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Abstract Objectives (1) To plot the trajectory of humoral and cellular immune responses to the primary (two‐dose) COVID‐19 mRNA series and the third/booster dose in B‐cell‐depleted multiple sclerosis (MS) patients up to 2 years post‐vaccination; (2) to identify predictors of immune responses to vaccination; and (3) to assess the impact of intercurrent COVID‐19 infections on SARS CoV‐2‐specific immunity. Methods Sixty ocrelizumab‐treated MS patients were enrolled from NYU (New York) and University of Colorado (Anschutz) MS Centers. Samples were collected pre‐vaccination, and then 4, 12, 24, and 48 weeks post‐primary series, and 4, 12, 24, and 48 weeks post‐booster. Binding anti‐Spike antibody responses were assessed with multiplex bead‐based immunoassay (MBI) and electrochemiluminescence (Elecsys®, Roche Diagnostics), and neutralizing antibody responses with live‐virus immunofluorescence‐based microneutralization assay. Spike‐specific cellular responses were assessed with IFNγ/IL‐2 ELISpot (Invitrogen) and, in a subset, by sequencing complementarity determining regions (CDR)‐3 within T‐cell receptors (Adaptive Biotechnologies). A linear mixed‐effect model was used to compare antibody and cytokine levels across time points. Multivariate analyses identified predictors of immune responses. Results The primary vaccination induced an 11‐ to 208‐fold increase in binding and neutralizing antibody levels and a 3‐ to 4‐fold increase in IFNγ/IL‐2 responses, followed by a modest decline in antibody but not cytokine responses. Booster dose induced a further 3‐ to 5‐fold increase in binding antibodies and 4‐ to 5‐fold increase in IFNγ/IL‐2, which were maintained for up to 1 year. Infections had a variable impact on immunity. Interpretation Humoral and cellular benefits of COVID‐19 vaccination in B‐cell‐depleted MS patients were sustained for up to 2 years when booster doses were administered.

Introduction Mounting evidence indicates that an individual's humoral adaptive immune response plays a critical role in the setting of SARS-CoV-2 infection, and that the efficiency of the response correlates with disease severity. The relationship between the adaptive immune dynamics in the lower airways with those in the systemic circulation, and how these relate to an individual's clinical response to SARS-CoV-2 infection, are less understood and are the focus of this study. Material and methods We investigated the adaptive immune response to SARS-CoV-2 in paired samples from the lower airways and blood from 27 critically ill patients during the first wave of the pandemic (median time from symptom onset to intubation 11 days). Measurements included clinical outcomes (mortality), bronchoalveolar lavage fluid (BALF) and blood specimen antibody levels, and BALF viral load. Results While there was heterogeneity in the levels of the SARS-CoV-2-specific antibodies, we unexpectedly found that some BALF specimens displayed higher levels than the paired concurrent plasma samples, despite the known dilutional effects common in BALF samples. We found that survivors had higher levels of anti-spike, anti-spike-N-terminal domain and anti-spike-receptor-binding domain IgG antibodies in their BALF (p

Therapeutic research and development for Alzheimer's disease (AD) has been an area of intense research to alleviate memory loss and neurodegeneration. There is growing interest in drug repositioning and repurposing strategies for FDA-approved medications as potential candidates that may further advance AD therapeutics. The FDA drug efavirenz has been investigated as a candidate drug for repurposing as an AD medication. The proposed mechanism of action of efavirenz (at low doses) is the activation of the neuron-specific enzyme CYP46A1 that converts excess brain cholesterol into 24-hydroxycholesterol (24-HC) that is exported to the periphery. Efavirenz at a low dose was found to improve memory deficit in the 5XFAD model of AD that was accompanied by elevated 24-HC and reduction in Aβ; furthermore, efavirenz reduced pTau and excess cholesterol levels in human iPSC-derived Alzheimer's neurons. The low dose of efavirenz used in the AD mouse model to increase 24-HC contrasts with the use of more than 100-fold higher doses of efavirenz for clinical treatment of human immunodeficiency virus (HIV) through inhibition of reverse transcriptase. Low doses of efavirenz may avoid neurotoxic adverse effects that occur at high efavirenz doses used for HIV treatment. This review evaluates the drug properties of efavirenz with respect to its preclinical data on regulating memory deficit, pharmacokinetics, pharmacodynamics, metabolites, and genetic variabilities in drug metabolism as well as its potential adverse effects. These analyses discuss the challenges and questions that should be addressed in future studies to consider the opportunity for low dose efavirenz as a candidate for AD drug development., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Objectives: To evaluate the perioperative morbidity and mortality associated with direct oral anticoagulants (DOACs) and warfarin for