MACOM (United States)

NaV (voltage-gated sodium) channels drive cardiac excitability. Although NaV1.5 is the primary cardiac isoform, the composition and functional contributions of non-NaV1.5 isoforms in the heart remain unclear. Here, we developed a chemical-genetic mouse model (NaV1.5GX/GX) in which NaV1.5 can be selectively and reversibly inhibited by acyl- and aryl-sulfonamide compounds (GX [acyl- and aryl-sulfonamide compounds typically denoted by the name GX-### and associated items] drugs). Cardiac activity was assessed by electrocardiograms in vivo, and optical mapping was used for imaging of ex vivo hearts. Whole-cell voltage-clamp in tandem with validated toxins and isoform-selective inhibitors were used to examine sodium current composition. NaV1.5GX/GX mice exhibited normal cardiac function at baseline, but acute GX drug administration caused profound conduction defects and arrhythmias. Whole-heart optical mapping revealed dose-dependent chamber-specific sensitivity to NaV1.5 inhibition, with the right ventricle being the most sensitive, followed by the left ventricle, left atrium, and right atrium. Patch-clamp recordings of isolated cardiomyocytes with application of NaV isoform-selective inhibitors showed that NaV1.5 contributed 93% of sodium current in the left ventricle, 79% in the right ventricle, and 78% in the atria. Non-NaV1.5 isoforms were differentially enriched across chambers: NaV1.8 in the left ventricle, NaV1.1/1.3 in the right ventricle, and NaV1.2/1.6/1.7 in the atria. These results reveal a surprising chamber-specific isoform landscape of cardiac sodium currents, which may underlie the right ventricular predominant phenotype of Brugada syndrome. These data highlight non-NaV1.5 isoforms as potential mediators of chamber-specific cardiac pathologies and as pharmacological targets.

Low-level light therapy (LLLT) has been shown to modulate recovery in patients with traumatic brain injury (TBI). However, the longitudinal impact of LLLT on brain metabolites has not been studied. The purpose of this study was to use MR spectroscopic imaging to assess the metabolic response of LLLT in patients with moderate TBI at acute (within 1 week), subacute (2-3 weeks), and late-subacute (3 months) recovery phases. This is a secondary analysis of a prospective single-site double-blind sham-controlled study conducted in patients with moderate TBI. Participants were randomized for LLLT and sham treatment. Three-Tesla 2D MR spectroscopic imaging was acquired. Our focus of investigation was the metabolic change in the corpus callosum (CC) and the changes in mIns/NAA, representing the combined effect of elevated neuroinflammation (mIns) and decreased neuronal/axonal health (NAA). A linear mixed-effects model was constructed to quantify the association between mIns/NAA and treatment, scan, and the interaction between treatment and scan. Thirty-four participants (18 men, age 49 ± 17 [range, 20-79]; 15 LLLT, 19 sham) were included in the final data set and were scanned at the following time points: acute (n=24), subacute (n=27), and late subacute (n=23). The mIns/NAA ratio in the CC of the sham-treated participants increased over time. Sham-treated participants revealed a significant increase in mIns/NAA from the acute to the late subacute phases (0.19; 95% CI, 0.09-0.29; P Holm = .005). mIns/NAA stayed relatively stable in participants undergoing LLLT treatment (all P Holm > .64). Consequently, mIns/NAA was significantly higher in the sham-treated participants compared with the LLLT-treated participants during the late subacute phase of recovery (-0.31; 95% CI, -0.50 to -0.12; P Holm = .019). Despite the small sample size, MR spectroscopic imaging indicates a metabolic response in participants treated with LLLT compared with those receiving sham treatment. This potentially suggests a neuroprotective and anti-inflammatory effect from the acute administration of LLLT in individuals with moderate TBI.

Background Online grocery shopping interventions using optimal defaults have improved the nutritional quality of grocery purchases, but no studies have explored impacts on dietary intake. This analysis examines the potential of an optimal defaults online grocery shopping intervention to promote healthier intake by assessing (1) the relationship between the nutritional quality of grocery shopping purchases and the nutritional quality of intake, and (2) intervention effects on the nutritional quality of participants' dietary intake. Methods A randomized controlled trial tested the effects of an optimal defaults intervention promoting grocery purchases consistent with a diabetic diet. As part of the 5-week, 3-arm study, participants were randomly assigned to grocery shop either (1) in person as usual (control group), (2) online (online group), or (3) online with a prefilled, default grocery shopping cart (defaults group) during a 3-week intervention. All groups received recipes corresponding to the Dietary Approaches to Stop Hypertension diet. Participants submitted grocery receipts and completed interviews weekly. Fifty-five adults provided a complete food frequency questionnaire post intervention. Linear regression tested the relationship between the nutritional quality of grocery shopping purchases and the nutritional quality of intake. Analysis of variance examined the effect of study group on the nutritional quality of dietary intake. Results The nutritional quality of household grocery purchases was positively associated with the nutritional quality of participants' intake ( P < .001). The effect of study group on the nutritional quality of intake was not significant ( P = .07), although trend-level results were in the expected direction with the defaults group having the highest nutritional quality of the 3 groups. Conclusions Optimal defaults interventions' effects on grocery purchases may extend to dietary intake. Future research using more precise and objective measures of dietary intake could elucidate potential effects.

