Rats exposed to widely approved levels of a common herbicide developed hypervigilance and an unnatural fear of harmless objects. The effect seems driven by the chemical’s ability to kill mood-regulating bacteria in the digestive tract.
Category: biotech/medical – Page 185
How “mindreading” AI detects hidden suicidal thoughts in the brains of young adults
A recent study published in Human Brain Mapping provides evidence that young adults experiencing suicidal thoughts process concepts related to death differently in their brains compared to healthy individuals. The findings indicate that these individuals reflexively associate death-related ideas with their own sense of self. This research suggests that brain imaging combined with artificial intelligence could eventually help identify people at risk for suicide based on how their brains represent specific words.
If you or someone you know is experiencing suicidal thoughts or a mental health crisis, help is available. Call or text 988 to reach the free and confidential Suicide & Crisis Lifeline, or chat live at 988lifeline.org.
While mental health professionals typically rely on patients to report their feelings, people at risk for suicide do not always disclose their struggles. Finding an objective physical measurement in the brain could help identify those in need of support.
Depression is linked to a genuine pessimistic bias rather than a realistic view of the world
A recent study published in the journal Behaviour Research and Therapy provides evidence that people experiencing symptoms of depression hold genuinely pessimistic biases about future positive events, rather than simply viewing the world more realistically. The research suggests that while individuals with depression can update their beliefs when desirable things happen, these hopeful shifts tend to be fragile and easily reversed.
The study was designed to test whether the negative thinking patterns seen in depression reflect a genuine bias or just an absence of normal optimism. For decades, experts have debated the idea of depressive realism, a concept suggesting that depressed individuals actually see the world more accurately than healthy individuals, who tend to be overly optimistic. To test this, the researchers wanted to see how people predict everyday life events and how they adjust those expectations when real life proves them wrong.
“We know that depression involves a generally pessimistic outlook on life. Previous research has shown that people with high depressive symptoms tend to underestimate the likelihood of positive outcomes in their lives,” said study author Joe Maffly-Kipp, a postdoctoral fellow in the Mood & Individual Differences Lab (MIND Lab) at The Ohio State University Wexner Medical Center.
Study of 6 Million People Could Rewrite How We Understand Mental Health
From the article:
The study also identified specific brain cell types associated with the genetic patterns.
For the schizophrenia bipolar group, the strongest genetic signals appeared in genes active in excitatory neurons. These neurons transmit signals that activate other brain cells and help different parts of the brain communicate.
In contrast, genetic risk tied to internalizing disorders such as depression, anxiety, and PTSD showed stronger links to oligodendrocytes. These cells help nerve signals travel more efficiently through the brain.
“The findings suggest these ‘support cells’ might play an important role in those conditions,” said Verhulst, research assistant professor and an expert in quantitative and statistical genetics.”
A massive genetic analysis of more than 6 million people is revealing new clues about why mental health disorders frequently overlap.
Pitfalls and Potential of Dementia Prevention Trials
💬 Editorial by Holly Elser, MD, PhD, and Jonathan Graff-Radford, MD:
Recent randomized clinical trials on dementia prevention highlight several challenges in interpreting lifestyle intervention studies, including practice and Hawthorne effects, modest changes in cognitive outcomes, and heterogeneity in both trial design and participant baseline risk.
The trial by Zhang et al—evaluating aerobic exercise and intensive vascular risk reduction—showed no significant cognitive benefit over 2 years in older adults at elevated risk, underscoring the potential influence of midlife vs late-life intervention timing and the need for longer trials or biomarker-enriched cohorts to better assess dementia prevention strategies.
Dementia prevention is a global public health priority,1,2 with up to 45% of cases potentially attributable to modifiable risk factors over the life course.3 While recent landmark trials, including FINGER, SPRINT MIND, and POINTER, suggest either single-or multidomain lifestyle interventions can improve cognitive outcomes,4-6 others have shown no clear benefit,7,8 thus highlighting ongoing uncertainty in the field.
In this issue of JAMA Neurol ogy, Zhang and colleagues9 report the results of a single-blind, multicenter randomized clinical trial of the effects of exercise and intensive vascular risk reduction on cognitive function. Eligible study participants were between the ages of 60 and 85 years at baseline with a history of hypertension, family history of dementia, or self-reported cognitive decline. The study used a 2 × 2 factorial design wherein participants were randomized to aerobic exercise training alone, intensive pharmacological reduction of cardiovascular risk factors (IRVR) alone, both aerobic exercise and IRVR, or usual care for a 24-month period. The IRVR protocol lowered systolic blood pressure to less than 130 mm Hg, and participants with baseline serum low-density lipoprotein cholesterol (LDL-C) of 70 mg/dL or higher were also treated with a high-intensity statin.
