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This study evaluated the effects of prolonged exposure to environmentally relevant levels of glyphosate, administered alone or in combination with dicamba and 2,4-dichlorophenoxyacetic acid (2,4-D), on behavioral outcomes and brain integrity in a rat model. Exposure was initiated during gestation and continued through postnatal development until early adulthood. Animals subjected to herbicide exposure exhibited alterations in locomotor activity, anxiety-related behavior, stress responses, and motor coordination, with more pronounced effects observed following combined exposure. These functional changes were associated with histopathological evidence of neuronal degeneration and vascular alterations, alongside biochemical indicators of oxidative imbalance in brain tissue. Our findings indicate that chronic exposure to low-dose herbicides during critical neurodevelopmental windows may induce persistent neurobehavioral and structural brain changes. The enhanced effects observed under mixture exposure conditions highlight the importance of considering combined environmental exposures in toxicological risk assessment. Acest studiu a evaluat efectele expunerii prelungite la niveluri relevante din punct de vedere ambiental de glifosat, administrat singur sau în combinație cu dicamba și acid 2,4-diclorofenoxiacetic (2,4-D), asupra comportamentului și integrității cerebrale într-un model experimental pe șobolan. Expunerea a fost inițiată în perioada gestațională și a continuat pe parcursul dezvoltării postnatale până la vârsta adultă timpurie. Animalele expuse la erbicide au prezentat modificări ale activității locomotorii, ale comportamentului de tip anxios, ale răspunsului la stres și ale coordonării motorii, efectele fiind mai pronunțate în cazul expunerii combinate. Aceste modificări funcționale au fost asociate cu dovezi histopatologice de degenerare neuronală și alterări vasculare, precum și cu dezechilibre oxidative la nivel cerebral. Rezultatele indică faptul că expunerea cronică la doze reduse de erbicide în perioade critice de neurodezvoltare poate induce modificări persistente neurocomportamentale și structurale.
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Retrospective cohort study. To investigate the association between preoperative body mass index (BMI) and 30-day mortality following metastatic spinal tumor surgery (MSTS), with particular emphasis on underweight status as a predictor of early postoperative mortality. Surgical intervention for spinal metastases carries substantial perioperative risk. BMI has emerged as a potential prognostic biomarker given its accessibility and relationship to nutritional status and physiological reserve. However, evidence regarding its predictive value remains conflicting. Moreover, the prognostic implications of low BMI are underexplored despite the high prevalence of cancer-related cachexia in this population. Data from the American College of Surgeons National Surgical Quality Improvement Program (2018-2023) were analyzed. Patients with disseminated cancer managed with MSTS were included. Underweight status was defined as BMI < 18.5 kg/m2. The primary endpoint was 30-day all-cause mortality. Univariable and multivariable logistic regression analyses were performed, with covariates selected a priori based on clinical relevance and established predictors of perioperative mortality. Among 2,098 patients (Mean age: 63 years; 60% male population), mean BMI was 27.3 kg/m2, with 4% (n = 90) patients classified as being underweight. The 30-day mortality rate was 8% (n = 164). On multivariable analysis, preoperative BMI as a continuous variable was independently associated with 30-day mortality (OR 0.96 [95% CI 0.93 to 0.99]; p = 0.016). Underweight status was also independently associated with nearly two-fold increased odds of 30-day mortality (OR 1.95 [95% CI 1.03 to 3.71]; p = 0.04). Lower preoperative BMI is independently associated with increased 30-day mortality following MSTS, with underweight patients facing nearly twice the odds of early postoperative death. Low BMI may serve as a simple, readily available marker of heightened physiologic vulnerability, warranting comprehensive preoperative evaluation of nutritional and functional status in this high-risk population.
Gallstone ileus is an uncommon cause of mechanical intestinal obstruction, classically associated with bilioenteric fistula formation that enables gallstone migration into the gastrointestinal tract. Its incidence increases among elderly patients and is associated with significant morbidity due to delayed diagnosis. Obstruction typically occurs at the terminal ileum, and diagnosis traditionally relies on Rigler's triad: intestinal obstruction, pneumobilia, and an ectopic gallstone. Gallstone ileus without a bilioenteric fistula is an exceptionally rare presentation that challenges conventional diagnostic paradigms. The absence of pneumobilia or identifiable fistulous communication may obscure clinical suspicion and delay treatment. Proposed mechanisms include transpapillary migration through the ampulla of Vater, transient biliary dilation, spontaneously closed microfistulas, or intraluminal stone enlargement within areas of intestinal stasis. This case highlights the importance of considering non-fistulous gallstone ileus, even when classical radiologic findings are incomplete. Computed tomography remains the diagnostic modality of choice, allowing accurate identification of ectopic gallstones and obstruction sites. Surgical management with enterolithotomy alone is generally safe and effective, particularly in elderly patients, as additional biliary surgery is usually unnecessary in the absence of a fistula. Recognition of this rare variant is essential to ensure timely diagnosis and appropriate surgical management in patients with small bowel obstruction and a history of gallstone disease.
