Associating frailty and dynamic dysregulation between motor and cardiac autonomic systems.

Frailty is a geriatric syndrome associated with the lack of physiological reserve and consequent adverse outcomes (therapy complications and death) in older adults. Recent research has shown associations between heart rate (HR) dynamics (HR changes during physical activity) with frailty. The goal of the present study was to determine the effect of frailty on the interconnection between motor and cardiac systems during a localized upper-extremity function (UEF) test. Fifty-six individuals aged 65 or above were recruited and performed the previously developed UEF test consisting of 20-s rapid elbow flexion with the right arm. Frailty was assessed using the Fried phenotype. Wearable gyroscopes and electrocardiography were used to measure motor function and HR dynamics. In this study, the interconnection between motor (angular displacement) and cardiac (HR) performance was assessed, using convergent cross-mapping (CCM). A significantly weaker interconnection was observed among pre-frail and frail participants compared to non-frail individuals (p < 0.01, effect size = 0.81 ± 0.08). Using logistic models, pre-frailty and frailty were identified with sensitivity and specificity of 82%-89%, using motor, HR dynamics, and interconnection parameters. Findings suggested a strong association between cardiac-motor interconnection and frailty. Adding CCM parameters in a multimodal model may provide a promising measure of frailty.

Variables associated with the prevalence of self-reported work-related musculoskeletal disorders in veterinary laparoscopic surgeons.

OBJECTIVE: To investigate the relationship between physical attributes and difficulty performing laparoscopic maneuvers with the prevalence of self-reported musculoskeletal injury. STUDY DESIGN: Online survey. SAMPLE POPULATION: Surgeons (n = 140) with 3 or more years of laparoscopic experience. METHODS: Electronic survey distributed via LISTSERVEs and Facebook groups. Responses collected included surgeon attributes, presence of musculoskeletal injuries, and surgical practice data. Statistical analysis was performed using the Shapiro-Wilk test, linear regression, logistic regression, and Wilcoxon rank sum tests. RESULTS: A total of 52 of the 140 respondents reported a musculoskeletal injury with 38 specifying at least one injury (72%). Neck strain was the most prevalent reported musculoskeletal injury (18/52, 34.6%), followed by shoulder tendinopathies (16/52, 30.8%), arm/hand tendonitis (8/52, 15.4%), carpal tunnel (7/52, 13.5%), back pain (4/52, 7.7%) and arm/hand arthritis (1/52, 1.9%). Women were significantly more likely to report a musculoskeletal problem than men (p = .011) with the odds of women reporting a musculoskeletal injury 2.59 times greater than men. Women and surgeons with smaller glove sizes were significantly more likely to report shoulder tendonitis (p = .034, p = .1) and neck strain (p = .009, p = .001). Respondents with a musculoskeletal problem experienced significantly more difficulty using rotating cup biopsy forceps (p < .001) and perceived this as difficult a greater amount of time (p = .006). CONCLUSION: Female surgeons report more musculoskeletal injuries than their male counterparts. Surgeons with musculoskeletal injuries experience more difficulty performing particular laparoscopic maneuvers. CLINICAL SIGNIFICANCE: Improving ergonomics for women and surgeons with smaller glove sizes must be prioritized to improve surgeon health and laparoscopic instrument use.

Repetitive element transcript accumulation is associated with inflammaging in humans.

Chronic, low-grade inflammation increases with aging, contributing to functional declines and diseases that reduce healthspan. Growing evidence suggests that transcripts from repetitive elements (RE) in the genome contribute to this "inflammaging" by stimulating innate immune activation, but evidence of RE-associated inflammation with aging in humans is limited. Here, we present transcriptomic and clinical data showing that RE transcript levels are positively related to gene expression of innate immune sensors, and to serum interleukin 6 (a marker of systemic inflammation), in a large group of middle-aged and older adults. We also: (1) use transcriptomics and whole-genome bisulfite (methylation) sequencing to show that many RE may be hypomethylated with aging, and that aerobic exercise, a healthspan-extending intervention, reduces RE transcript levels and increases RE methylation in older adults; and (2) extend our findings in a secondary dataset demonstrating age-related changes in RE chromatin accessibility. Collectively, our data support the idea that age-related RE transcript accumulation may play a role in inflammaging in humans, and that RE dysregulation with aging may be due in part to upstream epigenetic changes.

