Sex Differential in 15-Hydroxyprostaglandin Dehydrogenase Levels in the Lumen of Human Intracranial Aneurysms.

BACKGROUND: Aspirin is a promising medical therapy for the prevention of intracranial aneurysm (IA) rupture. Recently, we found that men have a better response to aspirin than women. The purpose of this study was to determine whether a sex differential exists in the level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in the lumen of human IAs. METHODS AND RESULTS: Consecutive patients undergoing coiling or stent-assisted coiling for a saccular IA at our institution were enrolled. Two samples (A and B) were collected from IA lumens, and the plasma level of 15-PGDH was measured using an ELISA-based method. The study included 38 patients, with 20 women and 18 men. Women and men were comparable on baseline characteristics. The mean plasma concentration of 15-PGDH did not differ statistically between sample A (62.8±16.2 ng/mL) and sample B (61.8±17.9 ng/mL; 95% confidence interval -6.6 to 9.4). The mean plasma concentration of 15-PGDH in IA lumens of samples A and B was significantly higher in men (73.8±13.5 ng/mL) than women (49.6±7.8 ng/mL; P\u3c0.0001). CONCLUSIONS: Higher enzyme levels of 15-PGDH exist in the lumen of IAs of men compared with women. This observation could explain why aspirin confers better protection against IA rupture in men than in women. The susceptibility of an individual to aspirin may differ according to the level of 15-PGDH

Effectiveness of an Intersection Violation Warning System

People age 65 years and older are the fastest growing segment of the U.S. population and the fastest growing sector of the driving population. When compared to other age groups, older drivers are overrepresented in intersection crashes (Subramanian & Lombardo, 2007; Braitman et al., 2006), and approximately half of the charges in fatal intersection crashes are for failure to obey the traffic control device. This project explored an in-vehicle warning system for failure-to-obey (running a stop sign or stop light) violations. Participants who were not using the system made nearly three times as many didnot-stop errors (27%) than participants who were using the system (10%). This effect was most pronounced in older drivers with more risk factors associated with crashes; however, the effect of age group was not statistically significant

Leg-length inequality is not associated with greater trochanteric pain syndrome

INTRODUCTION. Greater trochanteric pain syndrome (GTPS) is a common condition, the pathogenesis of which is incompletely understood. Although leg-length inequality has been suggested as a potential risk factor for GTPS, this widely held assumption has not been tested. METHODS. A cross-sectional analysis of greater trochanteric tenderness to palpation was performed in subjects with complaints of hip pain and no signs of hip osteoarthritis or generalized myofascial tenderness. Subjects were recruited from one clinical center of the Multicenter Osteoarthritis Study, a multicenter population-based study of community-dwelling adults aged 50 to 79 years. Diagnosis of GTPS was based on a standardized physical examination performed by trained examiners, and technicians measured leg length on full-limb anteroposterior radiographs. RESULTS. A total of 1,482 subjects were eligible for analysis of GTPS and leg length. Subjects' mean ± standard deviation age was 62.4 ± 8.2 years, and 59.8% were female. A total of 372 lower limbs from 271 subjects met the definition for having GTPS. Leg-length inequality (difference ≥ 1 cm) was present in 37 subjects with GTPS and in 163 subjects without GTPS (P = 0.86). Using a variety of definitions of leg-length inequality, including categorical and continuous measures, there was no association of this parameter with the occurrence of GTPS (for example, for ≥ 1 cm leg-length inequality, odds ratio = 1.17 (95% confidence interval = 0.79 to 1.73)). In adjusted analyses, female sex was significantly associated with the presence of GTPS, with an adjusted odds ratio of 3.04 (95% confidence interval = 2.07 to 4.47). CONCLUSION. The present study found no evidence to support an association between leg-length inequality and greater trochanteric pain syndrome.National Institutes of Health and National Institute of Child Health and Human Development (5K12HD001097-08); National Insititues of Health and National Institue on Aging (1 U01 AG18832; 1 U01 AG18820; 1 U01 AG19069, 1 U01 AG18947

The Association of Obesity with Walking Independent of Knee Pain: The Multicenter Osteoarthritis Study

