Cumulative Low Back Load at Work as a Risk Factor of Low Back Pain: A Prospective Cohort Study

Purpose Much research has been performed on physical exposures during work (e.g. lifting, trunk flexion or body vibrations) as risk factors for low back pain (LBP), however results are inconsistent. Information on the effect of doses (e.g. spinal force or low back moments) on LBP may be more reliable but is lacking yet. The aim of the present study was to investigate the prospective relationship of cumulative low back loads (CLBL) with LBP and to compare the association of this mechanical load measure to exposure measures used previously. Methods The current study was part of the Study on Musculoskeletal disorders, Absenteeism and Health (SMASH) study in which 1,745 workers completed questionnaires. Physical load at the workplace was assessed by video-observations and force measurements. These measures were used to calculate CLBL. Furthermore, a 3-year follow-up was conducted to assess the occurrence of LBP. Logistic regressions were performed to assess associations of CLBL and physical risk factors established earlier (i.e. lifting and working in a flexed posture) with LBP. Furthermore, CLBL and the risk factors combined were assessed as predictors in logistic regression analyses to assess the association with LBP. Results Results showed that CLBL is a significant risk factor for LBP (OR: 2.06 (1.32-3.20)). Furthermore, CLBL had a more consistent association with LBP than two of the three risk factors reported earlier. Conclusions From these results it can be concluded that CLBL is a risk factor for the occurrence of LBP, having a more consistent association with LBP compared to most risk factors reported earlier. © 2012 The Author(s)

Optimizing a Massive Parallel Sequencing Workflow for Quantitative miRNA Expression Analysis

BACKGROUND: Massive Parallel Sequencing methods (MPS) can extend and improve the knowledge obtained by conventional microarray technology, both for mRNAs and short non-coding RNAs, e.g. miRNAs. The processing methods used to extract and interpret the information are an important aspect of dealing with the vast amounts of data generated from short read sequencing. Although the number of computational tools for MPS data analysis is constantly growing, their strengths and weaknesses as part of a complex analytical pipe-line have not yet been well investigated. PRIMARY FINDINGS: A benchmark MPS miRNA dataset, resembling a situation in which miRNAs are spiked in biological replication experiments was assembled by merging a publicly available MPS spike-in miRNAs data set with MPS data derived from healthy donor peripheral blood mononuclear cells. Using this data set we observed that short reads counts estimation is strongly under estimated in case of duplicates miRNAs, if whole genome is used as reference. Furthermore, the sensitivity of miRNAs detection is strongly dependent by the primary tool used in the analysis. Within the six aligners tested, specifically devoted to miRNA detection, SHRiMP and MicroRazerS show the highest sensitivity. Differential expression estimation is quite efficient. Within the five tools investigated, two of them (DESseq, baySeq) show a very good specificity and sensitivity in the detection of differential expression. CONCLUSIONS: The results provided by our analysis allow the definition of a clear and simple analytical optimized workflow for miRNAs digital quantitative analysis

Work factors and smoking cessation in nurses' aides: a prospective cohort study

BACKGROUND: The prevalence of smoking in nursing personnel remains high. The aim of this study was to identify work factors that predict smoking cessation among nurses' aides. METHODS: Of 2720 randomly selected, Norwegian nurses' aides, who were smoking at least one cigarette per day when they completed a questionnaire in 1999, 2275 (83.6 %) completed a second questionnaire 15 months later. A wide spectrum of work factors were assessed at baseline. Respondents who reported smoking 0 cigarettes per day at follow-up were considered having stopped smoking. The odds ratios and 95 % confidence intervals of stopping smoking were derived from logistic regression models. RESULTS: Compared with working 1–9 hours per week, working 19–36 hours per week (odds ratio (OR) = 0.35; 95 % confidence interval (CI) = 0.13 – 0.91), and working more than 36 hours per week (i.e. more than full-time job) (OR = 0.27; CI = 0.09 – 0.78) were associated with reduced odds of smoking cessation, after adjustments for daily consumption of cigarettes at baseline, age, gender, marital status, and having preschool children. Adjusting also for chronic health problems gave similar results. CONCLUSION: There seems to be a negative association between hours of work per week and the odds of smoking cessation in nurses' aides. It is important that health institutions offer workplace-based services with documented effects on nicotine dependence, such as smoking cessation courses, so that healthcare workers who want to stop smoking, especially those with long working hours, do not have to travel to the programme or to dedicate their leisure time to it

Ethnic differences in Internal Medicine referrals and diagnosis in the Netherlands

As in other Western countries, the number of immigrants in the Netherlands is growing rapidly. In 1980 non-western immigrants constituted about 3% of the population, in 1990 it was 6% and currently it is more than 10%. Nearly half of the migrant population lives in the four major cities. In the municipality of Rotterdam 34% of the inhabitants are migrants. Health policy is based on the ideal that all inhabitants should have equal access to health care and this requires an efficient planning of health care resources, like staff and required time per patient. The aim of this study is to examine ethnic differences in the use of internal medicine outpatient care, specifically to examine ethnic differences in the reason for referral and diagnosis. Methods We conducted a study with an open cohort design. We registered the ethnicity, sex, age, referral reasons, diagnosis and living area of all ne

RNAi Screen of DAF-16/FOXO Target Genes in C. elegans Links Pathogenesis and Dauer Formation

