Content validity of the Work Rehabilitation Questionnaire (WORQ) for persons with spinal cord injury:A mixed methods study

STUDY DESIGN: Mixed methods. OBJECTIVES: The aim of our study was to investigate the content validity of the Work Rehabilitation Questionnaire (WORQ) for use in persons with post-acute and chronic spinal cord injury (SCI). SETTING: A university-based Rehabilitation Center in The Netherlands. METHODS: Contents of the WORQ, brief ICF core sets for SCI for post-acute care and for chronic situation were compared with semi-guided interviews with persons with SCI and controlled for relevance by SCI rehabilitation professionals in two group meetings. RESULTS: Fourteen interviews with persons with SCI were performed. Two group meetings with 8 and 9 SCI rehabilitation professionals were held. Thirty seven of the 46 ICF categories (80%) of the WORQ were confirmed by both sources: mentioned in interviews with persons with SCI and considered important by the SCI professionals. The remaining 9 categories (20%) were confirmed by either the persons with SCI or the SCI professionals. Fourteen ICF categories that are part of the brief ICF core set for SCI for acute care and/or chronic situation, however are not part of the WORQ, have revealed importance by persons with SCI and SCI professionals. CONCLUSION: Our study confirms that most categories of the WORQ are important to consider for VR in persons with SCI, however, there are ICF categories that are absent in the WORQ and deemed relevant for use in VR in persons with SCI. Consequently, the content validity of the WORQ without additional items is insufficient for persons with SCI

Mutations in splicing factor genes are a major cause of autosomal dominant retinitis pigmentosa in Belgian families

Purpose : Autosomal dominant retinitis pigmentosa (adRP) is characterized by an extensive genetic heterogeneity, implicating 27 genes, which account for 50 to 70% of cases. Here 86 Belgian probands with possible adRP underwent genetic testing to unravel the molecular basis and to assess the contribution of the genes underlying their condition. Methods : Mutation detection methods evolved over the past ten years, including mutation specific methods (APEX chip analysis), linkage analysis, gene panel analysis (Sanger sequencing, targeted next-generation sequencing or whole exome sequencing), high-resolution copy number screening (customized microarray-based comparative genomic hybridization). Identified variants were classified following American College of Medical Genetics and Genomics (ACMG) recommendations. Results : Molecular genetic screening revealed mutations in 48/86 cases (56%). In total, 17 novel pathogenic mutations were identified: four missense mutations in RHO, five frameshift mutations in RP1, six mutations in genes encoding spliceosome components (SNRNP200, PRPF8, and PRPF31), one frameshift mutation in PRPH2, and one frameshift mutation in TOPORS. The proportion of RHO mutations in our cohort (14%) is higher than reported in a French adRP population (10.3%), but lower than reported elsewhere (16.5-30%). The prevalence of RP1 mutations (10.5%) is comparable to other populations (3.5%-10%). The mutation frequency in genes encoding splicing factors is unexpectedly high (altogether 19.8%), with PRPF31 the second most prevalent mutated gene (10.5%). PRPH2 mutations were found in 4.7% of the Belgian cohort. Two families (2.3%) have the recurrent NR2E3 mutation p.(Gly56Arg). The prevalence of the recurrent PROM1 mutation p.(Arg373Cys) was higher than anticipated (3.5%). Conclusions : Overall, we identified mutations in 48 of 86 Belgian adRP cases (56%), with the highest prevalence in RHO (14%), RP1 (10.5%) and PRPF31 (10.5%). Finally, we expanded the molecular spectrum of PRPH2, PRPF8, RHO, RP1, SNRNP200, and TOPORS-associated adRP by the identification of 17 novel mutations

Prenatal Air Pollution and Newborns' Predisposition to Accelerated Biological Aging.

