Apolipoprotein(a) [apo(a)] exhibits a genetic size polymorphism explaining about 40% of the variability in lipoprotein(a) [Lp(a)] concentration in Tyroleans. Lp(a) concentrations and apo(a) phenotypes were determined in 7 ethnic groups (Tyrolean, Icelandic, Hungarian, Malay, Chinese, Indian, Black Sudanese) and the effects of the apo(a) size polymorphism on Lp(a) levels were estimated in each group. Average Lp(a) concentrations were highly significantly different among these populations, with the Chinese (7.0 mg/dl) having the lowest and the Sudanese (46 mg/dl) the highest levels. Apo(a) phenotype and derived apo(a) allele frequencies were also significantly different among the populations. Apo(a) isoform effects on Lp(a) levels were not significantly different among populations. Lp(a) levels were however roughly twice as high in the same phenotypes in the Indians, and several times as high in the Sudanese, compared with Caucasians. The size variation of apo(a) explains from 0.77 (Malays) to only 0.19 (Sudanese) of the total variability in Lp(a) levels. Together these data show (I) that there is considerable heterogeneity of the Lp(a) polymorphism among populations, (II) that differences in apo(a) allele frequencies alone do not explain the differences in Lp(a) levels among populations and (III) that in some populations, e.g. Sudanese Blacks, Lp(a) levels are mainly determined by factors that are different from the apo(a) size polymorphism.

BackgroundStudies on the association between sitting time and low back pain (LBP) have found contrasting results. This may be due to the lack of objectively measured sitting time or because socioeconomic confounders were not considered in the analysis.ObjectivesTo investigate the association between objectively measured sitting time (daily total, and occupational and leisure-time periods) and LBP among blue-collar workers.MethodsTwo-hundred-and-one blue-collar workers wore two accelerometers (GT3X+ Actigraph) for up to four consecutive working days to obtain objective measures of sitting time, estimated via Acti4 software. Workers reported their LBP intensity the past month on a scale from 0 (no pain) to 9 (worst imaginable pain) and were categorized into either low (≤5) or high (>5) LBP intensity groups. In the multivariate-adjusted binary logistic regression analysis, total sitting time, and occupational and leisure-time sitting were both modeled as continuous (hours/day) and categorical variables (i.e. low, moderate and high sitting time).ResultsThe multivariate logistic regression analysis showed a significant positive association between total sitting time (per hour) and high LBP intensity (odds ratio; OR=1.43, 95%CI=1.15-1.77, P=0.01). Similar results were obtained for leisure-time sitting (OR=1.45, 95%CI=1.10-1.91, P=0.01), and a similar but non-significant trend was obtained for occupational sitting time (OR=1.34, 95%CI 0.99-1.82, P=0.06). In the analysis on categorized sitting time, high sitting time was positively associated with high LBP for total (OR=3.31, 95%CI=1.18-9.28, P=0.03), leisure (OR=5.31, 95%CI=1.57-17.90, P=0.01), and occupational (OR=3.26, 95%CI=0.89-11.98, P=0.08) periods, referencing those with low sitting time.ConclusionSitting time is positively associated with LBP intensity among blue-collar workers. Future studies using a prospective design with objective measures of sitting time are recommended.

Objective The epidemiology and outcomes of Multiple Organ Dysfunction Syndrome (MODS) are incompletely characterized in the pediatric population due to small sample size and conflicting diagnoses of organ failure. We sought to describe the epidemiology and outcomes of early MODS in a large clinical database of PICU patients based on consensus definitions of organ failure. Design Retrospective analysis of a contemporaneously collected clinical PICU database. Setting VPICU Performance System (VPS) database patient admissions from 1/2004-12/2005 for 35 US children’s hospitals. Patients We evaluated 63,285 consecutive PICU admissions from 1/2004-12/2005 in the VPS database. We excluded patients <1 month or >18 years of age, and hospitals with >10% missing values for MODS variables. We identified day 1 MODS by International Pediatric Sepsis Consensus Conference (IPSCC) criteria with day 1 laboratory and vital sign values. We evaluated functional status using Pediatric Overall Performance Category (POPC) and Pediatric Cerebral Performance Category (PCPC) scores from PICU admission and discharge. Interventions Analysis: Student’s t-test, Χ2, Mann-Whitney rank sum, Kruskal-Wallis, linear and logistic regression. Measurements and Main Results We analyzed 44,693 admissions from 28 hospitals meeting inclusion criteria. Overall PICU mortality was 2.8%. We identified day 1 MODS in 18.6% of admissions. Patients with day 1 MODS had higher mortality (10.0% v. 1.2%, p<0.001), longer PICU length of stay (3.6 v. 1.3 days, p<0.001) and larger change from baseline POPC and PCPC scores at time of PICU discharge (p<0.001). Infants had the highest incidence of day 1 MODS (25.2% vs. 16.5%, p<0.001) compared to other age groups. Conclusions Using the largest clinical dataset to date and consensus definitions for organ failure, we found that children with MODS present on day one of ICU admission have worse functional outcomes, higher mortality, and longer PICU length of stay than children who do not have MODS on day one. Infants are disproportionally affected by MODS.