patients receiving transurethral resection of prostate (TURP)., Patients and Methods: This was a single-centre, retrospective cohort analysis of patients who underwent TURP for benign prostate hyperplasia from April 2019 to December 2023. The primary objective was to evaluate the perioperative bleeding and thromboembolic risk between anticoagulated (AC) vs no-AC patients. The secondary objective was to evaluate perioperative bleeding and thromboembolic risk between different formulations of DOACs. Patient demographics, prior treatment, prostate size, baseline bleeding risk, and operative details were collected. Bleeding and thromboembolic-related morbidity were captured within a 3-month postoperative period. Perioperative management of AC therapy was recorded, and all patients had their AC therapy withheld. Cohort characteristic between the AC vs no-AC, and DOAC groups were analysed with two-sided t-test, and chi-square test. Further logistic regression analyses were carried out to identified significant variables between the groups. These significant variables were used for adjustment in inverse probability-weighted treatment effect analysis to evaluate bleeding risk., Results: There were 629 patients in the cohort, and 113 (18%) patients were receiving AC therapy. The AC patients were at 1.6 times statistically significant increased risk of acute bleeding, and 11 times increased risk of prolonged haematuria for >14 days. When compared to apixaban, patients on rivaroxaban conferred a statistically significant increased risk of acute bleeding by 2.21 times. Patients receiving AC therapy had a statistically significant increased risk of stroke in the perioperative setting (no-AC vs AC: 0.4% vs 2.7%, P = 0.01)., Conclusion: This is the first study to evaluate risk of bleeding for TURP patients receiving DOACs. The AC patients are more likely to experience haematuria and stroke in the perioperative period despite withholding therapy. Apixaban appears to cause less bleeding-related complications than rivaroxaban., (© 2024 The Author(s). BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background and Objectives: Stereotactic radiosurgery (SRS) is effective for patients with medically refractory trigeminal neuralgia with a 75%-90% response rate. Consideration of the integral dose (ID) to the target nerve within the 50% isodose line was reported to help select prescription doses to maximize effectiveness and minimize bothersome numbness. The objective of this study was to externally validate the ID as a predictor of outcomes after SRS., Methods: We reviewed the outcomes and parameters of 94 consecutive patients of type 1 trigeminal neuralgia who had SRS for the first time where nerve ID was calculated. 70% of the prescription doses were 80 Gy, with 28% at 85 Gy, and 2% at 70 Gy., Results: The median follow-up time was 14.4 months. A total of 85 (90%) patients reported significant pain relief (Barrow Neurological Institute I-III) after initial SRS. The median pain recurrence-free survival was 82 months (95% CI 41.1-NA), and estimates at 1, 3, and 5 years were 80.5%, 65.5%, and 55.9%, respectively. The ID was not significantly associated with initial pain relief, or affect the risk of pain recurrence or sensory dysfunction after SRS using the Cox proportional hazards model. A nerve mean dose ≥65 Gy was associated with a reduced risk of pain recurrence on multivariate analysis (hazard ratio 0.408, P = .039). Twenty (21%) patients experienced sensory dysfunction after SRS with 3 (3%) requiring further medications, which was not correlated with the prescription dose or brainstem maximum dose., Conclusion: The ID did not predict recurrence-free survival or sensory dysfunction. Our observations suggest improved nerve coverage by the most powerful area of the isocenter, for instance, by targeting a narrower segment if feasible, could result in more durable pain relief. Further studies to validate these findings are needed., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Introduction: Bumetanide, a loop diuretic, was identified as a candidate drug for repurposing for Alzheimer's disease (AD) based on its effects on transcriptomic apolipoprotein E signatures. Cross-sectional analyses of electronic health records suggest that bumetanide is associated with decreased prevalence of AD; however, temporality between bumetanide exposure and AD development has not been established., Methods: We evaluated Medicare claims data using Cox proportional hazards regression to evaluate the association between time-dependent use of bumetanide and time to first AD diagnosis while controlling for patient characteristics. Multiple sensitivity analyses were conducted to test the robustness of the findings., Results: We sampled 833,561 Medicare beneficiaries, 60.8% female, with mean (standard deviation) age of 70.4 (12). Bumetanide use was not significantly associated with AD risk (hazard ratio 1.05; 95% confidence interval, 0.99-1.10)., Discussion: Using a nationwide dataset and a retrospective cohort study design, we were not able to identify a time-dependent effect of bumetanide lowering AD risk., Highlights: