Intra-Articular Mineralization on Computerized Tomography of the Knee and Risk of Cartilage Damage: The Multicenter Osteoarthritis Study.

OBJECTIVE: Intra-articular (IA) mineralization may contribute to osteoarthritis (OA) structural progression. We studied the association of IA mineralization on knee computed tomography (CT) with cartilage damage worsening on knee magnetic resonance imaging (MRI), with a focus on location- and tissue-specific effects. METHODS: Participants from the Multicenter Osteoarthritis Study with knee CT and MRI scans were included. Presence of IA mineralization on CT was defined as a Boston University Calcium Knee Score >0 anywhere in the knee. Cartilage worsening on MRI was defined as any increase in the MRI OA Knee Score, including incident damage. We evaluated the association of whole-knee, compartment-specific (ie, medial or lateral), and subregion-specific (ie, location-matched) IA mineralization at baseline with cartilage worsening at two years' follow-up in the corresponding locations using binomial regression with generalized estimating equations, adjusting for age, sex, and body mass index (BMI). RESULTS: We included 1,673 participants (mean age 60 years, 56% female, mean BMI 29). Nine percent had any IA mineralization in the knee, and 47.4% had any cartilage worsening on follow-up. Mineralization of any tissue in the knee, regardless of location, was not associated with MRI cartilage worsening. However, cartilage mineralization was associated with 1.39 (95% confidence interval 1.04-1.88) times higher risk of cartilage worsening in the same compartment, with similar results in subregion-specific analysis. CONCLUSION: CT-detected IA mineralization in the cartilage was associated with higher risk of MRI cartilage worsening in the same compartment and subregion over two years. These findings suggest potential localized, tissue-specific effects of IA mineralization on cartilage pathology in knee OA.

Essential Fatty Acids and Osteoarthritis.

OBJECTIVE: Inflammation worsens joint destruction in osteoarthritis (OA) and aggravates pain. Although n-3 fatty acids reduce inflammation, different n-3 fatty acids have different effects on inflammation and clinical outcomes, with eicosapentaenoic acid (EPA) having the strongest effect. We examined whether specific essential fatty acid levels affected the development of OA. METHODS: We studied participants from the Multicenter Osteoarthritis Study (MOST) at risk of developing knee OA. As part of MOST, participants were asked repeatedly about knee pain, and knee radiographs and magnetic resonance images (MRIs) were obtained. Using baseline fasting samples, we analyzed serum fatty acids with standard assays. After excluding participants with baseline OA, we defined two sets of cases based on their status through 60 months' follow-up: those developing incident radiographic OA and those developing incident symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of MRI cartilage damage and synovitis and worsening knee pain and evaluated the number of hand joints affected by nodules. In regression models, we tested the association of each OA outcome with levels of specific n-3 and n-6 fatty acids, adjusting for age, sex, body mass index, education, physical activity, race, baseline pain, smoking, statin use, and depressive symptoms. RESULTS: We studied 363 cases with incident symptomatic knee OA and 295 with incident radiographic knee OA. The mean age was 62 years (59% women). We found no associations of specific n-3 fatty acid levels, including EPA, or of n-6 fatty acid levels with incident OA (eg, for incident symptomatic knee OA, the odds ratio per SD increase in EPA was 1.0 [95% confidence interval 0.87-1.17]). Results for other OA outcomes also failed to suggest a protective effect of specific n-3 fatty acids with OA outcomes. CONCLUSION: We found no association of serum levels of EPA or of other specific n-3 fatty acids or n-6 fatty acids with risk of incident knee OA or other OA outcomes.

Assessing the association of epigenetic age acceleration with osteoarthritis in the Multicenter Osteoarthritis Study (MOST).

