Anticoagulation Versus Antiplatelets in Spontaneous Cervical Artery Dissection: A Systematic Review and Meta-Analysis.

BACKGROUND: It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection. METHODS: The systematic review was registered in PROSPERO (CRD42023468063). We searched 5 databases using a combination of keywords that encompass different antiplatelets and anticoagulants, as well as cervical artery dissection. We included relevant randomized trials and included observational studies of dissection unrelated to major trauma. Where studies were sufficiently similar, we performed meta-analyses for efficacy (ischemic stroke) and safety (major hemorrhage, symptomatic intracranial hemorrhage, and death) outcomes using relative risks. RESULTS: We identified 11 studies (2 randomized trials and 9 observational studies) that met the inclusion criteria. These included 5039 patients (30% [1512] treated with anticoagulation and 70% [3527]) treated with antiplatelets]. In meta-analysis, anticoagulation was associated with a lower ischemic stroke risk (relative risk, 0.63 [95% CI, 0.43 to 0.94]; P=0.02; I2=0%) but higher major bleeding risk (relative risk, 2.25 [95% CI, 1.07 to 4.72]; P=0.03, I2=0%). The risks of death and symptomatic intracranial hemorrhage were similar between the 2 treatments. Effect sizes were larger in randomized trials. There are insufficient data on the efficacy and safety of dual antiplatelet therapy or direct oral anticoagulants. CONCLUSIONS: In this study of patients with cervical artery dissection, anticoagulation was superior to antiplatelet therapy in reducing ischemic stroke but carried a higher major bleeding risk. This argues for an individualized therapeutic approach incorporating the net clinical benefit of ischemic stroke reduction and bleeding risks. Large randomized clinical trials are required to clarify optimal antithrombotic strategies for management of cervical artery dissection.

Anthropogenic Vector Ecology and Management to Combat Disease Spread in Aquaculture.

Anthropogenic vectors (transfer mechanisms) can facilitate the introduction and spread of aquatic disease in marine farming regions. Preventing or interrupting pathogen transfers associated with movements of these vectors is key to ensuring productivity and profitability of aquaculture operations. However, practical methods to identify and manage vector risks are lacking. We developed a risk analysis framework to identify disease risks and management gaps associated with anthropogenic vector movements in New Zealand's main aquaculture sectors - Chinook salmon (Oncorhynchus tshawytscha), green-lipped mussels (Perna canaliculus), and Pacific oysters (Crassostrea gigas). Vectors within each sector were identified and assigned categorical risk scores for (i) movement characteristics (size, frequency, likelihood of return to sea), (ii) biological association with pathogens (entrainment potential, contribution to previous aquaculture disease outbreaks) and (iii) available best practice biosecurity methods and tools, to inform unmitigated and mitigated risk rankings. Thirty-one vectors were identified to operate within the national network and association with livestock was found to be a primary driver of vector risk rankings. Movements of live growing stock and culture substrates (e.g., mussel ropes) in shellfish farming had high-risk vector profiles that are logistically challenging to address, while vessel vectors were identified as the salmon farming sector's priority. The framework and rankings can be used to inform both research and management priorities in aquaculture and other primary production systems, including risk validation, vector roles in disease epidemiology, compliance with permit conditions, policy development, and treatment options.

ACR Lung CT Screening Reporting and Data System, a Systematic Review and Meta-Analysis Before Change in US Preventative Services Taskforce Eligibility Criteria: 2014 to 2021.