Bumetanide was identified as a candidate for repurposing for Alzheimer's disease (AD). We evaluated the association between bumetanide use and risk of AD. We used Medicare data and accounted for duration of bumetanide use. Bumetanide use was not significantly associated with risk of AD., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Sexual violence and sexual harassment (SVSH) are prevalent among college and university students; however, the experiences of ethnic minority students, especially Asians, are understudied. This study aimed to reduce this gap by exploring Asian students' perceptions of SVSH on three public university campuses in Southern California. We examined their perceptions about the campus environment related to SVSH, attitudes, and behaviors toward help seeking, and utilization of on-campus resources. A total of 23 in-depth interviews were conducted with Asian students enrolled at the three University of California campuses. Thematic coding was conducted to generate main themes and subthemes. Five main themes emerged: (a) SVSH is considered a "taboo" topic in Asian culture and family systems, and Asian student survivors are often reluctant to disclose incidents or seek support services. (b) Students did not feel their campus environments were tailored to understand or meet the sociocultural realities and needs of Asian student survivors. (c) Campus SVSH services and reporting processes were seen as non-transparent. (d) Peers were the major source of support and SVSH information, as opposed to official campus-based resources and training. (e) Survivors often conduct an internal cost-benefit analysis evaluating their decision about whether to report. This study highlights the lack of conversation surrounding SVSH in Asian families, and how the cultural stigma of sex and sexual violence prevented Asian students from receiving knowledge and resources about these topics in their families. Instead of relying on formal campus resources (e.g., Title IX and confidential advocacy services, mental health services), many students turn to their peers for support. Thus, facilitating peer support groups, training university students to support each other through SVSH incidents, and tailoring campus services to the diverse cultural backgrounds of students are key considerations to foster a safe campus environment and prevent SVSH., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Introduction: In hypertension (HTN), biomechanical stress may drive matrix remodeling through dysfunctional VSMC activity. Prior evidence has indicated VSMC tension-induced signaling through the serum and glucocorticoid inducible kinase-1 (SGK-1) can impact cytokine abundance. Here, we hypothesize that SGK-1 impacts production of additional aortic pathologic markers (APMs) representing VSMC dysfunction in HTN., Methods: Aortic VSMC expression of APMs was quantified by QPCR in cyclic biaxial stretch (Stretch) +/- AngiotensinII (AngII). APMs were selected to represent VSMC dedifferentiated transcriptional activity, specifically Interleukin-6 (IL-6), Cathepsin S (CtsS), Cystatin C (CysC), Osteoprotegerin (OPG), and Tenascin C (TNC). To further assess the effect of tension alone, abdominal aortic rings from C57Bl/6 WT mice were held in a myograph at experimentally derived optimal tension (OT) or OT + 30% +/-AngII. Dependence on SGK-1 was assessed by treating with EMD638683 (SGK-1 inhibitor) and APMs were measured by QPCR. Then, WT and smooth muscle cell specific SGK-1 heterozygous knockout (SMC-SGK-1KO +/- ) mice had AngII-induced HTN. Systolic blood pressure and mechanical stress parameters were assessed on Day 0 and Day 21. Plasma was analyzed by ELISA to quantify APMs. Statistical analysis was performed by ANOVA., Results: In cultured aortic VSMCs, expression of all APMs was increased in response to biomechanical stimuli (Stretch +/-AngII,). Integrating the matrix contribution to signal transduction in the aortic rings led to IL-6 and CysC demonstrating SGK-1 dependence in response to elevated tension and interactive effect with concurrent AngII stimulation. CtsS and TNC, on the other hand, primarily responded to AngII, and OPG expression was unaffected in aortic ring experimentation. Both mouse strains had >30% increase in blood pressure with AngII infusion, reduced aortic distensibility and increased PPV, indicating increased aortic stiffness. In WT + AngII mice, IL-6, CtsS, CysC, and TNC plasma levels were significantly elevated, but these APMs were unaffected by HTN in the SMC-SGK-1KO +/- +AngII mice, suggesting SGK-1 plays a major role in VSMC biomechanical signaling to promote dysfunctional production of selected APMs., Conclusion: In HTN, changes in the plasma levels of markers associated with aortic matrix homeostasis can reflect remodeling driven by mechanobiologic signaling in dysfunctional VSMCs, potentially through the activity of SGK-1. Further defining these pathways may identify therapeutic targets to reduce cardiovascular morbidity and mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Gedney, Mattia, Figueroa, Barksdale, Fannin, Silverman, Xiong, Mukherjee, Jones and Ruddy.)