PURPOSE: Advancing age is one of the strongest risk factors for osteoarthritis (OA). DNA methylation-based measures of epigenetic age acceleration may provide insights into mechanisms underlying OA. METHODS: We analyzed data from the Multicenter Osteoarthritis Study in a subset of 671 participants ages 45-69 years with no or mild radiographic knee OA. DNA methylation was assessed with the Illumina Infinium MethylationEPIC 850K array. We calculated predicted epigenetic age according to Hannum, Horvath, PhenoAge, and GrimAge epigenetic clocks, then regressed epigenetic age on chronological age to obtain the residuals. Associations between the residuals and knee, hand, and multi-joint OA were assessed using logistic regression, adjusted for chronological age, sex, clinical site, smoking status, and race. RESULTS: Twenty-three percent met criteria for radiographic hand OA, 25% met criteria for radiographic knee OA, and 8% met criteria for multi-joint OA. Mean chronological age (SD) was 58.4 (6.7) years. Mean predicted epigenetic age (SD) according to Horvath, Hannum, PhenoAge, and GrimAge epigenetic clocks was 64.9 (6.4), 68.6 (5.9), 50.5 (7.7), and 67.0 (6.2), respectively. Horvath epigenetic age acceleration was not associated with an increased odds of hand OA, odds ratio (95% confidence intervals) = 1.03 (0.99-1.08), with similar findings for knee and multi-joint OA. We found similar magnitudes of associations for Hannum epigenetic age, PhenoAge, and GrimAge acceleration compared to Horvath epigenetic age acceleration. CONCLUSIONS: Epigenetic age acceleration as measured by various well-validated epigenetic clocks based on DNA methylation was not associated with increased risk of knee, hand, or multi-joint OA independent of chronological age.

Optimal Design of Clinical Trials Involving Persons with Disorders of Consciousness.

BACKGROUND: Limited data exist regarding the optimal clinical trial design for studies involving persons with disorders of consciousness (DoC), and only a few therapies have been tested in high-quality clinical trials. To address this, the Curing Coma Campaign Clinical Trial Working Group performed a gap analysis on the current state of clinical trials in DoC to identify the optimal clinical design for studies involving persons with DoC. METHODS: The Curing Coma Campaign Clinical Trial Working Group was divided into three subgroups to (1) review clinical trials involving persons with DoC, (2) identify unique challenges in the design of clinical trials involving persons with DoC, and (3) recommend optimal clinical trial designs for DoC. RESULTS: There were 3055 studies screened, and 66 were included in this review. Several knowledge gaps and unique challenges were identified. There is a lack of high-quality clinical trials, and most data regarding patients with DoC are based on observational studies focusing on patients with traumatic brain injury and cardiac arrest. There is a lack of a structured long-term outcome assessment with significant heterogeneity in the methodology, definitions of outcomes, and conduct of studies, especially for long-term follow-up. Another major barrier to conducting clinical trials is the lack of resources, especially in low-income countries. Based on the available data, we recommend incorporating trial designs that use master protocols, sequential multiple assessment randomized trials, and comparative effectiveness research. Adaptive platform trials using a multiarm, multistage approach offer substantial advantages and should make use of biomarkers to assess treatment responses to increase trial efficiency. Finally, sound infrastructure and international collaboration are essential to facilitate the conduct of trials in patients with DoC. CONCLUSIONS: Conduct of trials in patients with DoC should make use of master protocols and adaptive design and establish international registries incorporating standardized assessment tools. This will allow the establishment of evidence-based practice recommendations and decrease variations in care.

Relation of Intra-Articular Mineralization to Knee Pain in Knee Osteoarthritis: A Longitudinal Analysis in the MOST Study.

OBJECTIVE: Intra-articular (IA) calcium crystal deposition is common in knee osteoarthritis (OA), but of unclear significance. It is possible that low-grade, crystal-related inflammation may contribute to knee pain. We examined the longitudinal relation of computed tomography (CT)-detected IA mineralization to the development of knee pain. METHODS: We used data from the National Institutes of Health-funded longitudinal Multicenter Osteoarthritis Study. Participants had knee radiographs and bilateral knee CTs at baseline, and pain assessments every 8 months for 2 years. CT images were scored using the Boston University Calcium Knee Score. We longitudinally examined the relation of CT-detected IA mineralization to the risk of frequent knee pain (FKP), intermittent or constant knee pain worsening, and pain severity worsening using generalized linear mixed-effects models. RESULTS: We included 2,093 participants (mean age 61 years, 57% women, mean body mass index 28.8 kg/m2 ). Overall, 10.2% of knees had IA mineralization. The presence of any IA mineralization in the cartilage was associated with 2.0 times higher odds of having FKP (95% confidence interval [CI] 1.38-2.78) and 1.86 times more frequent intermittent or constant pain (95% CI 1.20-2.78), with similar results seen for the presence of any IA mineralization in the meniscus or joint capsule. A higher burden of IA mineralization anywhere within the knee was associated with a higher odds of all pain outcomes (odds ratio ranged from 2.14 to 2.21). CONCLUSION: CT-detected IA mineralization was associated with risk of having more frequent, persistent, and worsening knee pain over 2 years. Targeting IA mineralization may have therapeutic potential for pain improvement in knee OA.