OBJECTIVE: To review Lung CT Screening Reporting and Data System (Lung-RADS) scores from 2014 to 2021, before changes in eligibility criteria proposed by the US Preventative Services Taskforce. METHODS: A registered systematic review and meta-analysis was conducted in MEDLINE, Embase, CINAHL, and Web of Science in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines; eligible studies examined low-dose CT (LDCT) lung cancer screening at institutions in the United States and reported Lung-RADS from 2014 to 2021. Patient and study characteristics, including age, gender, smoking status, pack-years, screening timeline, number of individual patients, number of unique studies, Lung-RADS scores, and positive predictive value (PPV) were extracted. Meta-analysis estimates were derived from generalized linear mixed modeling. RESULTS: The meta-analysis included 24 studies yielding 36,211 LDCT examinations for 32,817 patient encounters. The meta-analysis Lung-RADS 1-2 scores were lower than anticipated by ACR guidelines, at 84.4 (95% confidence interval [CI] 83.3-85.6) versus 90% respectively (P < .001). Lung-RADS 3 and 4 scores were both higher than anticipated by the ACR, at 8.7% (95% CI 7.6-10.1) and 6.5% (95% CI 5.707.4), compared with 5% and 4%, respectively (P < .001). The ACR's minimum estimate of PPV for Lung-RADS 3 to 4 is 21% or higher; we observed a rate of 13.1% (95% CI 10.1-16.8). However, our estimated PPV rate for Lung-RADS 4 was 28.6% (95% CI 21.6-36.8). CONCLUSION: Lung-RADS scores and PPV rates in the literature are not aligned with the ACR's own estimates, suggesting that perhaps Lung-RADS categorization needs to be reexamined for better concordance with real-world screening populations. In addition to serving as a benchmark before screening guideline broadening, this study provides guidance for future reporting of lung cancer screening and Lung-RADS data.

Economic evaluation and costs of remote patient monitoring for cardiovascular disease in the United States: a systematic review.

BACKGROUND: Remote patient monitoring (RPM) has emerged as a viable and valuable care delivery method to improve chronic disease management. In light of the high prevalence and substantial economic burden of cardiovascular disease (CVD), this systematic review examines the cost and cost-effectiveness of using RPM to manage CVD in the United States. METHODS: We systematically searched databases to identify potentially relevant research. Findings were synthesized for cost and cost-effectiveness by economic study type with consideration of study perspective, intervention, clinical outcome, and time horizon. The methodological quality was assessed using the Joanna Briggs Institute Checklist for Economic Evaluations. RESULTS: Thirteen articles with fourteen studies published between 2011 and 2021 were included in the final review. Studies from the provider perspective with a narrow scope of cost components identified higher costs and similar effectiveness for the RPM group relative to the usual care group. However, studies from payer and healthcare sector perspectives indicate better clinical effectiveness of RPM relative to usual care, with two cost-utility analysis studies suggesting that RPM relative to usual care is a cost-effective tool for CVD management even at the conservative $50,000 per Quality-Adjusted Life-Year threshold. Additionally, all model-based studies revealed that RPM is cost-effective in the long run. CONCLUSIONS: Full economic evaluations identified RPM as a potentially cost-effective tool, particularly for long-term CVD management. In addition to the current literature, rigorous economic analysis with a broader perspective is needed in evaluating the value and economic sustainability of RPM.

Comparative efficacy of a novel Bacillus subtilis-based probiotic and pharmacological zinc oxide on growth performance and gut responses in nursery pigs.

In this study, we assessed the efficacy of a novel Bacillus subtilis probiotic in improving growth performance and gut responses in comparison to pharmacological zinc oxide (ZnO) in nursery pigs. A total of 96 piglets were randomly assigned to four groups: Negative control (NC), Positive control (PC, 3000 mg Zn /kg feed), B.subtilis low dose (BS9-L, 2 × 107 CFU/pig) and B.subtilis high dose (BS9-H, 2 × 109 CFU/pig). Growth performance, diarrhea rate, gut mucosal gene expression and fecal microbial populations were evaluated. B.subtilis administration did not improve piglet bodyweight. BS9-L showed (P < 0.05) higher average daily gain (ADG) in Period 2 (D14-D28). BS9 groups had (P < 0.001) lower feed conversion ratio (FCR) in Period 2 (D14-D28) and overall. Like the ZnO-group, BS9 groups had lower (P < 0.01) diarrhea rate. A significant reduction (P < 0.05) in fecal E. coli, total coliforms, and an increase in lactic acid bacteria and Bacillus spp. in BS9 groups was observed. BS9 group had reduced (P < 0.05) mRNA levels of intestinal IL-8 and higher levels of MUC-1 and occludin and TJP-1 compared to negative control. These findings suggest that probiotic BS9, may promote growth performance, and ameliorate various indicators of intestinal health in piglets. Hence, it may serve as a prospective alternative to ZnO growth promoter in commercial swine production.