Aim: Whether changes in oxygen metabolism, as measured by oxygen consumption (VO 2 ), carbon dioxide production (VCO 2 ) and the respiratory exchange ratio (RER), are associated with survival after cardiac arrest is poorly understood. In this prospective observational study, we investigated the association between VO 2 , VCO 2 , and RER in the initial 12 and 24 h after return of spontaneous circulation (ROSC) and survival to hospital discharge., Methods: Adults with ROSC after cardiac arrest, admitted to the intensive care unit, requiring mechanical ventilation and treated with targeted temperature management were included. VO 2 and VCO 2 were measured continuously for 24 h after ROSC, using a noninvasive anesthesia monitor. Area under the curve for VO 2 , VCO 2 & RER was calculated using all available values over 12 and 24 h after ROSC. Using logistic regression, we evaluated the relationship between these metabolic variables and survival to hospital discharge. Analyses were adjusted for temperature, vasopressors, and neuromuscular blockade., Results: Sixty four patients were included. Mean age was 64 ± 16 years, and 59% were women. There was no significant association between the area under the curve of VO 2 or VCO 2 and survival. A higher RER in the initial 12 h was associated with better survival (aOR = 3.97, 95% CI [1.01,15.6], p = 0.048). Survival was lower in those with median RER < 0.7 in the initial 12 h compared with those with a median RER ≥ 0.7 (25% vs 67%, p = 0.011)., Conclusion: Higher RER in the initial 12 h was associated with survival after cardiac arrest. The etiology of unusually low RERs in this patient population remains unclear., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Deep-sea habitats are currently recognized as a hot spot for mercury (Hg) accumulation from anthropogenic sources, resulting in elevated concentrations of total mercury (THg) in deep-sea megafauna. Among them, deep-sea sharks (Class Chondrichthyes) are characterized by high trophic position and extended longevity and are, therefore, at high risk for mercury contamination. Despite this, sharks are overexploited by fishing activity in increasingly deeper water, worldwide, imposing health risks to human consumption. While it is imperative to better understand long-term mercury contamination in deep-sea megafauna, few historical data sets exist to capture this process. Here we explore four decades (1985-2022) of THg accumulation in five species of deep-sea sharks (G. melastomus, E. spinax, S. rostratus, C. granulosus, and D. licha) of the ultra-oligotrophic Southeastern Mediterranean Sea (SEMS) sampled during 19 research cruises. We exhibited exceptionally high THg levels (per length/weight), the highest as 16.6 μg g -1 (wet wt.), almost entirely (98.9 %; n = 298 specimens) exceeding the limit for safe consumption (0.3-0.5 μg THg g -1 wet wt.). The maximal THg levels of the long-lived species D. licha and C. granulosus in the SEMS were enriched by a factor of ∼ 7 and >10 compared to counterpart species from other oceanic areas, respectively. We attribute this to the ultra-oligotrophic conditions of the SEMS, which cause slower growth rates and dwarfism in deep-sea sharks, resulting in an extended exposure time to mercury contamination. In the long-lived species, C. granulosus and D. licha, a temporal increase of average THg levels of ∼ 80 % was recorded between 1987-1999 and 2021-2022. This likely reflects the long-term accumulation of historical anthropogenic Hg in deep-sea environments, which is further amplified in marginal seas such as the Mediterranean, impacted by global air pollution crossroads and surrounded by land-based pollution sources. Future consumption of products from deep-sea sharks is potentially high risk to human health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The poultry industry is evolving towards antibiotic-free production to meet market demands and decelerate the increasing spread of the antimicrobial resistance. The growing need for antibiotic free products has challenged producers to decrease or completely stop using antimicrobials as feed supplements in broiler diet to improve feed efficiency, growth rate, and intestinal health. Natural feed additives (e.g., probiotics and phytobiotics) are promising alternatives to substitute antimicrobial growth promoters. The goal of our study was to characterize the effects of a Probiotic and an Essential Oils blend on broilers' performance and perform a time-series analysis to describe their excreta microbiome. A total of 320 Cobb 500 (1-day-old) chicks were raised for 21 d in 32 randomly allocated cages. Treatments consisted of 4 experimental diets: a basal diet, and a basal diet mixed with an Antibiotic (bacitracin methylene disalicylate), an essential oils blend (oregano oil, rosemary, and red pepper), or a Probiotic (Bacillus subtilis). Body weight (on 1, 10, and 21d), and feed intake (10d and 21d) were recorded and feed conversion ratio was calculated. Droppings were collected daily (1-21d) to characterize broilers' excreta microbiota by targeted sequencing of the bacterial 16S rRNA gene. The Probiotic significantly improved feed conversion ratio for starter phase 1 to 10d (P = 0.03), grower phase 10 to 21d (P = 0.05), and total period 1 to 21d (P = 0.01) compared to the Antibiotic. Feed supplements did not affect alpha diversity but did impact microbial beta diversity (P < 0.01). Age also impacted microbiome turnover as differences in alpha and