Dietary omega-6/omega-3 fatty acids and risk of prostate cancer; Is there any potential interaction by organophosphate insecticides among the agricultural health study population.

BACKGROUND: In the United States (US), the average annual increase in the incidence of prostate cancer (PCa) has been 0.5% between 2013 and 2017. Although some modifiable factors have been identified as the risk factors for PCa, the effect of lower ratio of omega-6 to omega-3 fatty acids intake (N-6/N-3) remains unknown. Previous studies of the Agricultural Health Study (AHS) reported a significant positive association between PCa and selected organophosphate pesticides (OPs) including terbufos and fonofos. OBJECTIVE: The aim of this study was to evaluate the association between N-6/N-3 and PCa and any interaction between N-6/N-3 and 2 selected OPs (i.e., terbufos and fonofos) exposure. DESIGN AND PARTICIPANTS: This case-control study, nested within a prospective cohort study, was conducted on a subgroup of the AHS population (1193 PCa cases and 14,872 controls) who returned their dietary questionnaire between 1999 and 2003 MAIN OUTCOME MEASURES: PCa was coded based on the International Classification of Diseases of Oncology (ICD-O-3) definitions and obtained from the statewide cancer registries of Iowa (2003-2017) and North Carolina (2003-2014). STATISTICAL ANALYSIS: Multivariate logistic regression analysis was applied to obtain the odds ratios adjusted (aORs) for age at dietary assessment (years), race/ethnicity (white, African American, other), physical activity (hours/week), smoking (yes/no), terbufos (yes/no), fonofos (yes/no), diabetes, lycopene intake (milligrams/day), family history of PCa, and the interaction of N-6/N-3 with age, terbufos and fonofos. Pesticide exposure was assessed by self-administrated questionnaires collecting data on ever/never use of mentioned pesticides during lifetime as a yes/no variable. Assessing the P value for the interaction between pesticides and N-6/N-3, we used the continuous variable of "intensity adjusted cumulative exposure" to terbufos and fonofos. This exposure score was based on duration, intensity and frequency of exposure. We also conducted a stratified regression analysis by quartiles of age. RESULTS: Relative to the highest N-6/N-3 quartile, the lowest quartile was significantly associated with a decreased risk of PCa (aOR=0.61, 95% CI: 0.41-0.90), and quartile-specific aORs decreased toward the lowest quartile (Ptrend=<0.01). Based on the age-stratified analysis, the protective effect was only significant for the lowest quartile of N-6/N-3 among those aged between 48 and 55 years old (aORs=0.97, 95% CI, 0.45-0.55). Among those who were exposed to terbufos (ever exposure reported as yes in the self-report questionnaires), lower quartiles of N-6/N-3 were protective albeit nonsignificant (aORs: 0.86, 0.92, 0.91 in quartiles 1,2, and 3, respectively). No meaningful findings were observed for fonofos and N-6/N-3 interaction. CONCLUSION: Findings showed that lower N-6/N-3 may decrease risk of PCa among farmers. However, no significant interaction was found between selected organophosphate pesticides and N-6/N-3.

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

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) â€‹= â€‹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 â€‹= â€‹1.16 (95% CI â€‹= â€‹1.03-1.31) and OR â€‹= â€‹1.21 (95% CI â€‹= â€‹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.

Development of a Magnetic Resonance Imaging-Based Definition of Knee Osteoarthritis: Data From the Multicenter Osteoarthritis Study.

