Evaluation of Pain Catastrophizing Scale for surgical referral to pain psychology in patients undergoing spinal surgery.

Background: Chronic pain is an issue that affects over 100 million Americans daily. Acceptance and Commitment Therapy (ACT) has been found to be beneficial for patients with chronic pain by focusing provider efforts on teaching coping mechanisms for pain instead of eliminating the pain entirely. Current studies demonstrate that ACT significantly improves post-operative chronic pain scores and outcomes. Methods: The 200 patients chosen via random generator were collected and presented to (institution) orthopedic spine surgeons along with additional information such as the patients' history of present illness, Visual Analog Scale (VAS) scores, PROMIS-CAT Pain Interference scores, and status of opiate usage. Surgeons were blinded to the PCS cutoff scores. The (institution) orthopedic spine surgeons then identified which patients they would indicate for ACT and their reasoning. Pre-determined PCS score cut-offs were separately used to determine if a patient was indicated for ACT. Results: The effectiveness of this screening tool was based on the frequency at which the surgeons and PCS scores were complimentary. A department epidemiologist assisted in the analysis of the data with the use of a ROC curve. ROC Curve demonstrated an area under the curve of 0.7784 with a Sensitivity of 0.68 and a Specificity of 0.79. The cut point according to Youden's index is 35. The data showed that the PCS is moderately accurate in its ability to distinguish coinciding patients that the [institution] orthopedic spine surgeons referred for ACT. The adjusted cut-point indicates that patients above a PCS of 35 would be referred to ACT by the orthopedic spine surgeons while those below a PCS score of 35 would not be referred. Conclusions: Using the PCS, a referral with the department pain psychologist would occur by [institution] orthopedic spinal surgeons for patients that are deemed at-risk with a score of at least 35. The goal following this study is to perform future investigations regarding PCS and ACT with patients regarding chronic opioid use and postoperative outcomes. Patients who would be referred for help with chronic pain would be compared to PCS-referred patients and non-referred patients. Pre-operative ACT would be compared to patient outcomes post-operatively. The future aim is to use the cut-offs established in this study for experimental design to evaluate if PCS-referred patients have better pain management post-operatively as compared to the control and previously referred patients. Level of Evidence: Level III diagnostic study.

Pilot study of a pedestrian collision detection test for a multisite trial of field expansion devices for hemianopia.

SIGNIFICANCE: Performance-based outcome measures are crucial for clinical trials of field expansion devices. We implemented a test simulating a real-world mobility situation, focusing on detection of a colliding pedestrian among multiple noncolliding pedestrians, suitable for measuring the effects of homonymous hemianopia and assistive devices in clinical trials. PURPOSE: In preparation for deploying the test in a multisite clinical trial, we conducted a pilot study to gather preliminary data on blind-side collision detection performance with multiperiscopic peripheral prisms compared with Fresnel peripheral prisms. We tested the hypothesis that detection rates for colliding pedestrians approaching on a 40° bearing angle (close to the highest collision risk when walking) would be higher with 100Δ oblique multiperiscopic (≈42° expansion) than 65Δ oblique Fresnel peripheral prisms (≈32° expansion). METHODS: Six participants with homonymous hemianopia completed the test with and without each type of prism glasses, after using them in daily mobility for a minimum of 4 weeks. The test, presented as a video on a large screen, simulated walking through a busy shopping mall. Colliding pedestrians approached from the left or the right on a bearing angle of 20 or 40°. RESULTS: Overall, blind-side detection was only 23% without prisms but improved to 73% with prisms. For multiperiscopic prisms, blind-side detection was significantly higher with than without prisms at 40° (88 vs. 0%) and 20° (75 vs. 0%). For Fresnel peripheral prisms, blind-side detection rates were not significantly higher with than without prisms at 40° (38 vs. 0%) but were significantly higher with prisms at 20° (94 vs. 56%). At 40°, detection rates were significantly higher with multiperiscopic than Fresnel prisms (88 vs. 38%). CONCLUSIONS: The collision detection test is suitable for evaluating the effects of hemianopia and prism glasses on collision detection, confirming its readiness to serve as the primary outcome measure in the upcoming clinical trial.

Role of the V2R-ßarrestin-Gßγ complex in promoting G protein translocation to endosomes.

