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Parkinson's disease (PD) is one of the most prevalent neurodegenerative brain diseases; it is accompanied by extensive loss of dopamine (DA) neurons of the substantia nigra that project to the putamen, leading to impaired motor functions. Several genes have been associated with hereditary forms of the disease and transgenic mice have been developed by a number of groups to produce animal models of PD and to explore the basic functions of these genes. Surprisingly, most of the various mouse lines generated such as Parkin KO, Pink1 KO, DJ-1 KO and LRRK2 transgenic have been reported to lack degeneration of nigral DA neuron, one of the hallmarks of PD. However, modest impairments of motor behavior have been reported, suggesting the possibility that the models recapitulate at least some of the early stages of PD, including early dysfunction of DA axon terminals. To further evaluate this possibility, here we provide for the first time a systematic comparison of DA release in four different mouse lines, examined at a young age range, prior to potential age-dependent compensations. Using fast scan cyclic voltammetry in striatal sections prepared from young, 6-8 weeks old mice, we examined sub-second DA overflow evoked by single pulses and action potential trains. Unexpectedly, none of the models displayed any dysfunction of DA overflow or reuptake. These results, compatible with the lack of DA neuron loss in these models, suggest that molecular dysfunctions caused by the absence or mutation of these individual genes are not sufficient to perturb the function and survival of mouse DA neurons.

As social issues like climate change become increasingly salient, digital traces left by scholarly documents can be used to assess their reach outside of academia. Our research examine who shared climate change research papers on Twitter by looking at the expressions used in profile descriptions. We categorized users in eight categories (academia, communication, political, professional, personal, organization, bots and publishers) associated to specific expressions. Results indicate how diverse publics may be represented in the communication of scholarly documents on Twitter. Supplementing our word detection analysis with qualitative assessments of the results, we highlight how the presence of unique or multiple categorizations in textual Twitter descriptions provides evidence of the publics of research in specific contexts. Our results show a more substantial communication by academics and organizations for papers published in 2016, whereas the general public comparatively participated more in 2015. Overall, there is significant participation of publics outside of academia in the communication of climate change research articles on Twitter, although the extent to which these publics participate varies between individual papers. This means that papers circulate in specific communities which need to be assessed to understand the reach of research on social media. Furthermore, the flexibility of our method provide means for research assessment that consider the contextuality and plurality of publics involved on Twitter.

Purpose The aim of our investigation was to conduct a quantitative meta-analysis of the present world literature comparing the major surgical outcomes of penetrating keratoplasty (PKP) to lamellar procedures. Our goal is that clinicians, eye bank administrators, and health policy makers will be able to utilize this study in implementing decisions in regards to corneal transplantation. Methods Pooled measures of association were with odds ratios and because of study heterogeneity, the pooled effects were assumed to follow a random effects model (DerSimonian-Laird). The comparisons were between 1) PKP’s and all lamellar procedures (anterior AND posterior) and then 2) between PKP’s and all anterior lamellar procedures and 3) PKP and all posterior lamellar procedures. Results For PKP vs anterior lamellar procedures, the pooled odds ratio for rejection of PKP over lamellar keratoplasty (LK) was 3.56 (95% CI: 1.76-7.20) and for outright failure, the pooled odds ratio of PKP failure vs LK was 2.85 (95% CI: 0.84-9.66). For posterior lamellar procedures, the pooled odds ratio for rejection of PKP over LK was 1.52 (95% CI: 1.00-2.32). The pooled odds ratio for outright failure of PKP over posterior lamellar procedures was 2.09 (95% CI: 0.57-7.59). The follow up time was significantly longer for full transplants than for lamellar procedures. Conclusions For both anterior and posterior lamellar procedures, the odds ratios comparing rejection of full transplants to lamellar procedures (both anterior and posterior individually) were significantly higher in the PKP group. For outright failure, the PKP group also had a higher risk of failure than the lamellar groups but this was not statistically significant in either instance (anterior or posterior). Some of the clinical differences benefitting lamellar procedures may at least be partly explained by follow up time differences between groups and this needs to be accounted for more rigorously in future studies.

Neutrophils play a critical role in host defense against Pseudomonas aeruginosa infection. Mechanisms underlying the negative regulation of neutrophil function in bacterial clearance remain incompletely defined. Here, we demonstrate that protein tyrosine phosphatase-1B (PTP1B) is a negative regulator of P. aeruginosa clearance by neutrophils. PTP1B-deficient neutrophils display greatly enhanced bacterial phagocytosis and killing, which are accompanied by increased Toll-like receptor 4 (TLR4) signaling activation and nitric oxide (NO) production following P. aeruginosa infection. Interestingly, PTP1B deficiency mainly upregulates the production of IL-6 and IFN-β, leads to enhanced TLR4-dependent STAT1 activation and iNOS expression by neutrophils following P. aeruginosa infection. Further studies reveal that PTP1B and STAT1 are physically associated. These findings demonstrate a negative regulatory mechanism in neutrophil underlying the elimination of P. aeruginosa infection though a PTP1B-STAT1 interaction.

