Tag: 4/5/22

Categories : AddictionTags :

Single Pathway Controls Drug Withdrawal-induced Anxiety

On By ModernMedia
Depression, young man
Source: Andrew Neel on Unsplash

New research published today in Cell Reports finds that drug withdrawal-induced anxiety and return to drug seeking behaviours are controlled by a single pathway in the brain and are centred on dopamine cells, which are normally associated with reward behaviours.

Addiction occurs in phases: the initial drug exposures are rewarding, and then repeated administration leads to tolerance or sensitisation to the drug’s effects, with withdrawal leading to anxiety and a negative affective state, which, in turn, contributes to a return to drug taking or seeking.

“In order to prevent relapse among drug users, specifically cocaine users, we need to understand the factors in the brain that contribute to drug seeking behaviours and the vulnerability to relapse,” said Kevin Beier, PhD, assistant professor of physiology and biophysics from the University of California, Irvine. “In this study, we identified a brain circuit that is responsible for drug withdrawal-induced anxiety as well as relapse-related behaviour, along with the identification of a potential target for therapeutic interventions.”

The negative affective state induced by drug withdrawal is a critical factor in the relapse of drug users.

“Both the drug withdrawal-induced anxiety and reinstatement of drug seeking are controlled by a single pathway centred around dopamine cells in the ventral midbrain,” explained Dr Beier. “That a single pathway controls both sets of behavioural changes may help to explain many addiction-related behavioural phenomena. Importantly, it links them both directly to dopamine, which is more typically linked to reward-related behaviours.”

While midbrain dopamine circuits are central to motivated behaviours, just how experience modifies these circuits to facilitate subsequent behavioural adaptations is not well understood. This study demonstrates the selective role of a ventral tegmental area dopamine projection to the amygdala for cocaine induced anxiety, but not for cocaine reward or sensitisation. Silencing this projection prevents development of anxiety during protracted withdrawal after cocaine use.

According to the National Center for Drug Abuse Statistics, there are roughly 70 000 drug overdoses each year in the United States. In 2017, nearly one in five drug overdose deaths was cocaine-related, with the highest rate of cocaine-related overdoses and deaths occurring among non-Hispanic black populations. Between 2012 and 2018, the rate of cocaine-related overdose deaths increased from 1.4 to 4.5%. The American Addiction Centers state recent drug relapse statistics show that more than 85% of individuals relapse and return to drug use within a year following treatment.

Source: University of California – Irvine

Categories : VaccinesTags :

BCG Vaccine Activates Immune System in Newborns

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Syringe
Source: Raghavendra V Konkathi on Unsplash

In the century since it was first used in humans, the Bacille Calmette-Guérin (BCG) vaccine against tuberculosis has become one of the world’s most widely used vaccines. Administered in countries with endemic TB, it has surprisingly been found to protect newborns and young infants against multiple bacterial and viral infections unrelated to TB. Some evidence even suggests that it can reduce severity of COVID. Now, a new study in Cell Reports sheds light on the mechanisms behind its extra protective effects.

Surprisingly little is known about how BCG exerts its many side benefits. To better understand its mechanism of action, researchers collected and comprehensively profile blood samples from newborns vaccinated with BCG, using a powerful ‘big data’ approach analysing lipid and metabolite biomarkers.

Their study found that the BCG vaccine induces specific changes in metabolites and lipids that correlate with innate immune system responses. The findings provide clues toward making other vaccines more effective in vulnerable populations with distinct immune systems, such as newborns.

First author Dr Joann Diray Arce and her colleagues started off with blood samples from low-birthweight newborns in Guinea Bissau who were enrolled in a randomised clinical trial to receive BCG either at birth or after a delay of six weeks. Blood samples were taken at four weeks for both groups (after BCG was given to the first group, and before it was given to the second group).

The researchers comprehensively profiled the impact of BCG immunisation on the newborns’ blood plasma. They found that BCG vaccines given at birth changed metabolite and lipid profiles in newborns’ blood plasma in a pattern distinct from those in the delayed-vaccine group. The changes were associated with changes in cytokine production, a key feature of innate immunity.