OBJECTIVE: Although magnetic resonance imaging (MRI) is the imaging modality of choice for research, there is no widely accepted MRI definition of knee osteoarthritis (OA). We undertook this study to test the performance of different MRI definitions of OA. METHODS: We studied Multicenter Osteoarthritis Study participants with knee symptoms using posteroanterior and lateral knee radiographs and MRIs. Radiographic OA was defined as Kellgren/Lawrence grade ≥2 in the tibiofemoral (TF) and/or patellofemoral (PF) joint. Symptomatic OA was defined using a validated questionnaire. MRI findings of cartilage damage, osteophytes, bone marrow lesions (BMLs), and synovitis were scored using the Whole-Organ MRI Score system. We compared definitions using combinations of MRI features to the validation criteria of prevalent radiographic OA and symptomatic OA. All combinations included cartilage damage score ≥2 (0-6 scale) and osteophyte score ≥2 (0-6 scale); addition of BMLs and synovitis score was also tested. We also evaluated a Delphi panel definition that defined OA differently for the PF and TF joints. For each definition, we calculated sensitivity, specificity, and the area under the curve (AUC). RESULTS: We included 1,185 knees from 1,185 participants (mean age 66 years, 62% female, 89% White). Among the 1,185 knees, 482 knees had radiographic OA, and 524 knees had symptomatic OA. The MRI definitions with a cartilage score ≥2 and osteophyte score ≥2 and definitions which added BMLs or synovitis score ≥1 had the highest sensitivities (95.2% and 94.5%, respectively) for prevalent radiographic OA (AUCs 0.67 and 0.69, respectively), and also had the highest sensitivities for symptomatic OA. The Delphi panel definition had similar performance but was more complex to apply. CONCLUSION: An MRI OA definition requiring cartilage damage and a small osteophyte with or without BMLs or synovitis had the best performance and was simplest for identifying radiographic OA and symptomatic OA.

Surgical stabilization of critical abdominal injuries in a mature rural trauma system: A retrospective study.

BACKGROUND: Worse outcomes following injuries are more likely in rural versus urban areas. In 2001, our state established an inclusive trauma system to improve mortality. In 2015, the trauma system had a consultation visit from the American College of Surgeons' Committee on Trauma, who made several recommendations. We hypothesized that continued maturation of this system would lead to more laparotomies prior to transfer to a higher level of care and better outcomes. METHODS: Our trauma registry was queried to identify all patients transferred between January 1, 2010, and December 31, 2020, who underwent laparotomy either before transfer or within 4 hours of arrival. The preconsultation (2010-2015) and postconsultation periods (2016-2020) were compared. Categorical and continuous variables were compared using χ2 and Mann-Whitney U tests, respectively. RESULTS: We included 213 patients; 63 had laparotomy before transfer and 150 within 4 hours after transfer. Age, injury severity scores, systolic blood pressure, and mechanism of injury were not different between periods. Proportions of laparotomy before and after transfer and outcomes (mortality, hospital length of stay, intensive care unit length of stay, ventilator days) were also similar (p = 0.368 for laparotomy, p = 0.840, 0.124, 0.286, 0.822 for outcomes). Compared with the preconsultation period, the proportion of laparotomy performed before transfer for severe injuries (abdominal Abbreviated Injury Scale score >3) significantly increased postconsultation (57.1% vs. 30.6%, p = 0.011). Incidence of damage-control laparotomies (43.9% vs. 23.6%; p = 0.020) and transfusion of plasma and platelets (33.6% vs. 13.2%; p < 0.001, 22.4% vs. 8.5%, p = 0.007, respectively) significantly increased. CONCLUSION: Identification and surgical stabilization of critical patients at the non-Level I facilities prior to transfer, as well as blood product use and damage-control techniques, improved postconsultation, suggesting a shift in the approaches to surgical stabilization and resuscitation efforts in our trauma system. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

3D aneurysm wall enhancement is associated with symptomatic presentation.

BACKGROUND: Aneurysm wall enhancement (AWE) is a potential surrogate biomarker for aneurysm instability. Previous studies have assessed AWE using 2D multiplanar methods, most of which were conducted qualitatively. OBJECTIVE: To use a new quantitative tool to analyze a large cohort of saccular aneurysms with 3D-AWE maps METHODS: Saccular aneurysms were imaged prospectively with 3T high resolution MRI. 3D-AWE maps of symptomatic (defined as ruptured or presentation with sentinel headache/cranial nerve neuropathy) and asymptomatic aneurysms were created by extending orthogonal probes from the aneurysm lumen into the wall. Three metrics were used to characterize enhancement: 3D circumferential AWE (3D-CAWE), aneurysm-specific contrast uptake (SAWE), and focal AWE (FAWE). Aneurysms with a circumferential AWE higher than the corpus callosum (3D-CAWE ≥1) were classified as 3D-CAWE+. Symptomatic presentation was analyzed with univariate and multivariate logistic models. Aneurysm size, size ratio, aspect ratio, irregular morphology, and PHASES and ELAPSS scores were compared with the new AWE metrics. Bleb and microhemorrhage analyses were also performed. RESULTS: Ninety-three aneurysms were analyzed. 3D-CAWE, SAWE, and FAWE were associated with symptomatic status (OR=1.34, 1.25, and 1.08, respectively). A multivariate model including aneurysm size, 3D-CAWE+, age, female gender, and FAWE detected symptomatic status with 80% specificity and 90% sensitivity (area under the curve=0.914, =0.967). FAWE was also associated with irregular morphology and high-risk location (p=0.043 and p=0.001, respectively). In general, blebs enhanced 56% more than the aneurysm body. Areas of microhemorrhage co-localized with areas of increased SAWE (p=0.047). CONCLUSIONS: 3D-AWE mapping provides a new set of metrics that could potentially improve the identification of symptomatic aneurysms.

