Cognitive Training During Midlife: A Systematic Review and Meta-Analysis.

Midlife has been suggested to be a crucial time to introduce interventions for improving cognitive functions. The effects of cognitive training (CT) in healthy middle-aged populations and more specifically during the menopausal transition have not been systematically investigated. To investigate the effects of CT on cognition in healthy middle-aged adults and specifically in females during the menopause transition, literature was searched inception to July 2023 and studies were included that examined the effects of CT on a defined cognitive outcome. The improvement on cognitive performance following CT was the main outcome measured as mean difference (from baseline to immediate post) estimates with corresponding 95% confidence intervals (CI) in meta-analysis and was discussed with the support of subgroup analysis based on outcome type (i.e., far or near-transfer) and cluster tabulations. Nineteen articles were included in the qualitative synthesis with a total of 7765 individuals, and eight articles were included in the meta-analyses. CT was categorized into six type clusters: Game-based CT, General CT, Speed of Processing Training, Working Memory Training, Strategy-based CT, and Cognitive Remediation. Cognitive outcome was divided into six clusters: working memory, verbal memory, language, executive function, attention/processing speed, and visual memory. Meta-analysis reported significant improvement in the domain of executive function (0.48, 95% CI 0.08-0.87), verbal memory (0.22, 95% CI 0.11-0.33), and working memory (0.16, 95% CI 0.05-0.26). CT confers benefits on various cognitive domains, suggesting a potential role of CT to promote optimal cognitive functioning in the midlife and specifically in women during the menopause transition.

Origin of the Laurentian Great Lakes fish fauna through upward adaptive radiation cascade prior to the Last Glacial Maximum.

The evolutionary histories of adaptive radiations can be marked by dramatic demographic fluctuations. However, the demographic histories of ecologically-linked co-diversifying lineages remain understudied. The Laurentian Great Lakes provide a unique system of two such radiations that are dispersed across depth gradients with a predator-prey relationship. We show that the North American Coregonus species complex ("ciscoes") radiated rapidly prior to the Last Glacial Maximum (80-90 kya), a globally warm period, followed by rapid expansion in population size. Similar patterns of demographic expansion were observed in the predator species, Lake Charr (Salvelinus namaycush), following a brief time lag, which we hypothesize was driven by predator-prey dynamics. Diversification of prey into deep water created ecological opportunities for the predators, facilitating their demographic expansion, which is consistent with an upward adaptive radiation cascade. This study provides a new timeline and environmental context for the origin of the Laurentian Great Lakes fish fauna, and firmly establishes this system as drivers of ecological diversification and rapid speciation through cyclical glaciation.

Weighing your options-intragastric balloon versus semaglutide.

INTRODUCTION: Over half of Americans and up to 78% of US Veteran population meet criteria for obesity. Perioperatively placed intragastric balloon (IGB) can accelerate weight loss goals for safe surgical candidacy, however weight regain is common after removal. Glucagon-like peptide-1-receptor agonists (GLP1RA) may provide a more sustainable weight loss solution after surgery. We hypothesize that weight regain will be less at 1 year after initiation of GLP1RA than IGB placement in Veterans. METHODS: Retrospective review of prospective databases of perioperatively placed intragastric balloon cohort from 1/2019-1/2023 compared to patients who received initiatory GLP1RA from 6/2021-8/2022 at a VA Medical Center(VAMC). All patients were enrolled in the VAMC MOVE! multidisciplinary weight management program for a minimum of 12 weeks. Outcomes measured were patients' weights at 0, 3, 6, and 12 months and weight change for these intervals. Exclusion criteria included history of bariatric surgery and incomplete weight loss data. RESULTS: Two-hundred-twenty-three patients met inclusion criteria; 110 (49%) patients excluded. Mean age was 54 ± 11 years, the majority (78, 69%) were male, and the mean initial BMI was 37 ± 5.9 kg/m2. Seventeen (15%) patients underwent IGB placement and 96 (85%) patients received semaglutide. Weight (kg) change was measured at intervals: 0-3 months:- 11.8(- 17,- 9.5) IGB vs. - 5.1(- 7.4,- 2.3) semaglutide, p < 0.0001; 0-6 months:- 12.7(- 18.4,- 9.9) vs. - 9.4(- 12.6,- 6.1), p = 0.03; 3-6 months:- 0.5(- 2.3,2.3) vs. - 4.3(- 6.8,- 1.6), p < 0.0001; 6-12 months:3(0,7.3) vs. - 1.9(- 4.7,1), p = 0.0006. CONCLUSION: Weight loss occurs more rapidly in the first 6 months after intragastric balloon placement compared to semaglutide (- 12.7 vs. - 9.4 kg, p = 0.03). Despite ongoing attendance in a comprehensive weight loss program, weight regain is common after IGB removal by an average of 3 kg (23.6%) at 1 year. In contrast, patients on GLP1RA (semaglutide) continue to lose weight during this period. Further studies are needed to determine if optimal long-term outcomes may result from combination therapy with intragastric balloon and semaglutide.