beta diversity were detected. Furthermore, when compared to the basal diet, the probiotic and antibiotic significantly impacted relative abundance of Bifidobacterium (log2 fold change -1.44, P = 0.03), Intestinimonas (log2 fold change 0.560, P < 0.01) and Ligilactobacillus (log2 fold change -1.600, P < 0.01). Overall, Probiotic supplementation but not essential oils supplementation positively impacted broilers' growth performance by directly causing directional shifts in broilers' excreta microbiota structure., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Elevated lactate is associated with mortality after cardiac arrest. Thiamine, a cofactor of pyruvate dehydrogenase, is necessary for aerobic metabolism. In a mouse model of cardiac arrest, thiamine improved pyruvate dehydrogenase activity, survival and neurologic outcome., Aim: To determine if thiamine would decrease lactate and increase oxygen consumption after in-hospital cardiac arrest., Methods: Randomized, double-blind, placebo-controlled phase II trial. Adult patients with arrest within 12 hours, mechanically ventilated, with lactate ≥ 3 mmol/L were included. Randomization was stratified by lactate > 5 or ≤ 5 mmol/L. Thiamine 500 mg or placebo was administered every 12 hours for 3 days. The primary outcome of lactate was checked at baseline, 6, 12, 24, and 48 hours, and compared using a linear mixed model, accounting for repeated measures. Secondary outcomes included oxygen consumption, pyruvate dehydrogenase, and mortality., Results: Enrollments stopped after 36 patients due Data Safety and Monitoring Board concern about potential harm in an unplanned subgroup analysis. There was no overall difference in lactate (mean difference at 48 hours 1.5 mmol/L [95% CI -3.1-6.1], global p = 0.88) or any secondary outcomes. In those with randomization lactate > 5 mmol/L, mortality was 92% (11/12) with thiamine and 67% (8/12) with placebo (p = 0.32). In those with randomization lactate ≤ 5 mmol/L mortality was 17% (1/6) with thiamine and 67% (4/6) with placebo (p = 0.24). There was a significant interaction between randomization lactate and the effect of thiamine on survival (p = 0.03)., Conclusions: In this single center trial thiamine had no overall effect on lactate after in-hospital cardiac arrest., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Thiamine is a key cofactor for aerobic metabolism, previously shown to improve mortality and neurological outcomes in a mouse model of cardiac arrest. We hypothesized that thiamine would decrease lactate and improve outcomes in post-arrest patients., Methods: Single center, randomized, blinded, placebo-controlled, Phase II trial of thiamine in adults within 4.5 hours of return of spontaneous circulation after out-of-hospital cardiac arrest (OHCA), with coma and lactate ≥ 3 mmol/L. Participants received 500 mg IV thiamine or placebo twice daily for 2 days. Randomization was stratified by lactate > 5 or ≤ 5 mmol/L. The primary outcome of lactate was checked at baseline, 6, 12, and 24 hours, and compared using a linear mixed model to account for repeated measures. Secondary outcomes included SOFA score, pyruvate dehydrogenase, renal injury, neurological outcome, and mortality., Results: Of 93 randomized patients, 76 were enrolled and included in the analysis. There was no difference in lactate over 24 hours (mean difference 0.34 mmol/L (95% CI: -1.82, 2.50), p = 0.43). There was a significant interaction between randomization lactate subgroup and the effect of the intervention on mortality (p = 0.01) such that mortality was higher with thiamine in the lactate > 5 mmol/L group and lower with thiamine in the < 5 mmol/L group. This subgroup difference prompted the Data and Safety Monitoring Board to recommend the study be terminated early. PDH activity increased over 72 hours in the thiamine group. There were no differences in other secondary outcomes., Conclusion: In this single-center randomized trial, thiamine did not affect lactate over 24 hours after OHCA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Every year, hundreds of thousands of youth across the country enter the juvenile legal system. A significantly disproportionate number of them are youth of color. While youth arrests have declined over the past several decades, racial disparities have increased and persist at every stage of the system. Many youth of color enter the juvenile legal system with a history of trauma and stress that compromises their health and well-being. Arrest, prosecution, and incarceration exacerbate these poor health outcomes. This paper examines several of the health impacts of structural racism in the policing and incarceration of youth of color. The paper begins by highlighting some of the most pressing social determinants of adolescent health and then considers how youth detention and incarceration contribute to unhealthy weight, hypertension, diabetes, and cardiovascular disease through unhealthy food environments, limited physical activity, and the added stress of the incarceration setting. This paper adds to the existing literature on the harms of youth detention and advocates for harms elimination strategies grounded in a public health approach to public safety and community-based alternatives to detention. For those youth who will remain in detention, the authors offer suggestions to reduce harms and improve the health of systems-involved youth, including opportunities for research., (© 2024. W. Montague Cobb-NMA Health Institute.)