Barriers to uptake of PrEP across the continuum among transgender women: A global scoping review.

BACKGROUND: Although preexposure prophylaxis (PrEP) has demonstrated high efficacy for HIV prevention, rates of PrEP uptake remain low among the transgender population, especially in transgender women (TGW). We conducted this scoping review to assess and characterize barriers to PrEP use along the PrEP care continuum among TGW. METHODS: We conducted this scoping review by searching studies in Embase, PubMed, Scopus, and Web of Science. Eligibility criteria included: reporting a PrEP related quantitative result among TGW; peer-reviewed and published in English between 2010-2021. RESULTS: Globally, high willingness (80%) to use PrEP was found, yet uptake and adherence (35.4%) were low. TGW experiencing hardship, including poverty, incarceration, and substance use, were associated with higher odds of PrEP awareness but lower odds of PrEP use. Structural and social barriers such as stigma, medical mistrust, and perceived racism can be important barriers for PrEP continuation. High social cohesion and hormone replacement therapy were associated with greater odds of awareness. In addition, our study confirmed prior research showing that PrEP does not lower feminizing hormone levels in TGW. CONCLUSIONS: Significant demographic factors among TGW that are associated with PrEP engagement. It is imperative to focus on TGW as a population with independent needs, requiring specific PrEP care guidelines and tailored resource allocation, that fully considers individual-, provider-, and community/structural-level barriers and facilitators. The present review also indicates that combining PrEP care with GAHT or broader gender-affirmation care may facilitate PrEP use.

Choline supplementation regulates gut microbiome diversity, gut epithelial activity, and the cytokine gene expression in gilts.

Choline is an essential nutrient that is necessary for both fetal development and maintenance of neural function, while its effect on female ovarian development is largely unexplored. Our previous study demonstrated that choline supplementation promotes ovarian follicular development and ovulation, although its underlying mechanism was unclear. To uncover the potential regulation pathway, eighteen female Yorkshire × Landrace gilts were fed with either standard commercial diet (Control group, n = 9) or choline supplemented diet (Choline group, additional 500 mg/kg of control diet, n = 9) from day 90 of age to day 186. At day 186, feces samples were analyzed for effects on the gut microbiome using 16S ribosomal RNA gene V3-V4 region sequencing with Illumina MiSeq, serum samples were analyzed for trimethylamine (TMA) and trimethylamine-N-oxide (TMAO) using HILIC method, and jejunum tissues were analyzed for immune related gene expression using qRT-PCR. Our results show that choline supplementation did not alter the circulating level of TMA and TMAO (P > 0.05), but rather increased gut microbiome alpha diversity (P < 0.05). Beta diversity analysis results showed that the choline diet mainly increased the abundance of Firmicutes, Proteobacteria, and Actinobacteria, but decreased the abundance of Bacteroidetes, Spirochaetes, and Euryarchaeota at the phyla level. Meta-genomic analysis revealed that choline supplementation activated pathways in the gut microbiota associated with steroid hormone biosynthesis and degradation of infertility-causing environmental pollutants (bisphenol, xylene, and dioxins). To further verify the effect of choline on intestinal activity, a porcine intestine cell line (IPEC-J2) was treated with serial concentrations of choline chloride in vitro. Our data demonstrated that choline promoted the proliferation of IPEC-J2 while inhibiting the apoptotic activity. qRT-PCR results showed that choline significantly increased the expression level of Bcl2 in both IPEC-J2 cells and jejunum tissues. The expression of IL-22, a cytokine that has been shown to impact ovarian function, was increased by choline treatment in vitro. Our findings reveal the beneficial effect of choline supplementation on enhancing the gut microbiome composition and intestinal epithelial activity, and offer insights into how these changes may have contributed to the ovarian development-promoting effect we reported in our previous study.