Mediation of the association between depression and coronary heart disease by metabolic syndrome components.

BACKGROUND: Depression is associated with incident coronary heart disease (CHD) via a pathway that may be causal, but the mechanisms underlying this association are unclear. We assessed the extent to which metabolic syndrome (MetS) and its components (i.e., elevated waist circumference, low high-density lipoprotein [HDL] cholesterol, elevated triglycerides, elevated blood pressure, and elevated fasting plasma glucose) may mediate this association. METHODS: Data were Framingham Heart Study Research Materials obtained from the National Heart, Lung, and Blood Institute (NHLBI) Biologic Specimen and Data Repository Information Coordinating Center. We used Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) representing the total effect (aHRTE) of probable depression, measured via the Centers for Epidemiological Studies - Depression scale, on incident CHD over approximately 18 years. Using inverse odds ratio weighting, we decomposed this estimate into natural direct effects (aHRNDE) and natural indirect effects (aHRNIE) through potential mediators (measured approximately three years after depression). RESULTS: Probable depression was associated with incident CHD (aHRTE=1.45, 95% confidence interval [CI]: 0.93, 2.25), and elevated waist circumference partially mediated this association (aHRNDE=1.34, 95% CI: 0.76-2.32; aHRNIE=1.08, 95% CI: 0.63-1.91). We did not find evidence of additional mediation by additional MetS components. CONCLUSIONS: Elevated waist circumference appears to play a role in the association between depression and CHD.

Clinical presentation and short-term outcomes of dogs ≥15 kg with extrahepatic portosystemic shunts.

OBJECTIVE: To describe demographics, clinical presentation, shunt anatomy, clinical progression, and complications in large dogs ≥15 kg with single extrahepatic portosystemic shunts (EHPSS) treated with or without surgery. STUDY DESIGN: Multicenter retrospective (10 university hospitals, one private referral institution). ANIMALS: Dogs ≥15 kg (n = 63). METHODS: Medical records of dogs ≥15 kg diagnosed with EHPSS between January 01, 2005 and December 31, 2020 were reviewed. Dogs had a minimum follow-up of 90 days. Signalment, clinical signs, diagnostics, shunt anatomy, treatment interventions, and perioperative complications were assessed. RESULTS: Median age was 21.9 months (IQR: 9-36.8). The breed most represented was the Golden retriever (17/63 dogs). Portocaval (17/63) and splenocaval (15/63) shunt configurations were most common. Portal vein hypoplasia was noted in 18 imaging reports. Of the surgically treated dogs, 14/45 (35.6%) had short-term complications, and 3/45 (6.7%) had shunt-related deaths. Medical management was discontinued in 15/40 and reduced in 9/40 of surviving dogs who had surgical attenuation. All medically managed, nonattenuated dogs (18/18) were maintained on their original shunt-related medication regimens. CONCLUSIONS: Clinical presentation of dogs ≥15 kg with extrahepatic portosystemic shunts was similar to the more commonly reported small breed dogs. Surgical management of single EHPSS in large dogs ≥15 kg had similar clinical short-term outcomes as small breed dogs. CLINICAL SIGNIFICANCE: Clinicians should be aware that large breed dogs with EHPSS share similar characteristics and clinical outcomes to small breed dogs. The significance of the presence of a hypoplastic portal vein warrants further research. Surgical treatment is a viable option for large breed dogs with EHPSS.

Variables affecting surgeons' use of, and preferences for, instrumentation in veterinary laparoscopy.

OBJECTIVE: To investigate the impact of variables on use and preference of common laparoscopic instruments. STUDY DESIGN: Online survey. SAMPLE POPULATION: Surgeons (n = 140) with 3 years or more laparoscopic experience. METHODS: Electronic survey distributed via specialty group LISTSERVEs and Facebook groups. Responses collected included surgeon attributes, preferences, and surgical practice data. Statistical analysis was performed using Fishers exact, ANOVA, Tukey Kramer honestly significant difference (HSD) test, linear regression, and logistic regression. RESULTS: Ninety-eight of 140 respondents answered instrument-related questions and the completion rate of these questions was 76%: 48% of females and 49% of males responded to the survey. The median glove size of respondents was size 7 (range, 5.5 to 8.5). Closing laparoscopic Babcock forceps (p = .018), rotating cup biopsy forceps (p = .003), and manipulating endoscopic staplers (p < .001) were more difficult for surgeons with smaller glove sizes. The median difficulty score for the endoscopic stapler was 4/10 and the median percentage of time this was found difficult was 25%. Reusable instruments were preferred over disposable single-use instruments. The pistol grip was preferred for grasping and retracting (54/98, 55%) and fine dissection (46/96, 48%), while the axial grip was preferred for suturing and knot tying (61/98, 62%). CONCLUSION: Surgeons with smaller glove sizes (<6.5) experience more difficulty when using common laparoscopic instruments. The endoscopic stapler was the most difficult to use. CLINICAL SIGNIFICANCE: When purchasing laparoscopic instrumentation, surgeons should review all available options in handle size and design to improve ergonomics during minimally invasive procedures.