The DAF-16/FOXO transcription factor is the major downstream output of the insulin/IGF1R signaling pathway controlling C. elegans dauer larva development and aging. To identify novel downstream genes affecting dauer formation, we used RNAi to screen candidate genes previously identified to be regulated by DAF-16. We used a sensitized genetic background [eri-1(mg366); sdf-9(m708)], which enhances both RNAi efficiency and constitutive dauer formation (Daf-c). Among 513 RNAi clones screened, 21 displayed a synthetic Daf-c (SynDaf) phenotype with sdf-9. One of these genes, srh-100, was previously identified to be SynDaf, but twenty have not previously been associated with dauer formation. Two of the latter genes, lys-1 and cpr-1, are known to participate in innate immunity and six more are predicted to do so, suggesting that the immune response may contribute to the dauer decision. Indeed, we show that two of these genes, lys-1 and clc-1, are required for normal resistance to Staphylococcus aureus. clc-1 is predicted to function in epithelial cohesion. Dauer formation exhibited by daf-8(m85), sdf-9(m708), and the wild-type N2 (at 27°C) were all enhanced by exposure to pathogenic bacteria, while not enhanced in a daf-22(m130) background. We conclude that knockdown of the genes required for proper pathogen resistance increases pathogenic infection, leading to increased dauer formation in our screen. We propose that dauer larva formation is a behavioral response to pathogens mediated by increased dauer pheromone production

Assessing the adequacy of self-reported alcohol abuse measurement across time and ethnicity: cross-cultural equivalence across Hispanics and Caucasians in 1992, non-equivalence in 2001–2002

<p>Abstract</p> <p>Background</p> <p>Do estimates of alcohol abuse reflect true levels across United States Hispanics and non-Hispanic Caucasians, or does culturally-based, systematic measurement error (i.e., measurement bias) affect estimates? Likewise, given that recent estimates suggest alcohol abuse has increased among US Hispanics, the field should also ask, "Does cross-ethnic change in alcohol abuse across time reflect true change or does measurement bias influence change estimates?"</p> <p>Methods</p> <p>To address these questions, I used confirmatory factor analyses for ordered-categorical measures to probe for measurement bias on two large, standardized, nationally representative, US surveys of alcohol abuse conducted in 1992 and 2001–2002. In 2001–2002, analyses investigated whether 10 items operationalizing DSM-IV alcohol abuse provided equivalent measurement across Hispanic (<it>n </it>= 4,893) and non-Hispanic Caucasians (<it>n </it>= 16,480). In 1992, analyses examined whether a reduced 6 item item-set provided equivalent measurement among 834 Hispanic and 14,8335 non-Hispanic Caucasians.</p> <p>Results</p> <p>In 1992, findings demonstrated statistically significant measurement bias for two items. However, sensitivity analyses showed that item-level bias did not appreciably bias item-set based alcohol abuse estimates among this cohort. For 2001–2002, results demonstrated statistically significant bias for seven items, suggesting caution regarding the cross-ethnic equivalence of alcohol abuse estimates among the current US Hispanic population. Sensitivity analyses indicated that item-level differences <it>did </it>erroneously impact alcohol abuse rates in 2001–2002, underestimating rates among Hispanics relative to Caucasians.</p> <p>Conclusion</p> <p>1992's item-level findings suggest that estimates of drinking related social or legal problems may underestimate these specific problems among Hispanics. However, impact analyses indicated no appreciable effect on alcohol abuse estimates resulting from the item-set. Efforts to monitor change in alcohol abuse diagnoses among the Hispanic community can use 1992 estimates as a valid baseline. In 2001–2002, item-level measurement bias on seven items did affect item-set based estimates. Bias underestimated Hispanics' self-reported alcohol abuse levels relative to non-Hispanic Caucasians. Given the cross-ethnic equivalence of 1992 estimates, bias in 2001–2002 speciously minimizes current increases in drinking behavior evidenced among Hispanics. Findings call for increased public health efforts among the Hispanic community and underscore the necessity for cultural sensitivity when generalizing measures developed in the majority to minorities.</p

Canine models of copper toxicosis for understanding mammalian copper metabolism

Hereditary forms of copper toxicosis exist in man and dogs. In man, Wilson’s disease is the best studied disorder of copper overload, resulting from mutations in the gene coding for the copper transporter ATP7B. Forms of copper toxicosis for which no causal gene is known yet are recognized as well, often in young children. Although advances have been made in unraveling the genetic background of disorders of copper metabolism in man, many questions regarding disease mechanisms and copper homeostasis remain unanswered. Genetic studies in the Bedlington terrier, a dog breed affected with copper toxicosis, identified COMMD1, a gene that was previously unknown to be involved in copper metabolism. Besides the Bedlington terrier, a number of other dog breeds suffer from hereditary copper toxicosis and show similar phenotypes to humans with copper storage disorders. Unlike the heterogeneity of most human populations, the genetic structure within a purebred dog population is homogeneous, which is advantageous for unraveling the molecular genetics of complex diseases. This article reviews the work that has been done on the Bedlington terrier, summarizes what was learned from studies into COMMD1 function, describes hereditary copper toxicosis phenotypes in other dog breeds, and discusses the opportunities for genome-wide association studies on copper toxicosis in the dog to contribute to the understanding of mammalian copper metabolism and copper metabolism disorders in man

The Human Phenotype Ontology in 2024: phenotypes around the world

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs

Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered