This Medical News article discusses a World Health Organization report on marketing tactics used to increase global nicotine pouch uptake.
Science Journals
The US Centers for Disease Control and Prevention (CDC) reported that drug overdose deaths decreased in 2025, marking the third consecutive year of decline.
This Medical News article discusses ongoing developments in the hantavirus cruise ship outbreak and the effect of the withdrawal of the US from the World Health Organization on managing the outbreak.
The heat of an olive grove in August staggers and stuns—cicadas drilling, the tall grass baked too dry for mulch.
In Reply We thank Drs Rader and Brownstein for their thoughtful Letter about our recent publication reporting estimates of US state-level adult obesity prevalence by race and ethnicity group through 2035. They correctly point out that our forecasts were based on past trends and raise the concern that our results did not account for the potential effect of recent changes in prescribing patterns of weight-management medications such as GLP-1 RAs on the prevalence of obesity.
This study evaluated whether addition of a locking fluid containing 4% tetrasodium EDTA (t-EDTA) reduced central venous access device (CVAD) complications compared with usual care among adults in intensive care units (ICUs).
Certain metrics of the sleep-wake cycle, a behavioral manifestation of the circadian rhythm, may be associated with dementia, a study published in JAMA Neurology found.
In Reply We appreciate the thoughtful comments and the opportunity to provide additional granularity regarding outcomes stratified by interval from declaration of death to flush or AWIT (<10 minutes vs ≥10 minutes) for our early experience with REUP for DCD heart recovery.
Muscle loss, weaker grip strength, and slower walking pace may all be connected to a higher risk of stroke, a recent study found.
Traditionally, health plans manage payment for care, while clinicians deliver care. Although these roles have typically been distinct, organizations have increasingly merged these functions, integrating care and coverage. The largest health insurers in the US now also operate extensive physician networks, while health systems are increasingly acquiring or partnering with payers. These payer-provider integrated entities, often referred to as payviders, are a variation of earlier integrated models and are driven by more contemporary features of the health care delivery landscape, including Medicare Advantage expansion, value-based care payment reforms, substantial capital investment in health care organizations, and limited federal oversight of vertical integration.
This JAMA Patient Page describes risk factors for gastric cancer, ways to prevent it, and the treatment and prognosis.
This randomized trial assesses the effect of 4% t-EDTA locking solution vs control locking fluid on composite incidence of central venous access device (CVAD)–associated bloodstream infection, catheter occlusion requiring alteplase use, and catheter removal due to occlusion among adult patients in the intensive care unit.
<p>by Ron Sender, Tal Kedar, Yoav Navon, Moriya Raz, Shirley Bikel, Rina Hemi, Ron Milo, Shai Fuchs</p>
The human endocrine system orchestrates critical physiological processes, yet a systematic quantitative synthesis of clinically relevant circulating hormones has been lacking. Here, we present a comprehensive, integrative analysis of circulating human hormones, leveraging clinically validated reference intervals across major endocrine subsystems. We use clinically validated reference intervals that we further validate using published datasets. Our analysis reveals that the total mass of circulating hormones is approximately 40 ± 2 mg. We find that this mass in healthy young adults is dominated by Adiponectin and DHEAS, which constitute over 90% of both total hormone weight and copy number. We show there are on the order of a million hormone molecules per cell in the human body. Females have about half the number of circulating hormone molecules compared to males. Across 56 hormones with curated affinity data, free (receptor-available) concentration correlates with receptor binding affinity, with class-specific scaling. Bioavailability mechanisms segregate by chemical class, consistent with chemical structure constraining available buffering strategies. Together, these data provide a quantitative reference for the human endocrine system and highlight relationships linking receptor affinity, bioavailability, and chemical class.