The Impact of Consumer Wearable Devices on Physical Activity and Adherence to Physical Activity in Patients with Cardiovascular Disease: A Systematic Review of Systematic Reviews and Meta-Analyses.

Objective: Consumer wearable devices allow physical activity to be measured objectively, which can be useful in remote cardiovascular disease management. This review aimed to summarize the effects of using wearable devices to monitor physical activity/adherence to physical activity in adults with cardiovascular disease. Methods: The review used The Cochrane Overview of Reviews Methodology. The databases searched were PubMed, EMBASE, CINAHL, Web of Science, and the Cochrane Database of Systematic Reviews, the date of the last search was October 12, 2021. Risk of bias was assessed using the AMSTAR-2® tool. Results: Of the 767 records, we identified 6 systematic reviews (SRs) and meta-analyses (MA) that met our inclusion criteria. The individual SRs did not consistently favor the use of wearables, but the MA syntheses each found significant effects, favoring wearable devices in measures, including mean steps per day and mean time spent completing moderate-to-vigorous physical activity. The MA on adherence to cardiac rehabilitation (CR) found greater adherence to CR with the use of a mobile app than with no app support. Summary: Within this review, there were SRs demonstrating no difference and reviews indicating a positive impact with the use of wearables for physical activity/adherence measures in individuals with cardiovascular conditions, with no studies demonstrating a negative impact. The six SR/MAs included had methodological flaws, which introduced potential biases. Additionally, the MAs included a small number of studies, which limits their generalizability. The protocol for this review was registered on PROSPERO, the international prospective register of systematic reviews (#CRD42021286699).

Identification of Candidate Salivary, Urinary and Serum Metabolic Biomarkers for High Litter Size Potential in Sows (Sus scrofa).

The selection of sows that are reproductively fit and produce large litters of piglets is imperative for success in the pork industry. Currently, low heritability of reproductive and litter-related traits and unfavourable genetic correlations are slowing the improvement of pig selection efficiency. The integration of biomarkers as a supplement or alternative to the use of genetic markers may permit the optimization and increase of selection protocol efficiency. Metabolite biomarkers are an advantageous class of biomarkers that can facilitate the identification of cellular processes implicated in reproductive condition. Metabolism and metabolic biomarkers have been previously implicated in studies of female mammalian fertility, however a systematic analysis across multiple biofluids in infertile and high reproductive potential phenotypes has not been explored. In the current study, the serum, urinary and salivary metabolomes of infertile (INF) sows and high reproductive potential (HRP) sows with a live litter size ≥ 13 piglets were examined using LC-MS/MS techniques, and a data pipeline was used to highlight possible metabolite reproductive biomarkers discriminating the reproductive groups. The metabolomes of HRP and INF sows were distinct, including significant alterations in amino acid, fatty acid, membrane lipid and steroid hormone metabolism. Carnitines and fatty acid related metabolites were most discriminatory in separating and classifying the HRP and INF sows based on their biofluid metabolome. It appears that urine is a superior biofluid than saliva and serum for potentially predicting the reproductive potential level of a given female pig based on the performance of the resultant biomarker models. This study lays the groundwork for improving gilt and sow selection protocols using metabolomics as a tool for the prediction of reproductive potential.

Screening for Psychological Distress and Risk of Cardiovascular Disease and Related Mortality: A SYSTEMATIZED REVIEW, META-ANALYSIS, AND CASE FOR PREVENTION.