Historical Southern Hemisphere biomass burning variability inferred from ice core carbon monoxide records.

Biomass burning plays an important role in climate-forcing and atmospheric chemistry. The drivers of fire activity over the past two centuries, however, are hotly debated and fueled by poor constraints on the magnitude and trends of preindustrial fire regimes. As a powerful tracer of biomass burning, reconstructions of paleoatmospheric carbon monoxide (CO) can provide valuable information on the evolution of fire activity across the preindustrial to industrial transition. Here too, however, significant disagreements between existing CO records currently allow for opposing fire histories. In this study, we reconstruct a continuous record of Antarctic ice core CO between 1821 and 1995 CE to overlap with direct atmospheric observations. Our record indicates that the Southern Hemisphere CO burden ([CO]) increased by 50% from a preindustrial mixing ratio of ca. 35 ppb to ca. 53 ppb by 1995 CE with more variability than allowed for by state-of-the-art chemistry-climate models, suggesting that historic CO dynamics have been not fully accounted for. Using a 6-troposphere box model, a 40 to 50% decrease in Southern Hemisphere biomass-burning emissions, coincident with unprecedented rates of early 20th century anthropogenic land-use change, is identified as a strong candidate for this mismatch.

Brief CBT-based psychological interventions to improve mental health outcomes in refugee populations: a systematic review and meta-analysis.

Background: Refugees, asylum seekers, and internally displaced people experience a high burden of mental health problems owing to their experiencing traumas and stressful events.Objective: To summarise the available evidence and analyse the efficacy of brief psychological interventions (< 3 months) on improving mental health outcomes, including depression, anxiety, and post-traumatic stress disorder (PTSD)-related symptoms in refugees.Method: We searched Medline, EMBASE, PsycINFO, CINAHL, and Global Index Medicus from inception to 19 December 2023. We included controlled studies using any cognitive behavioural therapy (CBT) or CBT-based therapies delivered over a short time (< 3 months), which reported mental health outcomes pre-and post-intervention. We conducted meta-analyses using random effects to derive pooled summary statistics. The quality of the evidence was assessed with the Cochrane Risk of Bias (RoB2) and ROBINS-I tools. This study is registered on the Open Science Framework, DOI 10.17605/OSF.IO/9CXU4.Results: 34 eligible studies across 37 publications were retrieved for analysis, and 33 studies with 4479 participants were included in the meta-analysis. There was an overall improvement in immediate mental health outcomes for all three domains, with analysis of 13 studies on anxiety outcomes (SMD -1.12, 95% CI -1.72 to -0.52), 20 studies on depression (SMD -1.04, 95% CI -1.97 to -0.11), and 24 studies on PTSD (SMD -0.82, 95% CI -1.20 to -0.45). At 3 to 6-month follow-up, however, analysis of mental health outcomes shows no significant change from baseline, with a SMD of 0.24 (95% CI -0.94 to 1.42) across 4 studies, -0.73 (95% CI -2.14 to 0.68) across 9 studies, and 0.29 (95% CI -0.94 to 1.53) across 12 studies for anxiety, depression, and PTSD respectively.Conclusion: Low-quality evidence shows brief psychological interventions have a positive immediate effect on refugees and internally displaced people's mental well-being. However, these effects do not persist in the short-term follow up. Heterogeneity was high, even among subgroups, impacting our findings' generalisability.

