BASELINE SUSCEPTABILITY AND FIRST OBSERVATION OF KNOCKDOWN RESISTANCE IN AEDES TAENIORHYNCHUS POPULATION OF ST. JOHNS COUNTY, FLORIDA.

The black saltmarsh mosquito, Aedes taeniorhynchus, is a prominent nuisance mosquito within St. Johns County, Florida. Due to their characteristically large outbreaks, and the elevated amount of insecticide application correlated with the outbreaks, local populations of Ae. taeniorhynchus are at an increased risk of developing insecticide resistance. This study was established to form a baseline susceptibility of Ae. taeniorhynchus against two technical grade materials, permethrin, and chlorpyrifos. Centers for Disease Control and Prevention bottle bioassays were conducted with technical-grade materials during two outbreaks in the fall of 2023. Results indicated a baseline susceptibility against the materials tested, but most notably, the phenotypic expression of knockdown resistance (kdr) was observed. Results highlight the need for continued monitoring and investigation into the resistance status and resistance level of this common Florida species.

HIF-2α expression and metabolic signaling require ACSS2 in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is an aggressive cancer driven by VHL loss and aberrant HIF-2α signaling. Identifying means to regulate HIF-2α thus has potential therapeutic benefit. Acetyl-CoA synthetase 2 (ACSS2) converts acetate to acetyl-CoA and is associated with poor patient prognosis in ccRCC. Here we tested the effects of ACSS2 on HIF-2α and cancer cell metabolism and growth in ccRCC models and clinical samples. ACSS2 inhibition reduced HIF-2α levels and suppressed ccRCC cell line growth in vitro, in vivo, and in cultures of primary ccRCC patient tumors. This treatment reduced glycolytic signaling, cholesterol metabolism, and mitochondrial integrity, all of which are consistent with loss of HIF-2α. Mechanistically, ACSS2 inhibition decreased chromatin accessibility and HIF-2α expression and stability. While HIF-2α protein levels are widely regulated through pVHL-dependent proteolytic degradation, we identify a potential pVHL-independent pathway of degradation via the E3 ligase MUL1. We show that MUL1 can directly interact with HIF-2α and that overexpression of MUL1 decreased HIF-2α levels in a manner partially dependent on ACSS2. These findings identify multiple mechanisms to regulate HIF-2α stability and ACSS2 inhibition as a strategy to complement HIF-2α-targeted therapies and deplete pathogenically stabilized HIF-2α.

Antenatal pyelonephritis hospitalisation trends, risk factors and associated adverse outcomes: A retrospective cohort study.

OBJECTIVE: To analyse trends, risk factors and adverse outcomes associated with antenatal pyelonephritis hospitalisations. DESIGN: Retrospective cohort. SETTING: A national sample of US delivery hospitalisations with associated antenatal hospitalisations. POPULATION: US delivery hospitalisations in the Nationwide Readmissions Database from 2010 to 2020. METHODS: Antenatal hospitalisations with a pyelonephritis diagnosis within the 9 months before delivery hospitalisation were analysed. Clinical, demographic and hospital risk factors associated with antenatal pyelonephritis hospitalisations were analysed with unadjusted and adjusted logistic regression models with unadjusted and adjusted odds ratios as measures of effect. Temporal trends in antenatal pyelonephritis hospitalisations were analysed with Joinpoint regression to determine the relative measure of average annual percent change (AAPC). Risk for severe maternal morbidity and sepsis during antenatal pyelonephritis hospitalisations was similarly analysed with Joinpoint regression. RESULTS: Of an estimated 10.2 million delivery hospitalisations, 49 140 (0.48%) had an associated antenatal pyelonephritis hospitalisation. The proportion of deliveries with a preceding antenatal pyelonephritis hospitalisation decreased by 29% from 0.56% in 2010 to 0.40% in 2020 (AAPC -2.9%, 95% CI -4.0% to -1.9%). Antenatal pyelonephritis decreased, but risk for sepsis diagnoses increased during these hospitalisations from 3.7% in 2010 to 18.0% in 2020 (AAPC 17.2%, 95% CI 14.2%-21.1%). Similarly, risk for severe morbidity increased from 2.6% in 2010 to 4.4% in 2020 (AAPC 5.5%, 95% CI 0.8%-10.7%). CONCLUSION: Antenatal pyelonephritis admissions appear to be decreasing in the USA. However, these hospitalisations are associated with a rising risk for sepsis and severe maternal morbidity.

