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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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

To assess (i) the impact of changes in body weight on changes in joint-adjacent subcutaneous fat (SCF) and cartilage thickness over 4 years and (ii) the relation between changes in joint-adjacent SCF and knee cartilage thickness. Individuals from the Osteoarthritis Initiative (total=399) with > 10% weight gain (n=100) and > 10% weight loss (n=100) over 4 years were compared to a matched control cohort with less than 3% change in weight (n=199). 3.0T Magnetic Resonance Imaging (MRI) of the right knee was performed at baseline and after 4 years to quantify joint-adjacent SCF and cartilage thickness. Linear regression models were used to evaluate the associations between the (i) weight change group and 4-year changes in both knee SCF and cartilage thickness, and (ii) 4-year changes in knee SCF and in cartilage thickness. Analyses were adjusted for age, sex, baseline body mass index (BMI), tibial diameter (and weight change group in analysis (ii)). Individuals who lost weight over 4-years had significantly less joint-adjacent SCF (beta range, medial/lateral joint sides: 2.2–4.2 mm, p < 0.001) than controls; individuals who gained weight had significantly greater joint-adjacent SCF than controls (beta range: −1.4 to −3.9 mm, p < 0.001). No statistically significant associations were found between weight change and cartilage thickness change. However, increases in joint-adjacent SCF over 4 years were significantly associated with decreases in cartilage thickness (p = 0.04). Weight change was associated with joint-adjacent SCF, but not with change in cartilage thickness. However, 4-year increases in joint-adjacent SCF were associated with decreases in cartilage thickness independent of baseline BMI and weight change group. [ABSTRACT FROM AUTHOR]

Youth homelessness remains an ongoing public health issue worldwide. We aimed to describe the burden of emergency department (ED) presentations and hospitalizations among a South Australian population of young people in contact with specialist homelessness services (SHS). This whole-of-population study used de-identified, linked administrative data from the Better Evidence Better Outcomes Linked Data (BEBOLD) platform on all individuals born between 1996 and 1998 (N = 57,509). The Homelessness2Home data collection was used to identify 2,269 young people in contact with SHS at ages 16–17 years. We followed these 57,509 individuals to age 18–19 years and compared ED presentations and hospital separations related to mental health, self-harm, drug and alcohol, injury, oral health, respiratory conditions, diabetes, pregnancy, and potentially preventable hospitalizations between those in contact and not in contact with SHS. Four percent of young people had contact with SHS at ages 16–17 years. Young people who had contact with SHS were 2 and 3 times more likely to have presented to an ED and hospital respectively, compared to those who did not contact SHS. This accounted for 13% of all ED presentations and 16% of all hospitalizations in this age group. Excess burden causes included mental health, self-harm, drug and alcohol, diabetes, and pregnancy. On average, young people in contact with SHS experienced an increased length of stay in ED (+0.6 hours) and hospital (+0.7 days) per presentation, and were more likely to not wait for treatment in ED and to self-discharge from hospital. The 4% of young people who contacted SHS at ages 16–17 years accounted for 13% and 16% of all ED presentations and hospitalizations respectively at age 18–19 years. Prioritizing access to stable housing and primary health-care services for adolescents in contact with SHS in Australia could improve health outcomes and reduce health-care costs. [ABSTRACT FROM AUTHOR]

Though rare, stroke in infants and children is an important cause of mortality and chronic morbidity in the pediatric population. Neuroimaging advances and implementation of pediatric stroke care protocols have led to the ability to rapidly diagnose stroke and in many cases determine the stroke etiology. Though data on efficacy of hyperacute therapies, such as intravenous thrombolysis and mechanical thrombectomy, in pediatric stroke are limited, feasibility and safety data are mounting and support careful consideration of these treatments for childhood stroke. Recent therapeutic advances allow for targeted stroke prevention efforts in high-risk conditions, such as moyamoya, sickle cell disease, cardiac disease, and genetic disorders. Despite these exciting advances, important knowledge gaps persist, including optimal dosing and type of thrombolytic agents, inclusion criteria for mechanical thrombectomy, the role of immunomodulatory therapies for focal cerebral arteriopathy, optimal long-term antithrombotic strategies, the role of patent foramen ovale closure in pediatric stroke, and optimal rehabilitation strategies after stroke of the developing brain. [ABSTRACT FROM AUTHOR]