Seawater reverse osmosis (SWRO) desalination facilities produce freshwater and, at the same time, discharge hypersaline brine that often includes various chemical additives such as antiscalants and coagulants. This dense brine can sink to the sea bottom and creep over the seabed, reaching up to 5 km from the discharge point. Previous reviews have discussed the effects of SWRO desalination brine on various marine ecosystems, yet little attention has been paid to the impacts on benthic habitats. This review comprehensibly discusses the effects of SWRO brine discharge on marine benthic fauna and flora. We review previous studies that indicated a suite of impacts by SWRO brine on benthic organisms, including bacteria, seagrasses, polychaetes, and corals. The effects within the discharge mixing zones range from impaired activities and morphological deformations to changes in the community composition. Recent modeling work demonstrated that brine could spread over the seabed, beyond the mixing zone, for up to several tens of kilometers and impair nutrient fluxes from the sediment to the water column. We also provide a possible perspective on brine's impact on the biogeochemical process within the mixing zone subsurface. Desalination brine can infiltrate into the sandy bottom around the discharge area due to gravity currents. Accumulation of brine and associated chemical additives, such as polyphosphonate-based antiscalants and ferric-based coagulants in the porewater, may change the redox zones and, hence, impact biogeochemical processes in sediments. With the demand for drinking water escalating worldwide, the volumes of brine discharge are predicted to triple during the current century. Future efforts should focus on the development and operation of viable technologies to minimize the volumes of brine discharged into marine environments, along with a change to environmentally friendly additives. However, the application of these technologies should be partly subsidized by governmental stakeholders to safeguard coastal ecosystems around desalination facilities.

Coral reefs provide ecosystem benefits to millions of people but are threatened by rapid environmental change and ever-increasing human pressures. Restoration is becoming a priority strategy for coral reef conservation, yet implementation remains challenging and it is becoming increasingly apparent that indirect conservation and restoration approaches will not ensure the long-term sustainability of coral reefs. The important role of environmental conditions in restoration practice are currently undervalued, carrying substantial implications for restoration success. Giving paramount importance to environmental conditions, particularly during the pre-restoration planning phase, has the potential to bring about considerable improvements in coral reef restoration and innovation. This Essay argues that restoration risk may be reduced by adopting an environmentally aware perspective that gives historical, contemporary, and future context to restoration decisions. Such an approach will open up new restoration opportunities with improved sustainability that have the capacity to dynamically respond to environmental trajectories., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Burdett et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background and Objectives: To study the clinical, imaging, and survival outcomes in patients with motor cortex brain metastases treated with stereotactic radiosurgery (SRS)., Methods: Imaging and clinical data were obtained from our prospective patient registry. Tumor volumes were obtained from serial imaging data., Results: The outcomes of 208 patients with metastases involving the motor cortex who underwent SRS between 2012 and 2021 were analyzed. A total of 279 metastases (0.01 cm 3 -12.18 cm 3 , mean 0.74 cm 3 ) were irradiated. The SRS margin dose varied from 10 to 20 Gy (mean 16.9 Gy). The overall tumor control rate was 97.8%. Perilesional edema was noted in 69 (25%) tumors at presentation. Adverse radiation effects (ARE) were noted in 6% of all tumors but were symptomatic in only 1.4%. Median time to appearance of symptomatic ARE was 8 months. Edema without ARE was observed in 13%. New focal seizures were noted in 5 patients (2%) and new generalized seizures in 1 patient (0.3%). Thirty-six patients (17%) presented with motor deficits. At final follow-up, 32 (85%) were improved or unchanged, 13 (41%) had a normal examination, 10 (31%) had mild deficits, and 9 (28%) still had moderate deficits. New remote brain metastases were found in 31% of patients at a median of 8 months. After treatment, the Karnofsky performance score distribution of the population showed an overall right shift and a median survival of 10 months. Patients with incidentally found brain metastases had significantly better survival than those presenting with deficits (median 13 vs 9 months) ( P = .048). Absence of a neurological deficit, recursive partitioning analysis Class I and II, and dose >18 Gy were each associated with a significant survival advantage., Conclusion: SRS for motor cortex metastases is safe in most patients and effective in providing tumor control. Patients treated before neurological deficits develop show better outcomes., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