Return-to-work (RTW) after medical rehabilitation is an important indicator of post-rehabilitation labour market participation, yet evidence on its association with occupation-based job exposure over longer follow-up periods remains limited. This nationwide retrospective cohort study examined the association between job exposure and RTW within 24 months post-rehabilitation using routine administrative data from the German Pension Insurance. The study included 621,695 individuals aged 18-63 years who completed medical rehabilitation between 2014 and 2019. Job exposure was assessed using the Overall Job Exposure Index, integrating physical and psychosocial exposures, and categorised into low, moderate, and high exposure. Initial RTW was defined as at least one month of employment, and stable RTW as at least four consecutive months within 24 months post-rehabilitation. Associations were analysed using Cox proportional hazards regression models with progressive adjustment for sociodemographic, work-related, and health-related factors. Within 24 months, 90.3% achieved initial RTW and 84.2% stable RTW. Higher job exposure was consistently associated with lower RTW rates. In fully adjusted models, moderate and high exposure were associated with a reduced likelihood of initial RTW (HR 0.903 [95% CI 0.897-0.909] and 0.872 [95% CI 0.866-0.878]) and stable RTW (HR 0.878 [95% CI 0.872-0.884] and 0.837 [95% CI 0.830-0.843]), compared with low exposure. These findings provide population-level evidence that occupation-based job exposure is associated with RTW after medical rehabilitation.
Human papillomavirus type 16 (HPV16) causes more cancer than any other virus. However, most HPV16 infections are controlled by the host's immune system and it remains unclear how viral and host genetic variation contribute to infection outcomes. Here, we analyze 4704 HPV16 whole genomes to identify 56 viral codons putatively under positive natural selection to change their amino acids, with evidence including dN/dS > 1, evolutionary convergence, and structural importance in the protein. We find that codons under positive selection disproportionately overlap known HPV16 immune epitopes recognized by cytotoxic T lymphocytes, particularly those restricted by the previously reported risk allele HLA-B*07:02 (odds ratio [OR] = 4.9; 95%CI = 2.1-10.3; PFisher = 0.00015), exemplified by position 10 of the E6 oncoprotein. Positively selected codons also disproportionately overlap 158 nucleotide sites at which the evolutionary sub/lineages of HPV16 have diverged (OR = 19.1; 95%CI = 10.5-34.7; PFisher < 2.2×10-16), and show more rare variation in cervical precancers/cancers than controls (benign or cleared HPV16 infections) in the E1 protein (OR = 9.34, 95%CI = 1.4-402.5; PFisher = 0.0084). Our results suggest that a small subset of HPV16 variants can improve viral persistence through escape of HLA-related immune recognition. The interaction of HPV16 and HLA variation may help to explain how similar or identical viral isolates can have such disparate infection outcomes.
Waldenström Macroglobulinemia (WM) is a rare plasma cell disorder with a prolonged smoldering phase, and treatment initiation is typically delayed. While multiple therapeutic options exist for WM, it remains unclear whether minoritized and low socioeconomic status (SES) patients experience equal or similar survival outcomes. We conducted a retrospective study using the SEER database, identifying WM patients diagnosed between 2006 and 2020. We examined overall survival (OS) and cancer-specific survival (CSS) disparities in 8256 WM patients by race/ethnicity and SES, as defined by the Yost index. Race/ethnicity was categorized as Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Hispanic, and Non-Hispanic Other. Logistic regression showed that lower SES was associated with greater chemotherapy use (OR = 1.33, 95% CI, 1.22-1.46). Low SES was linked to increased all-cause mortality (HR = 1.37, 95% CI, 1.27-1.47). In stratified analyses, low SES was associated with worse OS in NHW and Hispanic patients but not in NHB patients. No differences in CSS were seen between low and high SES groups in the univariate Cox regression. However, after adjustment and competing risk analysis low SES patients had worse CSS. These findings suggest that SES is associated with survival disparities in WM, underscoring the critical role of addressing social determinants of health to ensure equitable outcomes.