Studying 2 distinct human cohorts with recent exposure to TB
https://doi.org/10.1172/jci.insight.202134 Paul Ogongo & team find different individual Mycobacterium tuberculosis antigens induce distinct T cell responses, with important implications for TB vaccine development.
5Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
6Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, California, USA.
7Department of Infectious Disease and Immunology, Center for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark.
Long-term inflammatory memory driver identified!
The researchers first gave a bout of psoriasis to mice when they were young. They discovered that about 10–15% of the memories that persisted a month later stuck around even to the end of the mouse’s life (~2 years). To see why these long-term memories lingered while their short-term counterparts faded within six months, they analyzed the DNA sequence characteristics within each of the memories by using a deep learning model customized by the third co-first author.
“When we compared the DNA sequences of short and long-term memory domains, they looked very similar in terms of the numbers and kinds of transcription factor binding sites,” says the author. “We realized we needed to develop a new metric that specifically captures memory persistence across time, not just total accessibility at any one point.”
Soto-Ugaldi’s adaptation, called PersistNet, quickly identified a telling trait: The longest lasting memory domains had an unusually high frequency of CpG dinucleotides—short DNA sequences of cytosine followed by guanine, which are known to play a key role in gene regulation. In fact, the model predicted that CpG density hardwires a timer into every memory domain: The more CpG’s, the longer the memory.
When they tested the prediction, that’s exactly what they found. “Looking across all 1,000 memory domains, we discovered that these nucleotide densities alone, and no other DNA sequence pattern, could distinguish how long each memory would linger,” says the author.
Back in the lab, the team discovered that these genetically wired densities enabled a host of epigenetic changes in memory domains, including DNA demethylation (the removal of a methyl group specifically found on CpG dinucleotides); the binding of transcription factors that prefer demethylated states; and the recruitment of a histone variant called H2A.Z, which preferentially seeks out demethylated sites and boosts chromatin accessibility while staving off future re-methylation. Together, these changes stabilized the open chromatin formation and its gene-priming activity. As the authors discovered, this structure could crucially be passed down across cellular generations, essentially keeping the doors open for life. Science Mission sciencenewshighlights.
One of the most puzzling aspects of common chronic inflammatory skin diseases such as psoriasis is how they become chronic. What allows an ongoing condition to stay dormant for months or even years, then seemingly spring back out of nowhere?
Induced Hypertension Shows Promise for Managing Early Neurological Deterioration in Stroke Care
In this BloggingStroke post, Romil Singh discusses Stroke article by Kim et al.
Early neurological deterioration (END) remains one of the most challenging and feared complications during the acute phase of ischemic stroke. Affecting up to 40% of patients, END often signals the expansion of infarction, worsening hypoperfusion, or thrombus propagation. Despite its prevalence and its strong association with long-term disability, we lack clear evidence-based guidance on treatment strategies for inducing hypertension to improve perfusion and escalating antithrombotic therapy in hopes of stabilizing the patient.
A new nationwide study from South Korea, published in Stroke, now offers some much-needed clarity. Kim et al. analyzed data for more than 3,000 patients with no cardioembolic ischemic stroke who developed END due to stroke progression. They compared the real-world effectiveness of three treatment approaches: conservative treatment, change in antithrombotic therapy, and iHTN, and looked at associations with early neurological improvement (NI) during hospitalization and functional outcomes at 3 months. Because END was confirmed with imaging and standardized assessments, the cohort offers a clear view of how clinicians manage stroke progression in the absence of hemorrhage or metabolic causes.
Spatial profiling of patient-matched HER2 positive gastric cancer reveals resistance mechanisms to targeted therapy
Sheng et al. present “” via https://bit.ly/4spB5XM (Original research, GI cancer section).
Why do targeted therapies stop working? Using spatial transcriptomics, this study reveals how tumour heterogeneity, immune escape and metabolic shifts drive resistance in HER2-positive gastric cancer. A must-read for anyone interested in precision oncology and treatment optimisation.
Background Human epidermal growth factor receptor 2 (HER2; ERBB2) is overexpressed or amplified in 15–20% of gastric cancers (HER2+ GC). Within individual HER2+ GCs, HER2/ ERBB2 expression is often variable. Although HER2 therapeutic targeting improves outcomes for HER2+ GC patients, acquired resistance is frequent.
Objective To spatially interrogate HER2+ GC interpatient and intrapatient heterogeneity and resistance mechanisms associated with HER2-targeting agents (trastuzumab, trastuzumab deruxtecan (T-DXd)).
Design Spatial transcriptomic analysis (GeoMx Digital Spatial Profiler) was applied to 1,500 regions of interest in 30 GCs—these contained 15 HER2+ GCs treated with trastuzumab and T-DXd subsequently. Analysis of patient-matched samples with acquired trastuzumab or T-DXd resistance revealed escape mechanisms.