Recent studies focusing on autonomic nervous system (ANS) dysfunctions, together with theoretical pathophysiological models of musculoskeletal disorders, indicate the involvement of ANS regulation in development and maintenance of chronic muscle pain. Research has demonstrated the effectiveness of heart rate variability (HRV) biofeedback (BF) in increasing HRV and reducing the symptoms of different disorders characterized by ANS aberration. The study investigated the effects of resonance frequency HRV BF on autonomic regulation and perceived health, pain, stress and disability in 24 subjects with stress-related chronic neckshoulder pain. Twelve subjects participated in 10 weekly sessions of resonant HRV BF and were compared to a control group. Subjective reports and HRV measures during relaxation and in response to a standardized stress protocol were assessed for both groups pre-and postintervention. Group X time interactions revealed a significantly stronger increase over time in perceived health (SF-36) for the treatment group, including vitality, bodily pain and social functioning. Interactions were also seen for HRV during relaxation and reactivity to stress.The present pilot study indicates improvement in perceived health over a 10 week intervention with HRV-biofeedback in subjects with chronic neck-pain. Increased resting HRV as well as enhanced reactivity to hand grip and cold pressor tests might reflect beneficial effects on ANS regulation, and suggest that this intervention protocol is suitable for a larger controlled trial.

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To identify genetic loci for severe diabetic retinopathy, 286 Mexican-Americans with type 2 diabetes from Starr County, Texas, completed physical examinations including fundus photography for diabetic retinopathy grading. Individuals with moderate-to-severe non-proliferative and proliferative diabetic retinopathy were defined as cases. Direct genotyping was performed using the Affymetrix GeneChip Human Mapping 100 K Set, and SNPs passing quality control criteria were used to impute markers available in HapMap Phase III Mexican population (MXL) in Los Angeles, California. Two directly genotyped markers were associated with severe diabetic retinopathy at a P-value less than .0001: SNP rs2300782 (P = 6.04 × 10−5) mapped to an intron region of CAMK4 (calcium/calmodulin-dependent protein kinase IV) on chromosome 5, and SNP rs10519765 (P = 6.21 × 10−5) on chromosomal 15q13 in the FMN1 (formin 1) gene. Using well-imputed markers based on the HapMap III Mexican population, we identified an additional 32 SNPs located in 11 chromosomal regions with nominal association with severe diabetic retinopathy at P-value less than .0001. None of these markers were located in traditional candidate genes for diabetic retinopathy or diabetes itself. However, these signals implicate genes involved in inflammation, oxidative stress and cell adhesion for the development and progression of diabetic retinopathy.

Background The COVID-19 pandemic has triggered national recommendations encouraging people to work from home (WFH), but the possible impact of WFH on physical behaviors is unknown. This study aimed to determine the extent to which the 24-h allocation of time to different physical behaviors changes between days working at the office (WAO) and days WFH in office workers during the pandemic. Methods Data were collected on 27 office workers with full-time employment at a Swedish municipal division during the COVID-19 outbreak in May–July 2020. A thigh-worn accelerometer (Axivity) was used to assess physical behavior (sedentary, stand, move) during seven consecutive days. A diary was used to identify periods of work, leisure and sleep. 24-h compositions of sedentary, standing and moving behaviors during work and non-work time were examined using Compositional data analysis (CoDA), and differences between days WAO and days WFH were determined using repeated measures ANOVA. Results Days WFH were associated with more time spent sleeping relative to awake, and the effect size was large (F = 7.4; p = 0.01; ηp2 = 0.22). The increase (34 min) in sleep time during WFH occurred at the expense of a reduction in work and leisure time by 26 min and 7 min, respectively. Sedentary, standing and moving behaviors did not change markedly during days WFH compared to days WAO. Conclusion Days working from home during the COVID-19 pandemic in Sweden were associated with longer duration of sleep than days working at the office. This behavioral change may be beneficial to health.

Aims/hypothesis We conducted genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) analyses to identify and characterise risk loci for type 2 diabetes in Mexican-Americans from Starr County, TX, USA. Method Using 1.8 million directly interrogated and imputed genotypes in 837 unrelated type 2 diabetes cases and 436 normoglycaemic controls, we conducted Armitage trend tests. To improve power in this population with high disease rates, we also performed ordinal regression including an intermediate class with impaired fasting glucose and/or glucose tolerance. These analyses were followed by meta-analysis with a study of 967 type 2 diabetes cases and 343 normoglycaemic controls from Mexico City, Mexico. Result The top signals (unadjusted p value <1×10−5) included 49 single nucleotide polymorphisms (SNPs) in eight gene regions (PER3, PARD3B, EPHA4, TOMM7, PTPRD, HNT [also known as RREB1], LOC729993 and IL34) and six intergenic regions. Among these was a missense polymorphism (rs10462020; Gly639Val) in the clock gene PER3, a system recently implicated in diabetes. We also report a second signal (minimum p value 1.52× 10−6) within PTPRD, independent of the previously implicated SNP, in a population of Han Chinese. Top meta-analysis signals included known regions HNF1A and KCNQ1. Annotation of top association signals in both studies revealed a marked excess of trans-acting eQTL in both adipose and muscle tissues. Conclusions/Interpretation In the largest study of type 2 diabetes in Mexican populations to date, we identified modest associations of novel and previously reported SNPs. In addition, in our top signals we report significant excess of SNPs that predict transcript levels in muscle and adipose tissues.