Null T-cell phenotype mycosis fungoides with aberrant CD20 and CD56 expression: A diagnostic dilemma.

Mycosis fungoides (MF) represents the most common type of primary cutaneous T-cell lymphoma. Recognition of MF variants with divergent immunophenotypes is important for accurate diagnosis and appropriate management, as they can be confused with other lymphoma subtypes. We present a case of a 49-year-old male previously diagnosed with a cutaneous lymphoproliferative disorder with an unusual NK/T-cell phenotype. He presented with a 10-year history of pelvic girdle rash involving the right hip and upper thigh. The lesions were characterized as atrophic patches concentrated in sun-protected areas and involving 10% of the body surface area. Shave biopsies revealed an atypical epidermotropic infiltrate composed of hyperchromatic small to medium-sized lymphocytes with perinuclear halos and "tagging" along the dermal-epidermal junction. The immunophenotype was unusual in that the neoplastic lymphocytes showed complete loss of pan T-cell antigens along with expression of CD56, cytotoxic markers, and weak CD20. All other B-cell markers were negative. The combination of clinical findings, in addition to the histopathologic and immunophenotypic profile, were diagnostic of null T-cell phenotype MF with aberrant expression of CD56 and CD20. Null T-cell phenotype MF is very uncommon, can be diagnostically challenging, and can mislead the diagnosis of aggressive lymphoma subtypes.

Mechanical Ventilation in Older Adults With Dementia: Opportunities to Promote Goal-Concordant Care.

CONTEXT: Recent studies show increasing use of mechanical ventilation among people living with dementia. There are concerns that this trend may not be driven by patient preferences. OBJECTIVES: To better understand decision-making regarding mechanical ventilation in people living with dementia. METHODS: This was an electronic health record-based retrospective cohort study of older adults with dementia (n = 295) hospitalized at one of two teaching hospitals between 2015 and 2019 who were supported with mechanical ventilation (n = 191) or died without mechanical ventilation (n = 104). Multivariable logistic regression was used to examine associations between patient characteristics and mechanical ventilation use. RESULTS: The median age was 78 years (IQR 71-86), 41% were female, 28% resided in a nursing home, and 58% had clinical markers of advanced dementia (dehydration, weight loss, mobility limitations, or pressure ulcers). Among patients supported with mechanical ventilation, 70% were intubated within 24 hours of presentation, including 31% intubated before hospital arrival. Younger age, higher illness acuity, and absence of a treatment-limiting Physician Orders for Life-Sustaining Treatment document were associated with mechanical ventilation use; nursing home residence and clinical markers of advanced dementia were not. Most patients (89%) had a documented goals of care discussion (GOCD) during hospitalization. CONCLUSION: Future efforts to promote goal-concordant care surrounding mechanical ventilation use for people living with dementia should involve identifying barriers to goal-concordant care in pre-hospital settings, assessing the timeliness of in-hospital GOCD, and developing strategies for in-the-moment crisis communication across settings.

Pregnancy Outcomes in Women Who Developed Elevated Blood Pressure and Stage I Hypertension after 20 Weeks Gestation.