BACKGROUND: Psychological distress-elevated symptoms of depression, anxiety, post-traumatic stress disorder (PTSD), or psychosocial stress-has been associated with risk for cardiovascular disease (CVD). Despite increasing attention to the importance of these factors for CVD prevention, the state of this science requires updated synthesis to enable practice recommendations. Moreover, it is unknown whether psychological distress based on screeners, validated self-report instruments that efficiently identify those who may require mental health services or additional support, is associated with incident CVD. METHODS: MEDLINE, Embase, and PsycInfo were searched for studies published 2017-2022, including adults without a past psychiatric diagnosis, who were screened at baseline for depression, anxiety, PTSD, stress, or general mental health symptoms, and followed for >6 mo to determine their risk for incident CVD (ie, atrial fibrillation, acute coronary syndrome, coronary heart disease, peripheral vascular disease, heart failure, or a composite). A meta-analysis was used to aggregate results to determine whether clinically significant levels of psychological distress were associated with CVD onset. RESULTS: The search identified 28 investigations that represented 658 331 participants (58% women). Fifteen studies had adequate data for the primary meta-analysis, which indicated that those reporting high psychological distress showed a 28% greater risk of incident CVD compared with those with low or no distress. CONCLUSIONS: Rapid screening for psychological distress is a helpful and efficient approach to understanding the CVD risk profile of an individual. Additional investigations are needed to improve prospective evidence concerning psychosocial stress. Conducting analyses by sex may better elucidate the benefits of psychological distress screening for men and women, respectively, and encourage more widespread adoption in CVD prevention.

Cost of remote patient monitoring for cardiovascular disease: a systematic review protocol.

OBJECTIVE: This review aims to evaluate the costs and cost-effectiveness of remote patient monitoring for cardiovascular disease in the United States. INTRODUCTION: Cardiovascular disease is a leading public health concern in the United States, resulting in a substantial economic burden. Remote patient monitoring has emerged as a viable and valuable care delivery method to improve cardiovascular disease management at home. However, there is limited systematic research of the cost and cost-effectiveness of using remote patient monitoring to manage the disease. INCLUSION CRITERIA: This review will consider all studies evaluating the cost of remote patient monitoring for cardiovascular disease management in the United States. The population of interest includes all individuals with various types of chronic cardiovascular disease in the United States. METHODS: The search strategy will locate both published and unpublished studies. Systematic searches will be completed in PubMed, Embase, Web of Science, CINAHL, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, National Health Service Economic Evaluation Database, and the Cost-Effectiveness Analysis Registry. Two reviewers will independently screen titles and abstracts, followed by a full-text review against the inclusion criteria. Disagreements will be resolved through discussion between all study members. The JBI checklist for economic evaluations will be utilized to evaluate the methodological quality of studies. Data will be extracted using a modified version of the JBI data extraction form for economic evaluations. Reviewers will summarize studies and cost-related metrics. The Dominance Ranking Matrix will be used to synthesize full economic evaluation. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021270621.

Impact and variability of social determinants of health on the transmission and outcomes of COVID-19 across the world: a systematic review protocol.

INTRODUCTION: The COVID-19 pandemic has exacerbated health inequalities across the globe, disproportionately affecting those with poor social determinants of health (SDOHs). It is imperative to understand how SDOH influences the transmission and outcomes (positive case, hospitalisation and mortality) of COVID-19. This systematic review will investigate the impact of a wide range of SDOHs across the globe on the transmission and outcomes of COVID-19. METHODS AND ANALYSIS: This review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol guidelines. We will search three electronic bibliographical databases (MEDLINE via PubMed, Embase and Scopus), as well as the WHO COVID-19 Global Research on Coronavirus Disease database. We will consider observational studies that report statistical relationships between the SDOHs (as listed in PROGRESS-Plus and Healthy People 2020) and COVID-19 transmission and outcomes. There will be no limitation on the geographical location of publications. The quality of included observational studies will be assessed using a modified version of the Newcastle-Ottawa Scale. A narrative synthesis without meta-analysis reporting standards will be used to report the review findings. ETHICS AND DISSEMINATION: This review will be based on published studies obtained from publicly available sources, and therefore, ethical approval is not required. We will publish the results of this review in a peer-reviewed journal, as well as present the study findings at a national conference. PROSPERO REGISTRATION NUMBER: CRD42021228818.