<p>by Eun Seon Chung, William C. Johnson, Maliwan Kamkaew, Timothy A. Fitzgerald, Morgan E. McNellis, Trever C. Smith II, Srinivasan Vijay, Nguyen Thuy Thuong Thuong, Shumin Tan, Bree Beardsley Aldridge</p>
The ability of <i>Mycobacterium tuberculosis</i> (Mtb) to dynamically adjust its growth behavior in response to host environments is critical for survival under immune and drug stress, but how these behaviors shift at the single-cell level remains poorly understood. Here, using high-resolution single-cell analysis, we show that Mtb adapts to acidic conditions by increasing the proportion of bacteria in a growth-arrested state, rather than uniformly slowing the growth rate of the entire population. This nongrowing subpopulation exhibits enhanced tolerance to ethambutol, highlighting its role in drug survival. Clinical strains displayed higher proportions of growth-arrested cells under both neutral and acidic conditions, suggesting that growth arrest may serve as one of the strategies for persistence during infection. While the PhoPR two-component system partially regulates this state, our RNA sequencing analysis revealed additional transcriptional regulators that are upregulated following acidic adaptation and may contribute to entry into the growth-arrested state and increased tolerance to ethambutol. Our study demonstrates that increasing the proportion of nongrowing subpopulations is an active adaptive strategy that can influence antibiotic susceptibility under acidic conditions, offering new perspectives for targeting bacterial heterogeneity in tuberculosis therapy.
<p>by Yueyue Sapphire Hou, Pooya Laamerad, Liu D. Liu, Christopher C. Pack</p>
Fluctuations in single-neuron activity in the sensory cortex often correlate with perceptual decisions. This kind of correlation is often hypothesized to reflect a causal influence of sensory signals on decisions, but it can be attributed to various noncausal factors as well. To disentangle these different possibilities, we have examined local field potentials (LFPs) recorded from the middle temporal (MT) area and area V4 of nonhuman primates (<i>Macaca mulatta</i>) while they performed two different perceptual decision-making tasks. Compared to single-neuron spiking, LFPs have the advantage of being decomposable into frequency bands that are associated with different anatomical sources of input. More importantly, they persist when spiking activity is inactivated, which precludes a causal influence of the corresponding neural activity on behavior. We found that high-gamma frequency (70–150 Hz) LFP power was correlated with perceptual decisions and that this correlation disappeared when spikes were inactivated, consistent with a causal role for this frequency band in decision-making. These signals overlapped in time with decision signals in the lower gamma band (30–70 Hz), which persisted after spiking inactivation, suggesting a noncausal input. Interestingly, lower-frequency LFP signals (5–30 Hz) reflected both impending perceptual decisions and the outcome of preceding trials, suggesting a modulatory influence of recent experience on neural dynamics. Our results, therefore, reveal that neural activity multiplexes different sources of information about perceptual decisions and that these types of information can be estimated reliably from different LFP frequencies.
‘<i>Candidatus</i> Liberibacter asiaticus’ (<i>C</i>Las), the causal agent of citrus huanglongbing, is transmitted by the Asian citrus psyllid <i>Diaphorina citri</i>. While <i>C</i>Las-positive (<i>C</i>Las+) females exhibit increased fecundity and metabolic demands, their neuroendocrine regulation mechanisms remain unclear. We propose <i>C</i>Las manipulates dopamine (DA) signaling to enhance psyllid fecundity and <i>C</i>Las proliferation. Metabolomics revealed elevated DA in <i>C</i>Las+ females. Silencing DA synthesis genes and receptor <i>DcDop2</i> via RNAi reduced lipid reserves, fecundity, and ovarian <i>C</i>Las titers. Through combined <i>in vivo</i> and <i>in vitro</i> experiments, we demonstrated that the microRNA miR-31a suppresses <i>DcDop2</i> expression by binding to its 3’ untranslated region. Overexpression of miR-31a resulted in decreased <i>DcDop2</i> expression and <i>C</i>Las titers in the ovaries, eliciting phenotypic defects akin to <i>DcDop2</i> knockdown. Furthermore, <i>DcDop2</i> knockdown and miR-31a overexpression reduced juvenile hormone (JH) levels and adipokinetic hormone (AKH) signaling in fat bodies and ovaries. Consequently, <i>C</i>Las regulates the DA-<i>DcDop2</i> signaling axis to improve <i>D. citri</i> lipid metabolism and fecundity, while simultaneously promoting its replication. These findings reveal a coevolution between <i>C</i>Las proliferation and ovarian development in the insect host. This discovery enhances our understanding of the molecular interplay between plant pathogens and vector insects and offers novel targets and strategies for HLB field management.