Classically, G protein-coupled receptors (GPCRs) promote signaling at the plasma membrane through activation of heterotrimeric Gαßγ proteins, followed by the recruitment of GPCR kinases and ßarrestin (ßarr) to initiate receptor desensitization and internalization. However, studies demonstrated that some GPCRs continue to signal from internalized compartments, with distinct cellular responses. Both ßarr and Gßγ contribute to such non-canonical endosomal G protein signaling, but their specific roles and contributions remain poorly understood. Here, we demonstrate that the vasopressin V2 receptor (V2R)-ßarr complex scaffolds Gßγ at the plasma membrane through a direct interaction with ßarr, enabling its transport to endosomes. Gßγ subsequently potentiates Gαs endosomal translocation, presumably to regenerate an endosomal pool of heterotrimeric Gs. This work shines light on the mechanism underlying G protein subunits translocation from the plasma membrane to the endosomes and provides a basis for understanding the role of ßarr in mediating sustained G protein signaling.

Multi-level alignment processes in the sustainment of a youth substance use treatment model following a federal implementation initiative: A mixed method study.

INTRODUCTION: Government agencies have identified evidence-based practice (EBP) dissemination as a pathway to high-quality behavioral health care for youth. However, gaps remain about how to best sustain EBPs in treatment organizations in the U.S., especially in resource-constrained settings like publicly-funded youth substance use services. One important, but understudied, determinant of EBP sustainment is alignment: the extent to which multi-level factors that influence sustainment processes and outcomes are congruent, consistent, and/or coordinated. This study examined the role of alignment in U.S. states' efforts to sustain the Adolescent Community Reinforcement Approach (A-CRA), an EBP for youth substance use disorders, during the COVID-19 pandemic. METHODS: In this mixed methods study, the qualitative investigation preceded and informed the quantitative investigation. We interviewed state administrators and providers (i.e., supervisors and clinicians) from 15 states that had completed a federal A-CRA implementation grant; providers also completed surveys. The sample included 50 providers from 35 treatment organizations that reported sustaining A-CRA when the COVID-19 pandemic began, and 20 state administrators. In qualitative thematic analyses, we applied the EPIS (Exploration, Preparation, Implementation, Sustainment) framework to characterize alignment processes that interviewees described as influential on sustainment. We then used survey items to quantitatively explore the associations described in qualitative themes, using bivariate linear regressions. RESULTS: At the time of interview, staff from 80 % of the treatment organizations (n = 28), reported sustaining A-CRA. Providers from both sustainer and non-sustainer organizations, as well as state administrators, described major sources of misalignment when state agencies ceased technical assistance post-grant, and because limited staff capacity conflicted with A-CRA's training model, which was perceived as time-intensive. Participants described the pandemic as exacerbating preexisting challenges, including capacity issues. Sustainer organizations reported seeking new funding to help sustain A-CRA. Quantitative associations between self-rated extent of sustainment and other survey items largely followed the pattern predicted from the qualitative findings. CONCLUSIONS: The COVID-19 pandemic amplified longstanding A-CRA sustainment challenges, but treatment organizations already successfully sustaining A-CRA pre-pandemic largely continued. There are missed opportunities for state-level actors to coordinate with providers on the shared goal of EBP sustainment. A greater focus on alignment processes in research and practice could help states and providers strengthen sustainability planning.

Advancing Colorectal Cancer Detection With Blood-Based Tests: Qualitative Study and Discrete Choice Experiment to Elicit Population Preferences.

BACKGROUND: Colorectal cancer (CRC) is the second most deadly form of cancer, inducing an estimated 1.9 million incidence cases and 0.9 million deaths worldwide in 2020. Despite the availability of screening tests, their uptake remains suboptimal. However, blood-based tests that look for signs of cancer-specific markers in the body are increasingly available as an alternative for more invasive tests for cancer. Compared with existing tests, the benefits of blood-based tests for CRC include not needing pretest preparation, stool handling, and dietary or medication restrictions. OBJECTIVE: This study aims to explore the population's preferences for CRC screening tests, with a focus on blood-based tests, and investigate the factors influencing test uptake. METHODS: We used a mixed methods approach, combining semistructured interviews and a discrete choice experiment (DCE) survey. Interviews were analyzed using thematic analysis to identify salient attributes for CRC screening tests. These attributes informed the design of the DCE survey. The DCE data were analyzed using mixed logit and mixed-mixed multinomial logit models. RESULTS: Qualitative findings from 30 participants revealed that participants preferred blood-based tests due to their perceived low risk, minimal pain, and ease of sample collection. However, concerns about the test's lower accuracy were also expressed. The DCE survey was completed by 1189 participants. In the mixed logit model, participants demonstrated a stronger preference for blood-based tests over a 2-day stool-based test. The mixed-mixed multinomial logit model identified 2 classes, strong supporters and weak supporters, for CRC screening. Weak supporters, but not strong supporters, had a higher preference for blood-based tests. Women, ethnic Chinese, and people aged 40 to 60 years were more likely to be weak supporters. Both models highlighted the high influence of cost and test sensitivity on participants' preferences. Transitioning from a 2-day stool-based test to a blood-based test, assuming a national screening program at a base price of Singapore $5 (US $3.75), was estimated to have the potential to increase the relative uptake by 5.9% (95% CI 3.6%-8.2%). CONCLUSIONS: These findings contribute to our understanding of CRC screening preferences and provide insights into the factors driving test uptake. This study highlights the perceived advantages of blood-based tests and identifies areas of concern regarding their accuracy. Further research is needed to determine the actual increase in uptake rate when blood-based tests are made available.