OBJECTIVE: The American College of Obstetrics threshold for hypertension (≥140/90 mm Hg) differs from those of the American College of Cardiology (ACC) and the American Heart Association (AHA). It is unknown if ACC/AHA hypertension levels are associated with adverse pregnancy outcomes (APOs) after 20 weeks gestation. The purpose of this study is to analyze APOs in women with blood pressure (BP) in the elevated or stage 1 range after 20 weeks gestation. STUDY DESIGN: This was a secondary analysis of the nuMoM2b prospective cohort study of 10,038 nulliparous, singleton pregnancies between 2010 and 2014. BP was measured at three visits during the pregnancy using a standard protocol. Women without medical comorbidities, with normal BP by ACC/AHA guidelines (systolic BP [SBP] < 120 and diastolic BP [DBP] < 80 mm Hg) up to 22 weeks, were included. Exposure was BP between 22 and 29 weeks gestation: normal (SBP < 120 and DBP < 80 mm Hg), elevated (SBP: 120-129 and DBP < 80 mm Hg), and stage 1 (SBP: 130-139 or DBP: 80-89 mm Hg). The primary outcome was hypertensive disorder of pregnancy (HDP) at delivery. Secondary outcomes included fetal growth restriction (FGR), placental abruption, preterm delivery, and cesarean delivery. Multivariable-adjusted odds ratio (aORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. RESULTS: Of 4,460 patients that met inclusion criteria, 3,832 (85.9%) had BP in the normal range, 408 (9.1%) in elevated, and 220 (4.9%) in stage 1 range between 22 and 29 weeks. The likelihood of HDP was significantly higher in women with elevated BP (aOR 1.71, 95%CI: 1.18,2.48), and stage 1 BP (aOR: 2.79, 95%CI: 1.84,4.23) compared to normal BP (p < 0.001). Stage 1 BP had twice odds of FGR (aOR: 2.33, 95%CI: 1.22,4.47) and elevated BP had three times odds of placental abruption (aOR: 3.03; 95%CI: 1.24,7.39). CONCLUSION: Elevated or stage 1 BP >20 weeks of pregnancy are associated with HDP, FGR, and placental abruption. KEY POINTS: · Elevated and stage 1 BP increases risk for HDP.. · Elevated BP increases risk for placental abruption.. · Stage 1 BP increases risk for FGR..

Primary and Secondary Intracerebral Hemorrhage in Pregnant and Nonpregnant Young Adults by SMASH-UP Criteria.

BACKGROUND: Intracerebral hemorrhage (ICH) is a major cause of maternal morbidity, but its pathophysiology is poorly characterized. We investigated characteristics of pregnancy-associated ICH (P-ICH), compared with ICH in similar aged nonpregnant adults of both sexes. METHODS AND RESULTS: We performed a retrospective analysis of 134 adults aged 18 to 44 years admitted to our center with nontraumatic ICH from January 1, 2012, to December 31, 2021. We compared ICH characteristics among 3 groups: those with P-ICH (pregnant or within 12 months of end of pregnancy); nonpregnant women; and men. We categorized ICH pathogenesis according to a modified scheme, SMASH-UP (structural, medications, amyloid angiopathy, systemic, hypertension, undetermined, posterior reversible encephalopathy syndrome/reversible cerebral vasoconstriction syndrome), and calculated odds ratios and 95% CIs for primary (spontaneous small-vessel) ICH versus secondary ICH (structural lesions or coagulopathy related), using nonpregnant women as the reference. We also compared specific ICH pathogenesis by SMASH-UP criteria and functional outcomes between groups. Of 134 young adults with nontraumatic ICH, 25 (19%) had P-ICH, of which 60% occurred postpartum. Those with P-ICH had higher odds of primary ICH compared with nonpregnant women (adjusted odds ratio, 4.5 [95% CI, 1.4-14.7]). The odds of primary ICH did not differ between men and nonpregnant women. SMASH-UP pathogenesis for ICH differed significantly between groups (P<0.001). While the in-hospital mortality rate was lowest in the P-ICH group (4%) compared with nonpregnant women (13%) and men (24%), 1 in 4 patients with P-ICH were bedbound and dependent at the time of discharge. CONCLUSIONS: In our cohort of young adults with ICH, 1 in 5 was pregnancy related. P-ICH differed in pathogenesis compared with non-pregnancy-related ICH in young adults, suggesting unique pathophysiology.