The majority of South Australian pregnant women who smoke do not quit during pregnancy. Additionally, the prevalence of smoking is higher among pregnant women living in socially disadvantaged areas. Understanding challenges in midwives' provision of smoking cessation care can elucidate opportunities to facilitate women's smoking cessation. We aimed to understand midwives' perspectives on current practices, perceived barriers and facilitators to delivery of smoking cessation care, and potential improvements to models of smoking cessation care. An exploratory qualitative research methodology and thematic analysis was used to understand the perspectives of midwives in five focus groups. Four themes were generated from the data on how midwives perceived their ability to provide smoking cessation care: Tensions between providing smoking cessation care and maternal care; Organisational barriers in the delivery of smoking cessation care; Scepticism and doubt in the provision of smoking cessation care; and Opportunities to enable midwives' ability to provide smoking cessation care. A combination of interpersonal, organisational and individual barriers impeded on midwives' capacities to approach, follow-up and prioritise smoking cessation care. Working with women living with disadvantage and high rates of smoking, the midwife's role was challenging as it balanced delivering smoking cessation care without jeopardising antenatal care. Providing midwives with resources and skills may alleviate the sense of futility that surrounds smoking cessation care. Provision of routine training and education could also improve understandings of the current practice guidelines. [ABSTRACT FROM AUTHOR]

Objective: The patellofemoral joint is frequently affected by osteoarthritis (PFOA) and is incompletely imaged on radiographs (XR). Weight-Bearing CT (WBCT) could offer advantages for visualization. This study determined the sensitivity, specificity, and accuracy of axial WBCT and lateral XR for detection of PFOA features in comparison with cartilage damage on MRI.Design: A convenience sample of 60 right knees from the MOST cohort were analyzed. WBCT and XR were read for OARSI JSN score and MRI for MOAKS cartilage score by two experienced musculoskeletal radiologists blinded to participant. Using MOAKS scoring on MRI (referent standard), the sensitivity, specificity and accuracy of patellofemoral OARSI JSN scores based on WBCT and XR were compared.Results: The mean ± SD age and BMI for the participants included (66.7% women) were 67.6 ± 9.8 years and 30.0 ± 5.3 kg/m2 respectively. WBCT demonstrated significantly greater sensitivity (0.85-0.97 on WBCT vs 0.47-0.57 on XR) and accuracy (0.85-0.92 on WBCT vs 0.48-0.57 on XR) for all parameters except lateral full-thickness cartilage loss (McNemar's test p-values all <0.001). There was moderate-to-strong and low-to-moderate agreement between PFOA findings on WBCT and XR, respectively, and semi-quantitative scores of PF cartilage on MRI. Inter-rater reliability for XR JSN [weighted kappa = 0.83 (0.64, 1.0)], WBCT JSN [kappa = 0.60 (0.48, 0.72)] and MRI MOAKS-CM [kappa = 0.70 (0.61, 0.79)] readings were good.Conclusion: WBCT demonstrates significantly greater sensitivity and accuracy than radiographs for identification of PFOA. Given the same Relative Radiation Level as XR and improved visualization, WBCT holds promise to improve understanding of the weight-bearing patellofemoral joint. [ABSTRACT FROM AUTHOR]

ABCG2 is an important ATP-binding cassette transporter impacting the absorption and distribution of over 200 chemical toxins and drugs. ABCG2 also reduces the cellular accumulation of diverse chemotherapeutic agents. Acquired somatic mutations in the phylogenetically conserved amino acids of ABCG2 might provide unique insights into its molecular mechanisms of transport. Here, we identify a tumor-derived somatic mutation (Q393K) that occurs in a highly conserved amino acid across mammalian species. This ABCG2 mutant seems incapable of providing ABCG2-mediated drug resistance. This was perplexing because it is localized properly and retained interaction with substrates and nucleotides. Using a conformationally sensitive antibody, we show that this mutant appears "locked" in a non-functional conformation. Structural modeling and molecular dynamics simulations based on ABCG2 cryo-EM structures suggested that the Q393K interacts with the E446 to create a strong salt bridge. The salt bridge is proposed to stabilize the inward-facing conformation, resulting in an impaired transporter that lacks the flexibility to readily change conformation, thereby disrupting the necessary communication between substrate binding and transport. [ABSTRACT FROM AUTHOR]

• SARS-CoV-2 is an important cause of health care-acquired infection. • Asymptomatic SARS-CoV-2 infection was common in this cohort of elderly individuals. • Duration of PCR positivity was similar among symptomatic and asymptomatic patients. • Virus cycle thresholds were similar among symptomatic and asymptomatic patients. We describe key characteristics, interventions, and outcomes of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak within an inpatient geriatric psychiatry unit at the University of Washington Medical Center – Northwest. After identifying 2 patients with SARS-CoV-2 infection on March 11, 2020, we conducted an outbreak investigation and employed targeted interventions including: screening of patients and staff; isolation and cohorting of confirmed cases; serial testing; and enhanced infection prevention measures. We identified 10 patients and 7 staff members with SARS-CoV-2 infection. Thirty percent of patients (n = 3) remained asymptomatic over the course of infection. Among SARS-CoV-2 positive patients, fever (n = 5, 50%) and cough (n = 4, 40%) were the most common symptoms. Median duration of reverse transcription polymerase chain reaction (RT-PCR) positivity was 25.5 days (interquartile range [IQR] 22.8-41.8) among symptomatic patients and 22.0 days (IQR 19.5-25.5) among asymptomatic patients. Median initial (19.0, IQR 18.7-25.7 vs 21.7, IQR 20.7-25.6) and nadir (18.9, IQR 18.2-20.3 vs 19.8, IQR 17.0-20.7) cycle threshold values were similar across symptomatic and asymptomatic patients, respectively. Asymptomatic infection was common in this cohort of hospitalized, elderly individuals despite similar duration of SARS-CoV-2 RT-PCR positivity and cycle threshold values among symptomatic and asymptomatic patients. [ABSTRACT FROM AUTHOR]