Evaluation of Xpert point-of-care assays for detection of HIV infection in persons using long-acting cabotegravir for pre-exposure prophylaxis.

Detection of HIV infection may be challenging in persons using long-acting cabotegravir (CAB-LA) pre-exposure prophylaxis (PrEP) due to viral suppression and reduced/delayed antibody production. We evaluated two point-of-care tests for detecting HIV infection in persons who received CAB-LA in the HPTN 083 trial. Samples were obtained from 12 participants who received CAB-LA and had delayed detection of HIV infection using HIV rapid tests and an antigen/antibody test (52 plasma samples; 18 dried blood spot [DBS] samples). Plasma samples were tested with the Xpert HIV-1 Viral Load XC test (Xpert VL-XC); DBS samples were tested with the total nucleic acid Xpert HIV-1 Qual XC test (Xpert Qual-XC). Results from these assays were compared to results from three reference, laboratory-based, plasma RNA assays (Aptima HIV-1 Qualitative assay [Aptima Qual]; Aptima HIV-1 Quant DX Assay [Aptima Quant]; cobas HIV-1/HIV-2 Qualitative Test [cobas]). HIV RNA was detected with all four plasma assays for all samples with viral loads (VLs) ≥ 200 copies/mL; the number of samples with VLs < 200 copies/mL with HIV RNA detected was: Xpert VL-XC: 19/26 (73.1%); Aptima Qual: 17/26 (65.4%); Aptima Quant: 17/26 (65.4%); and cobas: 12/21 (57.1%). The Xpert Qual-XC assay was positive for all DBS samples with VLs ≥ 200 copies/mL and 1/10 DBS with VLs < 200 copies/mL. The performance of the Xpert VL-XC assay was comparable to the reference assays for detecting HIV infection in these cases. The Xpert Qual-XC assay was less sensitive than plasma-based HIV RNA assays for detecting HIV in the setting of CAB-LA PrEP. IMPORTANCE: HIV RNA assays can detect HIV infections earlier than HIV rapid tests or Ag/Ab tests in persons using CAB-LA PrEP. Earlier HIV diagnosis could allow for earlier treatment initiation and reduced risk of INSTI resistance. POC tests may help detect HIV infection before CAB-LA administration and may be more accessible than laboratory-based assays in some settings. In this study, the POC Xpert VL-XC assay detected HIV RNA in most samples from individuals who received CAB-LA PrEP and had delayed detection of HIV infection with HIV rapid tests and an Ag/Ab test. The performance of this assay was similar to laboratory-based HIV RNA assays in this cohort. The POC Xpert Qual-XC assay detects both HIV RNA and DNA, with a higher viral load cutoff for RNA detection. This assay was negative for most lower viral load samples and did not offer an advantage for HIV screening in persons using CAB-LA PrEP.

Hourly step recommendations to achieve daily goals for working and older adults.

