Effect of providing near glasses on productivity among rural Indian tea workers with presbyopia (PROSPER) a randomised trial

BACKGROUND: Presbyopia, age-related decline in near vision, is the most common cause of vision impairment globally, but no trials have assessed its workplace effects. We aimed to study the effect of near glasses on the productivity of tea workers with presbyopia.METHODS: This randomised trial was done in tea pickers aged 40 years or older in Assam, India, with unaided near visual acuity (NVA) lower than 6/12 in both eyes, correctable to 6/7·5 with near glasses; unaided distance vision 6/7·5 or greater; and no eye disease. Participants were randomly assigned (1:1) to receive free glasses optimising NVA at working distance (cost including delivery US$10·20 per person), either immediately (intervention group) or at closeout (control group). Participants were stratified by age, sex, and productivity. The primary outcome (investigator-masked) was the difference between groups in the change in mean daily weight of tea picked (productivity), between the 4-week baseline period (June, 2017) and the 11-week evaluation period (July 24, 2017, to Oct 7, 2017). Workers' income was tied to their productivity. Compliance with study glasses was assessed at seven unannounced visits. Results were analysed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT03228199.FINDINGS: Between July 3, 2017, and July 15, 2017, 1297 (48·1%) of 2699 permanent workers met the age criteria and consented for eye examinations. 751 (57·9%) fulfilled vision criteria and were randomly assigned to the intervention (n=376) or control (n=375) groups. Groups did not differ substantially in baseline characteristics. No participants owned glasses at baseline, 707 (94·1%) received the allocated intervention, and all were followed up and analysed. Between the baseline and evaluation periods, mean productivity in the intervention group increased from 25·0 kg per day to 34·8 kg per day (an increase of 9·84 kg per day), a significantly higher increase than in the control group (from 26·0 kg per day to 30·6 kg per day; an increase of 4·59 kg per day), corresponding to a between-group difference of 5·25 kg per day (95% CI 4·50-5·99; 21·7% relative productivity increase; effect size 1·01 [95% CI 0·86-1·16]; p&lt;0·0001). Intervention-group compliance with study glasses reached 84·5% by closeout. Regression model predictors of greater productivity increase included intervention group membership (5·25 kg per day [95% CI 4·60-5·91], p&lt;0·0001) and, among intervention participants, older age (p=0·039) and better compliance with the intervention (p&lt;0·0001).INTERPRETATION: A substantial productivity increase was achieved in this rural cohort by providing glasses to correct presbyopia, with little cost and high intervention uptake.FUNDING: Clearly.</p

Transferrin receptor 2 controls bone mass and pathological bone formation via BMP and Wnt signalling

Transferrin receptor 2 (Tfr2) is mainly expressed in the liver and controls iron homeostasis. Here, we identify Tfr2 as a regulator of bone homeostasis that inhibits bone formation. Mice lacking Tfr2 display increased bone mass and mineralization independent of iron homeostasis and hepatic Tfr2. Bone marrow transplantation experiments and studies of cell-specific Tfr2 knockout mice demonstrate that Tfr2 impairs BMP-p38MAPK signaling and decreases expression of the Wnt inhibitor sclerostin specifically in osteoblasts. Reactivation of MAPK or overexpression of sclerostin rescues skeletal abnormalities in Tfr2 knockout mice. We further show that the extracellular domain of Tfr2 binds BMPs and inhibits BMP-2-induced heterotopic ossification by acting as a decoy receptor. These data indicate that Tfr2 limits bone formation by modulating BMP signaling, possibly through direct interaction with BMP either as a receptor or as a co-receptor in a complex with other BMP receptors. Finally, the Tfr2 extracellular domain may be effective in the treatment of conditions associated with pathological bone formation

Psip1/p52 regulates posterior Hoxa genes through activation of lncRNA Hottip

Long noncoding RNAs (lncRNAs) have been implicated in various biological functions including the regulation of gene expression, however, the functionality of lncRNAs is not clearly understood and conflicting conclusions have often been reached when comparing different methods to investigate them. Moreover, little is known about the upstream regulation of lncRNAs. Here we show that the short isoform (p52) of a transcriptional co-activator—PC4 and SF2 interacting protein (Psip1), which is known to be involved in linking transcription to RNA processing, specifically regulates the expression of the lncRNA Hottip–located at the 5’ end of the Hoxa locus. Using both knockdown and knockout approaches we show that Hottip expression is required for activation of the 5’ Hoxa genes (Hoxa13 and Hoxa10/11) and for retaining Mll1 at the 5’ end of Hoxa. Moreover, we demonstrate that artificially inducing Hottip expression is sufficient to activate the 5’ Hoxa genes and that Hottip RNA binds to the 5’ end of Hoxa. By engineering premature transcription termination, we show that it is the Hottip lncRNA molecule itself, not just Hottip transcription that is required to maintains active expression of posterior Hox genes. Our data show a direct role for a lncRNA molecule in regulating the expression of developmentally-regulated mRNA genes in cis

Pathogenesis and prevention of immune reconstitution disease during antiretroviral therapy.