Adverse delivery hospitalisation outcomes in 2020 during the COVID-19 pandemic.

OBJECTIVE: To evaluate risk for adverse obstetric outcomes associated with the coronavirus disease 2019 (COVID-19) pandemic period and with COVID-19 diagnoses. DESIGN: Serial cross-sectional study. SETTING: A national sample of US delivery hospitalisations before (1/2016 to 2/2020) and during the first 10 months of (3/2020 to 12/2020) the COVID-19 pandemic. POPULATION: All 2016-2020 US delivery hospitalisations in the National Inpatient Sample. METHODS: Delivery hospitalisations were identified and stratified into pre-pandemic and pandemic periods and the likelihood of adverse obstetric outcomes was compared using logistic regression models with adjusted odds ratios (aOR) with 95% confidence intervals (CI) as measures of association. Risk for adverse outcomes was also analysed specifically for 2020 deliveries with a COVID-19 diagnosis. MAIN OUTCOME MEASURE: Adverse maternal outcomes including respiratory complications and cardiac morbidity. RESULTS: Of an estimated 18.2 million deliveries, 2.9 million occurred during the pandemic. The proportion of delivery hospitalisations with a COVID-19 diagnosis increased from 0.1% in March 2020 to 3.1% in December. Comparing the pandemic period to the pre-pandemic period, there were higher adjusted odds of transfusion (aOR 1.12, 95% CI 1.05-1.19), a respiratory complication composite (aOR 1.37, 95% CI 1.29-1.46), cardiac severe maternal morbidity (aOR 1.30, 95% 1.20-1.39), postpartum haemorrhage (aOR 1.19, 95% CI 1.15-1.24), placental abruption/antepartum haemorrhage (OR 1.04, 95% CI 1.00-1.08), and hypertensive disorders of pregnancy (OR 1.23, 95% CI 1.21-1.26). These associations were similar to unadjusted analysis. Risk for these outcomes during the pandemic period was significantly higher in the presence of a COVID-19 diagnosis. CONCLUSIONS: In a national estimate of delivery hospitalisations, the odds of cardiac and respiratory outcomes were higher in 2020 compared with 2016-2019. COVID-19 diagnoses were specifically associated with a range of serious complications.

Five Species of Wild Freshwater Sport Fish in Wisconsin, USA, Reveal Highly Diverse Viromes.

Studies of marine fish have revealed distant relatives of viruses important to global fish and animal health, but few such studies exist for freshwater fish. To investigate whether freshwater fish also host such viruses, we characterized the viromes of five wild species of freshwater fish in Wisconsin, USA: bluegill (Lepomis macrochirus), brown trout (Salmo trutta), lake sturgeon (Acipenser fulvescens), northern pike (Esox lucius), and walleye (Sander vitreus). We analyzed 103 blood serum samples collected during a state-wide survey from 2016 to 2020 and used a metagenomic approach for virus detection to identify known and previously uncharacterized virus sequences. We then characterized viruses phylogenetically and quantified prevalence, richness, and relative abundance for each virus. Within these viromes, we identified 19 viruses from 11 viral families: Amnoonviridae, Circoviridae, Coronaviridae, Hepadnaviridae, Peribunyaviridae, Picobirnaviridae, Picornaviridae, Matonaviridae, Narnaviridae, Nudnaviridae, and Spinareoviridae, 17 of which were previously undescribed. Among these viruses was the first fish-associated coronavirus from the Gammacoronavirus genus, which was present in 11/15 (73%) of S. vitreus. These results demonstrate that, similar to marine fish, freshwater fish also harbor diverse relatives of viruses important to the health of fish and other animals, although it currently remains unknown what effect, if any, the viruses we identified may have on fish health.

Insights and Challenges for the Development of Mosquito Control Action Thresholds Using Historical Mosquito Surveillance and Climate Datasets.

