Regulation of LRRK2 Expression Points to a Functional Role in Human Monocyte Maturation

Genetic variants of Leucine-Rich Repeat Kinase 2 (LRRK2) are associated with a significantly enhanced risk for Parkinson disease, the second most common human neurodegenerative disorder. Despite major efforts, our understanding of LRRK2 biological function and regulation remains rudimentary. In the present study we analyze LRRK2 mRNA and protein expression in sub-populations of human peripheral blood mononuclear cells (PBMCs). LRRK2 mRNA and protein was found in circulating CD19+ B cells and in CD14+ monocytes, whereas CD4+ and CD8+ T cells were devoid of LRRK2 mRNA. Within CD14+ cells the CD14+CD16+ sub-population of monocytes exhibited high levels of LRRK2 protein, in contrast to CD14+CD16- cells. However both populations expressed LRRK2 mRNA. As CD14+CD16+ cells represent a more mature subset of monocytes, we monitored LRRK2 expression after in vitro treatment with various stress factors known to induce monocyte activation. We found that IFN-γ in particular robustly increased LRRK2 mRNA and protein levels in monocytes concomitant with a shift of CD14+CD16− cells towards CD14+CD16+cells. Interestingly, the recently described LRRK2 inhibitor IN-1 attenuated this shift towards CD14+CD16+ after IFN-γ stimulation. Based on these findings we speculate that LRRK2 might have a role in monocyte maturation. Our results provide further evidence for the emerging role of LRRK2 in immune cells and regulation at the transcriptional and translational level. Our data might also reflect an involvement of peripheral and brain immune cells in the disease course of PD, in line with increasing awareness of the role of the immune system in PD

Within and between Individual Variability of Exposure to Work-Related Musculoskeletal Disorder Risk Factors

Industrial companies indicate a tendency to eliminate variations in operator strategies, particularly following implementation of the lean principle. Companies believe when the operators perform the same prescribed tasks, they have to execute them in the same manner (completing the same gestures and being exposed to the same risk factors). They attempt to achieve better product quality by standardizing and reducing operational leeway. However, operators adjust and modify ways of performing tasks to balance between their abilities and the requirements of the job. This study aims to investigate the variability of exposure to physical risk factors within and between operators when executing the same prescribed tasks. The Ergonomic Standard method was used to evaluate two workstations. Seven operators were observed thirty times between repeated cycle times at those workstations. The results revealed the variability of exposure to risk factors between and within operators in the repeated execution of the same tasks. Individual characteristics and operators’ strategies might generate the variability of exposure to risk factors that may be an opportunity to reduce the risks of work-related musculoskeletal disorders (WR-MSDs). However, sometimes operators’ strategies may cause overexposure to risk factors; operators most often adopt such strategies to undertake their tasks while reducing the workload

Quantification of Exposure to Risk Postures in Truck Assembly Operators: Neck, Back, Arms and Wrists

International audienceThe study assessed the proportion of time in risky postures for the main joints of the upper limbs in a truck assembly plant and explored the association with musculoskeletal symptoms. Fourteen workstations (13 individuals) of a truck assembly plant were selected, and seven sensors were placed on the body segments of the participants. The sensors included tri-axial accelerometers for the arms and back, inclinometers for the neck and electro-goniometry for quantifying flexion/extension of the right and left hands. The proportions of time in moderate awkward postures were high at all workstations. Neck and wrist excessive awkward postures were observed for most workstations. The average values of the 91st percentile for back flexion and right/left arm elevation were 25°, 62°, and 57°, respectively. The 91st and 9th percentile averages for neck flexion/extension were 35.9° and −4.7°, respectively. An insignificant relationship was found between the percentage of time spent in awkward upper limb posture and musculoskeletal symptoms. The findings provide objective and quantitative data about time exposure, variability, and potential risk factors in the real workplace. Quantitative measurements in the field provide objective data of the body postures and movements of tasks that can be helpful in the musculoskeletal disorders (MSDs) prevention program

Ergonomics interventions to reduce musculoskeletal risk factors in a truck manufacturing plant