Relation of Temporal Asymmetry During Walking to Two-Year Knee Pain Outcomes in Those With Mild-to-Moderate Unilateral Knee Pain: An Exploratory Analysis From the Multicenter Osteoarthritis Study.

OBJECTIVE: We aimed to explore the cross-sectional relation of unilateral knee pain severity and temporal asymmetry during walking and to determine relations of temporal asymmetry during walking to 2-year changes in ipsilateral and contralateral knee pain in those with mild-to-moderate unilateral knee pain. METHODS: The Multicenter Osteoarthritis Study is a prospective cohort study of adults with or at risk for knee osteoarthritis. The current study included participants with unilateral knee pain. Gait was assessed during self-selected and fast walking at baseline. Knee pain was assessed at baseline and 2 years. We calculated limb symmetry indices (LSIs; nonpainful limb/painful limb × 100) for stance, single-limb support time, and double-limb support time, then examined their relations to unilateral knee pain severity, incident contralateral knee pain, and persistent ipsilateral knee pain. RESULTS: Unilateral knee pain severity was not associated with temporal asymmetry during self-selected or fast walking. At 2 years, 17.1% of participants had incident contralateral knee pain and 51.4% had persistent ipsilateral knee pain. For self-selected walking, greater LSIs (i.e., longer time on the nonpainful limb) for stance and single-limb support time were associated with decreased odds of incident contralateral knee pain. Measures of temporal asymmetry were not associated with persistent ipsilateral knee pain, except for single-limb support time during fast walking. CONCLUSION: For those with unilateral knee pain, temporal asymmetry during walking is not associated with pain severity. However, select measures of stance and single-limb support time during self-selected and fast walking relate to longitudinal knee pain outcomes.

Online Screening and Personalized Education to Identify Post-Deployment Mental Health Need and Facilitate Access to Care.

INTRODUCTION: Reserve and National Guard (RNG) service members face increased risks for psychological and behavioral problems and are unlikely to seek mental health (MH) care after returning from military deployments. This article examines an online intervention (Web-Ed) with regard to participation, screening results, satisfaction, and intent to seek follow-up MH care, with comparisons by gender and post-deployment MH care receipt. MATERIALS AND METHODS: This was a cross-sectional study of 414 RNG service members (214 women and 200 men), who returned from deployments to or in support of the Iraq or Afghanistan wars within the prior 36 months. Participants completed Web-Ed, which includes screening, personalized education, and links to Veterans Health Administration health care. RESULTS: Positive post-deployment screening proportions, Web-Ed satisfaction, and intent to seek follow-up care were similar for men and women. Few had received MH care (33% women; 24% men), yet most screened positive on at least one screen (69% women; 72% men). Most indicated that they would recommend Web-Ed to other veterans (71% women; 67% men) and that they received useful information they may not have received otherwise (52% women; 53% men) regardless of gender or prior MH care. Almost half (40% women; 48% men) planned to seek further assessment from a health care provider as a direct result of Web-Ed. CONCLUSIONS: Efforts to facilitate access to MH care among post-deployed RNG veterans should be ongoing, regardless of the length of time since deployment, Veterans Affairs enrollment status, prior MH care receipt, or gender. Online screening and personalized education engage veterans who have not sought MH care and provide new information to those who have.

Association between history of attention-deficit/hyperactivity disorder diagnosis and cardiovascular disease in U.S. adults.