The risks of unmasking and paradoxical forms of immune reconstitution disease in HIV-infected patients starting antiretroviral therapy (ART) are fuelled by a combination of the late presentation of patients with advanced immunodeficiency, the associated high rates of opportunistic infections (OIs) and the need for rapid initiation of ART to minimize overall mortality risk. We review the risk factors and our current knowledge of the immunopathogenesis of immune reconstitution disease, leading to a discussion of strategies for prevention. Initiation of ART at higher CD4 counts, use of OI-preventive therapies prior to ART eligibility, intensified screening for OIs prior to ART initiation and optimum therapy for OIs are all needed. In addition, use of a range of pharmacological agents with immunosuppressive and immunomodulatory activity is being explored

Effect of providing near glasses on productivity among rural Indian tea workers with presbyopia (PROSPER): a randomised trial

Summary: Background: Presbyopia, age-related decline in near vision, is the most common cause of vision impairment globally, but no trials have assessed its workplace effects. We aimed to study the effect of near glasses on the productivity of tea workers with presbyopia. Methods: This randomised trial was done in tea pickers aged 40 years or older in Assam, India, with unaided near visual acuity (NVA) lower than 6/12 in both eyes, correctable to 6/7·5 with near glasses; unaided distance vision 6/7·5 or greater; and no eye disease. Participants were randomly assigned (1:1) to receive free glasses optimising NVA at working distance (cost including delivery US$10·20 per person), either immediately (intervention group) or at closeout (control group). Participants were stratified by age, sex, and productivity. The primary outcome (investigator-masked) was the difference between groups in the change in mean daily weight of tea picked (productivity), between the 4-week baseline period (June, 2017) and the 11-week evaluation period (July 24, 2017, to Oct 7, 2017). Workers' income was tied to their productivity. Compliance with study glasses was assessed at seven unannounced visits. Results were analysed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT03228199. Findings: Between July 3, 2017, and July 15, 2017, 1297 (48·1%) of 2699 permanent workers met the age criteria and consented for eye examinations. 751 (57·9%) fulfilled vision criteria and were randomly assigned to the intervention (n=376) or control (n=375) groups. Groups did not differ substantially in baseline characteristics. No participants owned glasses at baseline, 707 (94·1%) received the allocated intervention, and all were followed up and analysed. Between the baseline and evaluation periods, mean productivity in the intervention group increased from 25·0 kg per day to 34·8 kg per day (an increase of 9·84 kg per day), a significantly higher increase than in the control group (from 26·0 kg per day to 30·6 kg per day; an increase of 4·59 kg per day), corresponding to a between-group difference of 5·25 kg per day (95% CI 4·50–5·99; 21·7% relative productivity increase; effect size 1·01 [95% CI 0·86–1·16]; p<0·0001). Intervention-group compliance with study glasses reached 84·5% by closeout. Regression model predictors of greater productivity increase included intervention group membership (5·25 kg per day [95% CI 4·60–5·91], p<0·0001) and, among intervention participants, older age (p=0·039) and better compliance with the intervention (p<0·0001). Interpretation: A substantial productivity increase was achieved in this rural cohort by providing glasses to correct presbyopia, with little cost and high intervention uptake. Funding: Clearly

Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis

Background & Aims: Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that occasionally progresses to cirrhosis but usually has a benign course. The aim of this study was to investigate the role of the hemochromatosis mutation Cys282Tyr in development of the mild hepatic iron overload found in some patients with NASH and its association with hepatic damage in these patients. Methods: Fifty-one patients with NASH were studied. The presence of the Cys282Tyr mutation was tested in all patients, and the data were analyzed with respect to the histological grade of steatosis, inflammation, Perls' staining, hepatic iron concentration (HIC), and serum iron indices. Results: Thirty-one percent of patients with NASH were either homozygous or heterozygous for the Cys282Tyr mutation. This mutation was significantly associated with Perls' stain grade (P < 0.005), HIC (P < 0.005), and transferrin saturation percentage (P < 0.005) but not with serum ferritin levels. Linear regression analysis showed that increased hepatic iron (Perls' stain or HIC) had the greatest association with the severity of fibrosis (P < 0.0001). Conclusions: The Cys282Tyr mutation is responsible for most of the mild iron overload found in NASH and thus has a significant association with hepatic damage in these patients. Heterozygosity for the hemochromatosis gene mutation therefore cannot always be considered benign