Strategies to advance action threshold development can benefit both civilian and military vector control operations. The Anastasia Mosquito Control District (AMCD) has curated an extensive record database of surveillance programs and operational control activities in St. Johns County, Florida, since 2004. A thorough exploratory data analysis was performed on historical mosquito surveillance and county-wide climate data to identify climate predictors that could be used in constructing proactive threshold models for initiating control of Aedes, Culex, and Anopheles vector mosquitoes. Species counts pulled from Centers for Disease Control and Prevention (CDC) light trap (2004-2019) and BG trap (2014-2019) collection records and climate parameters of temperature (minimum, maximum, average), rainfall, and relative humidity were used in two iterations of generalized linear models. Climate readings were incorporated into models 1) in the form of continuous measurements, or 2) for categorization into number of "hot," "wet," or "humid" days by exceedance of selected biological index threshold values. Models were validated with tests of residual error, comparison of model effects, and predictive capability on testing data from the two recent surveillance seasons 2020 and 2021. Two iterations of negative binomial regression models were constructed for 6 species groups: container Aedes (Ae. aegypti, Ae. albopictus), standing water Culex (Cx. nigripalpus, Cx. quinquefasciatus), floodwater Aedes (Ae. atlanticus, Ae. infirmatus), salt-marsh Aedes (Ae. taeniorhyncus, Ae. sollicitans), swamp water Anopheles (An. crucians), and a combined Total Mosquitoes group. Final significant climate predictors varied substantially between species groups. Validation of models with testing data displayed limited predictive abilities of both model iterations. The most significant climate predictors for floodwater Aedes, the dominant and operationally influential species group in the county, were either total precipitation or frequency of precipitation events (number of "wet" days) at two to four weeks before trap collection week. Challenges hindering the construction of threshold models were discussed. Insights gained from these models provide initial feedback for streamlining the AMCD mosquito control program and analytical recommendations for future modelling efforts of interested mosquito control programs, in addition to generalized guidance for deployed armed forces personnel with needs of mosquito control but lacking active surveillance programs.

An intracellular hydrophobic nexus critical for hERG1 channel slow deactivation.

Slow deactivation is a critical property of voltage-gated K+ channels encoded by the human Ether-à-go-go-Related Gene 1 (hERG). hERG1 channel deactivation is modulated by interactions between intracellular N-terminal Per-Arnt-Sim (PAS) and C-terminal cyclic nucleotide-binding homology (CNBh) domains. The PAS domain is multipartite, comprising a globular domain (gPAS; residues 26-135) and an N-terminal PAS-cap that is further subdivided into an initial unstructured "tip" (residues 1-12) and an amphipathic α-helical region (residues 13-25). Although the PAS-cap tip has long been considered the effector of slow deactivation, how its position near the gating machinery is controlled has not been elucidated. Here, we show that a triad of hydrophobic interactions among the gPAS, PAS-cap α helix, and the CNBh domains is required to support slow deactivation in hERG1. The primary sequence of this "hydrophobic nexus" is highly conserved among mammalian ERG channels but shows key differences to fast-deactivating Ether-à-go-go 1 (EAG1) channels. Combining sequence analysis, structure-directed mutagenesis, electrophysiology, and molecular dynamics simulations, we demonstrate that polar serine substitutions uncover an intermediate deactivation mode that is also mimicked by deletion of the PAS-cap α helix. Molecular dynamics simulation analyses of the serine-substituted channels show an increase in distance among the residues of the hydrophobic nexus, a rotation of the intracellular gating ring, and a retraction of the PAS-cap tip from its receptor site near the voltage sensor domain and channel gate. These findings provide compelling evidence that the hydrophobic nexus coordinates the respective components of the intracellular gating ring and positions the PAS-cap tip to control hERG1 deactivation gating.

Mechanisms and consequences of sex differences in immune responses.