We analysed the evidence on the use of brief CBT-based psychological interventions to improve mental health outcomes in forcibly displaced persons.These interventions had a positive effect on anxiety, depression and PTSD, though there was high heterogeneity between studies.Positive effects on mental health disappeared at long-term follow-up.

Training in Cultural Competence for Mental Health Care: A Mixed-Methods Study of Students, Faculty, and Practitioners from India and USA.

Although the need to train clinicians to provide effective mental health care to individuals from diverse backgrounds has been recognized worldwide, a bulk of what we know about training in cultural competence (CC) is based on research conducted in the United States. Research on CC in mental health training from different world populations is needed due to the context-dependent nature of CC. Focusing on India and USA, two diverse countries that provide complementary contexts to examine CC, we explored graduate students', practicing clinicians', and faculty members' perspectives regarding CC training they received/provided and future training needs using mixed-methods. The data were collected using focus groups (n = 25 groups total: 15 in India, 11 in USA), and a survey (n = 800: 450 in India, 350 in USA). Our data highlight the salient social identities in these countries, and the corresponding constituents of CC training. Participants in India described a practical emphasis to their CC training (e.g., learning about CC through life experiences and clinical practice experiences) more so than through coursework, whereas participants in USA described varying levels of coursework related to CC along with practice. Participants in both countries considered enormity of CC as a challenge, while those in the US also identified CC training limited to a white, straight, male perspective, hesitancy in engaging with diversity topics, and limited time and competence of the faculty. Strengths of CC training in India and USA are mutually informative in generating recommendations for enhancing the training in both countries.

Heads up on concussion: Aboriginal and Torres Strait Islander peoples' knowledge and understanding of mild traumatic brain injury.

ISSUE ADDRESSED: Concussion awareness and knowledge among Aboriginal and Torres Strait Islander peoples residing in Perth, Western Australia and factors preventing presentation at a health service for assessment after such an injury. METHODS: Qualitative study with participants aged between 18 and 65 years. Recruitment was by Facebook advertising and snowball sampling. A semi-structured topic yarning guide was used to guide conversations through 1:1, multi-person or group yarns. Yarns were audio-recorded, transcribed and thematically analysed. RESULTS: Twenty-four participants were recruited. A good knowledge of modes of concussion injury was identified in these participants. However, they identified difficulty differentiating this injury from other injuries or medical conditions. Multiple factors contributed to a reluctance to seek assessment and further management of a potential concussion. Multiple strategies to enhance education and presentation for assessment were suggested by participants. CONCLUSIONS: Aboriginal and Torres Strait Islander-owned and led concussion education is the first step in enhancing understanding of this condition. Education must be coupled with improvements in the cultural safety of healthcare services, as without this, patients will continue to fail to present for assessment and management. SO WHAT?: It is recommended that concussion education focuses on the differentiation of concussion as a diagnosis from other injuries. Information regarding where and when to seek medical assessment is recommended, and this must be in a culturally safe environment. Typical recovery and potential sequelae must be explored, in programs led and devised by Aboriginal and Torres Strait Islander peoples engaged with the community for which the education is proposed.