OBJECTIVE: To examine the association between attention-deficit/hyperactivity disorder (ADHD) and cardiovascular disease (CVD) in a nationally representative population sample of adults in the United States. METHOD: We included adults aged 18 years or older who participated in the National Health Interview Survey 2007 and 2012, because information about ADHD diagnosis among adults was only available in these two cycles. Physician-diagnosed ADHD and CVD were defined based on an affirmative response in the questionnaire during a household interview. Logistic regression with survey sampling weights was used to estimate the odds ratio (OR) and 95% confidence intervals (CIs) of CVD. RESULTS: This analysis included 57,728 adults (weighted mean age 46.20 years; 47.66% males). Among them, 1,790 reported physician-diagnosed ADHD, 7,906 had CVD, 4,061 had coronary heart disease (CHD), and 1,749 had stroke. The age-adjusted prevalence of CVD was 19.72% (95% CI [16.56%, 22.88%]) among individuals with ADHD, and 12.09% (95% CI [11.75%, 12.43%]) among those without ADHD. After adjustment for age, sex, race/ethnicity, education level, family income level, smoking, alcohol drinking, physical activity, and body mass index, the OR of CVD, CHD and stroke in association with ADHD was 2.06 (95% CI [1.58, 2.68]), 1.88 (95% CI [1.31, 2.69]), and 1.75 (95% CI [1.07, 2.86]), respectively. CONCLUSIONS: In a nationally representative sample of U.S. adults, we found a significant, positive association between a history of ADHD diagnosis and CVD. Further investigation is needed to replicate our findings and determine the underlying mechanisms. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Days of Flooding Associated with Increased Risk of Influenza.

Influenza typically causes mild infection but can lead to severe outcomes for those with compromised lung health. Flooding, a seasonal problem in Iowa, can expose many Iowans to molds and allergens shown to alter lung inflammation, leading to asthma attacks and decreased viral clearance. Based on this, the hypothesis for this research was that there would be geographically specific positive associations in locations with flooding with influenza diagnosis. An ecological study was performed using influenza diagnoses and positive influenza polymerase chain reaction tests from a de-identified large private insurance database and Iowa State Hygienic Lab. After adjustment for multiple confounding factors, Poisson regression analysis resulted in a consistent 1% associated increase in influenza diagnoses per day above flood stage (95% confidence interval: 1.00-1.04). This relationship remained after removal of the 2009-2010 influenza pandemic year. There was no associated risk between flooding and influenza-like illness as a nonspecific diagnosis. Associated risks between flooding and increased influenza diagnoses were geographically specific, with the greatest risk in the most densely populated areas. This study indicates that populations who live, work, or volunteer in flooded environments should consider preventative measures to avoid environmental exposures to mitigate illness from influenza in the following year.

Computed Tomography-Based Stiffness Measures of Trabecular Bone Microstructure: Cadaveric Validation and In Vivo Application.

Osteoporosis causes bone fragility and elevates fracture risk. Applications of finite element (FE) analysis (FEA) for assessment of trabecular bone (Tb) microstructural strength at whole-body computed tomography (CT) imaging are limited due to challenges with Tb microstructural segmentation. We present a nonlinear FEA method for distal tibia CT scans evading binary segmentation of Tb microstructure, while accounting for bone microstructural distribution. First, the tibial axis in a CT scan was aligned with the FE loading axis. FE cubic mesh elements were modeled using image voxels, and CT intensity values were calibrated to ash density defining mechanical properties at individual elements. For FEA of an upright volume of interest (VOI), the bottom surface was fixed, and a constant displacement was applied at each vertex on the top surface simulating different loading conditions. The method was implemented and optimized using the ANSYS software. CT-derived computational modulus values were repeat scan reproducible (intraclass correlation coefficient [ICC] ≥ 0.97) and highly correlated (r ≥ 0.86) with the micro-CT (µCT)-derived values. FEA-derived von Mises stresses over the segmented Tb microregion were significantly higher (p < 1 × 10-11) than that over the marrow space. In vivo results showed that both shear and compressive modulus for males were higher (p < 0.01) than for females. Effect sizes for different modulus measures between males and females were moderate-to-high (≥0.55) and reduced to small-to-negligible (<0.40) when adjusted for pure lean mass. Among body size and composition attributes, pure lean mass and height showed highest (r ∈ [0.45 0.56]) and lowest (r ∈ [0.25 0.39]) linear correlation, respectively, with FE-derived modulus measures. In summary, CT-based nonlinear FEA provides an effective surrogate measure of Tb microstructural stiffness, and the relaxation of binary segmentation will extend the scope for FEA in human studies using in vivo imaging at relatively low-resolution. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Restricting Branched-Chain Amino Acids within a High-Fat Diet Prevents Obesity.