Significant cognitive impairment follows cardiac arrest, yet few interventions restore memory. We previously demonstrated that physical exercise (PE) after asphyxial cardiac arrest (ACA) mitigates memory deficits and cell loss in the septal nuclei, but not in the hippocampus in rats. Given the critical role of the septum in modulating hippocampal theta oscillations, essential for memory, we hypothesize that PE preserves memory by safeguarding septal pacemaker neurons and septo-hippocampal theta activity. Adult male and female rats underwent 8 minutes of ACA or sham surgery and were randomly assigned to 5 days of treadmill running PE or sedentary conditions. Long- and short-term memory were assessed using fear conditioning and Y-maze tests. Immunohistochemistry quantified septal cholinergic and gamma-aminobutyric acid-ergic neurons. Local field potential recordings evaluated oscillatory activity across the septo-hippocampal network. ACA induced persistent deficits in memory and disrupted theta oscillations throughout the septum and cornu ammonis 1 (CA1) laminae. These changes were accompanied by selective loss of cholinergic and gamma-aminobutyric acid-ergic septal neurons. PE markedly improved cognitive performance and restored theta power across the septo-hippocampal axis. Only cholinergic, not gamma-aminobutyric acid-ergic, neurons were preserved after PE. All effects were consistent across sexes. Importantly, enhancements in CA1 theta power closely tracked behavioral recovery, implying that reestablishment of cholinergic-driven network dynamics plays a central role in memory restoration. This study is the first to directly implicate PE-induced cholinergic neuron preservation in the reengagement of septo-hippocampal circuitry and cognitive recovery post cardiac arrest. Rather than relying on hippocampal cell survival, the observed memory improvements appear to stem from reinstated interregional theta synchrony. These findings define a novel mechanistic pathway for promoting functional recovery via targeted circuit-level rehabilitation after ischemic brain injury.

Objective: This study proposes the Exercise–Neuroprotection–Mental Health (ENM) model, an integrative framework explaining how exercise enhances mental health through multilevel neurobiological mechanisms. Methods: Drawing on evidence related to exercise-induced neurotrophic factors, myokines, neuroplasticity, and emotion-related neural circuits, we synthesized current findings and developed mechanistic inferences following the pathway from physiological activation to molecular signaling, neuroplastic changes, neural-circuit modulation, and mental-health outcomes. Results: The ENM model suggests that exercise triggers peripheral activation leading to increased BDNF, irisin, and anti-inflammatory and antioxidant responses. These molecular changes enhance synaptic plasticity, neurogenesis, and network efficiency in the hippocampus and prefrontal cortex. At the circuit level, improved functioning of the PFC–amygdala emotion-regulation pathway, the hippocampus–HPA axis, and the VTA–NAc reward system contributes to better emotional stability, stress resilience, and motivation. The model yields testable hypotheses regarding the mediating role of BDNF, the involvement of the PFC–amygdala circuit in anxiolytic effects, the role of the VTA–NAc pathway in antidepressant effects, and myokines and inflammation as intervention targets. Conclusion: The ENM model offers a coherent framework linking exercise to neuroprotection and mental-health improvement and provides theoretical guidance for targeted exercise prescriptions and future neuroimaging, biomarker, and clinical validation studies.

目的：探讨日间化疗胃癌患者癌症引起的疲劳与负面情绪之间的关系，并评估积极思维干预对改善癌症引起的疲劳、负面情绪和患者生活质量的影响。 方法： 选取 120 例胃癌患者，随机分为干预组和对照组，每组 60 例。对照组接受常规护理，干预组在常规护理基础上接受 8 周的积极思维干预。采用 Piper 疲劳量表评估癌症引起的疲劳，采用 SAS 和 SDS 评估负面情绪，EORTC QLQ-C30 分别评估干预前、干预后第 4 周和第 8 周的生活质量，记录干预依从性和不良反应。结果： 癌症引起的疲劳与消极情绪呈显著正相关 （P<0.05）。干预后，干预组癌症引起的疲劳评分显著低于对照组 （P<0.05），焦虑抑郁评分显著降低 （P<0.001），生活质量评分显著升高 （P<0.001），睡眠质量显著改善 （P<0.05）。干预组对干预的依从性为 93.33%，无严重不良事件，仅部分患者报告短暂不适，不影响干预的继续。结论： 积极思考干预可显著改善日间化疗胃癌患者癌症引起的疲劳、消极情绪、生活质量和睡眠质量，具有较高的依从性和安全性，适合在临床护理中推广应用。