The role of platelet desialylation as a biomarker in primary immune thrombocytopenia: mechanisms and therapeutic perspectives.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by the destruction of platelets. Although it was long believed that the critical role of autoantibodies in platelet destruction, primarily through the Fc-dependent platelet clearance pathway, recent findings indicate that the significance of the Fc-independent platelet clearance pathway mediated by hepatocytes, thus shedding light on a previously obscure aspect of ITP pathogenesis. Within this context, the desialylation of platelets has emerged as a pivotal biochemical marker. Consequently, targeting platelet desialylation emerges as a novel therapeutic strategy in the pathogenesis of ITP. Notably, prevailing research has largely focused on antiplatelet antibodies and the glycosylation-associated mechanisms of platelet clearance, while comprehensive analysis of platelet desialylation remains scant. In response, we retrospectively discuss the historical progression, inducing factors, generation process, and molecular regulatory mechanisms underlying platelet desialylation in ITP pathogenesis. By systematically evaluating the most recent research findings, we contribute to a comprehensive understanding of the intricate processes involved. Moreover, our manuscript delves into the potential application of desialylation regulatory strategies in ITP therapy, heralding novel therapeutic avenues. In conclusion, this manuscript not only fills a critical void in existing literature but also paves the way for future research by establishing a systematic theoretical framework. By inspiring new research ideas and offering insights into the development of new therapeutic strategies and targeted drugs, our study is poised to significantly advance the clinical management of ITP.

Deactivation and collective phasic muscular tuning for pointing direction: Insights from machine learning.

Arm movements in our daily lives have to be adjusted for several factors in response to the demands of the environment, for example, speed, direction or distance. Previous research has shown that arm movement kinematics is optimally tuned to take advantage of gravity effects and minimize muscle effort in various pointing directions and gravity contexts. Here we build upon these results and focus on muscular adjustments. We used Machine Learning to analyze the ensemble activities of multiple muscles recorded during pointing in various directions. The advantage of such a technique would be the observation of patterns in collective muscular activity that may not be noticed using univariate statistics. By providing an index of multimuscle activity, the Machine Learning (ML) analysis brought to light several features of tuning for pointing direction. In attempting to trace tuning curves, all comparisons were done with respects to pointing in the horizontal, gravity free plane. We demonstrated that tuning for direction does not take place in a uniform fashion but in a modular manner in which some muscle groups play a primary role. The antigravity muscles were more finely tuned to pointing direction than the gravity muscles. Of note, was their tuning during the first half of downward pointing. As the antigravity muscles were deactivated during this phase, it supported the idea that deactivation is not an on-off function but is tuned to pointing direction. Further support for the tuning of the negative portions of the phasic EMG was provided by the observation of progressively improving classification accuracies with increasing angular distance from the horizontal. We also demonstrated that the durations of these negative phases, without information on their amplitudes, is tuned to pointing directions. Overall, these results show that the motor system tunes muscle commands to exploit gravity effects and reduce muscular effort. It quantitatively demonstrates that phasic EMG negativity is an essential feature of muscle control. The ML analysis was done using Linear Discriminant analysis (LDA) and Support Vector Machines (SVM). The two led to the same conclusions concerning the movements being investigated, hence showing that the former, computationally inexpensive technique is a viable tool for regular investigation of motor control.

Novel Occupational Therapy Program (Step Up) to Facilitate the Transition from Early Intervention in Psychosis Services.

The purpose of this program evaluation was to examine preliminary outcomes associated with a novel stepdown program for clients of early intervention in psychosis services ("Step Up") that featured occupational therapy (OT) as a critical treatment component. Clients participated in Step Up for at least 6 months and were administered pre-post assessments of clinician-rated performance of daily living activities and self-perceived performance and satisfaction with daily occupational functioning. Paired samples Wilcoxon tests were used to compare outcomes across the two time points. Data from 23 participants of Step Up were analyzed. Clinician-rated performance of daily living (especially in the areas of money and time management and leisure engagement) and client-rated performance and satisfaction with daily occupational functioning improved significantly over time. Results demonstrate the promise of programs such as Step Up that capitalize on OT and promote functional outcomes during the transition from early intervention.

Collaborative approaches in psychiatric rehabilitation: Innovations in practice.