Bibliometric analysis with reference publication year spectroscopy showed how key programmes drove developmental care in newborn infants.

AIM: We investigated the historical origins of developmental care for newborn infants using Reference Publication Year Spectroscopy (RPYS), an innovative method of bibliometric analysis. METHODS: A Web of Science search query that combined infant and intervention-related synonyms was performed on 2 February 2022. RPYS analysis was performed on this dataset to identify the most referenced historical publications for developmental care in newborn infants. Median deviation analysis identified the peak publication years, including the most cited historical references. Landmark publications were defined as those belonging to the top 10% of the most frequently referenced publications for at least 20 years. RESULTS: The RPYS peaks showed an early phase (1936-1986), during which infant development was studied and analysed, leading to a conceptualisation of developmental care for newborn infants. The following years (1987-2020), showed an explosion of interest in developmental care and highlighted two main programmes. The Neonatal Individualized Developmental Care Assessment Program (NIDCAP) and the Infant Health and Development Program (IHDP) inspired numerous publications during those years, which strove to demonstrate evidence of their clinical benefits. CONCLUSION: Developmental care has become increasingly important, thanks to the implementation of NIDCAP and IHDP.

Antihypertensive Medications and PTSD Incidence in a Trauma Cohort.

Objective: Antihypertensive medications have been examined as agents for posttraumatic stress disorder (PTSD) prevention in trauma-exposed individuals, given well-documented associations between PTSD and increased risk of cardiovascular disease and purported trauma-relevant mechanisms of action for these medications. Evidence regarding the effectiveness of such drugs for this purpose remains mixed.Methods: We conducted a national population-based cohort study using data from Danish national registries to assess whether 4 classes of antihypertensive drugs (beta-adrenoceptor blockers [beta blockers], angiotensin II receptor blockers [ARBs], angiotensin-converting enzyme [ACE] inhibitors, and calcium channel blockers) were associated with a decreased incidence of PTSD (diagnosed according to ICD-10) over a 22-year study period. Data for this study originated from a population-based cohort of over 1.4 million persons who experienced a traumatic event between 1994 and 2016 in Denmark. We calculated the incidence rate of PTSD per 100,000 person-years among persons who filled a prescription for each class of drug in the 60 days prior to a traumatic event and for corresponding unexposed comparison groups. We then used Cox proportional hazards regression to compare the rate of PTSD among persons who filled an antihypertensive medication prescription within 60 days before their trauma to the rate among persons who did not.Results: We found evidence that calcium channel blockers were associated with a decreased incidence of PTSD (adjusted hazard ratio = 0.63, 95% confidence interval [CI] = 0.34, 1.2); all other antihypertensive medication classes had null or near null associations.Conclusions: These findings lay a foundation for additional research focusing on antihypertensive medications that appear most effective in reducing PTSD incidence following trauma and for additional replication work aimed at continuing to clarify the disparate findings reported in the literature to date.

Association of Early-, Middle-, and Late-Life Depression With Incident Dementia in a Danish Cohort.