Importance: Telomere length is a marker of biological aging that may provide a cellular memory of exposures to oxidative stress and inflammation. Telomere length at birth has been related to life expectancy. An association between prenatal air pollution exposure and telomere length at birth could provide new insights in the environmental influence on molecular longevity. Objective: To assess the association of prenatal exposure to particulate matter (PM) with newborn telomere length as reflected by cord blood and placental telomere length. Design, Setting, and Participants: In a prospective birth cohort (ENVIRONAGE [Environmental Influence on Ageing in Early Life]), a total of 730 mother-newborn pairs were recruited in Flanders, Belgium between February 2010 and December 2014, all with a singleton full-term birth (≥37 weeks of gestation). For statistical analysis, participants with full data on both cord blood and placental telomere lengths were included, resulting in a final study sample size of 641. Exposures: Maternal residential PM2.5 (particles with an aerodynamic diameter ≤2.5 μm) exposure during pregnancy. Main Outcomes and Measures: In the newborns, cord blood and placental tissue relative telomere length were measured. Maternal residential PM2.5 exposure during pregnancy was estimated using a high-resolution spatial-temporal interpolation method. In distributed lag models, both cord blood and placental telomere length were associated with average weekly exposures to PM2.5 during pregnancy, allowing the identification of critical sensitive exposure windows. Results: In 641 newborns, cord blood and placental telomere length were significantly and inversely associated with PM2.5 exposure during midgestation (weeks 12-25 for cord blood and weeks 15-27 for placenta). A 5-µg/m3 increment in PM2.5 exposure during the entire pregnancy was associated with 8.8% (95% CI, -14.1% to -3.1%) shorter cord blood leukocyte telomeres and 13.2% (95% CI, -19.3% to -6.7%) shorter placental telomere length. These associations were controlled for date of delivery, gestational age, maternal body mass index, maternal age, paternal age, newborn sex, newborn ethnicity, season of delivery, parity, maternal smoking status, maternal educational level, pregnancy complications, and ambient temperature. Conclusions and Relevance: Mothers who were exposed to higher levels of PM2.5 gave birth to newborns with shorter telomere length. The observed telomere loss in newborns by prenatal air pollution exposure indicates less buffer for postnatal influences of factors decreasing telomere length during life. Therefore, improvements in air quality may promote molecular longevity from birth onward

Osteopontin expression identifies a subset of recruited macrophages distinct from Kupffer cells in the fatty liver

Metabolic-associated fatty liver disease (MAFLD) represents a spectrum of disease states ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Hepatic macrophages, specifically Kupffer cells (KCs), are suggested to play important roles in the pathogenesis of MAFLD through their activation, although the exact roles played by these cells remain unclear. Here, we demonstrated that KCs were reduced in MAFLD being replaced by macrophages originating from the bone marrow. Recruited macrophages existed in two subsets with distinct activation states, either closely resembling homeostatic KCs or lipid-associated macrophages (LAMs) from obese adipose tissue. Hepatic LAMs expressed Osteopontin, a biomarker for patients with NASH, linked with the development of fibrosis. Fitting with this, LAMs were found in regions of the liver with reduced numbers of KCs, characterized by increased Desmin expression. Together, our data highlight considerable heterogeneity within the macrophage pool and suggest a need for more specific macrophage targeting strategies in MAFLD

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Foot segmental motion and coupling in stage II and III tibialis posterior tendon dysfunction

BACKGROUND: Classification systems developed in the field of posterior tibialis tendon dysfunction omit to include dynamic measurements. Since this may negatively affect the selection of the most appropriate treatment modality, studies on foot kinematics are highly recommended. Previous research characterised the foot kinematics in patients with posterior tibialis tendon dysfunction. However, none of the studies analysed foot segmental motion synchrony during stance phase, nor compared the kinematic behaviour of the foot in presence of different posterior tibialis tendon dysfunction stages. Therefore, we aimed at comparing foot segmental motion and coupling in patients with posterior tibialis tendon dysfunction grade 2 and 3 to those of asymptomatic subjects. METHODS: Foot segmental motion of 11 patients suffering from posterior tibialis tendon dysfunction stage 2, 4 patients with posterior tibialis tendon dysfunction stage 3 and 15 asymptomatic subjects was objectively quantified with the Rizzoli foot model using an instrumented walkway and a 3D passive motion capture system. Dependent variables were the range of motion occurring at the different inter-segment angles during subphases of stance and swing phase as well as the cross-correlation coefficient between a number of segments. RESULTS: Significant differences in range of motion were predominantly found during the forefoot push off phase and swing phase. In general, both patient cohorts demonstrated a reduced range of motion compared to the control group. This hypomobility occurred predominantly in the rearfoot and midfoot (p<0.01). Significant differences between both posterior tibialis tendon dysfunction patient cohorts were not revealed. Cross-correlation coefficients highlighted a loss of joint coupling between rearfoot and tibia as well as between rearfoot and forefoot in both posterior tibialis tendon dysfunction groups. INTERPRETATION: The current evidence reveals considerable mechanical alterations in the foot which should be considered in the decision making process since it may help explaining the success and failure of certain conservative and surgical interventions.publisher: Elsevier articletitle: Foot segmental motion and coupling in stage II and III tibialis posterior tendon dysfunction journaltitle: Clinical Biomechanics articlelink: http://dx.doi.org/10.1016/j.clinbiomech.2017.04.007 content_type: article copyright: © 2017 Elsevier Ltd. All rights reserved.status: publishe