BACKGROUND: The widespread use of physical activity trackers enables the collection of high-resolution health data, such as hourly step counts, to evaluate health promotion programmes. We aim to investigate how participants meet their daily step goals. METHODS: We used 24-h steps data from the National Steps ChallengeTM Season 3, wherein participants were rewarded with vouchers when achieving specified goals of 5000, 7500, and 10,000 steps per day. We extracted data from 3075 participants' including a total of 52,346 participant-days. We modelled the hourly step counts using a two-part model, in which the distribution for step counts was allowed to depend on the sum of step counts up to the previous hour and participant demographics. RESULTS: Participants have a mean age of 44.2 years (standard deviation = 13.9), and 40.4% are males. We show that on weekdays, the hourly mean step counts among participants aged 60 and above are higher than participants aged 30 to 59 from the start of the day till 6 p.m. We also find that participants who accumulate at least 7000 steps by 7 p.m. are associated with higher success of achieving 10,000 steps. CONCLUSIONS: We provide recommendations on the hourly targets to achieve daily goals, based on different participants' characteristics. Future studies could experimentally test if prompts and nudges at the recommended times of day could promote reaching step goals.

The National Steps Challenge^TM is a nationwide physical activity programme in Singapore that encourages participants to exercise more. We used daily step data from over 3000 adult participants to investigate how different types of participants met their daily step goals. We found that participants who had taken at least 7000 steps by 7 p.m. were more likely to achieve 10,000 steps by the end of the day. Based on our analysis, we propose specific recommendations for hourly targets based on characteristics such as age and sex. Our study provides a better understanding of the population's physical activity levels which will enable people to be given targeted recommendations based on their own characteristics that might facilitate them more easily meeting their exercise goals.

The epidemiologic and economic burden of dengue in Singapore: A systematic review.

BACKGROUND: Despite its well-regarded vector control program, Singapore remains susceptible to dengue epidemics. To assist evaluation of dengue interventions, we aimed to synthesize current data on the epidemiologic and economic burden of dengue in Singapore. METHODOLOGY: We used multiple databases (PubMed, Embase, Cochrane, international/national repositories, surveillance) to search for published and gray literature (2000-2022). We included observational and cost studies, and two interventional studies, reporting Singapore-specific data on our co-primary outcomes, dengue incidence and dengue-related costs. Quality was assessed using the Newcastle-Ottawa Scale and an adapted cost-of-illness evaluation checklist. We performed a narrative synthesis and grouped studies according to reported outcomes and available stratified analyses. FINDINGS: In total, 333 reports (330 epidemiological, 3 economic) were included. Most published epidemiological studies (89%) and all economic studies were of good quality. All gray literature reports were from the Ministry of Health or National Environment Agency. Based predominantly on surveillance data, Singapore experienced multiple outbreaks in 2000-2021, attaining peak incidence rate in 2020 (621.1 cases/100,000 person-years). Stratified analyses revealed the highest incidence rates in DENV-2 and DENV-3 serotypes and the 15-44 age group. Among dengue cases, the risk of hospitalization has been highest in the ≥45-year-old age groups while the risks of dengue hemorrhagic fever and death have generally been low (both <1%) for the last decade. Our search yielded limited data on deaths by age, severity, and infection type (primary, secondary, post-secondary). Seroprevalence (dengue immunoglobulin G) increases with age but has remained <50% in the general population. Comprising 21-63% indirect costs, dengue-related total costs were higher in 2010-2020 (SGD 148 million) versus the preceding decade (SGD 58-110 million). CONCLUSION: Despite abundant passive surveillance data, more stratified and up-to-date data on the epidemiologic and economic burden of dengue are warranted in Singapore to continuously assess prevention and management strategies.

Right-sided Morgagni diaphragmatic hernia presenting as isolated left shoulder pain.

A woman in her 60s presented to the emergency department with excruciating, deep left shoulder pain and was found to have a right-sided Morgagni hernia, a rare type of congenital diaphragmatic hernia (CDH). She did not have chest pain, palpitations, shortness of breath, cough, abdominal pain, constipation, diarrhoea, nausea, vomiting or other symptoms classically associated with CDHs in adults. Laparoscopic robotic-assisted repair with mesh placement was performed, and the patient's recovery was uncomplicated, with no recurrence of shoulder pain. Our patient's presentation was unusual due to the absence of symptoms typically seen with CDHs in adults, and the presence of contralateral, left-sided shoulder pain with a right-sided Morgagni hernia.

Mis-implementation of evidence-based behavioural health practices in primary care: lessons from randomised trials in Federally Qualified Health Centers.