The American Association for the Surgery of Trauma Organ Injury Scale (OIS) Committee published the original pancreatic OIS in 1990 with the authors acknowledging at the time that the classification would need to undergo "continued refinement as clinical experience dictates." The current OIS overemphasizes injury location over ductal integrity; modifications are needed to improve concordance between OIS, therapy, and outcomes and promote accuracy in quality assessment and research. A subcommittee of the American Association for the Surgery of Trauma and invited experts in radiology and interventional gastroenterology were chosen. Contemporary literature was reviewed, and a standardized iterative and collegial process was used to arrive at consensus. The pancreatic OIS is anatomically based on operative, radiographic, or pathologic findings. Major changes to the grading system include moving lacerations of the pancreatic head without ductal injury from Grade IV to Grade II. Injuries to the duct in the neck, body, or tail remain Grade III but are further subclassified to distinguish between deep parenchymal injuries without ductal interrogation, partial ductal injuries, and complete ductal transection. Grade IV injuries follow the same nomenclature but for injuries to the right of the portal vein or superior mesenteric vein. Grade V injuries are destructive injuries of the pancreatic head with nonviable parenchyma. These injuries are further subgraded based on ductal injuries. The pancreatic OIS schema is revised based on contemporary experience informed by the current understanding of outcomes and treatment, including operative management and outcomes. Increasing grades now more closely reflect increasing severity.

According to the dual syndrome hypothesis, patients with Parkinson disease (PD) with visuospatial deficits are more likely to progress to dementia, compared with patients with a prevalent dysexecutive syndrome. In this study, we aimed to investigate whether early connectivity changes in the dorsolateral prefrontal cortex (DLPFC) and the precuneus (PCun)-which are critical to fronto-executive and visuospatial functions, respectively-can identify distinct cognitive phenotypes in cognitively intact newly diagnosed patients with PD. Newly diagnosed, drug-naïve patients with PD (≤2 years from clinical onset) with normal Montreal Cognitive Assessment (MoCA), were consecutively enrolled from our Movement Disorders Clinics in Italy. Sex-matched and age-matched healthy controls (HCs) were enrolled among nonconsanguineous patients' relatives. Participants underwent 3T-fMRI to investigate resting-state functional connectivity (rs-FC) of DLPFC and PCun with a seed-based approach at baseline (T0). K-means cluster analysis was performed on z scores of rs-FC values of patients with PD to identify clusters of patients sharing common patterns of connectivity. Differences in neurophysiologic, motor, and nonmotor scales among PD clusters were assessed at T0 and after a 3.5-year follow-up (T1). The study included 68 patients with PD (27% women; mean age: 60 ± 9 years; Hoehn & Yahr score: 1.4 ± 0.5; MoCA score: 27.9 ± 1.6) and 31 HCs (39% women; mean age 64.2 ± 9.3 years) at T0. Forty-two patients completed T1 evaluation. Patients displayed reduced rs-FC of both DLPFC and PCun with several cortical and subcortical areas compared with HCs. Cluster 1 was defined by lower values of rs-FC in all investigated regions of interest while clusters 2 and 3, respectively, by higher and intermediate values. Despite none meeting criteria for mild cognitive impairment (MCI) at T0, cluster 1 was older and lower performing in global cognition, fronto-executive, and memory domains, compared with clusters 2 and 3 (all p < 0.031). At T1, a more evident worsening in global cognition, fronto-executive, and visuospatial domains and nonmotor and motor symptoms was observed in clusters 1 and 3 vs cluster 2 (all p < 0.04), with MCI being more frequent in clusters 1 and 3. Early connectivity changes of the DLPFC and the PCun occur in newly diagnosed patients with PD without MCI and can distinguish cognitive phenotypes, as confirmed after a longitudinal clinical observation.

Photo journalist Susan Schulman travelled to Iraq in July–August 2024 to investigate the impact of climate change on the country’s hospitals and schools, and its consequences for human security.

Petit guide de crole martiniquais, dont le titre masque avec modestie l'ampleur du travail engag par Loc Jean-Louis et Anne Zribi-Hertz est une belle contribution aux tudes sur les langues croles en gnral, sur le crole martiniquais en particulier.Loc Jean-Louis et Anne Zribi-Hertz proposent une excursion captivante et dynamique dans le ddale de la grammaire du crole martiniquais.Ce voyage passe par des couloirs dj explors dans d'autres ouvrages d'une part, tels que le systme Temps-Mode-Aspect, la dtermination ou la morphologie nominale.Loc Jean-Louis et Anne Zribi-Hertz y apportent leur propre clairage tout en faisant tat des travaux dj effectus.D'autre part, les co-auteur.e.s empruntent des pistes peu ou pas explores ce jour pour le crole martiniquais.Parmi elles, la richesse des subtilits et nuances smantiques des constructions grammaticales du crole martiniquais.Bien que les co-auteur.e.s signalent que leurs analyses smantiques relvent plus de questionnements liminaires et de propositions que d'un travail exhaustif et achev, leur entreprise initie les lecteurs et lectrices ce qui relve d'un emploi foncirement idiomatique des ressources de la langue. 2Toutes ces informations sont dlivres sous un format qui ouvre l'accessibilit de leur recherche une diversit de publics de lecteurs et lectrices.Tel tait l'un des objectifs que les co-auteur.e.s se sont fixs dans l'introduction et force est de constater que Loc Jean-Louis et Anne Zribi-Hertz y sont parvenu.e.s.En effet, les co-auteur.e.s adoptent une dmarche exploratoire dans une structuration diffrente de celles des grammaires traditionnelles.