Importance: Late-life depressive symptoms are associated with subsequent dementia diagnosis and may be an early symptom or response to preclinical disease. Evaluating associations with early- and middle-life depression will help clarify whether depression influences dementia risk. Objective: To examine associations of early-, middle-, and late-life depression with incident dementia. Design, Setting, and Participants: This was a nationwide, population-based, cohort study conducted from April 2020 to March 2023. Participants included Danish citizens from the general population with depression diagnoses who were matched by sex and birth year to individuals with no depression diagnosis. Participants were followed up from 1977 to 2018. Excluded from analyses were individuals followed for less than 1 year, those younger than 18 years, or those with baseline dementia. Exposure: Depression was defined using diagnostic codes from the International Classification of Diseases (ICD) within the Danish National Patient Registry (DNPR) and Danish Psychiatric Central Research Register (DPCRR). Main Outcomes and Measure: Incident dementia was defined using ICD diagnostic codes within the DPCRR and DNPR. Cox proportional hazards regression was used to examine associations between depression and dementia adjusting for education, income, cardiovascular disease, chronic obstructive pulmonary disease, diabetes, anxiety disorders, stress disorders, substance use disorders, and bipolar disorder. Analyses were stratified by age at depression diagnosis, years since index date, and sex. Results: There were 246 499 individuals (median [IQR] age, 50.8 [34.7-70.7] years; 159 421 women [64.7%]) with diagnosed depression and 1 190 302 individuals (median [IQR] age, 50.4 [34.6-70.0] years; 768 876 women [64.6%]) without depression. Approximately two-thirds of those diagnosed with depression were diagnosed before the age of 60 years (684 974 [67.7%]). The hazard of dementia among those diagnosed with depression was 2.41 times that of the comparison cohort (95% CI, 2.35-2.47). This association persisted when the time elapsed from the index date was longer than 20 to 39 years (hazard ratio [HR], 1.79; 95% CI, 1.58-2.04) and among those diagnosed with depression in early, middle, or late life (18-44 years: HR, 3.08; 95% CI, 2.64-3.58; 45-59 years: HR, 2.95; 95% CI, 2.75-3.17; ≥60 years: HR, 2.31; 95% CI, 2.25-2.38). The overall HR was greater for men (HR, 2.98; 95% CI, 2.84-3.12) than for women (HR, 2.21; 95% CI, 2.15-2.27). Conclusions and Relevance: Results suggest that the risk of dementia was more than doubled for both men and women with diagnosed depression. The persistent association between dementia and depression diagnosed in early and middle life suggests that depression may increase dementia risk.

Novel whole blood transcriptome signatures of changes in maximal aerobic capacity in response to endurance exercise training in healthy women.

Maximal aerobic exercise capacity [maximal oxygen consumption (V̇o2max)] is one of the strongest predictors of morbidity and mortality. Aerobic exercise training can increase V̇o2max, but inter-individual variability is marked and unexplained physiologically. The mechanisms underlying this variability have major clinical implications for extending human healthspan. Here, we report a novel transcriptome signature related to ΔV̇o2max with exercise training detected in whole blood RNA. We used RNA-Seq to characterize transcriptomic signatures of ΔV̇o2max in healthy women who completed a 16-wk randomized controlled trial comparing supervised, higher versus lower aerobic exercise training volume and intensity (4 training groups, fully crossed). We found significant baseline gene expression differences in subjects who responded to aerobic exercise training with robust versus little/no ΔV̇o2max, and differentially expressed genes/transcripts were mostly related to inflammatory signaling and mitochondrial function/protein translation. Baseline gene expression signatures associated with robust versus little/no ΔV̇o2max were also modulated by exercise training in a dose-dependent manner, and they predicted ΔV̇o2max in this and a separate dataset. Collectively, our data demonstrate the potential utility of using whole blood transcriptomics to study the biology of inter-individual variability in responsiveness to the same exercise training stimulus.

Keeping you posted: analysis of fertility-related social media posts after introduction of the COVID-19 vaccine.

PURPOSE: Our objective was to analyse information and sentiments posted regarding the COVID-19 vaccine on fertility-related social media. MATERIALS AND METHODS: The first fifty accounts on Instagram and Twitter were identified with the terms: fertility doctor, fertility, OBGYN, infertility, TTC, IVF. Accounts were categorised as physician (PH), individual (ID), or fertility center/organisation (FCO). The vaccine was approved on 12/11/2020 and Instagram and Twitter posts dated 12/1/2020 - 2/28/2021 were reviewed. Posts were analysed for sentiment, mention of research studies (RS), national guidelines (NG), personal experience (PE), side effects (SE), reproductive related (RR) content and activity, including likes and comments. RESULTS: A total of 276 accounts were included. Sentiments towards the vaccine were largely positive (PH 90.3%, ID 71.4%, FCO 70%), or neutral (PH 9.7%, ID 28.6%, FCO 30%). Instagram accounts showed an increase in activity on vaccine posts compared to baseline by likes (PH 4.86% v 3.76%*, ID 7.5% v 6.37%*, FCO 2.49% v 0.52%*) and comments (PH 0.35% v 0.28%, ID 0.90% v 0.69%,* FCO 0.10% v 0.02%*). CONCLUSION: Most posts expressed positive sentiments towards the vaccine. Evaluating the sentiment of the COVID-19 vaccine as it relates to fertility on social media represents an opportunity for understanding both the patient's and health care professional's opinion on the subject. Given the potential devastating effects of misinformation on public health parameters, like vaccination, social media offers one avenue for healthcare professionals to engage online and work to make their presences more effective and influential.SHORT CONDENSATIONThis article analyses content and sentiments posted regarding the COVID-19 vaccine on fertility-related social media in order to offer a deeper understanding of available information and beliefs.

