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Study of reproducibility issues points finger at the mice | Ars Technica

The first thing that's obvious from the results is that there's no single reproducibility problem. Some of the experiments reproduced just fine, with limited variability. Others, as you might expect, saw differences between the strains. But for half of those cases, the magnitudes of the strain differences varied such that one lab might see a statistically different effect while another wouldn't. In one case, the strains showed opposite behaviors in the different labs. Beyond that, results were all over the map. In some cases, the mouse strain was the biggest source of variability. In others, it was the lab. The impact of the individual researcher, which was significant in other studies, turned out to be minor in all but one or two of the tests. But one of the strongest results was how much of the variability couldn't be accounted for by anything tracked by the study. In nine of the 10 tests, the unaccounted-for variation was above 25 percent of the total, and it was above half in six of the 10. "Things we didn't think to test" could be an extremely large category, but in this case, it's hard to think of ways to perform the experiments more consistently than they were done here. So while variations could be due to a large number of factors, that may make little practical difference since we can't control those factors anyway.

Increase in pleasurable effects of alcohol over time can predict alcohol use disorder: New research challenges existing dogma that higher tolerance for stimulating and rewarding effects of alcohol leads to addiction -- ScienceDaily

"These pleasurable alcohol effects grow in intensity over time, and do not dissipate, in people progressing in excessive drinking," said King. "This tells us that having a higher sensitivity to the rewarding effects of alcohol in the brain puts such individuals at higher risk for developing addiction. It all fits a picture of persistent pleasure-seeking that increases the likelihood of habitual excessive drinking over time. Alcoholics were thought to need to drink more to finally get their desired effect when they drink, but these well-controlled data do not support that contention. They get the desirable alcohol effect early in the drinking bout and that seems to fuel wanting more alcohol." While it may seem relatively intuitive that individuals who experience alcohol's pleasurable effects most intensely are at the greatest risk for developing drinking problems, King's findings run counter to current prominent addiction theories. "Our results support a theory called incentive-sensitization," said King. "In response to a standard intoxicating dose of alcohol in the laboratory, ratings of wanting more alcohol increased substantially over the decade among the individuals who developed more severe AUD. Additionally, the hedonic response -- essentially, how much a person liked the effects -- remained elevated over this interval and didn't go down at all. This has traditionally been the crux of the lore of addiction -- that addicts don't like the drug (alcohol) but can't stop using it."

New clues why gold standard treatment for bipolar disorder doesn't work for majority of patients -- ScienceDaily

"Only one-third of patients respond to lithium with disappearance of the symptoms," says Renata Santos, co-first author on the study and a Salk research collaborator. "We were interested in the molecular mechanisms behind lithium resistance, what was blocking lithium treatment in nonresponders. We found that LEF1 was deficient in neurons derived from nonresponders. We were excited to see that it was possible to increase LEF1 and its dependent genes, making it a new target for therapeutic intervention in BD."

Racial Bias in Pulse Oximetry Measurement | NEJM

Thus, in two large cohorts, Black patients had nearly three times the frequency of occult hypoxemia that was not detected by pulse oximetry as White patients. Given the widespread use of pulse oximetry for medical decision making, these findings have some major implications, especially during the current coronavirus disease 2019 (Covid-19) pandemic. Our results suggest that reliance on pulse oximetry to triage patients and adjust supplemental oxygen levels may place Black patients at increased risk for hypoxemia. It is important to note that not all Black patients who had a pulse oximetry value of 92 to 96% had occult hypoxemia. However, the variation in risk according to race necessitates the integration of pulse oximetry with other clinical and patient-reported data.

Effectiveness of fitness-boosting strategies may be linked to personality traits: Approach could help identify subgroups likely to benefit from competitive, collaborative or supportive activities -- ScienceDaily

By reanalyzing the trial data, the researchers found that the competition-based strategy was effective in boosting physical activity for extroverted and motivated participants, but these participants were less likely to stay active after the program ended. Competition-, collaboration-, and social support-based strategies were all effective for less active and less social participants, who all stayed active afterwards. None of the strategies were effective for less motivated and at-risk participants.