Background: Implementing evidence-based practices (EBPs) within service systems is critical to population-level health improvements - but also challenging, especially for complex behavioral health interventions in low-resource settings. "Mis-implementation" refers to poor outcomes from an EBP implementation effort; mis-implementation outcomes are an important, but largely untapped, source of information about how to improve knowledge exchange. Aims and objectives: We present mis-implementation cases from three pragmatic trials of behavioral health EBPs in U.S. Federally Qualified Health Centers (FQHCs). Methods: We adapted the Consolidated Framework for Implementation Research and its Outcomes Addendum into a framework for mis-implementation and used it to structure the case summaries with information about the EBP and trial, mis-implementation outcomes, and associated determinants (barriers and facilitators). We compared the three cases to identify shared and unique mis-implementation factors. Findings: Across cases, there was limited adoption and fidelity to the interventions, which led to eventual discontinuation. Barriers contributing to mis-implementation included intervention complexity, low buy-in from overburdened providers, lack of alignment between providers and leadership, and COVID-19-related stressors. Mis-implementation occurred earlier in cases that experienced both patient- and provider-level barriers, and that were conducted during the COVID-19 pandemic. Discussion and conclusion: Multi-level determinants contributed to EBP mis-implementation in FQHCs, limiting the ability of these health systems to benefit from knowledge exchange. To minimize mis-implementation, knowledge exchange strategies should be designed around common, core barriers but also flexible enough to address a variety of site-specific contextual factors and should be tailored to relevant audiences such as providers, patients, and/or leadership.

Hypofractionated Radiation Therapy: A Cross-sectional Survey Study of US Radiation Oncologists.

OBJECTIVES: For many malignancies, hypofractionated radiotherapy (HFRT) is an accepted standard associated with decreased treatment time and costs. United States provider beliefs regarding HFRT likely impact its adoption but are poorly studied. We surveyed US-based radiation oncologists (ROs) to gauge HFRT utilization rates for prostate (PC), breast (BC), and rectal cancer (RC) and to characterize the beliefs governing these decisions. METHODS: From July to October 2021, an anonymized, online survey was electronically distributed to ROs actively practicing in the United States. Demographic and practice characteristic information was collected. Questions assessing rates of offering HFRT for PC, BC, and RC and perceived limitations towards using HFRT were administered. RESULTS: A total of 203 eligible respondents (72% male, 72% White, 53% nonacademic practice, 69% with 11+ years in practice) were identified. Approximately 50% offered stereotactic body radiation therapy (SBRT) for early/favorable intermediate risk PC. Although >90% of ROs offered whole-breast HFRT for early-stage BC, only 33% offered accelerated partial-breast irradiation (APBI). Overall, 41% of ROs offered short-course neoadjuvant RT for RC. The primary reported barriers to HFRT utilization were lack of data, inexperience, and referring provider concerns. CONCLUSIONS: HFRT is safe, effective, and beneficial, yet underutilized-particularly prostate SBRT, APBI, and short-course RT for RC. Skills retraining and education of ROs and referring providers may increase utilization rates.

Hepatitis C Virus Dysregulates Polyamine and Proline Metabolism and Perturbs the Urea Cycle.

Hepatitis C virus (HCV) is an oncogenic virus that causes chronic liver disease in more than 80% of patients. During the last decade, efficient direct-acting antivirals were introduced into clinical practice. However, clearance of the virus does not reduce the risk of end-stage liver diseases to the level observed in patients who have never been infected. So, investigation of HCV pathogenesis is still warranted. Virus-induced changes in cell metabolism contribute to the development of HCV-associated liver pathologies. Here, we studied the impact of the virus on the metabolism of polyamines and proline as well as on the urea cycle, which plays a crucial role in liver function. It was found that HCV strongly suppresses the expression of arginase, a key enzyme of the urea cycle, leading to the accumulation of arginine, and up-regulates proline oxidase with a concomitant decrease in proline concentrations. The addition of exogenous proline moderately suppressed viral replication. HCV up-regulated transcription but suppressed protein levels of polyamine-metabolizing enzymes. This resulted in a decrease in polyamine content in infected cells. Finally, compounds targeting polyamine metabolism demonstrated pronounced antiviral activity, pointing to spermine and spermidine as compounds affecting HCV replication. These data expand our understanding of HCV's imprint on cell metabolism.

A Cross-Sectional Study of Gender-Specific Influences of Orthopedic Subspecialty Selection.