Risk of transmission of hepatitis C virus (HCV) by clinical plasma remains high in countries with a high prevalence of hepatitis C, justifying the implementation of viral inactivation treatments. In this study, we assessed the extent of inactivation of HCV during minipool solvent/detergent (SD; 1% TnBP / 1% Triton X-45) treatment of human plasma. Luciferase-tagged infectious cell culture-derived HCV (HCVcc) particles were used to spike human plasma prior to treatment by SD at 31 ± 0.5°C for 30 min. Samples were taken before and after SD treatment and filtered on a Sep-Pak Plus C18 cartridge to remove the SD agents. Risk of cytotoxicity was assessed by XTT cell viability assay. Viral infectivity was analyzed based on the luciferase signals, 50% tissue culture infectious dose viral titer, and immunofluorescence staining for HCV NS5A protein. Total protein, cholesterol, and triglyceride contents were determined before and after SD treatment and C18 cartridge filtration. Binding analysis, using patient-derived HCV clinical isolates, was also examined to validate the efficacy of the inactivation by SD. SD treatment effectively inactivated HCVcc within 30 min, as demonstrated by the baseline level of reporter signals, total loss of viral infectivity, and absence of viral protein NS5A. SD specifically targeted HCV particles to render them inactive, with essentially no effect on plasma protein content and hemostatic function. More importantly, the efficacy of the SD inactivation method was confirmed against various genotypes of patient-derived HCV clinical isolates and against HCVcc infection of primary human hepatocytes. Therefore, treatment by 1% TnBP / 1% Triton X-45 at 31°C is highly efficient to inactivate HCV in plasma for transfusion, showing its capacity to enhance the safety of therapeutic plasma products. We propose that the methodology used here to study HCV infectivity can be valuable in the validation of viral inactivation and removal processes of human plasma-derived products.

International audience; Objective: Maternal mortality ratio due to postpartum haemorrhage (PPH) is higher in France than in Canada. We explored this difference by comparing PPH features between these two countries.Methods: Using data between 2004 and 2006, we compared the incidence, risk factors, causes and use of second-line treatments, of PPH between France (N = 6,660 PPH) and Canada (N = 9,838 PPH). We assessed factors associated with PPH through multivariate logistic models.Results: PPH incidence, overall (4.8% (95% CI 4.7–4.9) in Canada and 4.5% (95% CI 4.4–4.7) in France), and after vaginal delivery (5.3% (95%CI 5.2–5.4) in Canada and 4.8 (95%CI 4.7–4.9) in France), were significantly higher in Canada than in France, but not after caesarean delivery. Women delivering without PPH were similar between the two populations, except for macrosomia (11% in Canada, 7% in France, p<0.001), caesarean delivery (27% in Canada, 18% in France, p<0.001), and episiotomy (17% in Canada, 34% in France, p<0.001). After vaginal delivery, factors strongly associated with PPH were multiple pregnancy, operative delivery and macrosomia in both populations, and episiotomy only in France (Odds Ratio 1.39 (95% CI 1.23–1.57)). The use of second-line treatments for PPH management was significantly more frequent in France than in Canada after both vaginal and caesarean delivery.Conclusion: PPH incidence was not higher in France than in Canada and there was no substantial difference in PPH risk factors between the 2 countries. Greater use of second-line treatments in PPH management in France suggests a more frequent failure of first-line treatments and a higher rate of severe PPH, which may be involved in the higher maternal mortality ratio due to PPH.

Osteoarthritis (OA) exacerbates skeletal muscle functioning, leading to postural instability and increased falls risk. However, the link between impaired physical function, OA and falls have not been elucidated. We investigated the role of impaired physical function as a potential mediator in the association between OA and falls. This study included 389 participants [229 fallers (≥2 falls or one injurious fall in the past 12 months), 160 non-fallers (no history of falls)], age (≥65 years) from a randomized controlled trial, the Malaysian Falls Assessment and Intervention Trial (MyFAIT). Physical function was assessed using Timed Up and Go (TUG) and Functional Reach (FR) tests. Knee and hip OA were diagnosed using three methods: Clinical, Radiological and Self-report. OA symptom severity was assessed using the Western Ontario and McMaster Universities Arthritis Index (WOMAC). The total WOMAC score was categorized to asymptomatic, mild, moderate and severe symptoms. Individuals with radiological OA and 'mild' overall symptoms on the WOMAC score had reduced risk of falls compared to asymptomatic OA [OR: 0.402(0.172-0.940), p = 0.042]. Individuals with clinical OA and 'severe' overall symptoms had increased risk of falls compared to those with 'mild' OA [OR: 4.487(1.883-10.693), p = 0.005]. In individuals with radiological OA, mild symptoms appear protective of falls while those with clinical OA and severe symptoms have increased falls risk compared to those with mild symptoms. Both relationships between OA and falls were not mediated by physical limitations. Larger prospective studies are needed for further evaluation.