The emergence of coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 (SC2) virus, in late December 2019 has placed an overwhelming strain on healthcare institutions nationwide. The modern healthcare system has never managed a pandemic of this magnitude, the ramifications of which will undoubtedly lead to lasting changes in policy and protocol development for viral testing guidelines, personal protective equipment (PPE), surgical scheduling, and residency education and training. The State of Washington had the first reported case and death related to COVID-19 in the United States. Oral and maxillofacial surgeons have a unique risk of exposure to SC2 and developing COVID-19 because of our proximity of working in and around the oropharynx and nasopharynx. The present report has summarized the evolution of COVID-19 guidelines in 4 key areas: 1) preoperative SC2 testing; 2) PPE stewardship; 3) surgical scheduling guidelines; and 4) resident education and training for oral and maxillofacial surgery at the University of Washington, Seattle, Washington. [ABSTRACT FROM AUTHOR]

Abstract Agriculture is a significant source of anthropogenic greenhouse gas (GHG) emissions, and beef cattle are particularly emissions intensive. GHG emissions are typically expressed as a carbon dioxide equivalent (CO 2 e) 'carbon footprint' per unit output. The 100-year Global Warming Potential (GWP 100) is the most commonly used CO 2 e metric, but others have also been proposed, and there is no universal reason to prefer GWP 100 over alternative metrics. The weightings assigned to non-CO 2 GHGs can differ significantly depending on the metric used, and relying upon a single metric can obscure important differences in the climate impacts of different GHGs. This loss of detail is especially relevant to beef production systems, as the majority of GHG emissions (as conventionally reported) are in the form of methane (CH 4) and nitrous oxide (N 2 O), rather than CO 2. This paper presents a systematic literature review of harmonised cradle to farm-gate beef carbon footprints from bottom-up studies on individual or representative systems, collecting the emissions data for each separate GHG, rather than a single CO 2 e value. Disaggregated GHG emissions could not be obtained for the majority of studies, highlighting the loss of information resulting from the standard reporting of total GWP 100 CO 2 e alone. Where individual GHG compositions were available, significant variation was found for all gases. A comparison of grass fed and non-grass fed beef production systems was used to illustrate dynamics that are not sufficiently captured through a single CO 2 e footprint. Few clear trends emerged between the two dietary groups, but there was a non-significant indication that under GWP 100 non-grass fed systems generally appear more emissions efficient, but under an alternative metric, the 100-year global temperature potential (GTP 100), grass-fed beef had lower footprints. Despite recent focus on agricultural emissions, this review concludes there are insufficient data available to fully address important questions regarding the climate impacts of agricultural production, and calls for researchers to include separate GHG emissions in addition to aggregated CO 2 e footprints. Highlights • Multi-gas footprints are typically converted to a total carbon dioxide equivalent. • Different carbon dioxide equivalence metrics emphasize different climate behaviours. • Reporting emissions of all gases as a combined total loses important information. • Disaggregated data could not be retrieved from most (71%) full beef LCAs. • Relative emissions intensity is highly dependent on metric choice. [ABSTRACT FROM AUTHOR]

Abstract Objective Osteoarthritis (OA) is a disease with a substantial public health burden. Quantitative assessments of periarticular bone may be a biomarker capable of monitoring early disease progression. The purpose of this study was to evaluate whether measures of periarticular bone associate with longitudinal structural progression. Methods We conducted a 12–18 months longitudinal study using the Osteoarthritis Initiative (OAI). Participants received knee dual-energy x-ray absorptiometry (DXA), trabecular magnetic resonance (MR) imaging, and x-rays. Knee DXAs generated proximal tibial medial:lateral periarticular bone mineral density (paBMD) measures. Proximal tibial trabecular MR images were assessed for trabecular morphometry: apparent bone volume fraction (BVF), trabecular number, thickness, and spacing. Weight-bearing x-rays were assessed for medial tibiofemoral joint space narrowing (JSN). Chi-squared analyses assessed whether periarticular bone measures were predictive of worsening medial tibiofemoral JSN, adjusted for age, sex, and BMI. Results In all, 444 participants, mean age 64.2 ± 9.2 years, BMI 29.5 ± 4.6 kg/m2, and 52% male at baseline. Medial JSN (radiographic progression) occurred in 40 participants (9%). Higher baseline medial:lateral paBMD, apparent BVF, trabecular number and thickness, and lower baseline and decreased trabecular spacing were all associated with more progression of JSN in the medial compartment. From lowest to highest baseline medial:lateral paBMD quartile groups, 2%, 5%, 11%, and 18% had medial JSN progression, respectively, between the 36- and 48-month visits, p -values = 0.001 and 0.002 unadjusted and adjusted. The rate of change in medial:lateral paBMD, apparent BVF, and spacing were associated with more medial JSN. For rate of medial:lateral paBMD change from lowest to highest quartile, the proportion of each group that experienced medial JSN progression were 5%, 5%, 11%, and 18%, with an unadjusted and adjusted p -value of 0.005. Conclusion Baseline and most rates of periarticular bone change associate with knee OA structural progression, highlighting the close relationship between subchondral bone and JSN. Future studies should focus on developing these measures as predictive and pathophysiological biomarkers, and evaluating their deployment in clinical trials testing bone-targeted therapeutics. [ABSTRACT FROM AUTHOR]