Background: Per the American Academy of Orthopaedic Surgeons, 6.5% of practicing orthopedic surgeons are female and a majority subspecialize in pediatrics, hand, and foot and ankle surgery. The study purpose is to evaluate influences of orthopedic subspecialty selection, specifically factors such as perceived strength, lifestyle, and mentorship influence on subspecialty decisions and to identify if gender plays a role in these perceptions. Methods: An IRB approved cross-sectional study was conducted via email distribution of a REDCapTM survey to U.S. licensed orthopedic surgeons. Data regarding demographics, professional degree, training and current practice location, and perceptions regarding orthopedic surgery was obtained using Likert rating scales. Data was analyzed using descriptive statistics with two-tailed student's t-tests (α=0.05). Results: The survey yielded 282 responses (182 females and 100 males). Overall, the distribution of residents (28%), fellows (6%), and attendings (66%) correlates well with the prevalence of each respective physician category in the field of orthopedic surgery. The study demonstrated no difference in subspecialty choice based on mentorship, work-life-balance, career advancement, subspecialty culture, salary potential, family planning, or schedule. However, a statistically significant difference exists regarding stereotypes, perceived strength required, and perception of discrimination from pursuing a specific orthopedic subspecialty. 27% of females and 10% of males reported discouragement from any subspecialty (p<0.05). Adult reconstructive and oncology were most frequently discouraged. Women reported not choosing a subspecialty because of perceived physical demands more often than men (p<0.001). Women reported an increased use of adaptive strategies in the operating room (p<0.001). Women were also more likely to report feeling discouraged from pursuing a subspecialty due to their gender (p<0.001). Both men and women reported mentorship as the most influential factor in subspecialty selection. Conclusion: Women and men reported different factors were important in their decision of subspecialty. Women were more likely to be discouraged from a subspecialty and experience discrimination based on their perceived strength compared to male peers. Residents, fellows, and attending surgeons valued mentorship as the most influential in their subspeciality choice. This study suggests intrinsic and extrinsic influences that may differentially affect male and female orthopedic surgeons when they choose a subspecialty. Level of Evidence: III.

Supportive Housing for Sexual and Gender Minority Individuals with Criminal Justice Histories: Challenges and Opportunities Identified by Providers and Clients.

Sexual and gender minority (SGM) individuals experience high rates of homelessness and criminal justice system involvement, underscoring the need for supportive housing services. To explore the service needs of this population, we interviewed providers (n = 11) and clients (n = 10) from eight supportive housing organizations working with SGM populations in Los Angeles County, USA. We used the Consolidated Framework for Implementation Research to synthesize interview responses into themes (by domain and cross-cutting). Take-aways included the need for investment in systems of care for vulnerable SGM populations; the particular marginalization of Trans individuals and providers that serve them; the roles of supportive housing staff, residents, and leadership in cultivating an affirming environment; prevalence of discrimination and stigma within supportive housing programs and broader society; and the complex interrelationships among SGM identity, homelessness, and criminal justice system involvement. These findings have important implications for supportive housing services and related policy.

Integrated organismal responses induced by projected levels of CO2 and temperature exposures in the early life stages of lake sturgeon.

Atmospheric CO2 and temperature are rising concurrently, and may have profound impacts on the transcriptional, physiological and behavioural responses of aquatic organisms. Further, spring snowmelt may cause transient increases of pCO2 in many freshwater systems. We examined the behavioural, physiological and transcriptomic responses of an ancient fish, the lake sturgeon (Acipenser fulvescens) to projected levels of warming and pCO2 during its most vulnerable period of life, the first year. Specifically, larval fish were raised in either low (16°C) or high (22°C) temperature, and/or low (1000 µatm) or high (2500 µatm) pCO2 in a crossed experimental design over approximately 8 months. Following overwintering, lake sturgeon were exposed to a transient increase in pCO2 of 10,000 µatm, simulating a spring melt based on data in freshwater systems. Transcriptional analyses revealed potential connections to otolith formation and reduced growth in fish exposed to high pCO2 and temperature in combination. Network analyses of differential gene expression revealed different biological processes among the different treatments on the edges of transcriptional networks. Na+/K+-ATPase activity increased in fish not exposed to elevated pCO2 during development, and mRNA abundance of the ß subunit was most strongly predictive of enzyme activity. Behavioural assays revealed a decrease in total activity following an acute CO2 exposure. These results demonstrate compensatory and compounding mechanisms of pCO2 and warming dependent on developmental conditions in lake sturgeon. Conserved elements of the cellular stress response across all organisms provide key information for how other freshwater organisms may respond to future climate change.

Evolutionary and biomedical implications of sex differences in the primate brain transcriptome.

