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BACKGROUND:The pro-fibrogenic cytokine connective tissue growth factor (CTGF) plays an important role in the development and progression of fibrosis in many organ systems, including liver. However, its role in the pathogenesis of hepatitis C virus (HCV)-induced liver fibrosis remains unclear. METHODS:In the present study, we assessed CTGF expression in HCV-infected hepatocytes using replicon cells containing full-length HCV genotype 1 and the infectious HCV clone JFH1 (HCV genotype 2) by real-time PCR, Western blot analysis and confocal microscopy. We evaluated transforming growth factor β1 (TGF-β1) as a key upstream mediator of CTGF production using neutralizing antibodies and shRNAs. We also determined the signaling molecules involved in CTGF production using various immunological techniques. RESULTS:We demonstrated an enhanced expression of CTGF in two independent models of HCV infection. We also demonstrated that HCV induced CTGF expression in a TGF-β1-dependent manner. Further dissection of the molecular mechanisms revealed that CTGF production was mediated through sequential activation of MAPkinase and Smad-dependent pathways. Finally, to determine whether CTGF regulates fibrosis, we showed that shRNA-mediated knock-down of CTGF resulted in reduced expression of fibrotic markers in HCV replicon cells. CONCLUSION:Our studies demonstrate a central role for CTGF expression in HCV-induced liver fibrosis and highlight the potential value of developing CTGF-based anti-fibrotic therapies to counter HCV-induced liver damage.

A hallmark of cancer cells is hypermethylation of CpG islands (CGIs), which probably arises from upregulation of one or more DNA methyltransferases. The purpose of this study was to identify the targets of DNMT3B, an essential DNA methyltransferase in mammals, in colon cancer.Chromatin immunoprecipitation with DNMT3B specific antibody followed by CGI microarray identified genes with or without CGIs, repeat elements and genomic contigs in RKO cells. ChIP-Chop analysis showed that the majority of the target genes including P16, DCC, DISC1, SLIT1, CAVEOLIN1, GNA11, TBX5, TBX18, HOXB13 and some histone variants, that harbor CGI in their promoters, were methylated in multiple colon cancer cell lines but not in normal colon epithelial cells. Further, these genes were reactivated in RKO cells after treatment with 5-aza-2'-deoxycytidine, a DNA hypomethylating agent. COBRA showed that the CGIs encompassing the promoter and/or coding region of DCC, TBX5, TBX18, SLIT1 were methylated in primary colorectal tumors but not in matching normal colon tissues whereas GNA11 was methylated in both. MassARRAY analysis demonstrated that the CGI located approximately 4.5 kb upstream of HOXB13 +1 site was tumor-specifically hypermethylated in primary colorectal cancers and cancer cell lines. HOXB13 upstream CGI was partially hypomethylated in DNMT1(-/-) HCT cells but was almost methylation free in cells lacking both DNMT1 and DNMT3B. Analysis of tumor suppressor properties of two aberrantly methylated transcription factors, HOXB13 and TBX18, revealed that both inhibited growth and clonogenic survival of colon cancer cells in vitro, but only HOXB13 abolished tumor growth in nude mice.This is the first report that identifies several important tumor suppressors and transcription factors as direct DNMT3B targets in colon cancer and as potential biomarkers for this cancer. Further, this study shows that methylation at an upstream CGI of HOXB13 is unique to colon cancer.

BackgroundThe majority of childhood blindness causes in low-income countries are treatable or avoidable. Parents or guardians are responsible for making decisions regarding a child's eye care. Understanding parents' awareness and perception of eye problems in crucial in helping to know parents' eye care-seeking behavior.ObjectiveTo determine parental knowledge, attitudes and practice regarding child eye health.MethodsSeven focus groups were carried out in Northwest Ethiopia on knowledge, attitude and practice of parents towards child eye health. Their responses were tape-recorded and later transcribed. A thematic phenomenological approach was used for the analysis.ResultSeventy-one parents participated in the focus groups. Participants were aware of common eye problems like trachoma, trauma, and glaucoma. However, they were unaware of the causes and etiologies of childhood blindness. Participants perceived that eye problems could be treated with hygiene and food, and often held misconceptions about the cause of strabismus and utilization of wearing spectacles.ConclusionThe study revealed that parents are often unaware of the causes and etiologies of common childhood eye diseases, which has downstream effects on health-seeking behavior. Health promotion efforts, potentially through mass and social media, could be helpful to raise awareness, coupled with training of health professionals at primary and secondary health facility levels.