There is a continued need to monitor the environmental impacts of agricultural systems while also ensuring sufficient agricultural production. However, it can be difficult to collect relevant environmental data on a large enough number of farms and studies that do so often neglect to consider the financial drivers that ultimately determine many aspects of farm management and performance. This paper outlines a methodology for generating environmental indicators from the Farm Business Survey (FBS), an extensive annual economic survey of representative farms in England and Wales. Data were extracted from the FBS for a sample of East Anglian cereal farms and south western dairy farms and converted where necessary to use as inputs in ‘Farmscoper’; farm-level estimates of nitrate, phosphorus and sediment loadings and ammonia and greenhouse gas emissions were generated using the Farmscoper model. Nitrate losses to water, ammonia and greenhouse gas emissions were positively correlated with food energy production per unit area for both farm types; phosphorus loading was also correlated with food energy on the dairy farms. Environmental efficiency indicators, as measured by either total food energy or financial output per unit of negative environmental effect, were calculated; greenhouse gas emission efficiency (using either measure of agricultural output) and nitrate loading efficiency (using financial output) were positively correlated with profitability on cereal farms. No other environmental efficiency measures were significantly associated with farm profitability and none were significant on the dairy farms. These findings suggest that an improvement in economic performance can also improve environmental efficiency, but that this depends on the farm type and negative environmental externality in question. In a wider context, the augmentation of FBS-type data to generate additional environmental indicators can provide useful insights into ongoing research and policy issues around sustainable agricultural production. [ABSTRACT FROM AUTHOR]

Background and Purpose: Anterior choroidal artery (AChA) strokes have a varied pattern of tissue injury, prognosis, and clinical outcome. It is unclear whether perfusion deficit in AChA stroke is associated with the clinical outcome. This study aims to determine the frequency of perfusion abnormalities in AChA stroke and association with clinical outcome.Methods: The study cohort was derived from ischemic stroke patients admitted to 2 stroke centers between July 2001 and July 2014. All patients received an acute magnetic resonance imaging (MRI) scan. Patients with ischemic stroke restricted to the AChA territory were included in the study. Lesion size was measured as the largest diameter on diffusion-weighted imaging (DWI) or apparent diffusion coefficient and divided into 2 groups (<20 mm or ≥20 mm). Group comparisons were performed among patients with and without perfusion abnormalities and based on diffusion diameter. Favorable clinical outcome was defined as discharge to home.Results: A total of 120 patients were included in the study. Perfusion deficits were identified in 67% of patients. The admission National Institutes of Health Stroke Scale (NIHSS) was higher in patients with perfusion abnormalities (P = .027). Diameter lesion size on DWI was larger among patients with a perfusion deficit median [interquartile range], 1.63 [1.3-2.0], as compared with those without, 1.18 [1.0-1.7], P < .0001. Patients with a perfusion deficit were less likely to be discharged to home than those without (36% versus 60%, P = .013).Conclusions: Two thirds of patients with an AChA stroke have a perfusion deficit on MRI, higher admission NIHSS, and larger DWI lesion size at presentation. [ABSTRACT FROM AUTHOR]

Case logs of stroke patients undergoing intervention, who were seen from February 2017 to August 2017, at facility A, which previously sent stroke patients to other facilities for intervention, were reviewed. Several possible uses for helicopter-physician transport are proposed: (i) Low-density, large geographic regions: a single, stably staffed stroke center can partner with regional hospitals within reasonable flight radii to provide interventional stroke coverage in adjacent hospitals (Fig 2). 6 A. Hawk, C. Marco, M. Huang, B. Chow, Helicopter scene response for stroke patients: a 5-year experience, Air Med J, 35, 6 2016, 352-354Hawk A, Marco C, Huang M, Chow B. Helicopter scene response for stroke patients: a 5-year experience. [Extracted from the article]