Animals integrate knowledge about how the state of the environment evolves to choose actions that maximise reward. Such goal-directed behaviour – or model-based (MB) reinforcement learning (RL) – can flexibly adapt choice to changes, being thus distinct from simpler habitual – or model-free (MF) RL – strategies. Previous inactivation and neuroimaging work implicates prefrontal cortex (PFC) and the caudate striatal region in MB-RL; however, details are scarce about its implementation at the single-neuron level. Here, we recorded from two PFC regions – the dorsal anterior cingulate cortex (ACC) and dorsolateral PFC (DLPFC), and two striatal regions, caudate and putamen – while two rhesus macaques performed a sequential decision-making (two-step) task in which MB-RL involves knowledge about the statistics of reward and state transitions. All four regions, but particularly the ACC, encoded the rewards received and tracked the probabilistic state transitions that occurred. However, ACC (and to a lesser extent caudate) encoded the key variables of the task – namely the interaction between reward, transition, and choice – which underlies MB decision-making. ACC and caudate neurons also encoded MB-derived estimates of choice values. Moreover, caudate value estimates of the choice options flipped when a rare transition occurred, demonstrating value update based on structural knowledge of the task. The striatal regions were unique (relative to PFC) in encoding the current and previous rewards with opposing polarities, reminiscent of dopaminergic neurons, and indicative of an MF prediction error. Our findings provide a deeper understanding of selective and temporally dissociable neural mechanisms underlying goal-directed behaviour.
Exposure to stress can cause long-lasting enhancement of fear and other defensive responses that extend beyond the cues or contexts associated with the original traumatic event. These nonassociative consequences of stress, referred to as fear sensitization, are thought to underlie some symptoms of trauma-related disorders. Fear sensitization has been predominantly studied using the stress-enhanced fear learning (SEFL) paradigm, which models the stress-induced amplification of fear learning. Less is known about the mechanisms through which unlearned fear responses are sensitized by stress. Here, we investigated the neural mechanisms for sensitization of unlearned fear responses using a paradigm we termed stress-enhanced fear responding (SEFR). In this model, mice exposed to a single session of footshock stress exhibit enhanced freezing to a novel tone stimulus. To investigate brain regions that might mediate SEFR, we first used c-Fos mapping to identify neural activity changes associated with stress-induced enhancement of unlearned fear. Our c-Fos screen identified the posterior paraventricular thalamus (pPVT) as a region that was persistently hyperactive after footshock stress and whose activity correlated with behavioral expression of SEFR. Using fiber photometry, we observed that SEFR, but not SEFL, was associated with increased activity in the pPVT. Next, we found that chemogenetic inhibition of the pPVT blocked both the induction of SEFR during stress and its later expression, while artificial stimulation of pPVT in stress-naive mice was sufficient to recapitulate SEFR. Interestingly, pPVT inhibition or stimulation did not affect acquisition or expression of SEFL. In conclusion, our results indicate that sensitization of fear learning (SEFL) and sensitization of unlearned fear (SEFR) have distinct neural mechanisms. Our results identify pPVT hyperactivity as a mechanism for stress-induced sensitization of unlearned fear and highlight pPVT as a potential targe…
APOE4, the major genetic risk factor for Alzheimer’s disease (AD), and ATP-binding cassette-A1 (ABCA1), required for lipidation of APOE are gene products of the liver X receptor (LXR) receptor. LXR agonists have been validated in animal models as therapeutics for AD, atherosclerosis, and many other diseases. Clinical progress has been thwarted by unwanted hepatic lipogenesis. Structurally diverse LXR ligands were profiled in coregulator TR-FRET (CRT) assays analyzing ligand-induced coactivator recruitment, coactivator selectivity, corepressor dissociation, and LXR isoform selectivity. A multiplex CRT assay was developed to measure synchronous ligand-induced displacement of corepressor by coactivator. Potency for coactivator recruitment to LXRβ correlated with induction of ABCA1 in human astrocytoma cells. Correlation with lipogenic activation of sterol response element (SRE) in hepatocarcinoma cells, was more complex. CRT response was diverse revealing ligands with theoretical full agonist, partial agonist, antagonist, inverse agonist, and other signatures within the same chemical series, suggesting the scope for precision CRT to guide nonlipogenic LXR agonist design.