Lack of females in drug dose trials leads to overmedicated women: Gender gap leaves women experiencing adverse drug reactions nearly twice as often as men, study shows -- ScienceDaily

Researchers analyzed data from several thousand medical journal articles and found clear evidence of a drug dose gender gap for 86 different medications approved by the Federal Drug Administration (FDA), including antidepressants, cardiovascular and anti-seizure drugs and analgesics, among others. "When it comes to prescribing drugs, a one-size-fits-all approach, based on male-dominated clinical trials, is not working, and women are getting the short end of the stick," said study lead author Irving Zucker, a professor emeritus of psychology and of integrative biology at UC Berkeley. The findings, published in the journal Biology of Sex Differences, confirm the persistence of a drug dose gender gap stemming from a historic disregard of the fundamental biological differences between male and female bodies, Zucker said.

Researchers identify genetic factors that may influence COVID-19 susceptibility -- ScienceDaily

These findings demonstrate a possible association between ACE2 and TMPRSS2 polymorphisms and COVID-19 susceptibility, and indicate that a systematic investigation of the functional polymorphisms these variants among different populations could pave the way for precision medicine and personalized treatment strategies for COVID-19. However, all investigations in this study were performed in general populations, not with COVID-19 patient genetic data. Therefore, Dr. Cheng calls for a human genome initiative to validate his findings and to identify new clinically actionable variants to accelerate precision medicine for COVID-19.

Your microbiome may change how drugs affect you, research confirms

For the Cell study, the researchers grew the microbes from a patient’s fecal matter in test tubes. They added one of 575 drugs in separate tubes and waited to see if the microbiome had an effect — and in particular, whether it rendered the drug inactive or even changed it into a more toxic substance, which could trigger side effects in a patient. The gut microbes broke down capecitabine very differently from the way it is processed by the liver, for example. While scientists had already observed that capecitabine often affects patients differently, how and if it was broken down by the microbiome was unknown before this study, and the new findings could shed light on those variations. The authors used 20 more patient fecal samples to test differences between how individual patients’ gut microbes break down the same drug, examining 23 drugs from the first experiment. There were huge differences between patients — some drugs were only broken down by one patient. Only three patients broke down digoxin, a drug used to treat arrhythmia, for example — suggesting that the other patients might not see the same benefit or side effects from the drug.

Clostridioides difficile infection flourishes with a high-protein, high-fat diet -- ScienceDaily

The group studied 4 groups of mice with 5 animals each. Each group received antibiotics and was fed a different diet: one was high-fat, high-protein; another was high-fat, low-protein; a third was high-carbohydrate; and the fourth was a standard laboratory diet for experimental mice. The results were startling. In the high-protein, high-fat group, all the animals developed severe infections and died within 4 days. In the high-fat, low-protein group, only 2 animals died. In the high-carbohydrate group, 2 mice showed mild symptoms and recovered and in the standard diet group, all of the animals showed signs of infection but also recovered.

Using Open Questions to Understand 650 People’s Experiences With Antipsychotic Drugs | Schizophrenia Bulletin | Oxford Academic

In this study, 650 people, from 29 countries, responded, in an online survey, to “Overall in my life antipsychotic medications have been _____?” and “Is there anything else you would like to say, or emphasise, about your experiences with antipsychotic drugs?” Of the total participants, 14.3% were categorized as reporting purely positive experiences, 27.9% had mixed experiences, and 57.7% reported only negative ones.

Mechanisms of tissue and cell-type specificity in heritable traits and diseases | Nature Reviews Genetics

Hundreds of heritable traits and diseases that are caused by germline aberrations in ubiquitously expressed genes manifest in a remarkably limited number of cell types and tissues across the body. Unravelling mechanisms that govern their tissue-specific manifestations is critical for our understanding of disease aetiologies and may direct efforts to develop treatments.

Before bed may be the best time to take blood pressure meds, study suggests | MinnPost

“The same medication ingested at different times of the day actually has different pharmacological properties, behaving like totally different medications,” explained Ramón Hermida, the study’s lead author and a chronobiologist at the University of Vigo in Spain, in an interview with NBC News.