Practice guidelines recommend addressing obesity for people with knee OA, however, the association of obesity with walking independent of pain is not known. We investigated this association within the Multicenter Osteoarthritis Study, a cohort of older adults who have or are at high risk of knee OA. Subjects wore a StepWatch to record steps taken over 7 days. We measured knee pain from a visual analogue scale and obesity by BMI. We examined the association of obesity with walking using linear regression adjusting for pain and covariates. Of 1788 subjects, the mean steps/day taken was 8872.9 ± 3543.4. Subjects with a BMI ≥35 took 3355 fewer steps per day independent of knee pain compared with those with a BMI ≤25 (95% CI −3899, −2811). BMI accounted for 9.7% of the variability of walking while knee pain accounted for 2.9%. BMI was associated with walking independent of knee pain

Methodologic issues in a population-based health survey of Gulf War veterans

This report describes the principal methods used in the development, conduct, and analysis of the research study “Health Assessment of Persian Gulf War Veterans from Iowa” (Iowa Gulf War Study). The methods presented include an outline of the organizational structure, study timeline, hypotheses, outcome definitions, and study design. Adhering to a strict timeline, the study protocol and instruments were developed, and a stratified sample of 3,695 military personnel (76% participation) was located and surveyed by structured telephone interview. The study tracked personnel from all service branches residing nationally and internationally, including those discharged from service. This study required development and implementation of methods appropriate to analysis of data collected in a complex sampling framework and methodological procedures to ensure scientific rigor in a highly public and politicized environment. Statistical analyses were conducted on a priori health outcomes and required development of methods to compute Cochran-Mantel-Haenszel adjusted rate differences. This environment facilitated rapid implementation, critique by scientific and public advisors, a high participation rate, and rapid publication

Do associations with hand OA vary by knee osteoarthritis phenotype? : Cross-sectional data from the Multicenter Osteoarthritis Study

© 2022 The Author(s).OBJECTIVE: Osteoarthritis (OA) is highly heterogeneous and has both biomechanical and systemic components that may not have the same etiology. We therefore aimed to identify specific knee OA phenotypes that may be more strongly associated with hand OA to refine the criteria used to define multi-joint OA. DESIGN: We assessed data from the Multicenter Osteoarthritis Study (MOST). We ascertained hand OA from bilateral hand photographs; scores for each joint row were summed to yield an aggregate hand OA score. Knee OA was ascertained from bilateral posteroanterior knee radiographs read for Kellgren-Lawrence grade and individual radiographic features. We tested associations between hand and knee OA with phenotypes including symptomatic OA, hyper- and atrophic knee OA, and one excluding post-traumatic OA. Associations between hand and knee OA were assessed with logistic regression, adjusted for age. RESULTS: We studied 2493 participants with hand and knee OA measures. Median age was 63 years with 57% women. 55% had an aggregate hand OA score ≥2; frequency of knee OA phenotypes ranged from 8% to 34%. The age-adjusted odds ratio (OR) was 1.14 (95% confidence interval (CI) ​= ​1.04-1.26) for knee OA per standard deviation of the hand OA aggregate score. Hand OA associations with symptomatic knee OA and knee OA excluding post-traumatic knee OA were OR ​= ​1.16 (95% CI ​= ​1.03-1.31) and OR ​= ​1.21 (95% CI ​= ​1.08-1.35), respectively. No other knee OA phenotype reached statistical significance. CONCLUSIONS: Age-adjusted associations between hand and knee OA were modest and were largely similar across knee OA phenotypes.Peer reviewe