OBJECTIVE: This special section is dedicated to collaborative approaches in psychiatric rehabilitation, which are rooted in foundational values such as service user involvement and self-determination. METHODS: Five articles featuring collaborative approaches are included and briefly reviewed here. RESULTS: These articles highlight innovations in collaborative approaches, addressing existing limitations in research and practice and advancing understanding of collaborative psychiatric care among diverse populations. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: They underscore the ongoing need for research and policy reform to promote more routine and widespread implementation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Awareness and understanding of concussion among Aboriginal Australians with high health literacy.

Aim: Indigenous Australians have higher rates of traumatic brain injury, with 74-90% of such injuries being concussion. This study explores concussion awareness and knowledge in Aboriginal Western Australians with high health literacy. Materials & methods: Participants, aged 18-65 years, engaged in research topic yarning, and thematic analysis of the qualitative data then undertaken. Results: There was awareness that direct head trauma can result in concussion, but a lack of differentiation between concussion and other head injuries. Knowledge was gained from sport, media or lived-experience. Symptom minimization and diversity of concussion symptoms prevented participants from seeking medical treatment. This was exacerbated by a mistrust of the medical system. Conclusion: Research findings highlight knowledge and service gaps where co-designed strategies can be targeted.

Despite higher injury rates in Indigenous Australians, literature relating to brain injuries such as concussion in these populations is lacking. This article provides information regarding awareness and knowledge of concussion in Aboriginal peoples with health or first responder experience. Through the process of yarning, 25 Aboriginal participants shared their awareness and knowledge of concussion. While there was good understanding of how concussion injury can occur, it was found that identification of concussion as a diagnosis is complex, and it is hard to differentiate from other conditions. Minimization of concussion symptoms was commonly reported, and multiple barriers to seeking healthcare after a potential concussion occurs were identified. Despite having health or first responder experience, participants reported their concussion knowledge was gained from community and televised sport, other aspects of media, and word of mouth. These results support the need for Indigenous Australian led and co-designed concussion education. They also support the need for further research in this space, targeting Indigenous Australian populations without high health literacy.

Bilateral insular cortical lesions reduce sensitivity to the adverse consequences of acute ethanol intoxication in Pavlovian conditioning procedures.

BACKGROUND: Sensitivity to the adverse post-ingestive effects of ethanol likely serves as a deterrent to initiate alcohol consumption early in drinking and later may contribute to efforts to remain abstinent. Administering ethanol to naïve rats prior to Pavlovian conditioning procedures elicits robust ethanol-conditioned taste and place avoidance (CTA; CPA) mediated by its subjective interoceptive properties. The insular cortex (IC) has been implicated as a region involved in mediating sensitivity to the interoceptive properties of ethanol. Here, we examined whether bilateral lesions of the IC affect the acquisition and expression of taste and place avoidance in ethanol-induced CTA and CPA paradigms. METHODS: Adult male and female Wistar rats received bilateral excitotoxic lesions (ibotenic acid; 20 mg/mL; 0.3 µL) of the IC prior to conditioning procedures. Subsequently, rats were conditioned to associate a novel taste stimulus (0.1% saccharin) and context with the effects of ethanol (1.0 g/kg) in a combined CTA/CPP procedure. Conditioning occurred over 8 alternating CS+/CS- days, followed by tests for expression of taste and place preferences. Data from IC-lesioned rats were compared with neurologically intact rats. RESULTS: Our findings revealed that neurologically intact rats showed a significantly stronger ethanol-induced CTA than IC-lesioned rats. There were no significant differences in total fluid intake when rats consumed water (CS-). As with CTA effects, intact rats showed a strong CPA, marked by a greater reduction in time spent on the drug-paired context, while IC-lesioned rats failed to display CPA to ethanol. CONCLUSION: These results indicate that proper IC functioning is necessary for responding to the adverse interoceptive properties of ethanol regardless of which Pavlovian paradigm is used to assess interoceptive responsivity to ethanol. Blunted IC functioning from chronic ethanol use may reduce interoceptive signaling specifically of ethanol's adverse effects thus contributing to increased alcohol use.