Protective and Anti-Inflammatory Effects of Protegrin-1 on Citrobacter rodentium Intestinal Infection in Mice.

Infectious intestinal colitis, manifesting as intestinal inflammation, diarrhea, and epithelial barrier disruption, affects millions of humans worldwide and, without effective treatment, can result in death. In addition to this, the significant rise in antibiotic-resistant bacteria poses an urgent need for alternative anti-infection therapies for the treatment of intestinal disorders. Antimicrobial peptides (AMPs) are potential therapies that have broad-spectrum antimicrobial activity due to their (1) unique mode of action, (2) broad-spectrum antimicrobial activity, and (3) protective role in GI tract maintenance. Protegrin-1 (PG-1) is an AMP of pig origin that was previously shown to reduce the pathological effects of chemically induced digestive tract inflammation (colitis) and to modulate immune responses and tissue repair. This study aimed to extend these findings by investigating the protective effects of PG-1 on pathogen-induced colitis in an infection study over a 10-day experimental period. The oral administration of PG-1 reduced Citrobacter rodentium intestinal infection in mice as evidenced by reduced histopathologic change in the colon, prevention of body weight loss, milder clinical signs of disease, and more effective clearance of bacterial infection relative to challenged phosphate-buffered saline (PBS)-treated mice. Additionally, PG-1 treatment altered the expression of various inflammatory mediators during infection, which may act to resolve inflammation and re-establish intestinal homeostasis. PG-1 administered in its mature form was more effective relative to the pro-form (ProPG-1). To our knowledge, this is the first study demonstrating the protective effects of PG-1 on infectious colitis.

Associations between sleep and academic performance in US adolescents: a systematic review and meta-analysis.

This systematic review and meta-analysis aim to investigate the relationship between sleep and academic performance in students enrolled in secondary education programs in the United States. The study team conducted a literature search of 4 databases-PubMed, Embase, CINAHL, and ERIC-on September 19 and repeated December 17, 2020. Studies were included if they were observational, published in a peer-reviewed, non-predatory journal, available in full-text, written in English, included adolescents enrolled in an organized academic program, took place in the US, and evaluated the effect of sleep duration and/or sleep quality on academic performance. After excluding reviews, editorials, interventions, and those targeting diagnostic groups, 14 studies met inclusion criteria. Risk of bias was assessed using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies; 12 studies were found to be good or high quality, 2 were adequate/fair or poor quality. A meta-analysis of 11 of the included studies revealed that sleep duration (r = 0.03; 95%CI -0.027, 0.087; p = 0.087) and sleep quality (r = 0.089; 95%CI 0.027, 0.151; p = 0.005) had negligible correlations with academic performance (non-significant and significant, respectively). Inconsistencies in definitions, methods, and measures utilized to assess sleep duration, sleep quality, and academic performance constructs may offer insight into seemingly conflicting findings. Given the pivotal role sleep plays in development, future investigations utilizing validated and objective sleep and academic performance measures are needed in adolescents.

Impacts of a putative invasive ascidian on rocky shore communities.

The number and distribution of non-indigenous species in coastal habitats is increasing. Our ability to prioritise the management of this threat is limited by our understanding of their impacts. We investigated the density dependent effects of the non-indigenous solitary ascidian Pyura doppelgangera on native mussels and rocky shore communities in northern New Zealand. Minimal recruitment of P. doppelgangera was recorded during a 1.5-year experiment. Mussels showed no sign of overgrowth or spatial competition with P. doppelgangera, and their physiological condition was not impacted. We found marginal effects of the ascidian on community development, associated with small increases in diversity. We concluded that P. doppelgangera is not an aggressive competitor nor a threat to native communities, as previously thought, and that it has a very limited natural recruitment and spread potential. Reports from local Maori and a literature review suggest that P. doppelgangera has been present in the area for longer than previously thought, raising questions about its 'introduction' status and its current designation as a pest.