Obesity is a global pandemic, but there is yet no effective measure to control it. Recent metabolomics studies have identified a signature of altered amino acid profiles to be associated with obesity, but it is unclear whether these findings have actionable clinical potential. The aims of this study were to reveal the metabolic alterations of obesity and to explore potential strategies to mitigate obesity. We performed targeted metabolomic profiling of the plasma/serum samples collected from six independent cohorts and conducted an individual data meta-analysis of metabolomics for body mass index (BMI) and obesity. Based on the findings, we hypothesized that restriction of branched-chain amino acids (BCAAs), phenylalanine, or tryptophan may prevent obesity and tested our hypothesis in a dietary restriction trial with eight groups of 4-week-old male C57BL/6J mice (n = 5/group) on eight different types of diets, respectively, for 16 weeks. A total of 3397 individuals were included in the meta-analysis. The mean BMI was 30.7 ± 6.1 kg/m2, and 49% of participants were obese. Fifty-eight metabolites were associated with BMI and obesity (all p ≤ 2.58 × 10-4), linked to alterations of the BCAA, phenylalanine, tryptophan, and phospholipid metabolic pathways. The restriction of BCAAs within a high-fat diet (HFD) maintained the mice's weight, fat and lean volume, subcutaneous and visceral adipose tissue weight, and serum glucose and insulin at levels similar to those in the standard chow group, and prevented obesity, adipocyte hypertrophy, adipose inflammation, and insulin resistance induced by HFD. Our data suggest that four metabolic pathways, BCAA, phenylalanine, tryptophan, and phospholipid metabolic pathways, are altered in obesity and restriction of BCAAs within a HFD can prevent the development of obesity and insulin resistance in mice, providing a promising strategy to potentially mitigate diet-induced obesity.

Inclusion of environmentally themed search terms improves Elastic net regression nowcasts of regional Lyme disease rates.

Lyme disease is the most widely reported vector-borne disease in the United States. 95% of confirmed human cases are reported in the Northeast and upper Midwest (25,778 total confirmed cases from Northeast and upper Midwest / 27,203 total US confirmed cases). Human cases typically occur in the spring and summer months when an infected nymph Ixodid tick takes a blood meal. Current federal surveillance strategies report data on an annual basis, leading to nearly a year lag in national data reporting. These lags in reporting make it difficult for public health agencies to assess and plan for the current burden of Lyme disease. Implementation of a nowcasting model, using historical data to predict current trends, provides a means for public health agencies to evaluate current Lyme disease burden and make timely priority-based budgeting decisions. The objective of the study was to develop and compare the performance of nowcasting models using free data from Google Trends and Centers of Disease Control and Prevention surveillance reports. We developed two sets of elastic net models for five regions of the United States: 1. Using only monthly proportional hit data from the 21 disease symptoms and tick related terms, and 2. Using monthly proportional hit data from terms identified via Google correlate and the disease symptom and vector terms. Elastic net models using the full-term list were highly accurate (Root Mean Square Error: 0.74, Mean Absolute Error: 0.52, R2: 0.97) for four of the five regions of the United States and improved accuracy 1.33-fold while reducing error 0.5-fold compared to predictions from models using disease symptom and vector terms alone. Many of the terms included and found to be important for model performance were environmentally related. These models can be implemented to help local and state public health agencies accurately monitor Lyme disease burden during times of reporting lag from federal public health reporting agencies.

Experiencing Sexual Assault and/or Stalking-Related Behavior is Associated with Binge Drinking and Substance Use Consequences in Deployed U.S. Servicewomen.

BACKGROUND: Being deployed is a risk factor for poor postdeployment mental health outcomes in U.S. servicewomen, including harmful drinking. However, to our knowledge, no studies have examined deployment-related sexual assault and exposure to stalking-related behavior in relation to binge drinking and substance use consequences in this population. METHODS: A community sample of post-9/11 servicewomen from the Midwest, including both veterans and those actively serving (N = 991), completed computer-assisted telephone interviews after deployment. Logistic regression models examined associations between deployment-related sexual assault (attempted or completed) and stalking-related behavior (e.g., being left unwanted things, having property vandalized), and the likelihood of reporting binge drinking and substance use consequences after controlling for covariates. RESULTS: U.S. servicewomen experiencing deployment-related sexual assault and/or stalking-related behavior were more likely to report binge drinking in the past 4 weeks and at least one negative consequence of substance use in the past year. Also, 21.56% of the sample reported experiencing any deployment-related sexual assault and/or stalking-related behavior, 17.34% reported any stalking-related behavior and no sexual assault, 2.42% reported both sexual assault and stalking-related behavior, and 1.80% reported sexual assault and no stalking-related behavior. The most commonly endorsed behaviors were being followed or spied on (9.09%), receiving unsolicited correspondence (8.34%-8.74%), and having someone show up at places you were (6.90%). CONCLUSIONS: U.S. servicewomen experiencing sexual assault and/or stalking-related behavior during deployment may be at higher risk for binge drinking and experiencing negative consequence of substance use when compared with their peers not reporting these stressors.