Objectives: To evaluate the association between post-endovascular thrombectomy (EVT) blood-brain barrier (BBB) disruption on MRI or CT and average systolic blood pressure (SBP) with favorable 90-day functional outcome. Observational studies have found elevated SBP associated with worse outcomes post-EVT, while recent randomized trials found no difference in targeted BP reduction. There may be a subgroup of patients who benefit from targeted BP reduction post-EVT.Methods: This is a single-center study of 1) anterior large vessel occlusion stroke patients treated with EVT from 2015 to 2021, 2) achieved mTICI grade 2b or 3. Hyperintense acute reperfusion marker (HARM), hemorrhagic transformation (HT), and midline shift at 3 h post-EVT and 24 h imaging were assessed independently by multiple raters. Binary logistic regression models were used to determine the association of post-EVT SBP with outcomes. BBB disruption was defined as HT or HARM on 3h post-EVT imaging.Results: Of 103 patients, those with SBP 100-129 versus SBP 130-160 found no significant difference in favorable 90-day outcome (64% vs. 46%, OR 2.11, 95% CI 0.78-5.76, p=0.143). However, among 71 patients with BBB disruption, a significant difference in favorable outcome of 64% in SBP 100-129 vs. 39% in SBP 130-160 group (OR 5.93, 95% CI 1.50-23.45, p=0.011) was found. There was no difference in symptomatic ICH, 90-day mortality, midline shift (≥5 mm), and hemicraniectomy, between BP or BBB groups.Conclusions: BBB disruption on 3h post-EVT imaging and lower SBP was associated with favorable outcome. This imaging finding may guide targeted BP therapy and suggests need for a randomized control trial. [ABSTRACT FROM AUTHOR]

Objectives Risk of knee osteoarthritis (OA) is much higher in women than in men. Previous studies have shown that bone shape is a risk factor for knee OA. However, few studies have examined whether knee bone shape differs between men and women. The purpose of the present study was to determine whether there are differences between men and women in knee bone shape. Methods We used information from the NIH-funded Osteoarthritis Initiative (OAI), a cohort of persons aged 45–79 at baseline who either had symptomatic knee OA or were at high risk of it. Among participants aged between 45 and 60 years, we randomly sampled 340 knees without radiographic OA (i.e., Kellgren/Lawrence grade of 0 in central readings on baseline radiograph). We characterized distal femur and proximal tibia shape of these selected radiographs using statistical shape modeling (SSM). We performed linear regression analysis to examine the association between sex and each knee shape mode (proximal tibia and distal femur), adjusting for age, race, body mass index (BMI), and clinic site. Results The mean age was 52.7 years (±4.3 SD) for both men and women. There were 192 female and 147 male knees for the distal femur analysis. Thirteen modes were derived for femoral shape, accounting for 95.5% of the total variance. Distal femur mode 1 had the greatest difference in standardized score of knee shape between females and males (1.04, p < 0.01); modes 3, 5, 6, 8, and 12 were also significantly associated with sex. For tibial shape, 191 female knees and 149 male knees were used for the analysis. Overall, 10 modes explained 95.5% of shape variance. Of the significantly associated modes in the proximal tibia, mode 2 had the greatest difference in standardized score of bone shape between males and females (−0.30, p = 0.01); modes 3 and 4 were also significantly associated. Conclusion The shapes of the distal femur and proximal tibia that form the knee joint differ by sex. Additional analyses are warranted to assess whether the difference in risk of OA between the sexes arises from bone shape differences. [ABSTRACT FROM AUTHOR]

The development of and adherence to quality indicators in gastroenterology, as in all of medicine, is increasing in importance to ensure that patients receive consistent high-quality care. In addition, government-based and private insurers will be expecting documentation of the parameters by which we measure quality, which will likely affect reimbursements. Barrett’s esophagus remains a particularly important disease entity for which we should maintain up-to-date guidelines, given its commonality, potentially lethal outcomes, and controversies regarding screening and surveillance. To achieve this goal, a relatively large group of international experts was assembled and, using the modified Delphi method, evaluated the validity of multiple candidate quality indicators for the diagnosis and management of Barrett’s esophagus. Several candidate quality indicators achieved >80% agreement. These statements are intended to serve as a consensus on candidate quality indicators for those who treat patients with Barrett’s esophagus. [ABSTRACT FROM AUTHOR]