The researchers had parallel findings when they tested BCG in cord blood samples from a cohort of Boston newborns and samples from a separate study of newborns in The Gambia and Papua New Guinea.

“We now have some lipid and metabolic biomarkers of vaccine protection that we can test and manipulate in mouse models,” said Dr Arce. “We studied three different BCG formulations and showed that they converge on similar pathways of interest. Reshaping of the metabolome by BCG may contribute to the molecular mechanisms of a newborn’s immune response.”

“A growing number of studies show that BCG vaccine protects against unrelated infections,” said Ofer Levy, MD, PhD, the study’s senior investigator. “It’s critical that we learn from BCG to better understand how to protect newborns. BCG is an ‘old school’ vaccine – it’s made from a live, weakened germ – but live vaccines like BCG seem to activate the immune system in a very different way in early life, providing broad protection against a range of bacterial and viral infections. There’s much work ahead to better understand that and use that information to build better vaccines for infants.”

Source: Boston Children’s Hospital via News-Medical.Net

Categories : COVID Medical Research & TechnologyTags :

Natural Facial Asymmetry Affects Mask Fit

On By ModernMedia
Image by Quicknews

In research published in Physics of Fluids, researchers used computer modelling investigate mask fit and found that face shape, especially natural facial asymmetry, influences the most ideal fit. The findings suggested that double masking with improperly fitted masks may not greatly improve mask efficiency and produces a false sense of security.

Using more layers results in a less porous face covering, leading to more flow forced out the sides, top, and bottom of masks with a less secure fit. Double layers increase filtering efficiency only with good mask fit, however they could also lead to difficulties in breathing.

The researchers modelled a moderate cough jet from a mouth of an adult male wearing a cloth mask over the nose and mouth with elastic bands wrapped around the ears. They calculated the maximum volume flow rates through the front of mask and peripheral gaps at different material porosity levels.

To create a more realistic 3D face shape and size, the researchers used head scan data for 100 adult male and 100 adult female heads.

Their model showed how the slight asymmetry typical in all facial structures can affect proper mask fitting. For example, a mask can have a tighter fit on the left side of the face than on the right side.

“Facial asymmetry is almost imperceivable to the eye but is made obvious by the cough flow through the mask,” explained co-author Tomas Solano, from Florida State University. “For this particular case, the only unfiltered leakage observed is through the top. However, for different face shapes, leakage through the bottom and sides of the mask is also possible.”

Producing individually customised ‘designer masks’ is not practical at large scales. Still, better masks can be designed for different populations by revealing general differences between male and female or child versus elderly facial structures and the associated air flow through masks.

Source: American Institute of Physics

Categories : Respiratory DiseasesTags :

WHO Announces Guidance Updates to Treatment of Drug-resistant TB

On By ModernMedia
Source: Pixabay CC0

The World Health Organization (WHO) Global Tuberculosis Programme has announced upcoming updates to the guidance on the treatment of drug-resistant tuberculosis (DR-TB). These updates are announced in a Rapid Communication and include shorter novel 6-month all-oral regimens for the treatment of multidrug- and rifampicin-resistant TB (MDR/RR-TB), with or without additional resistance to fluoroquinolones (pre-XDR-TB), and also an alternative 9-month all-oral regimen for the treatment of MDR/RR-TB.

The Rapid Communication is released ahead of updated WHO consolidated guidelines to come later in the year which will inform national programmes and stakeholders.

Dr Tereza Kasaeva, Director of WHO’s Global TB Programme said: “We now have more and much better treatment options for people with drug-resistant TB thanks to research generating new evidence. This is major progress compared to what was available even a few years ago, and will be of great benefit for people struggling with TB and drug-resistant TB, resulting in better outcomes, saving lives and reducing suffering.”