High-speed volumetric imaging of the brain is essential for linking diverse cellular events to tissue-level functions. However, the brain’s structural and dynamic heterogeneity—spanning microns to millimeters and milliseconds to hours—requires imaging techniques with tunable spatiotemporal resolution, flexible 3D sampling, and compatibility with targeted perturbations. Here, we present tunable Bessel beam two-photon fluorescence microscopy (tBessel-TPFM), a compact, low-cost, and versatile platform for intravital brain imaging across millimeter scale with subcellular resolution. tBessel-TPFM transforms slow 3D volume scans into fast 2D frame scans via an axially elongated Bessel focus, achieving acquisition rates ~100 fold faster and reduced motion artifacts compared with conventional TPFM. Exploiting its full tunability of the Bessel focus, we applied tBessel-TPFM for quantitative mapping of cerebral blood flow and neurovascular coupling in normal and ischemic stroke mice. Unlike existing Bessel focus generation methods, the axial center of tBessel-TPFM remains fixed at the objective focal plane during profile tuning. Leveraging this advantage, we integrated tBessel-TPFM with simultaneous 3D targeted optogenetic stimulation for volumetric neuronal connectivity mapping. We also tracked microglial process dynamics following single-cell laser ablation, revealing diverse neuroimmune responses across spatial and temporal scales. By combining high speed, deep penetration, tunable sampling, and multimodal perturbation, tBessel-TPFM empowers a broad spectrum of neurobiological investigations—from vascular physiology and functional connectivity to neuroimmune interactions.
Trained immunity (TI) is defined as a form of innate immune memory characterised by a long-lasting ability to develop enhanced responses to a secondary challenge, whether of the same or a different nature than the initial stimulus. This process is mediated by several established hallmarks, most prominently the existence of activating epigenetic marks and metabolic adaptations. The activating epigenetic marks prime the expression of immune-related genes and are a direct driving force behind the increased cytokine production after secondary stimulation of trained monocytes and macrophages. Training stimuli also induce specific metabolic adaptations, such as the upregulation of glycolysis and lactate production or the activation of glutaminolysis leading to fumarate accumulation, which in turn promotes epigenetic changes. However, the mechanisms linking these epigenetic and metabolic changes to a TI phenotype are varied, and not all stimuli that increase glycolysis promote training, whereas some stimuli such as lipopolysaccharide (LPS) display a non-monotonic induction of TI. In addition to metabolism directly driving epigenetic changes, early gene expression changes can also reshape cell metabolism to promote a trained phenotype. In this review we aim to separate two main types of metabolic rewiring that have not been previously uncoupled. Firstly, those primary metabolic changes occurring during the initial stimulation, which precede TI induction by altering the epigenomic landscape around inflammatory genes. Secondly, those metabolic adaptations arising later as a consequence of the first wave of epigenetic regulation, which support an enhanced functional state of macrophages.