The aim of this study has been to test reproducibility of fractal signature analysis (FSA) in a young, active patient population taking into account several parameters including intra- and inter-reader placement of regions of interest (ROIs) as well as various aspects of projection geometry. In total, 685 patients were included (135 athletes and 550 non-athletes, 18–36 years old). Regions of interest (ROI) were situated beneath the medial tibial plateau. The reproducibility of texture parameters was evaluated using intraclass correlation coefficients (ICC). Multi-dimensional assessment included: (1) anterior–posterior (A.P.) vs. posterior–anterior (P.A.) (Lyon-Schuss technique) views on 102 knees; (2) unilateral (single knee) vs. bilateral (both knees) acquisition on 27 knees (acquisition technique otherwise identical; same A.P. or P.A. view); (3) repetition of the same image acquisition on 46 knees (same A.P. or P.A. view, and same unitlateral or bilateral acquisition); and (4) intra- and inter-reader reliability with repeated placement of the ROIs in the subchondral bone area on 99 randomly chosen knees. ICC values on the reproducibility of texture parameters for A.P. vs. P.A. image acquisitions for horizontal and vertical dimensions combined were 0.72 (95% confidence interval (CI) 0.70–0.74) ranging from 0.47 to 0.81 for the different dimensions. For unilateral vs. bilateral image acquisitions, the ICCs were 0.79 (95% CI 0.76–0.82) ranging from 0.55 to 0.88. For the repetition of the identical view, the ICCs were 0.82 (95% CI 0.80–0.84) ranging from 0.67 to 0.85. Intra-reader reliability was 0.93 (95% CI 0.92–0.94) and inter-observer reliability was 0.96 (95% CI 0.88–0.99). A decrease in reliability was observed with increasing voxel sizes. Our study confirms excellent intra- and inter-reader reliability for FSA, however, results seem to be affected by acquisition technique, which has not been previously recognized. [ABSTRACT FROM AUTHOR]

Objective To examine the association between domain-specific qualities of formal childcare at age 2-3 years and children's task attentiveness and emotional regulation at age 4-5 and 6-7 years. Study design We used data from the Longitudinal Study of Australian Children (n = 1038). Three domain-specific aspects of childcare quality were assessed: provider and program characteristics of care, activities in childcare, and carer--child relationship. Two self-regulatory abilities were considered: task attentiveness and emotional regulation. Associations between domain-specific qualities of childcare and self-regulation were investigated in linear regression analyses adjusted for confounding, with imputation for missing data. Results There was no association between any provider or program characteristics of care and children's task attentiveness and emotional regulation. The quality of activities in childcare were associated only with higher levels of emotional regulation at age 4-5 years (β = 0.24; 95% CI, 0.03-0.44) and 6-7 years (β = 0.26; 95% CI, 0.04-0.48). Higher-quality carer--child relationships were associated with higher levels of task attentiveness (β = 0.20; 95% CI, 0.05-0.36) and emotional regulation at age 4-5 years (β = 0.19; 95% CI, 0.04-0.34) that persisted to age 6-7 years (β = 0.26; 95% CI, 0.10-0.42; β = 0.31; 95% CI, 0.16-0.47). Conclusion Among children using formal childcare, those who experienced higher-quality relationships were better able to regulate their attention and emotions as they started school. Higher emotional regulation was also observed for children engaged in more activities in childcare. Beneficial effects were stable over time. [ABSTRACT FROM AUTHOR]

The IM-UNITI study and long-term extension (LTE) evaluated the long-term efficacy, safety, and immunogenicity of subcutaneous ustekinumab maintenance therapy in patients with Crohn's disease. Here, we report the final results of IM-UNITI LTE through 5 years. Patients completing safety and efficacy evaluations at week 44 of the maintenance study were eligible to participate in the LTE and continue the treatment they were receiving. Unblinding occurred after completion of maintenance study analyses (August 2015), and patients receiving placebo were discontinued from the study after unblinding. No dose adjustment occurred in the LTE. Efficacy assessments were conducted every 12 weeks until unblinding and at dosing visits thereafter through week 252. Serum ustekinumab concentrations and antidrug antibodies were evaluated through weeks 252 and 272, respectively. Using an intent-to-treat analysis of all patients randomized to ustekinumab at maintenance baseline, 34.4% of patients in the every-8-weeks group and 28.7% in the every-12-weeks group were in clinical remission at week 252. Corresponding remission rates among patients who entered the LTE were 54.9% and 45.2%. Overall, adverse event rates (per 100 patient-years) from maintenance week 0 through the final visit generally were similar in the placebo and combined ustekinumab groups for all adverse events (440.3 vs 327.6), serious adverse events (19.3 vs 17.5), infections (99.8 vs 93.8), and serious infections (3.9 vs 3.4). Serum ustekinumab concentrations were maintained throughout the LTE. Antidrug antibodies occurred in 5.8% of patients who received ustekinumab during induction and maintenance and continued in the LTE. Patients receiving subcutaneous ustekinumab maintained clinical remission through 5 years. No new safety signals were observed. ClinicalTrials.gov number NCT01369355. [ABSTRACT FROM AUTHOR]