Humans exhibit sex differences in the prevalence of many neurodevelopmental disorders and neurodegenerative diseases. Here, we generated one of the largest multi-brain-region bulk transcriptional datasets for the rhesus macaque and characterized sex-biased gene expression patterns to investigate the translatability of this species for sex-biased neurological conditions. We identify patterns similar to those in humans, which are associated with overlapping regulatory mechanisms, biological processes, and genes implicated in sex-biased human disorders, including autism. We also show that sex-biased genes exhibit greater genetic variance for expression and more tissue-specific expression patterns, which may facilitate rapid evolution of sex-biased genes. Our findings provide insights into the biological mechanisms underlying sex-biased disease and support the rhesus macaque model for the translational study of these conditions.

A myzozoan-specific protein is an essential membrane-anchoring component of the succinate dehydrogenase complex in Toxoplasma parasites.

Succinate dehydrogenase (SDH) is a protein complex that functions in the tricarboxylic acid cycle and the electron transport chain of mitochondria. In most eukaryotes, SDH is highly conserved and comprises the following four subunits: SdhA and SdhB form the catalytic core of the complex, while SdhC and SdhD anchor the complex in the membrane. Toxoplasma gondii is an apicomplexan parasite that infects one-third of humans worldwide. The genome of T. gondii encodes homologues of the catalytic subunits SdhA and SdhB, although the physiological role of the SDH complex in the parasite and the identity of the membrane-anchoring subunits are poorly understood. Here, we show that the SDH complex contributes to optimal proliferation and O2 consumption in the disease-causing tachyzoite stage of the T. gondii life cycle. We characterize a small membrane-bound subunit of the SDH complex called mitochondrial protein ookinete developmental defect (MPODD), which is conserved among myzozoans, a phylogenetic grouping that incorporates apicomplexan parasites and their closest free-living relatives. We demonstrate that TgMPODD is essential for SDH activity and plays a key role in attaching the TgSdhA and TgSdhB proteins to the membrane anchor of the complex. Our findings highlight a unique and important feature of mitochondrial energy metabolism in apicomplexan parasites and their relatives.

Factors affecting sexual health in individuals with spinal cord injury: A systematic scoping review.

PURPOSE: This study aims to review the literature to explore some factors affecting sexual and partnership adjustment in individuals with spinal cord injury (SCI). METHODS: This study was based on the methodological framework of scoping reviews, including 3 methodological steps: (1) identifying relevant studies (searching for related studies); (2) selecting related studies; (3) collecting key findings, summarizing, and reporting the results. The electronic databases were searched including Medline (PubMed), Scopus, Web of Science, Embase, and Cochrane Library. Studies were included if they reported data about the related factors of sexual and partnership adjustment in individuals with SCI. No limitations were considered in terms of time or methodology of the search. RESULTS: After the full-text screening, 52 studies were included from the year of 1978 - 2019 with various methodologies. The present review demonstrated that proper sexual health among individuals with SCI is related to several factors including the anatomical factor, level of the injury, completeness of the injury, psycho-social factor, socio-economic status, and type of relationship. CONCLUSION: With consideration of factors affecting sexual and partnership adjustment in individuals with SCI, a better estimation of sexual health can be achieved in clinical to improve the relationship and quality of life.

Type IV-A3 CRISPR-Cas systems drive inter-plasmid conflicts by acquiring spacers in trans.

Plasmid-encoded type IV-A CRISPR-Cas systems lack an acquisition module, feature a DinG helicase instead of a nuclease, and form ribonucleoprotein complexes of unknown biological functions. Type IV-A3 systems are carried by conjugative plasmids that often harbor antibiotic-resistance genes and their CRISPR array contents suggest a role in mediating inter-plasmid conflicts, but this function remains unexplored. Here, we demonstrate that a plasmid-encoded type IV-A3 system co-opts the type I-E adaptation machinery from its host, Klebsiella pneumoniae (K. pneumoniae), to update its CRISPR array. Furthermore, we reveal that robust interference of conjugative plasmids and phages is elicited through CRISPR RNA-dependent transcriptional repression. By silencing plasmid core functions, type IV-A3 impacts the horizontal transfer and stability of targeted plasmids, supporting its role in plasmid competition. Our findings shed light on the mechanisms and ecological function of type IV-A3 systems and demonstrate their practical efficacy for countering antibiotic resistance in clinically relevant strains.