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.

Advances in sickle cell retinopathy screening techniques, tests, and practices: A systematic review.

Sickle cell retinopathy (SCR) is a progressive, sight-threatening ophthalmic complication of sickle cell disease (SCD). Current SCR screening focuses on the detection of pathologic sea fan neovascularization, the first sign of proliferative sickle cell retinopathy (PSR). If untreated, PSR can lead to severe visual impairment and blindness through progression to vitreous hemorrhage and/or retinal detachment. SCR screening with dilated fundus examination (DFE) is recommended every 1-2 years starting at age 10, but data underlying this recommendation are of poor quality and based upon expert consensus. We performed a systematic review to characterize imaging techniques, laboratory-based tests, and clinical practices for SCR screening. This PROSPERO-registered systematic review included relevant texts identified through predetermined searches in online databases. Collected test accuracy data facilitated the calculation of likelihood ratios. Forty-four studies evaluating 4928 patients were included. DFE demonstrated moderate test accuracy (LR+ of 8.0, LR- of 0.3). Ultra-widefield-fundus photography demonstrated superior accuracy (LR+ 32.5, LR- 0.03). Optical coherence tomography angiography applications were highly accurate for PSR identification (machine learning LR+ 32.5, LR- 0.03; human grader LR+ 2.8-213.1, LR- 0.1-0.2). Most techniques and tests were more accurate at detecting PSR than staging SCR or detecting lower-grade SCR. Our findings support the integration of advanced image-based approaches, such as computer-based image analysis and ultra-wide-field fundus imaging, for SCR screening in SCD patients given the superior accuracy in PSR detection compared with the current standard of care. Rigorous SCR screening implementation studies are needed to support evidence-based SCR screening recommendations.

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.

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.

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).

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.

Naturally occurring antibodies isolated from PD patients inhibit synuclein seeding in vitro and recognize Lewy pathology.

Deposition of α-synuclein into Lewy bodies and Lewy neurites is the hallmark of Parkinson's disease (PD). It is hypothesized that α-synuclein pathology spreads by a "prion-like" mechanism (i.e., by seeded aggregation or templated misfolding). Therefore, various extracellular α-synuclein conformers and/or posttranslational modifications may serve as biomarkers of disease or potential targets for novel interventions. To explore whether the antibody repertoires of PD patients contain anti-α-synuclein antibodies that can potentially be used as markers or immunotherapy, we interrogated peripheral IgG+ memory B cells from PD patients for reactivity to α-synuclein. In total, ten somatically mutated antibodies were recovered, suggesting the presence of an ongoing antigen-driven immune response. The three antibodies that had the highest affinity to recombinant full-length α-synuclein, aSyn-323.1, aSyn-336.1 and aSyn-338.1, were characterized further and shown to recognize epitopes in the C terminus of α-synuclein with binding affinities between 0.3 and 2.8 µM. Furthermore, all three antibodies were able to neutralize the "seeding" of intracellular synuclein aggregates in an in vitro α-synuclein seeding assay. Finally, differential reactivities were observed for all three human anti-α-synuclein antibodies across tissue treatment conditions by immunohistochemistry. Our results suggest that the memory B-cell repertoire of PD patients might represent a potential source of biomarkers and therapies.

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.

Immunological memory to hyperphosphorylated tau in asymptomatic individuals.

Several reports have described the presence of antibodies against Alzheimer's disease-associated hyperphosphorylated forms of tau in serum of healthy individuals. To characterize the specificities that can be found, we interrogated peripheral IgG+ memory B cells from asymptomatic blood donors for reactivity to a panel of phosphorylated tau peptides using a single-cell screening assay. Antibody sequences were recovered, cloned, and expressed as full-length IgGs. In total, 52 somatically mutated tau-binding antibodies were identified, corresponding to 35 unique clonal families. Forty-one of these antibodies recognize epitopes in the proline-rich and C-terminal domains, and binding of 26 of these antibodies is strictly phosphorylation dependent. Thirteen antibodies showed inhibitory activity in a P301S lysate seeded in vitro tau aggregation assay. Two such antibodies, CBTAU-7.1 and CBTAU-22.1, which bind to the proline-rich and C-terminal regions of tau, respectively, were characterized in more detail. CBTAU-7.1 recognizes an epitope that is similar to that of murine anti-PHF antibody AT8, but has different phospho requirements. Both CBTAU-7.1 and CBTAU-22.1 detect pathological tau deposits in post-mortem brain tissue. CBTAU-7.1 reveals a similar IHC distribution pattern as AT8, immunostaining (pre)tangles, threads, and neuritic plaques. CBTAU-22.1 shows selective detection of neurofibrillary changes by IHC. Taken together, these results suggest the presence of an ongoing antigen-driven immune response against tau in healthy individuals. The wide range of specificities to tau suggests that the human immune repertoire may contain antibodies that can serve as biomarkers or be exploited for therapy.

It's a wrap: encapsulation as a management tool for marine biofouling.

Encapsulation of fouled structures is an effective tool for countering incursions by non-indigenous biofoulers. However, guidelines for the implementation of encapsulation treatments are yet to be established. This study evaluated the effects of temperature, biomass, community composition, treatment duration and the biocide acetic acid on biofoulers. In laboratory trials using the model organisms Ciona spp. and Mytilus galloprovincialis, increasing the temperature or biomass speeded up the development of a toxic environment. Total mortality for Ciona spp. occurred within 72 and 24 h at 10 and 19°C, respectively. M. galloprovincialis survived up to 18 days, with high biomass increasing mortality at 10°C only. In a field study, three-month-old and four-year-old communities were encapsulated with and without acetic acid. Mortality took up to 10 days for communities encapsulated without acetic acid, compared to 48 h with acetic acid. The insights gained from this study will be useful in developing standardised encapsulation protocols.