The reverse transcriptase inhibitor 3TC protects against age-related cognitive dysfunction.

Aging is the primary risk factor for most neurodegenerative diseases, including Alzheimer's disease. Major hallmarks of brain aging include neuroinflammation/immune activation and reduced neuronal health/function. These processes contribute to cognitive dysfunction (a key risk factor for Alzheimer's disease), but their upstream causes are incompletely understood. Age-related increases in transposable element (TE) transcripts might contribute to reduced cognitive function with brain aging, as the reverse transcriptase inhibitor 3TC reduces inflammation in peripheral tissues and TE transcripts have been linked with tau pathology in Alzheimer's disease. However, the effects of 3TC on cognitive function with aging have not been investigated. Here, in support of a role for TE transcripts in brain aging/cognitive decline, we show that 3TC: (a) improves cognitive function and reduces neuroinflammation in old wild-type mice; (b) preserves neuronal health with aging in mice and Caenorhabditis elegans; and (c) enhances cognitive function in a mouse model of tauopathy. We also provide insight on potential underlying mechanisms, as well as evidence of translational relevance for these observations by showing that TE transcripts accumulate with brain aging in humans, and that these age-related increases intersect with those observed in Alzheimer's disease. Collectively, our results suggest that TE transcript accumulation during aging may contribute to cognitive decline and neurodegeneration, and that targeting these events with reverse transcriptase inhibitors like 3TC could be a viable therapeutic strategy.

Daily blueberry consumption for 12 weeks improves endothelial function in postmenopausal women with above-normal blood pressure through reductions in oxidative stress: a randomized controlled trial.

Estrogen-deficient postmenopausal women have oxidative stress-mediated suppression of endothelial function that is exacerbated by high blood pressure. Previous research suggests blueberries may improve endothelial function through reductions in oxidative stress, while also exerting other cardiovascular benefits. The objective of this study was to examine the efficacy of blueberries to improve endothelial function and blood pressure in postmenopausal women with above-normal blood pressure, and to identify potential mechanisms for improvements in endothelial function. A randomized, double-blind, placebo-controlled, parallel-arm clinical trial was performed, where postmenopausal women aged 45-65 years with elevated blood pressure or stage 1-hypertension (total n = 43, endothelial function n = 32) consumed 22 g day-1 of freeze-dried highbush blueberry powder or placebo powder for 12 weeks. Endothelial function was assessed at baseline and 12 weeks through ultrasound measurement of brachial artery flow-mediated dilation (FMD) normalized to shear rate area under the curve (FMD/SRAUC) before and after intravenous infusion of a supraphysiologic dose of ascorbic acid to evaluate whether FMD improvements were mediated by reduced oxidative stress. Hemodynamics, arterial stiffness, cardiometabolic blood biomarkers, and plasma (poly)phenol metabolites were assessed at baseline and 4, 8, and 12 weeks, and venous endothelial cell protein expression was assessed at baseline and 12 weeks. Absolute FMD/SRAUC was 96% higher following blueberry consumption compared to baseline (p < 0.05) but unchanged in the placebo group (p > 0.05), and changes from baseline to 12 weeks were greater in the blueberry group than placebo (+1.09 × 10-4 ± 4.12 × 10-5vs. +3.82 × 10-6 ± 1.59 × 10-5, p < 0.03, respectively). The FMD/SRAUC response to ascorbic acid infusion was lower (p < 0.05) at 12 weeks compared to baseline in the blueberry group with no change in the placebo group (p > 0.05). The sum of plasma (poly)phenol metabolites increased at 4, 8, and 12 weeks in the blueberry group compared to baseline, and were higher than the placebo group (all p < 0.05). Increases in several plasma flavonoid and microbial metabolites were also noted. No major differences were found for blood pressure, arterial stiffness, blood biomarkers, or endothelial cell protein expression following blueberry consumption. These findings suggest daily consumption of freeze-dried blueberry powder for 12 weeks improves endothelial function through reduced oxidative stress in postmenopausal women with above-normal blood pressure. The clinical trial registry number is NCT03370991 (https://clinicaltrials.gov).