PURPOSE:To assess the pattern, presentation and risk factors of ocular trauma among patients treated at Hawassa University, Referral Hospital, Ophthalmology Department, South Ethiopia, 2014. METHODS:The medical records of all patients treated for ocular trauma at Hawassa University, Referral Hospital, Ophthalmology Department, during the period January 01, 2012 to July 31, 2014, were retrospectively reviewed. Trained optometrists, ophthalmic nurses and ophthalmic officer collected the data using a pretested data abstraction form. The descriptive and analytic statistics was carried out. RESULTS:A total of 773 patients (549 males and 224 females) were included in the study. Closed globe injury was more common in males (P = 0.019) and open globe injury was significantly common in children (P < 0.001). Corneal tear was the most frequently observed finding (39.33%). Surgery, secondary to trauma, was common in open globe injury (P < 0.001). About 98% of the patients presented after 6 hours post trauma. Among 84.61% patients whose visual acuity (VA) was recorded at presentation, 12.23% had VA of 6/6 and 65.90% had VA of

INTRODUCTION:To achieve measles elimination, two doses of measles-containing vaccine (MCV) are provided through routine immunization services or vaccination campaigns. In May 2016, Kenya conducted a measles-rubella (MR) vaccination campaign targeting 19 million children aged 9 months-14 years, with a goal of achieving ≥95% coverage. We conducted a post-campaign cluster survey to estimate national coverage and classify coverage in Kenya's 47 counties. METHODS:The stratified multi-stage cluster survey included data from 20,011 children in 8,253 households sampled using the recently revised World Health Organization coverage survey methodology (2015). Point estimates and 95% confidence intervals (95% CI) of national campaign coverage were calculated, accounting for study design. County vaccination coverage was classified as 'pass,' 'fail,' or 'intermediate,' using one-sided hypothesis tests against a 95% threshold. RESULTS:Estimated national MR campaign coverage was 95% (95% CI: 94%-96%). Coverage differed significantly (p < 0.05) by child's school attendance, mother's education, household wealth, and other factors. In classifying coverage, 20 counties passed (≥95%), two failed (

In the context of the current global pandemic and the limitations of the RT-PCR test, we propose a novel deep learning architecture, DFCN (Denoising Fully Connected Network). Since medical facilities around the world differ enormously in what laboratory tests or chest imaging may be available, DFCN is designed to be robust to missing input data. An ablation study extensively evaluates the performance benefits of the DFCN as well as its robustness to missing inputs. Data from 1088 patients with confirmed RT-PCR results are obtained from two independent medical facilities. The data includes results from 27 laboratory tests and a chest x-ray scored by a deep learning model. Training and test datasets are taken from different medical facilities. Data is made publicly available. The performance of DFCN in predicting the RT-PCR result is compared with 3 related architectures as well as a Random Forest baseline. All models are trained with varying levels of masked input data to encourage robustness to missing inputs. Missing data is simulated at test time by masking inputs randomly. DFCN outperforms all other models with statistical significance using random subsets of input data with 2-27 available inputs. When all 28 inputs are available DFCN obtains an AUC of 0.924, higher than any other model. Furthermore, with clinically meaningful subsets of parameters consisting of just 6 and 7 inputs respectively, DFCN achieves higher AUCs than any other model, with values of 0.909 and 0.919., Competing Interests: The authors have declared that no competing interests exist.

The passage of leukocytes across the endothelium and into arterial walls is a critical step in the development of atherosclerosis. Previously, we showed in vitro that the RhoG guanine nucleotide exchange factor SGEF (Arhgef26) contributes to the formation of ICAM-1-induced endothelial docking structures that facilitate leukocyte transendothelial migration. To further explore the in vivo role of this protein during inflammation, we generated SGEF-deficient mice. When crossed with ApoE null mice and fed a Western diet, mice lacking SGEF showed a significant decrease in the formation of atherosclerosis in multiple aortic areas. A fluorescent biosensor revealed local activation of RhoG around bead-clustered ICAM-1 in mouse aortic endothelial cells. Notably, this activation was decreased in cells from SGEF-deficient aortas compared to wild type. In addition, scanning electron microscopy of intimal surfaces of SGEF(-/-) mouse aortas revealed reduced docking structures around beads that were coated with ICAM-1 antibody. Similarly, under conditions of flow, these beads adhered less stably to the luminal surface of carotid arteries from SGEF(-/-) mice. Taken together, these results show for the first time that a Rho-GEF, namely SGEF, contributes to the formation of atherosclerosis by promoting endothelial docking structures and thereby retention of leukocytes at athero-prone sites of inflammation experiencing high shear flow. SGEF may therefore provide a novel therapeutic target for inhibiting the development of atherosclerosis.