Desiccation as a mitigation tool to manage biofouling risks: trials on temperate taxa to elucidate factors influencing mortality rates.

The desiccation tolerance of biofouling taxa (adults and early life-stages) was determined under both controlled and 'realistic' field conditions. Adults of the ascidian Ciona spp. died within 24 h. Mortality in the adult blue mussel Mytilus galloprovincialis occurred within 11 d under controlled conditions, compared with 7 d when held outside. The Pacific oyster Crassostrea gigas was the most desiccation-tolerant taxon tested (up to 34 d under controlled conditions). Biofouling orientated to direct sunlight showed faster mortality rates for all the taxa tested. Mortality in Mytilus juveniles took up to 24 h, compared with 8 h for Ciona, with greater survival at the higher temperature (18.5°C) and humidity (~95% RH) treatment combination. This study demonstrated that desiccation can be an effective mitigation method for a broad range of fouling taxa, especially their early life-stages. Further work is necessary to assess risks from other high-risk species such as algae and cyst forming species.

Spatial distribution of insulin-like growth factor binding protein-2 following hypoxic-ischemic injury.

BACKGROUND: Insulin-like growth factor binding protein-2 (IGFBP-2) regulates the bioavailability, transportation, and localization of insulin-like growth factor-I (IGF-I), an effective neuroprotectant in animal stroke models especially when administered intranasally. Therefore, determining IGFBP-2's endogenous distribution in the normal and ischemic brain is essential in maximizing the neuroprotective potential of the intranasal IGF-I treatment approach. However, current data on IGFBP-2 is limited to mRNA and in situ hybridization studies. The purpose of this study was to determine if there are any changes in IGFBP-2 protein levels and distribution in ischemic brain and also to determine if IGFBPs play a role in the transportation of intranasally administered IGF-I into the brain. RESULTS: Using an in vitro approach, we show that ischemia causes changes in the distribution of IGFBP-2 in primary cortical neurons and astrocytes. In addition, we show using the transient middle cerebral artery occlusion (MCAO) model in mice that there is a significant increase in IGFBP-2 levels in the stroke penumbra and core after 72 h. This correlated with an overall increase in IGF-I after stroke, with the highest levels of IGF-I in the stroke core after 72 h. Brain sections from stroke mice indicate that neurons and astrocytes located in the penumbra both have increased expression of IGFBP-2, however, IGFBP-2 was not detected in microglia. We used binding competition studies to show that intranasally administered exogenous IGF-I uptake into the brain is not receptor mediated and is likely facilitated by IGFBPs. CONCLUSIONS: The change in protein levels indicates that IGFBP-2 plays an IGF-I-dependent and -independent role in the brain's acute (neuroprotection) and chronic (tissue remodeling) response to hypoxic-ischemic injury. Competition studies indicate that IGFBPs may have a role in rapid transportation of exogenous IGF-I from the nasal tissue to the site of injury.

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.

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.

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.

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.

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.

Erythropoietin plus insulin-like growth factor-I protects against neuronal damage in a murine model of human immunodeficiency virus-associated neurocognitive disorders.

OBJECTIVE: Prolonged human immunodeficiency virus-1 (HIV-1) infection leads to neurological debilitation, including motor dysfunction and frank dementia. Although pharmacological control of HIV infection is now possible, HIV-associated neurocognitive disorders (HAND) remain intractable. Here, we report that chronic treatment with erythropoietin (EPO) and insulin-like growth factor-I (IGF-I) protects against HIV/gp120-mediated neuronal damage in culture and in vivo. METHODS: Initially, we tested the neuroprotective effects of various concentrations of EPO, IGF-I, or EPO+IGF-I from gp120-induced damage in vitro. To assess the chronic effects of EPO+IGF-I administration in vivo, we treated HIV/gp120-transgenic or wild-type mice transnasally once a week for 4 months and subsequently conducted immunohistochemical analyses. RESULTS: Low concentrations of EPO+IGF-I provided neuroprotection from gp120 in vitro in a synergistic fashion. In vivo, EPO+IGF-I treatment prevented gp120-mediated neuronal loss, but did not alter microgliosis or astrocytosis. Strikingly, in the brains of both humans with HAND and gp120-transgenic mice, we found evidence for hyperphosphorylated tau protein (paired helical filament-I tau), which has been associated with neuronal damage and loss. In the mouse brain following transnasal treatment with EPO+IGF-I, in addition to neuroprotection we observed increased phosphorylation/activation of Akt (protein kinase B) and increased phosphorylation/inhibition of glycogen synthase kinase (GSK)-3beta, dramatically decreasing downstream hyperphosphorylation of tau. These results indicate that the peptides affected their cognate signaling pathways within the brain parenchyma. INTERPRETATION: Our findings suggest that chronic combination therapy with EPO+IGF-I provides neuroprotection in a mouse model of HAND, in part, through cooperative activation of phosphatidylinositol 3-kinase/Akt/GSK-3beta signaling. This combination peptide therapy should therefore be tested in humans with HAND.