Nicotine normalises brain activity in schizophrenia patients

January 25, 2017

Washington, Jan 25: A steady stream of nicotine normalises genetically-induced impairments in brain activity associated with schizophrenia, according to a new study that could lead to new non-addictive, nicotine-based treatments for the 51 million people worldwide who suffer from the disease.

BrainThe finding sheds light on what causes the disease and why those who have it tend to smoke heavily.

It could also potentially have applications for treating addiction, Attention Deficit Hyperactivity Disorder, Bipolar disorder and other psychiatric conditions.

"Our study provides compelling biological evidence that a specific genetic variant contributes to risk for schizophrenia, defines the mechanism responsible for the effect and validates that nicotine improves that deficit," said Jerry Stitzel, researcher at the Institute for Behavioural Genetics (IBG) in the US.

The study found that when mice with schizophrenic characteristics were given nicotine daily, their sluggish brain activity increased within two days. Within one week it had normalised.

"Basically the nicotine is compensating for a genetically determined impairment. No one has ever shown that before," said Stitzel.

The scientists set out to explore the underlying causes of "hypofrontality"?a reduction of neuronal firing in the prefrontal cortex of the brain.

Hypofrontality is believed to be the root cause of many of the signature cognitive problems experienced by schizophrenics, including trouble paying attention, remembering things, making decisions and understanding verbal explanations.

Previous genome-wide association studies have suggested that people with a variation in a gene called CHRNA5 are more likely to have schizophrenia, but the mechanism for that association has remained unclear. People with that variant are also more likely to smoke.

Eighty to 90 per cent of people with schizophrenia smoke and most are very heavy smokers, a fact that has long led researchers to suspect they are self-medicating.

The research team first took mice with the CHRNA5 gene variant and used state-of-the-art brain imaging technologies to see if they had hypofrontality.

Then they conducted behavioural tests to see if the mice shared key characteristics of schizophrenics, like being unable to suppress a startle response and being averse to social interaction.

The results validated that the gene variant likely plays a role in schizophrenia by causing hypofrontality, said Stitzel.

Nicotine appeared to reverse this in the mice, normalising brain activity by acting on nicotinic receptors in regions of the brain key to healthy cognitive function.

The study appears in the journal Nature Medicine.

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Agencies
July 2,2020

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.

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Agencies
August 2,2020

Washington, Aug 2: Children under the age of five have between 10 to 100 times greater levels of genetic material of the coronavirus in their noses compared to older children and adults, a study in JAMA Pediatrics said Thursday.

Its authors wrote this meant that young children might be important drivers of Covid-19 transmission within communities -- a suggestion at odds with the current prevailing narrative.

The paper comes as the administration of US President Donald Trump is pushing hard for schools and daycare to reopen in order to kickstart the economy.

Between March 23 and April 27, researchers carried out nasal swab tests on 145 Chicago patients with mild to moderate illness within one week of symptom onset.

The patients were divided into three groups: 46 children younger than five-years-old, 51 children aged five to 17 years, and 48 adults aged 18 to 65 years.

The team, led by Dr Taylor Heald-Sargent of the Ann & Robert H. Lurie Children's Hospital, observed, "a 10-fold to 100-fold greater amount of SARS-CoV-2 in the upper respiratory tract of young children."

15 countries with the highest number of cases, deaths due to the Covid-19 pandemic

The authors added that a recent lab study had demonstrated that the more viral genetic material was present, the more infectious virus could be grown.

It has also previously been shown that children with high viral loads of the respiratory syncytial virus (RSV) are more likely to spread the disease.

"Thus, young children can potentially be important drivers of SARS-CoV-2 spread in the general population," the authors wrote.

"Behavioral habits of young children and close quarters in school and daycare settings raise concern for SARS-CoV-2 amplification in this population as public health restrictions are eased," they concluded.

The new findings are at odds with the current view among health authorities that young children -- who, it has been well established, are far less likely to fall seriously ill from the virus -- don't spread it much to others either.

However, there has been fairly little research on the topic so far.

One recent study in South Korea found children aged 10 to 19 transmitted Covid-19 within households as much as adults, but children under nine transmitted the virus at lower rates.

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Agencies
May 6,2020

Washington D.C., May 5: Working from home has become the new normal ever since the outbreak of coronavirus and in today's time the work duties can be easily dealt with by means of mobile devices at home.

However, this easy use of technology, mobile devices for that matter, has the potential to blur the fine line between work and the other daily life routines.

But, contrary to the belief, a study at the University of Jyvaskyla reveals that the mixing of work and other daily life routines may have more benefits than previously assumed, and points to the importance of boundary-spanning communication.

A smartphone enables phone calls, email, and file transfers from the comfort of home. The study shows that there may be more effective ways to maximise the benefits of smartphone use, without diminishing employees' flexibility and the use of these technologies.

"People often forget to talk about positive effects, such as autonomy and freedom the employees gain when they have the flexibility to schedule their work," said Postdoctoral Researcher Ward van Zoonen from JYU, who with his colleagues examined the use of smartphones for work matters outside working hours.

The study paid special attention to the benefits of talking about domestic matters with the immediate supervisor outside the working hours given to an employee.

"This reduces the conflict between work and other life," van Zoonen said.

"If people in an organisation strive for more dialogue between employees' different life domains, it is possible to create a functional environment where people can talk about different matters."

The research findings show that when employees communicate across boundaries and talk at work about their life in other respects, they can receive new kinds of support and understanding from their immediate supervisor.

"This kind of communication creates a low threshold for contacting one's supervisor, which helps employees build a balance between the different domains of their lives and strengthens their organisational identification," said Professor Anu Sivunen describing the findings.

This means that tight working time restrictions to protect employees might not be beneficial after all, if they hinder reaching the positive results indicated in this research.

For the study, a survey was taken of 367 employees who were asked questions such as -- how much they talk about their work with their family, and how much they talk about their family with their immediate supervisor.

"Both supervisors and their employees answered the surveys, and the study actually focused on their mutual communication," Sivunen said.

"Usually people at workplaces are interested in how communication within the work community is succeeding. It is often forgotten how an immediate supervisor can take an employer's other life into account and thereby help the employee gain work-related benefits."

"Communication with one's immediate supervisor during flexible working hours, also on matters other than work, could ease the daily lives of many employees if they could share the possible challenges of their family life or free time with their supervisor in these settings," Sivunen added.

According to the study, such a practice could make the supervisor aware of the employee's situation as he/she works from home and the related impacts on their work performances.

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