This study explores the accumulation of total mercury (THg) in deep-sea sediments and demersal megafauna of the ultra-oligotrophic Southeastern Mediterranean Sea (SEMS) across bathymetric gradients in the range 35-1900 m, sampled in seven cruises during 2013, 2017-2021, and 2023. Measurements of THg were conducted in surficial (0.0-0.5 cm) and subsurface (9.0-10 cm) sediments, demersal sharks, demersal teleost fish, and benthic crustaceans. Sedimentary organic carbon and biota δ 13 C and δ 15 N values were determined to explore possible foraging habitats and dietary sources of THg. The results exhibit an increasing trend of THg in surficial sediments with increasing bottom depth, while in the subsurface, pre-industrial sediments, THg remains lower, slightly increasing with depth. Having no major terrestrial point sources in this area, this increasing trend of THg in surficial sediments across bathymetric gradients is controlled by atmospheric mercury deposition, scavenged by the biological pump, and by lateral transport of particulate Hg in winnowed fine particles from the shelf. Similarly, the THg in benthic crustaceans and demersal fish ranged between 0.02 and 2.71 μg g -1 wet weight (0.06 and 10.8 μg g -1 dry weight) and increased with muscle δ 13 C as a function of distance offshore, while presenting a low THg-δ 15 N bio-magnification power. Our results suggest that foraging habitats, longevity, and species-specific depth distribution control their muscle THg bioaccumulation. Despite this complexity, the pooling of THg in megafauna into specific deep zones reflected the trend of increasing anthropogenic THg across bathymetric gradients. Furthermore, many of the biota measurements exceeded safe consumption thresholds for Hg and therefore, should be considered carefully in the development and regulation of deep-sea trawling in this region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Despite the effects of ocean acidification (OA) on seagrasses have been widely investigated, predictions of seagrass performance under future climates need to consider multiple environmental factors. Here, we performed a mesocosm study to assess the effects of OA on shallow and deep Posidonia oceanica plants. The experiment was run in 2021 and repeated in 2022, a year characterized by a prolonged warm water event, to test how the effects of OA on plants are modulated by thermal stress. The response of P. oceanica to experimental conditions was investigated at different levels of biological organization. Under average seawater temperature, there were no effects of OA in both shallow and deep plants, indicating that P. oceanica is not limited by current inorganic carbon concentration, regardless of light availability. In contrast, under thermal stress, exposure of plants to OA increased lipid peroxidation and decreased photosynthetic performance, with deep plants displaying higher levels of heat stress, as indicated by the over-expression of stress-related genes and the activation of antioxidant systems. In addition, warming reduced plant growth, regardless of seawater CO 2 and light levels, suggesting that thermal stress may play a fundamental role in the future development of seagrass meadows. Our results suggest that OA may exacerbate the negative effects of future warming on seagrasses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The Mediterranean Sea has been sampled irregularly by research vessels in the past, mostly by national expeditions in regional waters. To monitor the hydrographic, biogeochemical and circulation changes in the Mediterranean Sea, a systematic repeat oceanographic survey programme called Med-SHIP was recommended by the Mediterranean Science Commission (CIESM) in 2011, as part of the Global Ocean Ship-based Hydrographic Investigations Program (GO-SHIP). Med-SHIP consists of zonal and meridional surveys with different frequencies, where comprehensive physical and biogeochemical properties are measured with the highest international standards. The first zonal survey was done in 2011 and repeated in 2018. In addition, a network of meridional (and other key) hydrographic sections were designed: the first cycle of these sections was completed in 2016, with three cruises funded by the EU project EUROFLEETS2. This paper presents the physical and chemical data of the meridional and key transects in the Western and Eastern Mediterranean Sea collected during those cruises., (© 2024. The Author(s).)