Assessing Advance Care Planning in Individuals with Lynch Syndrome.

Lynch syndrome (LS) is a hereditary cancer syndrome characterized by an increased risk of multiple cancers, predominantly endometrial and colorectal, at a younger age (typically < 50). In prior research, high death anxiety and a lack of provider-initiated communication about advance care planning (ACP) have been shown to decrease a patient's likelihood of having advance directives. Providers often have gaps in knowledge and are uncomfortable with these conversations. We used a mixed methods approach (quantitative survey with a follow-up telephone interview) to assess knowledge, preferences, and attitudes regarding ACP in individuals with LS (n = 20). This study also assessed which ACP documents individuals already had in place and which persons (providers, family, or friends) an individual made aware of the documentation and/or preferences. These data were analyzed to determine patient preferences for who is responsible for initiating these conversations, identify motivating factors and barriers to these conversations, and determine whether the current conversations are adequate to meet the needs of this patient population. Participants recognized the importance of ACP and expressed interest in creating these documents. However, knowledge and confidence about these topics were lacking, with many participants attributing this to their young age and lack of experience. Although uncomfortable, many patients want to have ACP discussions with their providers, but frequently patients were only asked if these documents are completed with no further discussion. These findings can inform educational efforts to improve knowledge of ACP and interventional research to increase use of ACP by individuals with LS.

Human Responses to Visually Evoked Threat.

Vision is the primary sense humans use to evaluate and respond to threats. Understanding the biological underpinnings of the human threat response has been hindered by lack of realistic in-lab threat paradigms. We established an immersive virtual reality (VR) platform to simultaneously measure behavior, physiological state, and neural activity from the human brain using chronically implanted electrodes. Subjects with high anxiety showed increased visual scanning in response to threats as compared to healthy controls. In both healthy and anxious subjects, the amount of scanning behavior correlated with the magnitude of physiological arousal, suggesting that visual scanning behavior is directly linked to internal state. Intracranial electroencephalography (iEEG) recordings from three subjects suggested that high-frequency gamma activity in the insula positively correlates with physiological arousal induced by visual threats and that low-frequency theta activity in the orbitofrontal cortex (OFC) negatively correlates with physiological arousal induced by visual threats. These findings reveal a key role of eye movements and suggest that distinct insula and OFC activation dynamics may be important for detecting and adjusting human stress in response to visually perceived threats.

Choline supplementation influences ovarian follicular development.