Lymphatic malformations are benign disorders of the lymphatic system and represent a rare diagnosis in adulthood, particularly when involving the breast. This report describes the case of a 64-year-old patient referred to our service with two suspicious masses located in different areas of right breast. Imaging studies reinforced the suspicion of malignancy, and further investigation was conducted with an ultrasound-guided core needle biopsy, which confirmed the diagnosis of lymphatic malformation. As illustrated in this report, although lymphatic malformation may present with imaging findings, histopathological evaluation is often required to exclude malignancy before complete surgical excision. Therefore, lymphatic malformation should be considered as a potential differential diagnosis in the investigation of breast masses suspicious for breast cancer.
Meningiomas are typically managed with surgery or radiotherapy, but recurrent or surgically inaccessible tumors present a persistent therapeutic gap, particularly for progressive higher grade disease. Intra-arterial yttrium-90 (90Y) transarterial radioembolization (TARE) is well established for hepatocellular carcinoma to deliver high dose, short range β-brachytherapy in the form of 20-60µm radioactive microspheres. This technology could plausibly be adapted to meningiomas, exploiting their dominant dural arterial supply. We performed systematic searches of PubMed and Google Scholar for literature directly addressing intracranial TARE planning or delivery, supplemented by a scoping review of adjacent fields: meningioma radionuclide therapy, peptide receptor radionuclide therapy (PRRT), hepatic TARE, bland meningioma embolization, and the radiobiology relevant to meningioma vascular behavior, dosimetry, hypoxia, and imaging. Five studies and one ongoing clinical trial directly addressed intracranial TARE or its planning. Seventy-four supporting studies informed synthesis across meningioma embolization, vascular anatomy, hepatic TARE dosimetry and device characteristics, and foundational radiobiology. Currently two TARE platforms exist (glass and resin), with differences in dose-per sphere and physical density which may impact deliverability. The compartmentalized dural arterial supply of most meningiomas supports catheter-based access and may permit single-compartment dosimetry modeling, with generally low-to-moderate arterial shunting risk. The established but incomplete efficacy of radioligand therapies provides a biologic rationale for TARE, while underscoring the need for higher tumor radiation delivery, which early dosimetry work suggests may be achievable with TARE. TARE is a plausible treatment for recurrent and inoperable meningiomas due to their compartmentalized vascular supply. Four considerations should anchor early phase trial design: (1) microsphere platform selection between glass and resin spheres, with their differing embolic burden and dosimetric profiles; (2) whether to limit treatment to external carotid artery territories or include internal carotid artery supplied tumor; (3) compartmental dosimetric planning calibrated to meningioma angiosomes; and (4) a structured safety framework non-target deposition, peri-procedural risks, and delayed radiation necrosis.
Frailty is frequently present in patients admitted to ICU and associated with worse outcomes. Standard severity-of-illness scores (SOISs) do not account for frailty. We investigated the impact of frailty burden (proportion of frail patients per ICU) on performance indicators estimated by Simplified Acute Physiology Score (SAPS) 3 and Mortality Probability Model (MPM)0-III. Retrospective cohort study using prospectively collected data. One hundred fifty-nine ICUs in Brazil and Uruguay. Two hundred forty-two thousand one hundred forty-one patients admitted in 2022-2023. Frailty was defined as a Modified Frailty Index (MFI) of 3 or higher. None. Outcomes were hospital mortality and ICU length of stay. Performance indicators were standardized mortality rate (SMR) and standardized resource use (SRU). SAPS 3 and MPM0-III were recalibrated, and SRU parameters reestimated. Associations between frailty burden and SMR or SRU were examined with scatter plots, Spearman correlations, and efficiency matrices. The median frailty burden was 23.0% (interquartile range [IQR], 16.8-31.7%); median hospital mortality was 14.8% (IQR, 9.1-25.2%). Although higher frailty burden ICUs showed greater mortality, no consistent trend emerged. Frailty burden was not significantly correlated with performance indicators: MPM0-III (SMR: r = -0.123 [95% CI, -0.262 to 0.035] and SRU: r = -0.091 [95% CI, -0.252 to 0.081]) and SAPS 3 (SMR: r = -0.105 [95% CI, -0.258 to 0.044] and SRU: r = -0.074 [95% CI, -0.236 to 0.096]). Recalibrating models with the addition of MFI did not improve estimates. These results were consistent in practically all sensitivity analyses. ICUs with varying frailty burdens were evenly distributed across efficiency matrix quadrants. Frailty burden had no significant impact on ICU benchmarking with SAPS 3 or MPM0-III, suggesting limited relevance for performance comparisons.