International audienceErgonomic interventions may potentially reduce MSDs, but the context of industries (barriers, ever-changing situations, dialogue processes) might play a significant role in the success of interventions. This study evaluates the effectiveness of ergonomic interventions including engineering/technical and organizational interventions, and the involvement of the stakeholders in reducing musculoskeletal risk factors/symptoms. A pre-post-test experimental study in non-randomized groups was performed over three years in a sector of a truck assembly plant. The mean age of the operators in the sector for the initial and second assessment time was 42.0 (±7.6) years and 39.0 (±8.7), respectively. The mean length of work experience in the current job was 15.2 (±7.2) years and 13.9 (±7.3) for the initial and second assessment times, respectively. Five engineering ergonomic solutions and organizational interventions were implemented after a comprehensive ergonomic analysis. The organizational interventions consisted mostly of transferring and redistributing the tasks, i.e., ergonomically balancing and redesigning of the workstations. Before performing the interventions, the findings of the ergonomic study were presented at several meetings to encourage the involvement of the stakeholders (including managers, engineers, and operators) in the interventions. This study showed that a combination of ergonomic measures—engineering and organizational interventions—could reduce physical workloads. Musculoskeletal symptoms decreased after interventions although the difference was not significant

Volume of neonatal care and survival without disability at 2 years in very preterm infants: results of a french national cohort study.

International audienceObjectives To investigate the relation between neonatal intensive care unit (NICU) volume and survival, and neuromotor and sensory disabilities at 2 years in very preterm infants. Study design The EPIPAGE-2 (Etude Epidémiologique sur les Petits Âges Gestationnels-2) national prospective population-based cohort study was used to include 2447 babies born alive in 66 level III hospitals between 24 and 30 completed weeks of gestation in 2011. The outcome was survival without disabilities (levels 2-5 of the Gross Motor Function Classification System for cerebral palsy with or without unilateral or bilateral blindness or deafness). Units were grouped in quartiles according to volume, defined as the annual admissions of very preterm babies. Multivariate logistic regression analyses with population average models were used. Results Survival at discharge was lower in hospitals with lower volumes of neonatal activity (aOR 0.55, 95% CI 0.33-0.91). Survival without neuromotor and sensory disabilities at 2 years increased with hospital volume, from 75% to 80.7% in the highest volume units. After adjustment for gestational age, small for gestational age, sex, maternal age, infertility treatment, multiple pregnancy, principal cause of prematurity, parental socioeconomic status, and mother's country of birth, survival without neuromotor or sensory disabilities was significantly lower in hospitals with a lower volume of neonatal activity (aOR 0.60, 95% CI 0.38-0.95) than in the highest quartile hospitals. Conclusions These results suggest that lower neonatal intensive care unit volume is associated with lower survival without an increase in disabilities at 2 years. These results could be useful to generate improvements of perinatal regionalization

Risk factors for very preterm delivery out of a level III maternity unit: The EPIPAGE‐2 cohort study

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Association Between Planned Cesarean Delivery and Neonatal Mortality and Morbidity in Twin Pregnancies

International audienceOBJECTIVE: To evaluate the association between the planned mode of delivery and neonatal mortality and morbidity in an unselected population of women with twin pregnancies. METHODS: The JUmeaux MODe d'Accouchement (JUMODA) study was a national prospective population-based cohort study. All women with twin pregnancies and their neonates born at or after 32 weeks of gestation with a cephalic first twin were recruited in 176 maternity units in France from February 2014 to March 2015. The primary outcome was a composite of intrapartum mortality and neonatal mortality and morbidity. Comparisons were performed according to the planned mode of delivery, planned cesarean or planned vaginal delivery. The primary analysis to control for potential indication bias used propensity score matching. Subgroup analyses were conducted, one according to gestational age at delivery and one after exclusion of high-risk pregnancies. RESULTS: Among 5,915 women enrolled in the study, 1,454 (24.6%) had planned cesarean and 4,461 (75.4%) planned vaginal deliveries, of whom 3,583 (80.3%) delivered both twins vaginally. In the overall population, composite neonatal mortality and morbidity was increased in the planned cesarean compared with the planned vaginal delivery group (5.2% compared with 2.2%; odds ratio [OR] 2.38, 95% confidence interval [CI] 1.86–3.05). After matching, neonates born after planned cesarean compared with planned vaginal delivery had higher composite neonatal mortality and morbidity rates (5.3% compared with 3.0%; OR 1.85, 95% confidence interval 1.29–2.67). Differences in composite mortality and morbidity rates applied to neonates born before but not after 37 weeks of gestation. Multivariate and subgroup analyses after exclusion of high-risk pregnancies found similar trends.CONCLUSION: Planned vaginal delivery for twin pregnancies with a cephalic first twin at or after 32 weeks of gestation was associated with low composite neonatal mortality and morbidity. Moreover, planned cesarean compared with planned vaginal delivery before 37 weeks of gestation might be associated with increased composite neonatal mortality and morbidity