Whereas the influence of pregnancy diet and milk feeding on children's health and development is well characterized, the role of early food intake and eating behaviors is largely unexplored. This study aimed to determine whether the degree of adherence to complementary feeding guidelines was associated with dietary, obesity, cardiovascular, and cognitive outcomes at 7-8 y of age. Data were analyzed from the Avon Longitudinal Study of Parents and Children using parent-completed dietary questionnaires at 6 mo of age to calculate a Complementary Feeding Utility Index score. Regression analysis was used to explore associations between the index score and dietary patterns derived via principal component analysis (n = 4326), body-mass index (BMI) (n = 4801), waist circumference (n = 4798), blood pressure (n = 4685), and lipids (n = 3232) measured at age 7 y; and intelligence quotient (IQ) measured at age 8 y (n = 4429) after adjustment for covariates. The index score was negatively associated with a "processed" dietary pattern (β = -0.16; 95% CI: -0.20, -0.13; P < 0.001) but positively associated with a "health conscious" dietary pattern [β = 0.18 (95% CI: 0.14, 0.21); P < 0.001]. A higher index score was also positively associated with total, verbal, and performance IQ scores at 8 y of age [β = 1.92 (95%CI: 1.38, 2.47); P < 0.001 for total IQ). The index score was weakly associated with waist circumference [β = -0.15 (95%CI: -0.31, -0.002); P = 0.046] and diastolic blood pressure [β = -0.24 (95%CI: -0.47, -0.01); P = 0.043] at 7 y of age but was not associated with BMI or other cardiovascular risk factors. These findings suggest that adherence to current complementary feeding guidelines may have implications for some, but not all, health and development outcomes in childhood. [ABSTRACT FROM AUTHOR]

Objective: Synovitis is thought to be a secondary phenomenon in the osteoarthritis (OA) process and the menisci might be triggers of localized synovitis. The aim was to assess the cross-sectional associations of posterior horn meniscal damage with perimeniscal synovitis, and with synovitis posterior to the posterior cruciate ligament (PCL) using contrast enhanced (CE) MRI. Design: The Multicenter Osteoarthritis (MOST) Study is a longitudinal observational study of subjects with or at risk for knee OA. Subjects are a subset of MOST who were examined with 1.5T CE MRI and had semiquantitative synovitis (scored from 0 to 2 at 11 locations) and meniscal readings (scored with WORMS from 0 to 4) available. Logistic regression was used to assess the association of posterior meniscal damage and perimeniscal synovitis in the same compartment, and between posterior meniscal damage and synovitis posterior to the PCL. Results: Three hundred and seventy seven knees were included (mean age 61.1 years±6.9, mean BMI 29.6±4.9, 44.3% women). The odds for ipsi-compartmental perimeniscal synovitis were increased for knees with medial posterior horn meniscal damage (adjusted odds ratio [aOR] 2.5, 95% confidence intervals [95% CI] 1.3,4.8), but not for lateral damage (aOR 1.7, 95% CI 0.4,6.6). No positive associations were found for meniscal damage and presence of synovitis posterior to the PCL (aOR 0.9, 95% CI 0.6,1.5). Conclusions : Meniscal damage of the posterior horns is associated with ipsi-compartmental perimensical synovitis. No associations were found for posterior horn meniscal damage with synovitis posterior to the PCL, which suggests that synovitis posterior to the PCL is likely to be triggered by different pathomechanisms. [Copyright &y& Elsevier]

Background: Diet in the first 2 y of life may be a pivotal period regarding effects on future blood pressure (BP). However, data on early-life diet and BP in childhood are sparse. Objective: We prospectively assessed associations between types of diet spanning infancy and toddlerhood (ie, transition diets across the complementary feeding period) and BP at age 7.5 y. Design: In a birth cohort study (Avon Longitudinal Study of Parents and Children; United Kingdom), a total of !229 children had complete dietary intake data at 6, 15, and 24 mo; BP data at 7.5 y of age; and all 18 covariables. Results: Of the 2 transition diets that were extracted by using principal components analysis, the less-healthy diet was associated with an increase in systolic BP of 0.62 mm Hg (95% CI: 0.00, 1.24 mm Hg) and an increase in diastolic BP of 0.55 mm Hg (95% CI: 0.10, 1.00 mm Hg) for every one-unit (SD) increase in the less-healthy-diet score after adjustment for 15 potential confounders, including maternal characteristics and sociodemographic factors, birth variables, and breasffeeding duration. In contrast with systolic BE the positive association between the less-healthy transition-diet score and diastolic BP persisted after additional adjustment for child body-size factors [height, body mass index (BMI), and waist circumference] at 7.5 y. Conclusions: A less-healthy transition diet by age 2 y was associated with higher BP at 7.5 y. The BMI-related reduction in effect size reinlbrces the importance of BMI on the diet-BP relation. [ABSTRACT FROM AUTHOR]