This work investigates the enhancement of channel capacity in photon-starved deep-space optical links by leveraging inter-photon correlations. We analyze an M-ary pulse-position modulation (PPM) photon-counting channel in the presence of Poisson background noise and compare conventional signal sources with recently proposed correlated photonic-dimer sources. In the low-photon-rate regime, the dimer sources in both the Bose-Einstein condensate (BEC) and Bardeen-Cooper-Schrieffer (BCS) limits yield substantial capacity improvements over conventional sources. Specifically, at the operationally relevant PPM order of M = 128, the increase relative to lasers reaches up to ∼37% (BEC) and ∼94% (BCS), respectively. These results underscore photon-statistics and correlation engineering as a promising degree of freedom for maximizing photon information efficiency under stringent power and transceiver constraints.
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Rheumatic heart disease (RHD) remains a major cause of cardiovascular morbidity and premature mortality among children and young adults, particularly in low- and middle-income countries. Current management relies on antibiotic prophylaxis and late-stage valve interventions, with no approved pharmacologic therapies targeting the immune-inflammatory and fibrotic processes driving disease progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, originally developed for glycemic control, have demonstrated cardiovascular and renal benefits beyond metabolic effects. Their pleiotropic properties - including anti-inflammatory, antifibrotic, antithrombotic, and endothelial-protective actions - align with key mechanisms underlying RHD progression. Preclinical and translational evidence suggests that SGLT2 inhibition can attenuate valvular inflammation, limit fibrosis, and reduce maladaptive remodeling. Emerging clinical data from other valvular diseases indicate potential improvements in hemodynamics and outcomes. This review highlights SGLT2 inhibitors as promising disease-modifying therapies for RHD and underscores the need for dedicated clinical trials to confirm their therapeutic potential.
Slaughter without prior stunning as practiced under Jewish and Islamic religious law raises certain particular animal welfare issues, notably the time between the incision and loss of consciousness (LOC). LOC marks the point at which cortical processing required for perception, including pain, is no longer possible. Quantifying time to LOC in animals is challenging. To date, the most direct and potentially objective means of doing so is the use of electrophysiologic methods. These are the focus of this paper. This paper includes a concise discussion of electrophysiology as applied to slaughter, addressing a critical gap in foundational electrophysiologic knowledge required to interpret LOC and insensibility in the veterinary literature. Then, using a PRISMA-guided systematic approach, this review synthesizes neurophysiologic evidence on time to LOC in cattle. A review was conducted using PubMed/MEDLINE, Web of Science, Cochrane Library, and Google Scholar (through December 2025). Experimental cattle studies using EEG, ECoG, or evoked potentials were included, while non-bovine, behavioral-only, or methodologically insufficient studies were excluded. Nine studies were included, and risk of bias was assessed using ROBINS-I. Overall risk of bias across included studies was judged to be moderate. Studies using electrocorticography (ECoG) reported electrophysiologic markers consistent with LOC occurring between 4.4 and 13 seconds after incision, with mean values ranging from 7.5 to 10.8 seconds. Reported times vary across studies, particularly those using scalp EEG, likely due to methodological differences and limitations. The highest-quality available electrophysiologic data, suggests that LOC occurs rapidly following slaughter without stunning.
Transgender and gender diverse (TGD) people weather stigma and discrimination and experience significant barriers to preventive health care, contributing to disproportionate burdens of chronic diseases. Affirming approaches to preventive care improve trust, and every encounter presents an opportunity to support affirming clinical relationships with TGD patients. This article reviews best practices in preventive health in TGD populations including cancer screening, bone health, vaccinations, sexual health, cardiovascular risk, and behavioral health. Given limited data specific to trans patients, clinicians must use shared decision-making approaches to reduce disparities and improve the health of TGD individuals.