All patients with MDR/RR-TB, including those with additional resistance to fluoroquinolones, stand to benefit from effective all-oral treatment regimens, either shorter or longer, implemented under programmatic conditions.

The summary of the updates are as follows:

The 6-month BPaLM regimen, comprising bedaquiline, pretomanid, linezolid (600 mg) and moxifloxacin, may be used programmatically in place of 9-month or longer (>18 months) regimens, in patients (aged ≥ 15 years) with MDR/RR-TB who have not had previous exposure to bedaquiline, pretomanid and linezolid (defined as > 1 month exposure). This regimen may be used without moxifloxacin (BPaL) in the case of documented resistance to fluoroquinolones (in patients with pre-XDR-TB). Drug susceptibility testing (DST) to fluoroquinolones is strongly encouraged, but DST should not delay treatment initiation.

The 9-month, all-oral, bedaquiline-containing regimens are preferred over the longer (>18 months) regimen in adults and children with MDR/RR-TB, without previous exposure to second-line treatment (including bedaquiline), without fluoroquinolone resistance and with no extensive pulmonary TB disease or severe extrapulmonary TB. In these regimens, 2 months of linezolid (600 mg) can be used as an alternative to 4 months of ethionamide. Access to rapid DST for ruling out fluoroquinolone resistance is required before starting a patient on one of these regimens.

Patients with extensive forms of DR-TB (eg XDR-TB4) or those who are not eligible for or have failed shorter treatment regimens will benefit from an individualised longer regimen designed using the priority grouping of medicines recommended in current WHO guidelines.6

Decisions on appropriate regimens should be made according to clinical judgement and patient preference, considering results of DST, patient treatment history, risk of adverse events, and severity and site of the disease.

All treatment should be delivered under WHO-recommended standards, including patient-centred care and support, informed consent where necessary, principles of good clinical practice, active drug safety monitoring and management, and regular monitoring of patients and of drug resistance to assess regimen effectiveness.

The full details of the regimens included in the review are available in the Rapid Communication.

Source: World Health Organization

Categories : Environmental Effects PaediatricsTags :

PFAS and Phthalates Linked to Reduced Bone Density in Teen Boys

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Photo by Gayatri Malhotra on Unsplash

Per- and polyfluoroalkyl substances (PFAS) and phthalates (two types of endocrine-disrupting chemicals) may be associated with lower areal bone mineral density (aBMD) in teenage boys, according to a new study published in the Journal of Clinical Endocrinology and Metabolism.

Endocrine disrupting chemicals (EDCs) and potential EDCs are mostly man-made found in various materials. By interfering with the body’s endocrine system, endocrine disruptors produce adverse developmental, reproductive, neurological, and immune effects in humans, abnormal growth patterns and neurodevelopmental delays in children. These include per- and polyfluoroalkyl substances (PFAS) are used in non-stick pots and pans, clothing and food packaging, and are increasingly being found in US water supplies. Phthalates are used in medical devices, personal care products, food processing and children’s toys.

“Adolescence is an important time when our bodies build up bone. Almost all US children and adolescents are exposed to PFAS and phthalates, but few studies have looked at how these chemicals could be impacting our bone health,” said Abby F. Fleisch, MD, MPH, of the Maine Medical Center Research Institute and Maine Medical Center. “Our research found an association between certain PFAS and phthalates and reduced bone mineral density in adolescent males. Because bone accrual primarily occurs during adolescence, if replicated, this finding may have implications for lifelong bone health.”

The researchers accessed data on urine and blood samples from 453 boys and 395 girls from the National Health and Nutrition Examination Survey (NHANES). Participants were on average 15.1 years old, and found that higher levels of PFAS and phthalates may be associated with lower aBMD in adolescent males. The same effect was not found in girls; rather a slight increase in aBMD was observed for certain PFAS and phthalates.

The researchers noted that bone mineral density tracks across a lifetime, so if the same results are seen in longitudinal cohorts, this finding may have implications for lifelong skeletal health.

Source: The Endocrine Society