BACKGROUND: Female infertility is a health issue for both humans and animals and despite developments in medical interventions, there are still some conditions that cannot be treated successfully. It is important to explore other potential therapies or remedies that could improve reproductive health. Choline is an over-the-counter supplement and essential nutrient that has many health benefits. It has been suggested to be beneficial in various aspects of fertility, including fetal development and endocrine disorders like polycystic ovarian syndrome (PCOS). However, choline's impact on ovarian function has not been explored. METHODS: To study the effects of choline on ovarian development, 36 female Yorkshire × Landrace pigs were fed the following four supplemented diets between 90 and 186 days of age: (1) Control (corn and soybean meal-based diet that met estimated nutrient requirements, n = 9); (2) Choline (additional 500 mg choline per 1 kg of control diet, n = 8); (3) Omega-3 (additional 5556 mg Omega-3 per 1 kg control diet by introducing fish oil); (4) Choline + Omega-3 (500 mg choline + 5556 mg Omega-3 per 1 kg control diet). Pigs fed the choline-supplemented diet were compared to the control group and those fed diets supplemented with Omega-3 as fertility-promoting agent. RESULTS: It was found that the number of corpus luteum per ovary in the Choline (16.25 ± 2.88), Omega-3 (10.78 ± 1.71) and Choline + Omega-3 (14.89 ± 2.97) groups were all higher in comparison to that of the control group (5.56 ± 1.72, p < 0.05). The percentage of antral follicles in the Choline + Omega-3 group were higher compared to the control group (p < 0.05). To elucidate the potential molecular mechanism of choline on these improved ovarian phenotypes, the expression of a group of genes that are involved in ovarian development, including cytochrome P450 family 11 subfamily A member 1 (CYP11A1), follicle stimulating hormone receptor (FHSR) and luteinizing hormone receptor (LHR), was analyzed using RT-qPCR. The expression of both LHR and CYP11A1 was significantly upregulated in the choline-supplemented group (p < 0.05), while there are no differences in FSHR expression among all the groups. Additionally, the expression of miR-21, -378, -574, previously found to be important in ovarian function, were examined. Our data showed that miR-574 was upregulated in the Choline group while miR-378 was upregulated in the Choline + Omega-3 group in comparison to the control group (p < 0.05). Further, serum metabolite analysis showed that 1-(5Z, 8Z, 11Z, 14Z, 17Z-eicosapentaenoyl)-sn-glycero-3-phosphocholine, a form of phosphatidylcholine metabolite, was significantly increased in all the treatment groups (p < 0.05), while testosterone was significantly increased in both Omega-3 and Choline + Omega-3 groups (p < 0.05) and tended to be reduced in the choline-supplemented group (p = 0.08) compared to the control group. CONCLUSIONS: Our study demonstrated choline's influence on ovarian function in vivo, and offered insights into the mechanisms behind its positive effect on ovarian development phenotype.

Acetazolamide Treatment Prevents Redistribution of Astrocyte Aquaporin 4 after Murine Traumatic Brain Injury.

After traumatic brain injury (TBI), multiple ongoing processes contribute to worsening and spreading of the primary injury to create a secondary injury. One major process involves disrupted fluid regulation to create vascular and cytotoxic edema in the affected area. Although understanding of factors that influence edema is incomplete, the astrocyte water channel Aquaporin 4 (AQP4) has been identified as an important mediator and therefore attractive drug target for edema prevention. The FDA-approved drug acetazolamide has been administered safely to patients for years in the United States. To test whether acetazolamide altered AQP4 function after TBI, we utilized in vitro and in vivo models of TBI. Our results suggest that AQP4 localization is altered after TBI, similar to previously published reports. Treatment with acetazolamide prevented AQP4 reorganization, both in human astrocyte in vitro and in mice in vivo. Moreover, acetazolamide eliminated cytotoxic edema in our in vivo mouse TBI model. Our results suggest a possible clinical role for acetazolamide in the treatment of TBI.

Impact of acute handling stress, anaesthesia, and euthanasia on fish plasma biochemistry: implications for veterinary screening and metabolomic sampling.

Impacts of pre-sampling practices on fish plasma biochemistry may bias the outcome of a study if not considered within the general sampling strategy. Acute handling stresses can be imposed on fish during capture, and it is common practice to immobilise fish via sedation prior to obtaining blood samples for non-lethal extraction purposes, and/or to reduce stress, pain, or suffering before being euthanised. We investigated these potential influences using a Chinook salmon model (Oncorhynchus tshawytscha) by measuring levels of 119 biochemical targets comprising ions, metabolites, and enzymes in plasma. Multivariate analyses showed that 2 min of confinement with mild handling manipulation led to a significant departure from baseline metabolism, which was further exasperated during a prolonged 5-min challenge. These changes were characterised by a disruption in osmoregulation, a switch towards anaerobic metabolism, and shifts in ammonia recycling, among others. Sedation of fish with clove oil and AQUI-S® had major impacts on plasma biochemical profiles, with alterations signalling changes in glycolytic metabolism, respiratory modes, carbon flux through the TCA cycle, and lipid compartmentalisation. Sedation also enhanced levels of plasma amino acids, revealing a key difference between responses to handling stress and sedation. These results demonstrate that pre-harvest practices should be carefully managed during fish sampling for biochemical/metabolomic-based analyses, and if manipulations are essential, they should be standardised.