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Middle meningeal artery embolization (MMAE) is increasingly used for chronic subdural hematoma (cSDH), but outcomes in patients with chronic kidney disease (CKD) remain poorly defined. Because CKD is associated with medical complexity and renal vulnerability, we evaluated whether CKD is associated with worse outcomes after MMAE and whether MMAE remains beneficial among patients with CKD. We performed a retrospective cohort study using the TriNetX US Collaborative Network. Adults with cSDH who underwent MMAE between January 1, 2016, and April 12, 2026, were identified using ICD-10-CM and ICD-10-PCS codes. Patients were stratified by baseline CKD status. Propensity-score matching was performed using 35 baseline characteristics, including demographics, comorbidities, cSDH subtype, concurrent procedures, antiplatelet exposure, hemodialysis, serum creatinine, estimated glomerular filtration rate, and blood urea nitrogen. Outcomes over 180 days included all-cause mortality, subsequent cSDH surgery, and acute kidney failure. A supplementary CKD-only analysis compared matched CKD patients treated with MMAE versus non-MMAE management. Among 2,710 patients with cSDH treated with MMAE, 576 had CKD and 2,134 did not. After matching, 531 patients were included in each cohort. CKD was associated with higher 180-day mortality (17.9% vs 11.5%; HR, 1.55; 95% CI, 1.12-2.14; p = 0.007) and acute kidney failure (25.2% vs 8.9%; HR, 3.06; 95% CI, 2.20-4.27; p < 0.001), while subsequent cSDH surgery was similar (10.4% vs 10.9%; HR, 0.93; 95% CI, 0.64-1.35; p = 0.513). In the CKD-only matched analysis, MMAE was associated with lower subsequent cSDH surgery compared with non-MMAE management (10.1% vs 18.0%; HR, 0.53; 95% CI, 0.38-0.73; p < 0.001), similar acute kidney failure (26.3% vs 27.8%; HR, 0.93; 95% CI, 0.75-1.17; p = 0.547), and a trend toward lower mortality (18.7% vs 23.3%; HR, 0.78; 95% CI, 0.60-1.00; p = 0.052). CKD was associated with higher mortality and acute kidney failure among cSDH patients undergoing MMAE, while subsequent cSDH surgery rates were similar to those of non-CKD patients. In the CKD-only analysis, MMAE was associated with lower subsequent cSDH surgery and similar acute kidney failure compared with non-MMAE management, supporting its feasibility in appropriately selected CKD patients.
Accurate recognition of others' emotional facial expressions, referred to as emotion sensitivity (ES), is a central component of nonverbal communication. Previous research suggests that personality traits such as neuroticism and extraversion may shape nonverbal emotion decoding but findings have been mixed. The present study examined whether these traits predict performance on the Belmont Emotion Sensitivity Test (BEST), a task designed to measure subtle discrimination of anger, fear, and happiness while minimizing response bias. A sample of 289 college students completed self-report measures of neuroticism and extraversion, as well as the Belmont Emotion Sensitivity Test (BEST), which assesses the ability to discriminate subtle differences in facial expressions of fear, anger, and happiness. Depression, anxiety, and stress levels were also measured. Female participants reported higher levels of neuroticism (t = 4.39, p < .001; d = .59) and extraversion (t = 2.33, p = .02; d = .33) than male participants. Neuroticism severity was positively correlated with depression, anxiety, and stress. Extraversion was negatively correlated with depression, anxiety, and stress (range of rs = .55-.68, p < .001). Multiple regressions showed that neither neuroticism nor extraversion significantly predicted ES scores for any emotion category. Although women reported higher levels of neuroticism and extraversion, these traits did not predict performance on a validated emotion sensitivity task. These findings suggest that, in this nonclinical young adult sample, neuroticism and extraversion were not robust predictors of performance on this measure of emotion sensitivity. Implications are discussed for theories linking personality, psychopathology, and nonverbal emotion perception.
Aging research has made remarkable progress in describing aging through the genetic architecture of longevity, epigenetic clocks, proteomic signatures, and systems-level analyses. Yet a critical dimension remains underrepresented: the role of genome integrity, germline and somatic mutation accumulation in individual-specific vulnerability, frailty, and multimorbidity across the life course. The need for individual-level thinking has deep roots, from Darwin's emphasis on individual variation in natural selection, to Garrod's chemical individuality, to Lewontin's genotype-phenotype (G-P) map and reaction norms. This tradition in evolutionary biology and medicine treats the individual as a primary unit of both selection and intervention. Here, we argue for an N-of-1 framework in aging research. Population-level epidemiology and genetics of aging based on means and variances can produce a "curse of the average," obscuring the individual genetic variation that impacts relative aging among individuals. The individual-centered N-of-1 framework would integrate longitudinal tracking of mutation accumulation ranging from individual cells, tissues, and organs into comprehensive individual aging profiles aligned with the G-P map concept. The emerging idea of "mosaic aging" further emphasizes that cells, cell types, tissues, organs, and organ systems within an individual reflect heterogeneous aging trajectories. We discuss how somatic mutations, operating through Muller's ratchet-like dynamics in stem cell populations, generate hierarchical vulnerabilities across biological scales. The extreme rarity of centenarians who may maintain superior genome integrity illustrates the relevance of this framework. We suggest that an integrated G-P map approach, grounded in evolutionary genetics, would advance both precision medicine and geroscience.