Biological sex differences refer to differences between males and females caused by the sex chromosome complement (that is, XY or XX), reproductive tissues (that is, the presence of testes or ovaries), and concentrations of sex steroids (that is, testosterone or oestrogens and progesterone). Although these sex differences are binary for most human individuals and mice, transgender individuals receiving hormone therapy, individuals with genetic syndromes (for example, Klinefelter and Turner syndromes) and people with disorders of sexual development reflect the diversity in sex-based biology. The broad distribution of sex steroid hormone receptors across diverse cell types and the differential expression of X-linked and autosomal genes means that sex is a biological variable that can affect the function of all physiological systems, including the immune system. Sex differences in immune cell function and immune responses to foreign and self antigens affect the development and outcome of diverse diseases and immune responses.

Mental and Physical Health-Related Cannabis Motives Mediate the Relationship between Childhood Trauma and Problematic Cannabis Use over Time among Emerging Adult Cannabis Users.

BACKGROUND: While growing evidence has identified mental and physical health-related cannabis use motives as significant mechanisms between childhood trauma and problematic cannabis use (PCU) for emerging adults (EA), there is a need to understand the longitudinal stability of these pathways and how they impact PCU as cannabis users age into later adulthood. METHODS: The current study extends an analysis examining the impact of childhood trauma (e.g., emotional abuse, sexual abuse) on multiple indicators of PCU through a range of cannabis use motives. 339 medical cannabis patient and non-patient EA users from the Los Angeles area were sampled at baseline (mean age = 21.23; SD = 2.48). The present analysis used four waves of follow-up data collected from 2016 to 2018 (W3, W4) and 2019-2020 (W5, W6). RESULTS: Use of cannabis to cope with nausea, sleep, pain, and emotional distress mediated the relationships between some types of childhood abuse and PCU at W4, though most associations attenuated by later adulthood (W6). Specifically, greater emotional distress and nausea motives were associated with greater PCU in models of emotional abuse and neglect and sexual abuse, with emotional distress continuing to mediate at W6. Conversely, sleep and pain motives were associated with lower PCU in models for emotional neglect. CONCLUSIONS: Mental and physical health-related motives reflect potential intervenable factors that predict PCU in emerging adulthood among EA cannabis users with histories of childhood trauma. Results highlight the importance of and value for assessing a wide range of motives and PCU outcomes to target and address areas for intervention.

Trends in and outcomes of delivery hospitalizations with lupus and antiphospholipid syndrome.

OBJECTIVE: To assess trends and outcomes associated with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) during US delivery hospitalizations. STUDY DESIGN: The National Inpatient Sample from 2000 to 2019 was used for this repeated cross-sectional analysis. We identified delivery hospitalizations with and without SLE. Temporal trends in SLE during delivery hospitalizations were determined using joinpoint regression. Adjusted logistic regression models accounting for demographic, clinical, and hospital factors were used to determine adjusted odds ratios (aORs) for adverse outcomes based on the presence or absence of SLE. RESULTS: Of an estimated 76 698 775 delivery hospitalizations identified in the NIS, 79386 (0.10%) had an associated diagnosis of SLE. Over the study period, SLE increased from 6.7 to 14.6 cases per 10 000 delivery hospitalizations (average annual percent change 4.5%, 95% CI 4.0-5.1). Deliveries with SLE had greater odds of non-transfusion severe morbidity (aOR 2.21, 95% CI 2.00, 2.44) and underwent a larger absolute increase in morbidity risk over the study period. SLE was associated with a range of other adverse outcomes including preterm delivery, eclampsia, cesarean delivery, and blood transfusion. CONCLUSION: The proportion of deliveries to women with SLE has increased over time in the US, and SLE and APS are associated with a broad range of adverse outcomes.

Gulf War toxicant-induced reductions in dendritic arbors and spine densities of dentate granule cells are improved by treatment with a Nrf2 activator.

Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting approximately 30 % of Veterans deployed to the Persian Gulf from 1990 to 91. GWI encompasses a wide spectrum of symptoms which frequently include neurological problems such as learning and memory impairments, mood disorders, and an increased incidence of neurodegenerative disorders. Combined exposure to both reversible and irreversible acetylcholinesterase (AChE) inhibitors has been identified as a likely risk factor for GWI. It is possible that the exposures affected connectivity in the brain, and it was also unknown whether this could benefit from treatment. We assessed chronic changes in dendritic architecture in granule cells of the dentate gyrus following exposure to pyridostigmine bromide (PB, 0.7 mg/kg), chlorpyrifos (CPF, 12.5 mg/kg), and N,N-diethyl-m-toluamide (DEET, 7.5 mg/kg) in male C57Bl/6J mice. We also evaluated the therapeutic effects of dietary administration for eight weeks of 1 % tert-butylhydroquinone (tBHQ), a Nrf2 activator, on long-term neuronal morphology. We found that Gulf War toxicant exposure resulted in reduced dendritic length and branching as well as overall spine density in dentate granule cells at 14 weeks post-exposure and that these effects were ameliorated by treatment with tBHQ. These findings indicate that Gulf War toxicant exposure results in chronic changes to dentate granule cell morphology and that modulation of neuroprotective transcription factors such as Nrf2 may improve long-term neuronal health in the hippocampus.

Non-pharmacological rehabilitation interventions for individuals with antiphospholipid syndrome: A scoping review.

OBJECTIVE: The objective of this study was to explore what non-pharmacological interventions have been examined for individuals with antiphospholipid syndrome (APS). METHODS: We conducted a systematic literature search of the databases PubMed, Embase, Scopus, Web of Science, CINAHL, and ClinicalTrials.gov from 1983-Feb. 2023. Our scoping review included studies that examined non-pharmacological interventions for individuals with APS using patient-reported outcome measures. We excluded studies that reported physiological outcomes only. RESULTS: The review yielded one case study on the safety and efficacy of an exercise program for a 15-year-old male with secondary APS using physiological and patient-reported outcome measures. Despite the lack of evidence of non-pharmacological interventions for individuals with APS, one excluded study reported that individuals with APS want guidance about physical activity and exercise. We also found several types of potentially relevant non-pharmacological interventions for individuals with lupus, a disease that often co-occurs with APS. CONCLUSIONS: Non-pharmacological interventions may offer a solution for addressing some non-thrombotic or non-obstetric APS symptoms, such as neurological, physical, and cognitive symptoms that are not well-controlled by anticoagulation. Due to the unique risks associated with APS, research is needed to determine the safety and efficacy of non-pharmacological interventions, particularly those involving exercise. Adopting a comprehensive, multidisciplinary approach to managing patients with APS and involving rehabilitation professionals, who are experts in the design and delivery of non-pharmacological interventions, may provide a foundation for developing and testing novel interventions that improve health outcomes while also fulfilling unmet needs reported by patients.

Personal relevance affects the perceived immorality of politically-charged threats.

Personal similarities to a transgressor makes one view the transgression as less immoral. We investigated whether personal relevance might also affect the perceived immorality of politically-charged threats. We hypothesized that increasing the personal relevance of a threat would lead participants to report the threat as more immoral, even for threats the participant might otherwise view indifferently. U.S. participants recruited online (N = 488) were randomly assigned to write about the personal relevance of either a liberal threat (pollution), conservative threat (disrespecting an elder), neutral threat (romantic infidelity), or given a control filler task. Participants then rated how immoral and personally relevant each political threat was, as well as reported their political ideology. Partial support for our hypothesis emerged: when primed with conservative writing prompts, liberal-leaning participants rated the conservative threat as more immoral, compared with the same threat after a liberal writing prompt. We did not find these results for conservative-leaning participants, perhaps because all participants cared relatively equally about the liberal threat.

Developing a Translational Team Training Program using the Wisconsin Interventions in Team Science Framework.