Efficacy and Safety of Vibegron for Persistent Symptoms of Overactive Bladder in Men Being Pharmacologically Treated for Benign Prostatic Hyperplasia: Results From the Phase 3 Randomized Controlled COURAGE Trial.

PURPOSE: The efficacy and safety of vibegron, a ß3-adrenergic receptor agonist, was assessed among men with symptoms of overactive bladder (OAB) receiving pharmacologic treatment for benign prostatic hyperplasia (BPH) in a phase 3 randomized controlled trial. MATERIALS AND METHODS: Men ≥ 45 years with OAB symptoms and BPH, treated with α-blocker with/without 5α-reductase inhibitors, were randomized 1:1 to vibegron or placebo for 24 weeks. Coprimary end points were change from baseline at week 12 in mean daily micturitions and urgency episodes. Secondary end points were change from baseline at week 12 in mean nightly nocturia and daily urge urinary incontinence episodes, International Prostate Symptom Score‒storage score, and volume voided per micturition. Safety was evaluated via adverse events (AEs). RESULTS: Of 1105 participants randomized, 965 (87.3%) completed the trial. At week 12, vibegron was associated with significant reductions vs placebo in daily micturitions (least squares mean difference [95% CI], -0.74 [-1.02, -0.46]; P < .0001) and urgency episodes (-0.95 [-1.37, -0.54]; P < .0001). Vibegron was also associated with significant improvements vs placebo at week 12 in nocturia episodes (least squares mean difference, -0.22 [-0.36, -0.09]; P = .002), urge urinary incontinence episodes (-0.80 [-1.33, -0.27]; P = .003), International Prostate Symptom Score‒storage scores (-0.9 [-1.2, -0.6]; P < .0001), and volume voided (15.07 mL [9.13-21.02]; P < .0001). AE rates were similar in vibegron (45.0%) and placebo (39.0%) arms; AEs occurring in ≥ 2% of participants were hypertension (9.0% vs 8.3%), COVID-19 (4.0% vs 3.1%), UTI (2.5% vs 2.2%), and hematuria (2.0% vs 2.5%). CONCLUSIONS: In this trial, vibegron met all primary and secondary end points and was safe and well tolerated in men with OAB symptoms and pharmacologically treated BPH.

The use of accelerometers to improve estimation of the thermic effect of food in whole room calorimetry studies.

We tested whether spontaneous physical activity (SPA) from accelerometers could be used in a whole room calorimeter to estimate thermic effect of food (TEF). Eleven healthy participants (n = 7 females; age: 27 ± 4 yr; body mass index: 22.8 ± 2.6 kg/m2) completed two 23-h visits in randomized order: one "fed" with meals provided and one "fasted" with no food. SPA was measured by ActivPAL and Actigraph accelerometers. Criterion TEF was calculated as the difference in total daily energy expenditure (TDEE) between fed and fasted visits and compared with three methods of estimating TEF: 1) SPA-adjusted TEF (adjTEF)-difference in TDEE without SPA between visits, 2) Wakeful TEF-difference in energy expenditure obtained from linear regression and basal metabolic rate during waking hours, 3) 24-h TEF-increase in TDEE above SPA and sleeping metabolic rate. Criterion TEF was 9.4 ± 4.5% of TDEE. AdjTEF (difference in estimated vs. criterion TEF: activPAL: -0.3 ± 3.3%; Actigraph: -1.8 ± 8.0%) and wakeful TEF (activPAL: -0.9 ± 6.1%; Actigraph: -2.8 ± 7.6%) derived from both accelerometers did not differ from criterion TEF (all P > 0.05). ActivPAL-derived 24-h TEF overestimated TEF (6.8 ± 5.4%, P = 0.002), whereas Actigraph-derived 24-h TEF was not significantly different (4.3 ± 9.4%, P = 0.156). TEF estimations using activPAL tended to show better individual-level agreement (i.e., smaller coefficients of variation). Both accelerometers can be used to estimate TEF in a whole room calorimeter; wakeful TEF using activPAL is the most viable option given strong group-level accuracy and reasonable individual agreement.NEW & NOTEWORTHY Two research-grade accelerometers can effectively estimate spontaneous physical activity and improve the estimation of thermic effect of food (TEF) in whole room calorimeters. The activPAL demonstrates strong group-level accuracy and reasonable individual-level agreement in estimating wakeful TEF, whereas a hip-worn Actigraph is an acceptable approach for estimating 24-h TEF. These results highlight the promising potential of accelerometers in advancing energy balance research by improving the assessment of TEF within whole room calorimeters.