Introduction: The purpose of this study was to evaluate the role of body mass index (BMI) in predicting postoperative complications following myocutaneous free flap transfer. In addition, we sought to identify certain body composition variables that may be used to stratify patients into low- versus high-risk for gracilis myocutaneous free flap with skin paddle failure., Methods: Using the National Surgical Quality Improvement Program database, we collected data for all patients who underwent myocutaneous free flap transfer from 2015 to 2021. Demographic data, medical history, surgical characteristics, and postoperative outcomes, including complications, reoperations, and readmissions, were collected. Body mass index was correlated with outcome measures to determine its role in predicting myocutaneous free flap reliability. Subsequently, we retrospectively obtained measurements of perigracilis anatomy in patients who underwent computed tomography angiography bilateral lower extremity scans with intravenous contrast at our institution. We compared body composition data with mathematical equations calculating the potential area along the skin of the thigh within which the gracilis perforator may be found., Results: Across the United States, 1549 patients underwent myocutaneous free flap transfer over the 7-year study period. Being in obesity class III (BMI ≥40 kg/m2) was associated with a 4-times greater risk of flap complications necessitating a return to the operating room compared with being within the normal BMI range. In our computed tomography angiography analysis, average perigracilis adipose thickness was 18.3 ± 8.0 mm. Adipose thickness had a strong, positive exponential relationship with the area of skin within which the perforator may be found., Conclusions: In our study, higher BMI was associated with decreased myocutaneous free flap reliability. Specifically, inner thigh adipose thickness can be used to estimate the area along the skin within which the gracilis perforator may be found. This variable, along with BMI, can be used to identify patients who are considered high-risk for flap failure and who may benefit from additional postoperative monitoring, such as the use of a color flow Doppler probe and more frequent and prolonged skin paddle monitoring., Competing Interests: Conflicts of interest and sources of funding: The American College of Surgeons National Surgical Quality Improvement Program and the hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program are the sources of the data used herein; they have not verified and are not responsible for the statistical validity of the data analysis or the conclusions derived by the authors., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The Levantine basin (LB) in the Southeastern Mediterranean Sea is a high-risk oil pollution hot spot owing to its dense maritime traffic and intense oil and gas exploration and exploitation activities. In February 2021 the Israeli LB shorelines were impacted by an exceptional tar pollution event (~550 tons; average distribution: ~3 kg tar m -1 front beach) of an unknown oil spill source. Here we report on the immediate numerical modelling assessment of the oil spill propagation and tar distribution; operational use of underwater gliders for tracking water column anomalies of dissolved polycyclic aromatic hydrocarbons (PAHs) and turbidity signals; the beached tar composition and amounts and the short-term response of the microbial population along the ~180 km shoreline. This pollution event emphasizes the need for improving the early warning systems for oil spills and implementing continuous operational monitoring at high-risk, ecologically sensitive and valuable resource areas like the Israeli LB waters., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Huntington's disease (HD) is a neurodegenerative disorder caused by expanded cytosine-adenine-guanine (CAG) repeats in the Huntingtin gene, resulting in the production of mutant huntingtin proteins (mHTT). Previous research has identified urea as a key metabolite elevated in HD animal models and postmortem tissues of HD patients. However, the relationship between disease course and urea elevations, along with the molecular mechanisms responsible for these disturbances remain unknown., Objective: To better understand the molecular disturbances and timing of urea cycle metabolism across different stages in HD., Methods: We completed a global metabolomic profile of cerebrospinal fluid (CSF) from individuals who were at several stages of disease: pre-manifest (PRE), manifest (MAN), and late manifest (LATE) HD participants, and compared to controls., Results: Approximately 500 metabolites were significantly altered in PRE participants compared to controls, although no significant differences in CSF urea or urea metabolites were observed. CSF urea was significantly elevated in LATE participants only. There were no changes in the urea metabolites citrulline, ornithine, and arginine., Conclusions: Overall, our study confirms that CSF elevations occur late in the HD course, and these changes may reflect accumulating deficits in cellular energy metabolism.