The Clinical and Translational Science Awards (CTSA) Program supports a national network of medical research institutions working to improve the translational process. High-performing translational teams (TTs) are critical for advancing evidence-based approaches that improve human health. When focused on content-appropriate knowledge, skills, and attitudes, targeted training results in the substantial internalization of training content, producing new skills that can be applied to improve team outputs, outcomes, and benefits. More rigorous approaches to develop, test, and evaluate interventions are needed, and we used the Wisconsin Interventions in Team Science framework as a model to systematize our efforts. We designed, built, and tested a five-session TT Training Program for translational researchers. The 90-minute sessions were pilot-tested with 47 postdoctoral fellows and evaluated through a structured evaluation plan. Ninety-five percent of post-session survey respondents indicated that the content and skills provided would make them more effective collaborators, and one hundred percent would recommend the sessions to colleagues. Respondents' scores increased from pretest to posttest for most learning outcomes. Refinements from participant feedback are described. This work provides a foundation for the continued evolution of evidence-based training programs in the CTSA environment.

Assessment of the AAOS guidelines using the AGREE II instrument: An update.

Background: The American Academy of Orthopaedic Surgeons (AAOS) provides clinical guidelines and frequently updates and expands on the recommendations. High quality, up-to-date, and applicable clinical guidelines are increasingly important tools for physicians to have. Assessing these continuously updating guidelines' overall quality has most recently been done in 2013 when there were 14 guidelines. Since then, nearly all guidelines have been updated and now 28 guidelines are provided. Our goal was to evaluate the updated 2023 AAOS guidelines using the well-established Advancing Guideline Development, Reporting and Evaluation in Health Care (AGREE II) tool. Methods: On April 23, 2023, all 28 guidelines set forth by AAOS were compiled. Using the AGREE II tool, a well-recognized and established tool for evaluation of guideline quality used across all disciplines, three independent reviewers appraised the current guidelines. These data were used to run descriptive statistics and assessed accordingly. Results: Across the 28 guidelines, the average AGREE II domain scores were as follows: Scope and Purpose (median score, 85%), Stakeholder Involvement (median score, 87%), Rigor of Development (median score, 87%), Clarity of Presentation (median score, 87%), Applicability (median score, 48%), Editorial Independence (median score, 87%), and Overall Assessment (median score, 80s%). Conclusions: Five of the six AGREE II domains, including the overall assessment, tested achieved a median score above the 50% mark. These results indicate that the AAOS guidelines met many criteria for high quality based on a critical appraisal.

A Clinical Model to Predict the Occurrence of Select High-risk Infections in the First Year Following Heart Transplantation.

Background: Invasive infection remains a dangerous complication of heart transplantation (HT). No objectively defined set of clinical risk factors has been established to reliably predict infection in HT. The aim of this study was to develop a clinical prediction model for use at 1 mo post-HT to predict serious infection by 1 y. Methods: A retrospective cohort study of HT recipients (2000-2018) was performed. The composite endpoint included cytomegalovirus (CMV), herpes simplex or varicella zoster virus infection, blood stream infection, invasive fungal, or nocardial infection occurring 1 mo to 1 y post-HT. A least absolute shrinkage and selection operator regression model was constructed using 10 candidate variables. A concordance statistic, calibration curve, and mean calibration error were calculated. A scoring system was derived for ease of clinical application. Results: Three hundred seventy-five patients were analyzed; 93 patients experienced an outcome event. All variables remained in the final model: aged 55 y or above, history of diabetes, need for renal replacement therapy in first month, CMV risk derived from donor and recipient serology, use of induction and/or early lymphodepleting therapy in the first month, use of trimethoprim-sulfamethoxazole prophylaxis at 1 mo, lymphocyte count under 0.75 × 103cells/µL at 1 mo, and inpatient status at 1 mo. Good discrimination (C-index 0.80) and calibration (mean absolute calibration error 3.6%) were demonstrated. Conclusion: This model synthesizes multiple highly relevant clinical parameters, available at 1 mo post-HT, into a unified, objective, and clinically useful prediction tool for occurrence of serious infection by 1 y post-HT.