Crohn's disease study identifies genetic variant with potential to personalize treatment -- ScienceDaily

This research identified a genetic marker HLA-DQA1*05, carried by 40 per cent of the European population that increases risk of development of antibodies against infliximab and adalimumab 2-fold.

Gut bacteria 'fingerprint' predicts radiotherapy side effects: First clinical study to show link between types of gut bacteria and radiotherapy-induced gut damage -- ScienceDaily

The researchers found that patients who had a high risk of gut damage had 30-50 per cent higher levels of three bacteria types, and lower overall diversity in their gut microbiome, than patients who had not undergone any radiotherapy. This suggests that patients with less diverse gut microbiomes and high levels of the bacteria -- Clostridium IV, Roseburia and Phascolarctobacterium -- are more susceptible to gut damage. The researchers also believe these patients may require more 'good bacteria' to maintain a healthy gut -- and so may be more susceptible to side effects when these bacteria are killed by radiation.

African American children respond differently to asthma medications: BARD trial suggests shortcomings in treatment guidelines and demonstrates need for trials of specific subgroups -- ScienceDaily

More adult African Americans responded better to adding long-acting beta agonists (49 percent) versus increasing inhaled steroids alone (28 percent). Caucasians have shown a similar response in previous trials. However, even numbers of African American children responded better to increasing the dose of inhaled corticosteroids along (46 percent) and adding long-acting beta agonists (46 percent). "These results indicate that asthma treatment guidelines do not necessarily apply to African American children and that physicians should consider alternatives," said Dr. Wechsler. "We need to do a better job of understanding how different subgroups respond to asthma treatment."

Biological clock influences immune response efficiency -- ScienceDaily

"Our study shows that T cells are more prone to be activated at certain times of the day. Identifying the mechanisms through which the biological clock modulates the T cell response will help us better understand the processes that regulate optimal T cell responses. This knowledge will contribute to improving vaccination strategies and cancer immune therapies," states Nathalie Labrecque, Professor at the Departments of Medicine and Microbiology, Infectious Diseases and Immunology at Université de Montréal.

Some high-cholesterol genes differ between countries -

They found that the results were broadly consistent across European and Asian groups, with about three quarters of genetic markers applied similarly across the different groups, but only 10% of the genetic markers for triglycerides (the most common type of fat in the body) were implicated in the same cardiovascular risk factors among people from Uganda.

Mapping human microbiome drug metabolism by gut bacteria and their genes | Nature

Individuals vary widely in their responses to medicinal drugs, which can be dangerous and expensive owing to treatment delays and adverse effects. Although increasing evidence implicates the gut microbiome in this variability, the molecular mechanisms involved remain largely unknown. Here we show, by measuring the ability of 76 human gut bacteria from diverse clades to metabolize 271 orally administered drugs, that many drugs are chemically modified by microorganisms.

Gut bacteria may be linked to high blood pressure and depression -- ScienceDaily

The researchers isolated DNA (deoxyribonucleic acid, the carrier of genetic information) from gut bacteria obtained from the stool samples of 105 volunteers. They used a new technique involving artificial-intelligence software to analyze the bacteria, which revealed four distinct types of bacterial genes and signature molecules. Surprisingly, the investigators discovered unique patterns of bacteria from people with 1) high blood pressure plus depression; 2) high blood pressure without depression; 3) depression with healthy blood pressure; or 4) healthy subjects without depression or high blood pressure.

N-of-1 Clinical Trials: Removing the Hay to Find the Needle | Clinical Chemistry

an observed lack of universality in response to interventions and a greater focus on the individual with the emergence of precision medicine. A strong focus on the uniqueness of each individual has led to many discoveries in cancer diagnostics and drug efficacy and has prompted the US Food and Drug Administration to relabel numerous approved drugs to include pharmacogenomics information.

Evaluation of person-level heterogeneity of treatment effects in published multiperson N-of-1 studies: systematic review and reanalysis | BMJ Open

person-level HTE is common and often substantial