The central nervous system (CNS) can effectively control body movements despite environmental changes. While much is known about adaptation to external environmental changes, less is known about responses to internal bodily changes. This study investigates how the CNS adapts to long-term alterations in the musculoskeletal system using a tendon transfer model in nonhuman primates (<i>Macaca fuscata</i>). We surgically relocated finger flexor and extensor muscles to examine how the CNS adapts its strategy for finger movement control by measuring muscle activities during grasping tasks. Two months post-surgery, the monkeys demonstrated significant recovery of grasping function despite the initial disruption. Our findings suggest a two-phase CNS adaptation process: an initial phase enabling function with the transferred muscles, followed by a later phase abandoning this enabled function and restoring a control strategy that, while potentially less conflicted than the maladaptive state, resembled the original pattern, possibly representing a ‘good enough’ solution. These results highlight a multi-phase CNS adaptation process with distinct time constants in response to sudden bodily changes, offering potential insights into understanding and treating movement disorders.
Mating and other behaviors emerge during adolescence through the coordinated actions of steroid hormone signaling throughout the nervous system and periphery. In this study, we investigated the transcriptional dynamics of the medial preoptic area (MPOA), a critical region for reproductive behavior, using single-cell RNA sequencing (scRNA-seq) and in situ hybridization techniques in male and female mice throughout adolescence development. Our findings reveal that estrogen receptor 1 (Esr1) plays a pivotal role in the transcriptional maturation of GABAergic neurons within the MPOA during adolescence. Deletion of the estrogen receptor gene, <i>Esr1</i>, in GABAergic neurons (Vgat+) disrupted the developmental progression of mating behaviors in both sexes, while its deletion in glutamatergic neurons (Vglut2+) had no observable effect. In males and females, these neurons displayed distinct transcriptional trajectories, with hormone-dependent gene expression patterns emerging throughout adolescence and regulated by <i>Esr1. Esr1</i> deletion in MPOA GABAergic neurons, prior to adolescence, arrested adolescent transcriptional progression of these cells and uncovered sex-specific gene-regulatory networks associated with <i>Esr1</i> signaling. Our results underscore the critical role of <i>Esr1</i> in orchestrating sex-specific transcriptional dynamics during adolescence, revealing gene regulatory networks implicated in the development of hypothalamic-controlled reproductive behaviors.
The quality of stable long-term recordings from chronically implanted electrode arrays is essential for experimental neuroscience and brain-computer interfaces. This work uses scanning electron microscopy (SEM) to image and analyze eight 96-channel Utah arrays previously implanted in motor cortical regions of four subjects (subject H = 2242 days implanted, F = 1875, U = 2680, C = 594), providing important contributions to a growing body of long-term implant research leveraging this imaging technology. Four of these arrays have been used in electrolytic lesioning experiments (H = 10 lesions, F = 1, U = 4, C = 1), a recently developed electrolytic perturbation technique demonstrated compatible with continued neuroelectrophysiology using small direct currents. Previously, our group showed that electrolytic lesioning can be used as a technique to create regions of controlled neuron loss without significantly changing recording quality (Bray, Clarke et al., 2024). Here, by surveying physical damage such as biological debris and material deterioration, we show that electrolytic lesioning causes no statistically significant material damage to the implanted electrode arrays. In addition to surveying physical damage, such as biological debris and material deterioration, this work also analyzes whether electrolytic lesioning created damage beyond what is typical for these arrays. These findings also indicate that there are no statistically significant differences between the damage observed on normal electrodes versus those used for electrolytic lesioning, yielding no evidence that electrolytic lesioning significantly affects the material quality of chronically implanted electrode arrays. Finally, this work also includes the largest collection of single-electrode SEM images for previously implanted multielectrode Utah arrays, spanning 11 different intact arrays and one broken array. As the clinical relevance of chronically implanted electrodes with single-neuron resolution…