Effect of Quadriceps Strength and Proprioception on Risk for Knee Osteoarthritis

. Purpose: Impaired quadriceps strength and joint position sense (JPS) have been linked with knee osteoarthritis (OA) crosssectionally. Although neither has been independently associated with incident radiographic OA, their combination may mediate risk. The purpose of this study was to determine whether better sensorimotor function protects against the development of incident radiographic or symptomatic knee OA. Methods: The Multicenter Osteoarthritis study is a longitudinal study of adults aged 50-79 yr at high risk for knee OA. Participants underwent bilateral, weight-bearing, fixed-flexion radiographs, JPS acuity tests, and isokinetic quadriceps strength tests. The relationships between combinations of the tertiles of sex-specific baseline peak strength and mean JPS and development of incident radiographic (Kellgren-Lawrence (KL) grade Q2) or symptomatic knee OA (KL grade Q2 and frequent knee pain or stiffness) at a 30-month follow-up were evaluated. Secondary analyses defined JPS as the variance during the 10 JPS trials and also assessed the interaction of strength and JPS in predicting each outcome. Results: The study of incident radiographic knee OA included 1390 participants (age = 61.2 T 7.9 yr and body mass index = 29.4 T 5.1 kgIm j2 ), and the study of incident symptomatic knee OA included 1829 participants (age = 62.2 T 8.0 yr and body mass index = 30.0 T 5.4 kgIm j2 ). Greater strength at baseline protected against incident symptomatic but not radiographic knee OA regardless of JPS tertile. There was no significant relationship between the strength-JPS interaction and the development of radiographic or symptomatic knee OA. Conclusions: The finding that quadriceps strength protected against incident symptomatic but not radiographic knee OA regardless of JPS tertile suggests that strength may be more important than JPS in mediating risk for knee OA

Giant tortoise genomes provide insights into longevity and age-related disease

© 2018, The Author(s), under exclusive licence to Springer Nature Limited. Giant tortoises are among the longest-lived vertebrate animals and, as such, provide an excellent model to study traits like longevity and age-related diseases. However, genomic and molecular evolutionary information on giant tortoises is scarce. Here, we describe a global analysis of the genomes of Lonesome George—the iconic last member of Chelonoidis abingdonii—and the Aldabra giant tortoise (Aldabrachelys gigantea). Comparison of these genomes with those of related species, using both unsupervised and supervised analyses, led us to detect lineage-specific variants affecting DNA repair genes, inflammatory mediators and genes related to cancer development. Our study also hints at specific evolutionary strategies linked to increased lifespan, and expands our understanding of the genomic determinants of ageing. These new genome sequences also provide important resources to help the efforts for restoration of giant tortoise populations

Rescue therapy for vasospasm following aneurysmal subarachnoid hemorrhage:a propensity score-matched analysis with machine learning

OBJECTIVE Rescue therapies have been recommended for patients with angiographic vasospasm (aVSP) and delayed cerebral ischemia (DCI) following subarachnoid hemorrhage (SAH). However, there is little evidence from randomized clinical trials that these therapies are safe and effective. The primary aim of this study was to apply game theory-based methods in explainable machine learning (ML) and propensity score matching to determine if rescue therapy was associated with better 3-month outcomes following post-SAH aVSP and DCI. The authors also sought to use these explainable ML methods to identify patient populations that were more likely to receive rescue therapy and factors associated with better outcomes after rescue therapy. METHODS Data for patients with aVSP or DCI after SAH were obtained from 8 clinical trials and 1 observational study in the Subarachnoid Hemorrhage International Trialists repository. Gradient boosting ML models were constructed for each patient to predict the probability of receiving rescue therapy and the 3-month Glasgow Outcome Scale (GOS) score. Favorable outcome was defined as a 3-month GOS score of 4 or 5. Shapley Additive Explanation (SNAP) values were calculated for each patient-derived model to quantify feature importance and interaction effects. Variables with high S HAP importance in predicting rescue therapy administration were used in a propensity score-matched analysis of rescue therapy and 3-month GOS scores. RESULTS The authors identified 1532 patients with aVSP or DCI. Predictive, explainable ML models revealed that aneurysm characteristics and neurological complications, but not admission neurological scores, carried the highest relative importance rankings in predicting whether rescue therapy was administered. Younger age and absence of cerebral ischemia/ infarction were invariably linked to better rescue outcomes, whereas the other important predictors of outcome varied by rescue type (interventional or noninterventional). In a propensity score-matched analysis guided by SHAP-based variable selection, rescue therapy was associated with higher odds of 3-month GOS scores of 4-5 (OR 1.63, 95% CI 1.22-2.17). CONCLUSIONS Rescue therapy may increase the odds of good outcome in patients with aVSP or DCI after SAH. Given the strong association between cerebral ischemia/infarction and poor outcome, trials focusing on preventative or therapeutic interventions in these patients may be most able to demonstrate improvements in clinical outcomes. Insights developed from these models may be helpful for improving patient selection and trial design

Multidisciplinary Consensus on Assessment of Unruptured Intracranial Aneurysms Proposal of an International Research Group

Peer reviewe