A New Angle on Transcranial Magnetic Stimulation Coil Orientation: A Targeted Narrative Review.

Transcranial magnetic stimulation (TMS) is used to treat several neuropsychiatric disorders including depression, where it is effective in approximately one half of patients for whom pharmacological approaches have failed. Treatment response is related to stimulation parameters such as the stimulation frequency, pattern, intensity, location, total number of pulses and sessions applied, and target brain network engagement. One critical but underexplored component of the stimulation procedure is the orientation or yaw angle of the commonly used figure-of-eight TMS coil, which is known to impact neuronal response to TMS. However, coil orientation has remained largely unchanged since TMS was first used to treat depression and continues to be based on motor cortex anatomy, which may not be optimal for the dorsolateral prefrontal cortex treatment site. In this targeted narrative review, we evaluate experimental, clinical, and computational evidence indicating that optimizing coil orientation may improve TMS treatment outcomes. The properties of the electric field induced by TMS, the changes to this field caused by the differing conductivities of head tissues, and the interaction between coil orientation and the underlying cortical anatomy are summarized. We describe evidence that the magnitude and site of cortical activation, surrogate markers of TMS dosing and brain network targeting considered central in clinical response to TMS, are influenced by coil orientation. We suggest that coil orientation should be considered when applying therapeutic TMS and propose several approaches to optimizing this potentially important treatment parameter.

Acute nicotine administration reduces the efficacy of punishment in curbing remifentanil consumption in a seeking-taking chain schedule of reinforcement.

RATIONALE: Nicotine dependence is highly comorbid with opioid use disorders (OUDs). The use of nicotine-containing products increases the propensity to misuse prescription opioids and addressing both nicotine and opioid use simultaneously is more efficacious for treatment of OUDs than treating opioid use alone. OBJECTIVES: Given this extreme comorbidity, further elucidation of the effects of nicotine as a factor in promoting vulnerability to development of OUDs is needed. Here, we sought to further explore the effects of nicotine administration on operant self-administration of remifentanil (RMF), a fast-acting synthetic µ-opioid receptor agonist, using a heterogenous seeking-taking chain schedule of reinforcement in unpunished and punished conditions. METHODS: Male and female rats received nicotine (0.4 mg/kg) or saline prior to operant self-administration sessions. These sessions consisted of pressing a 'seeking' lever to gain access to a 'taking' lever that could be pressed for delivery of 3.2 µg/kg RMF. After acquisition, continued drug seeking/taking was punished through contingent delivery of foot-shock. RESULTS: Nicotine, relative to saline, increased RMF consumption. Furthermore, nicotine treatment resulted in significantly higher seeking responses and cycles completed, and this effect became more pronounced during punished sessions as nicotine-treated rats suppressed RMF seeking significantly less than controls. Nicotine treatment functionally reduced the efficacy of foot-shock punishment as a deterrent of opioid-seeking. CONCLUSIONS: Nicotine administration enhanced both appetitive and consummatory responding for RMF and engendered a punishment-insensitive phenotype for RMF that was less impacted by contingent administration of foot-shock punishment. These findings provide further support for the hypothesis that nicotine augments vulnerability for addiction-like behaviors for opioids.