Association of Serum Low-Density Lipoprotein, High-Density Lipoprotein, and Total Cholesterol With Development of Knee Osteoarthritis.

OBJECTIVE: Studies suggest an association between elevated total serum cholesterol, particularly low-density lipoprotein (LDL), and osteoarthritis (OA). The present study was undertaken to evaluate the association between total cholesterol, LDL, and high-density lipoprotein (HDL) and risk of knee OA. METHODS: We studied participants from the Multicenter Osteoarthritis study (MOST) cohort at risk of developing knee OA. From baseline through 7 years, repeated knee radiographs and magnetic resonance images (MRIs) were obtained, and knee symptoms were queried. From baseline fasting blood samples, lipids and lipoproteins were analyzed using standard assays. After excluding participants with baseline OA, we defined 2 sets of patients: those developing radiographic OA, and those developing symptomatic OA (knee pain and radiographic OA). Controls did not develop these outcomes. Additionally, we examined worsening of cartilage loss and synovitis on MRI and of knee pain using the Western Ontario and McMaster Universities Osteoarthritis Index scale. We carried out logistic regression adjusting for age, sex, body mass index, education, baseline pain, and depressive symptoms, testing total cholesterol and lipoproteins as continuous measures, and we performed sensitivity analyses examining whether commonly used thresholds for high cholesterol, LDL, or low HDL increased risk. RESULTS: We studied 337 patients with incident symptomatic OA and 283 patients with incident radiographic OA. The mean age at baseline was 62 years (55% women). Neither total cholesterol, LDL, nor HDL showed a significant association with radiographic or symptomatic OA. Additionally, we found no association of these lipid measures with cartilage loss, worsening synovitis, or worsening knee pain. CONCLUSION: Our data do not support an association between total cholesterol, LDL, or HDL with OA outcomes.

Magnetic Resonance Imaging-Defined Osteoarthritis Features and Anterior Knee Pain in Individuals With, or at Risk for, Knee Osteoarthritis: A Multicenter Study on Osteoarthritis.

OBJECTIVE: The lack of strong association between knee osteoarthritis (OA) structural features and pain continues to perplex researchers and clinicians. Evaluating the patellofemoral joint in addition to the tibiofemoral joint alone has contributed to explaining this structure-pain discordance, hence justifying a more comprehensive evaluation of whole-knee OA and pain. The present study, therefore, was undertaken to evaluate the association between patellofemoral and tibiofemoral OA features with localized anterior knee pain (AKP) using 2 study designs. METHODS: Using cross-sectional data from the Multicenter Osteoarthritis Study, our first approach was a within-person, knee-matched design in which we identified participants with unilateral AKP. We then assessed magnetic resonance imaging (MRI)-derived OA features (cartilage damage, bone marrow lesions [BMLs], osteophytes, and inflammation) in both knees and evaluated the association of patellofemoral and tibiofemoral OA features to unilateral AKP. In our second approach, MRIs from 1 knee per person were scored, and we evaluated the association of OA features to AKP in participants with AKP and participants with no frequent knee pain. RESULTS: Using the first approach (n = 71, 66% women, mean ± SD age 69 ± 8 years), lateral patellofemoral osteophytes (odds ratio [OR] 5.0 [95% confidence interval (95% CI) 1.7-14.6]), whole-knee joint effusion-synovitis (OR 4.7 [95% CI 1.3-16.2]), and infrapatellar synovitis (OR 2.8 [95% CI 1.0-7.8]) were associated with AKP. Using the second approach (n = 882, 59% women, mean ± SD age 69 ± 7 years), lateral and medial patellofemoral cartilage damage (prevalence ratio [PR] 2.3 [95% CI 1.3-4.0] and PR 1.9 [95% CI 1.1-3.3], respectively) and lateral patellofemoral BMLs (PR 2.6 [95% CI 1.5-4.7]) were associated with AKP. CONCLUSION: Patellofemoral but not tibiofemoral joint OA features and inflammation were associated with AKP.