Opportunities and challenges in using instrumental variables to study causal effects in nonrandomized stress and trauma research.

OBJECTIVE: Researchers are often interested in assessing the causal effect of an exposure on an outcome when randomization is not ethical or feasible. Estimating causal effects by controlling for confounders can be unconvincing because important potential confounders remain unmeasured. Study designs leveraging instrumental variables (IVs) offer alternatives to confounder-control methods but are rarely used in stress and trauma research. METHOD: We review the conceptual foundations and implementation of IV methods. We discuss strengths and limitations of IV approaches, contrasting with confounder-control methods, and illustrate the relevance of IVs for stress and trauma research. RESULTS: IV approaches leverage an external or exogenous source of variation in the exposure. Instruments are variables that meet three conditions: relevance (variation in the IV is associated with variation in the chance of exposure), exclusion (the IV only affects the outcome through the exposure), and exchangeability (no unmeasured confounding of the IV-outcome relationship). Interpreting estimates from IV analyses requires an additional assumption, such as monotonicity (the instrument does not change the chance of exposure in different directions for any two individuals). Valid IVs circumvent the need to correctly identify, measure, and control for all confounders of the exposure-outcome relationship. The primary challenge is identifying a valid instrument. CONCLUSIONS: IV approaches have strengths and weaknesses compared with confounder-control approaches. IVs offers a promising complementary study design to improve evidence about the causal effects of exposures on outcomes relevant to stress and trauma. Collaboration with scientists who are experienced with identifying and analyzing IVs will support this work. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Risk of psychopathology following traumatic events among immigrants and native-born persons in Denmark.

PURPOSE: Immigrants may have increased risk of mental disorders compared with native-born persons. We aimed to expand the limited research on immigrants' posttraumatic psychopathology related to traumatic experiences in their country of resettlement. METHODS: We obtained data from a cohort of Danish residents with ≥ 1 traumatic event recorded in health and administrative national registries during 1994-2016. We calculated risks of posttraumatic stress disorder (PTSD), depression, and substance use disorders (SUD) within 5 years post-trauma among native-born Danes and immigrants who had been in Denmark for ≥ 10 years at the time of their index trauma (including immigrants overall and immigrants from specific regions). Risks were compared via age- and sex-standardized risk ratios (SRR) with 95% confidence intervals (CI). We restricted to persons with no record of the disorder under investigation in the 10 years pre-trauma, and stratified by non-interpersonal (e.g., transport accidents) versus interpersonal trauma (e.g., assaults). RESULTS: Following non-interpersonal trauma, immigrants were more likely than native-born Danes to be diagnosed with PTSD (SRR = 5.2, 95% CI 4.6, 5.9), about as likely to be diagnosed with depression (SRR = 0.98, 95% CI 0.92, 1.1), and less likely to be diagnosed with SUD (SRR = 0.89, 95% CI 0.82, 0.95). Results were similar following interpersonal trauma, except the SRR for PTSD was reduced in magnitude (SRR = 3.0, 95% CI 1.7, 5.4). There were differences by region of birth. CONCLUSION: Immigrants to Denmark have higher risk of PTSD following traumatic experiences than do native-born Danes, possibly due to the combined influence of adverse pre-, peri-, and/or post-migration experiences.

Central retinal artery occlusion: a retrospective study of disease presentation, treatment, and outcomes.