Measurement, Reporting, and Verification (MRV) systems are thought to be essential for effective carbon accounting and joint REDD+ carbon, conservation, and social development goals. Community participation in MRV (PMRV) has been shown to be both cost effective and accurate, as well as a method to potentially advance stakeholder empowerment and perceptions of legitimacy. Recognizing land tenure as a long-standing point of tension in REDD+ planning, we argue that its engagement also has a key role to play in developing a legitimate PMRV. Using household surveys, key informant interviews, and participatory mapping exercises, we present three 'lived' land tenure contexts in Indonesia to highlight their socially and ecologically situated natures and to consider the role of tenure pluralism in shaping PMRV. We then raise and interrogate three questions for incorporating lived land tenure contexts into a legitimate PMRV system: 1) Who holds the right to conduct PMRV activities?; 2) How are the impacts of PMRV differentially distributed within local communities?; and 3) What is the relationship between tenure security and motivation to participate in PMRV? We conclude with implementation lessons for REDD+ practitioners, including the benefits of collaborative practices, and point to critical areas for further research.

Purpose To determine the effect of 1% cyclopentolate on the refractive status of children aged 4 to 18 years. Methods Using a random cluster sampling in a cross-sectional school-based study design, children with an age of 4–18 years were selected from kindergardens, primary schools, junior and senior high schools in a rural county and a city. Auto-refractometry was performed before and after inducing cycloplegia which was achieved by 1% cyclopentolate eye drops. Results Out of 6364 eligible children, data of 5999 (94.3%) children were included in the statistical analysis. Mean age was 10.0±3.3 years (range: 4–18 years). Mean difference between cycloplegic and non-cycloplegic refractive error (DIFF) was 0.78±0.79D (median: 0.50D; range: -1.00D to +10.75D). In univariate analysis, DIFF decreased significantly with older age (P<0.001;correlation coefficient r:-0.24), more hyperopic non-cycloplegic refractive error (P<0.001;r = 0.13) and more hyperopic cycloplegic refractive error (P<0.001;r = 0.49). In multivariate analysis, higher DIFF was associated with higher cycloplegic refractive error (P<0.001; standardized regression coefficient beta:0.50; regression coefficient B: 0.19; 95% confidence interval (CI): 0.18, 0.20), followed by lower intraocular pressure (P<0.001; beta: -0.06; B: -0.02; 95%CI: -0.03, -0.01), rural region of habitation (P = 0.001; beta: -0.04; B: -0.07; 95%CI: -0.11, -0.03), and, to a minor degree, with age (P = 0.006; beta: 0.04; B: 0.009; 95%CI: 0.003, 0.016). 66.4% of all eyes with non-cycloplegic myopia (≤-0.50D) remained myopic after cycloplegia while the remaining 33.6% of eyes became emmetropic (18.0%) or hyperopic (15.7%) under cycloplegia. Prevalence of emmetropia decreased from 37.5% before cycloplegia to 19.8% after cycloplegia while the remaining eyes became hyperopic under cycloplegia. Conclusions The error committed by using non-cycloplegic versus cycloplegic refractometry in children with mid to dark-brown iris color decreased with older age, and in parallel manner, with more myopic cycloplegic refractive error. Non-cycloplegic refractometric measures lead to a misclassification of refractive error in a significant proportion of children.

Many metabolic studies employ tissue-specific gene knockout mice, which requires breeding of floxed gene mice, available mostly on C57BL/6N (NN) genetic background, with cre or Flp recombinase-expressing mice, available on C57BL/6J (JJ) background, resulting in the generation of mixed C57BL/6NJ (NJ) genetic background mice. Recent awareness of many genetic differences between NN and JJ strains including the deletion of nicotinamide nucleotide transhydrogenase (nnt), necessitates examination of the consequence of mixed NJ background on glucose tolerance, beta cell function and other metabolic parameters. Male mice with NN and NJ genetic background were fed with normal or high fat diets (HFD) for 12 weeks and glucose and insulin homeostasis were studied. Genotype had no effect on body weight and food intake in mice fed normal or high fat diets. Insulinemia in the fed and fasted states and after a glucose challenge was lower in HFD-fed NJ mice, even though their glycemia and insulin sensitivity were similar to NN mice. NJ mice showed mild glucose intolerance. Moreover, glucose- but not KCl-stimulated insulin secretion in isolated islets was decreased in HFD-fed NJ vs NN mice without changes in insulin content and beta cell mass. Under normal diet, besides reduced fed insulinemia, NN and NJ mice presented similar metabolic parameters. However, HFD-fed NJ mice displayed lower fed and fasted insulinemia and glucose-induced insulin secretion in vivo and ex vivo, as compared to NN mice. These results strongly caution against using unmatched mixed genetic background C57BL/6 mice for comparisons, particularly under HFD conditions.