Mapping neurodegeneration across the Huntington's disease spectrum: a five-year longitudinal analysis of plasma neurofilament light.

BACKGROUND: Neurofilament light (NfL) has previously been highlighted as a potential biomarker for Huntington's Disease (HD) using cross-sectional analyses. Our study aim was to investigate how longitudinal trajectories of plasma NfL relate to HD disease stage. METHODS: 108 participants [78 individuals with the HD mutation, and 30 healthy controls (HC)] were included in this study. Individuals with the HD mutation were categorised separately by both HD-Integrated Staging System (HD-ISS) (Study 1) and PIN score-Approximated Staging System (PASS) (Study 2) criteria. Plasma NfL trajectories were examined using Mixed Linear Modeling (MLM); associations with symptom presentation were assessed using Spearman's rho correlations. FINDINGS: The MLM coefficients for disease stage (HD-ISS ß = 32.73, p < 0.0001; PASS ß = 33.00, p < 0.0001) and disease stage∗time (HD-ISS ß = 7.85, p = 0.004; PASS ß = 6.58, p = 0.0047) suggest these are significant contributors to plasma NfL levels. In addition, the plasma NfL rate of change varied significantly across time (HD-ISS ß = 3.14, p = 0.04; PASS ß = 2.94, p = 0.050). The annualised rate of change was 8.32% for HC; 10.55%, 12.75% and 15.62% for HD-ISS Stage ≤1, Stage 2, and Stage 3, respectively; and 12.13%, 10.46%, 10.33%, 17.52%, for PASS Stage 0, Stage 1, Stage 2, and Stage 3, respectively. Plasma NfL levels correlated with the Symbol Digit Modalities Test (SDMT) in HD-ISS Stage ≤1, and both SDMT and Total Motor Score in Stage 3 (ps < 0.01). INTERPRETATION: Our findings suggest that plasma NfL levels increase linearly across earlier disease stages, correlating with the cognitive SDMT measure. Thereafter, an increase or surge in plasma NfL levels, paired with correlations with both cognitive and motor measures, suggest a late acceleration in clinical and pathological progression. FUNDING: NIH (NS111655); the UCSD HDSA CoE; the UCSD ADRC (NIH-NIA P30 AG062429).

Liver paired exchange U.S. single center experience - pairs, chains, and use of compatible pairs'.

BACKGROUND: In the United States, the discrepancy between organ availability and need has persisted despite changes in allocation, innovations in preservation, and policy initiatives. Living donor liver transplant (LDLT) remains an underutilized means of improving access to timely liver transplantation and decreasing waitlist mortality. Liver paired exchange (LPE) represents an opportunity to overcome LDLT pair incompatibility due to size, anatomy, or blood type. METHODS: LPE was adopted as a strategy to augment access to liver transplantation at our institution. Specific educational materials, consent forms, and selection processes were developed to facilitate LPE. RESULTS: From 2019 through October 2023, our center performed 11 LPEs, resulting in 23 LDLT pairs. The series included several types of LPE: those combining complementary incompatible pairs, the inclusion of compatible pairs to overcome incompatibility, and the use of altruistic non-directed donors to initiate chains. These exchanges facilitated transplantation for 23 recipients, including 1 pediatric patient. CONCLUSIONS: LPE improved access to liver transplantation at our institution. The ethical application of LPE includes tailored patient education, assessment and disclosure of exchange balance, mitigation of risk and maximization of benefit for donors and recipients.

The Effect of Ophthalmic Antibiotics on Clinical Outcomes and Transmissibility of Conjunctivitis Associated with Haemophilus influenzae versus Other Pathogens: Secondary Analysis of a Randomized Controlled Trial.

Transmission rates among children with conjunctivitis were low and antibiotic use was not associated with reduced transmission. Policies recommending exclusion from daycare and school for conjunctivitis should be scrutinized as they may not reduce transmission and may increase unnecessary antibiotic use.