that make up the sympathetic nervous system (SNS) control automatic processes in the body such as digestion, heart rate and respiration. The SNS is typically associated with ‘fight-or-flight’ responses.

Researchers in this study made a genetically modified mouse model by blocking sympathetic heart neurons in developing mouse embryos, and analysed the drivers of heart muscle cell proliferation through the first two weeks of life after birth.

What they found was a significant decrease in the activity of a pair of genes – the period 1 and period 2 genes – already known to control the circadian cycle. Remarkably, removing those two circadian genes in mouse embryos, the researchers saw increased neonatal heart size and an increase in the number of cardiomyocytes, or heart muscle cells, by up to 10%. Thus, sympathetic nerves on heart muscle cells could likely be mediated through these two circadian genes.

Circadian, or ‘clock’, genes are components of the circadian rhythm pattern that in mammals regulates bodily functions on a roughly 24-hour cycle aligned with hours of daylight and darkness.

“Shortly after birth, mammals, including people and mice, stop producing heart muscle cells. And unlike other organs, like the liver, the heart can’t regenerate after it’s damaged,” said Prof Tampakakis. “We’ve shown that it may be possible to manipulate nerves and/or circadian genes, either through drugs or gene therapies, to increase the number of heart cells after birth.”

Up to a billion heart muscle cells can be lost after a heart attack, and Prof Tampakakis says there is scientific evidence that hearts tend to recover faster after an attack when the total number of cells to begin with is higher. By manipulating sympathetic nerves and clock genes (a technique called neuromodulation) researchers believe the heart could be made to respond to injury much better.

“Neuromodulation is a pretty new concept in cardiology, and we believe these are the first reports that associate clock genes with new growth of heart muscle cells.” saidChulan Kwon, PhD, MS, associate professor of medicine at the Johns Hopkins University School of Medicine. “Our study, maybe for the first time, shows what’s happening if you block the supply of nerves to the heart, and provides new insights for developing neuromodulation strategies for cardiac regeneration.”

Source: Johns Hopkins Medicine