Background: The portrayal of diet over time is a natural progression from the characterization of diet at single time points. The transition dietary period, a dynamic period of rapid dietary change spanning infancy and toddlerhood when children shift from a milk-based to a food-based diet, has not been characterized. Objective: The objective was to summarize variation in dietary intakes spanning infancy and toddlerhood. Design: A prospective principal components analysis was applied to dietary intakes from 3 successive follow-ups of children enrolled in the ALSPAC (Avon Longitudinal Study of Parents and Children). The frequency of food and beverage consumption was assessed via questionnaire at ages 6, 15, and 24 mo (n = 2169). Results: Two types of transition diet were identified. The first transition diet was characterized by the consumption of home-prepared and raw foods ("healthy") at all time points and the second by ready-prepared and discretionary foods ("less healthy") consistently over time. Higher educational level and maternal age were associated with higher scores on the "healthy" diet, whereas younger maternal age and a lower educational level were associated with higher scores on the "less healthy" diet. Maternal BMI, number of older siblings, and lower social class were associated with the less-healthy transition diet but not with the healthy transition diet. Conclusions: Unique transition diets, including a less-healthy type, emerge by age 2 y. These diets are consistent with childhood and adult dietary patterns reported at single time points and show convergent validity both with known maternal sociodemographic predictors of childhood diet and with intake gradients across diet scores. [ABSTRACT FROM AUTHOR]

The complementary feeding period is an important stage of child development. The study aim was to develop an index reflecting the degree of adherence to complementary feeding guidelines, evaluate its convergent validity, and explore associations with socio-demographic factors and dietary pattern scores in childhood. Data were analyzed from the Avon Longitudinal Study of Parents and Children (n = 6065) using parent-completed dietary questionnaires at 6 mo of age, socio-demographic information, and dietary patterns derived by principal component analysis at age 3 y. The Complementary Feeding Utility Index (CFUI) consists of 14 components: breastfeeding duration, feeding to appetite, timing of introduction to solids, exposure to iron-rich cereals, fruit and vegetable intake, exposure to high-fat/-salt/-sugar foods including sugary drinks, food texture, and meal/snack frequency. Regression analyses were undertaken to investigate associations between index scores, socio-demographic factors, food and nutrient intakes, and dietary pattern scores at age 3 y. Milk and food intake at 6 mo and nutrient intake at 8 mo of age varied across quintiles of index score in largely the expected directions. Associations were found among index score, maternal age, education, social class, maternal smoking history, and prepregnancy BMI. After adjustment for socio-demographic factors, the index score was associated with "processed" [β = -0.234 (95% CI = -0.260, -0.209)] and "healthy" [β = 0.185 (95% CI = 0.155, 0.215)] dietary pattern scores at age 3 y. The CFUI is able to discriminate across food intake, nutrient intake, and socio-demographic factors and is associated with later dietary patterns. [ABSTRACT FROM AUTHOR]

Abcb6 is a mammalian mitochondrial ATP-binding cassette (ABC) transporter that regulates de novo porphyrin synthesis. In previous studies, haploinsufficient (Abcb6+/-) embryonic stem cells showed impaired porphyrin synthesis. Unexpectedly, Abcb6-/- mice derived from these stem cells appeared phenotypically normal. We hypothesized that other ATP-dependent and/or -independent mechanisms conserve porphyrins. Here, we demonstrate that Abcb6-/- mice lack mitochondrial ATP-driven import of coproporphyrin III. Gene expression analysis revealed that loss of Abcb6 results in up-regulation of compensatory porphyrin and iron pathways, associated with elevated protoporphyrin IX (PPIX). Phenylhydrazine-induced stress caused higher mortality in Abcb6-/- mice, possibly because of sustained elevation of PPIX and an inability to convert PPIX to heme despite elevated ferrochelatase levels. Therefore, Abcb6 is the sole ATP-dependent porphyrin importer, and loss of Abcb6 produces up-regulation of heme and iron pathways necessary for normal development. However, under extreme demand for porphyrins (e.g. phenylhydrazine stress), these adaptations appear inadequate, which suggests that under these conditions Abcb6 is important for optimal survival. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To investigate whether help-seeking intentions for depressive symptoms vary for adolescents experiencing low, mild-to-moderate, and high levels of depressive symptoms. Methods: A total of 5,362 participants aged 12–14 years had completed the baseline assessment for a randomized controlled trial evaluating the effectiveness of a universal intervention designed to reduce depressive symptoms among high school students. The participants reported their help-seeking intentions in response to a vignette describing an individual experiencing depressive symptoms consistent with a diagnosis of a minor depressive disorder. Standard measures were used to assess participants'' level of depressive symptoms and perceived level of social support. Results: Logistic regression models examined relationships between help-seeking intentions and levels of depression, after adjustment for demographic characteristics and perceived support. As compared with those with low levels of depressive symptoms, adolescents with high levels of symptoms reported less intention to seek help from friends (odds ratio [OR] = .42) or family members (OR = .29). They were also four times more likely to report that they would not seek help from anybody (OR = 4.55). A similar pattern was evident during comparisons of help-seeking intentions reported by adolescents with mild-to-moderate levels of depressive symptoms versus those with low levels of symptoms. Conclusions: Targeted and universal interventions need to encourage peers and family members to actively engage with young adolescents experiencing depressive symptoms rather than waiting for them to initiate help-seeking. This is particularly important for adolescents experiencing higher levels of depressive symptoms who may not initiate help-seeking themselves. [Copyright &y& Elsevier]