OBJECTIVE: A central retinal artery occlusion (CRAO) represents a form of ocular stroke with poor visual prognosis. CRAO shares a common pathophysiology with cerebral ischemic stroke but presents unique diagnostic and management challenges leading to variability in clinical practice. This study aims to assess the presentation, treatment, and outcomes of CRAO at a tertiary care centre in Canada over 2 years and elucidate potential areas for improvement in the care of these patients. METHODS: Single-institution retrospective review including 27 patients diagnosed with CRAO from March 2018 to March 2020 in Edmonton, Alberta. RESULTS: Most patients with CRAO presented to eye care providers (14 of 27); others presented to the emergency department (10 of 27) or family physicians (2 of 27). Three patients (11.1%) presented within 4.5 hours of symptom onset. At presentation, 81% of patients had visual acuity of 20/400 or worse in the affected eye. No patients received thrombolysis. The majority of CRAO cases had a nonarteritic etiology (92.6%). All patients had at least one pre-existing vascular risk factor. Forty-eight percent of patients received escalated medical therapy. Ipsilateral carotid stenosis was identified in 5 patients (18.5%); 3 patients required carotid endarterectomy. Two patients were diagnosed with atrial fibrillation. Two patients experienced symptomatic cerebral ischemia within 6 weeks of CRAO. CONCLUSIONS: The majority of patients with CRAO presented to eye care providers, and few present within the potential window for thrombolysis of 4.5 hours, highlighting the need for public awareness strategies. Our cohort highlights the significant rate of systemic comorbidity that exists in these patients.

SARS-CoV-2 VOC type and biological sex affect molnupiravir efficacy in severe COVID-19 dwarf hamster model.

SARS-CoV-2 variants of concern (VOC) have triggered infection waves. Oral antivirals such as molnupiravir promise to improve disease management, but efficacy against VOC delta was questioned and potency against omicron is unknown. This study evaluates molnupiravir against VOC in human airway epithelium organoids, ferrets, and a lethal Roborovski dwarf hamster model of severe COVID-19-like lung injury. VOC were equally inhibited by molnupiravir in cells and organoids. Treatment reduced shedding in ferrets and prevented transmission. Pathogenicity in dwarf hamsters was VOC-dependent and highest for delta, gamma, and omicron. All molnupiravir-treated dwarf hamsters survived, showing reduction in lung virus load from one (delta) to four (gamma) orders of magnitude. Treatment effect size varied in individual dwarf hamsters infected with omicron and was significant in males, but not females. The dwarf hamster model recapitulates mixed efficacy of molnupiravir in human trials and alerts that benefit must be reassessed in vivo as VOC evolve.

Validation of the Patient Health Questionnaire-9 (PHQ-9) for Detecting Depression Among Pregnant Women in Lima, Peru.

Depression during pregnancy is linked to adverse perinatal and offspring outcomes. The Patient Health Questionnaire-9 (PHQ-9) has been validated for identifying depression in pregnant women in limited cultural contexts. Construct validity and reliability have been assessed in Lima, Peru, but criterion validity has not. This study aimed to comprehensively evaluate the PHQ-9 among pregnant Peruvian women in the Pregnancy Outcomes, Maternal and Infant Study (PrOMIS). Using Composite International Diagnostic Interview (CIDI) criteria for past-12-month major depressive disorder as the reference standard, sensitivity, specificity, and predictive value of the PHQ-9 for detecting depression were assessed at various cutpoints of the PHQ-9. Confirmatory factor analysis (CFA) was used to evaluate one- and two-factor structures for the PHQ-9. Cronbach's alpha was computed for the entire PHQ-9 scale and for subscales supported by CFA. A cutpoint of ≥8 maximized combined sensitivity (61%) and specificity (62%). At this cutpoint, positive predictive value was low (15%) and negative predictive values was high (93%). Reliability for the full scale was high (α=0.80). Both one- and two-factor solutions were appropriate for this population, but a two-factor solution containing an affective/mood factor (α=0.67) and a somatic factor (α=0.75) was optimal (CFI=0.93, RMSEA=0.075). Among pregnant women in Lima, screening with the PHQ-9 can identify those in need of mental health care, but may identify a large number of false positive cases.

Validation of the French translation of a self-administered questionnaire looking for a history of pre-eclampsia.

We evaluated the diagnostic performances of the French translation of a self-administered questionnaire designed by Diehl et al. looking for a history of pre-eclampsia. After a phone call, 206 women who gave birth at Brest University Hospital responded to the questionnaire online. Then, their responses were compared to their medical files. The sensitivity of the questionnaire was 95.2% and its specificity was 98.0%. This French questionnaire has then demonstrated its validity. It can now be used to explore the role of a pre-eclampsia history on various pathologies and, by this mean, to improve knowledge about women's health.