Epidemiological characteristics and real-world treatment outcomes of hepatitis C among HIV/HCV co-infected patients in Myanmar: A prospective cohort study.

Background and Aims: In Myanmar, public sector treatment programs for hepatitis C virus (HCV) infection were nonexistent until June 2017. WHO highlights the importance of simplification of HCV service delivery through task-shifting among health workers and decentralization to the primary health care level. Between November 2016 and November 2017, a study was conducted to describe the epidemiological data and real-world outcomes of treating HIV/HCV coinfected patients with generic direct acting antiviral (DAA) based regimens in the three HIV clinics run by nonspecialist medical doctors in Myanmar. Methods: HCV co-infection among people living with HIV (PLHIV) from two clinics in Yangon city and one clinic in Dawei city was screened by rapid diagnostic tests and confirmed by testing for viral RNA. Nonspecialist medical doctors prescribed sofosbuvir and daclatasvir based regimens (with or without ribavirin) for 12 or 24 weeks based on the HCV genotype and liver fibrosis status. Sustained virologic response at 12 weeks after treatment (SVR12) was assessed to determine cure. Results: About 6.5% (1417/21,777) of PLHIV were co-infected with HCV. Of 864 patients enrolled in the study, 50.8% reported history of substance use, 27% history of invasive medical procedures and 25.6% history of incarceration. Data on treatment outcomes were collected from 267 patients of which 257 (96.3%) achieved SVR12, 7 (2.6%) failed treatment, 2 (0.7%) died and 1 (0.4%) became loss to follow-up. Conclusion: The study results support the integration of hepatitis C diagnosis and treatment with DAA-based regimens into existing HIV clinics run by nonspecialist medical doctors in a resource-limited setting. Epidemiological data on HIV/HCV co-infection call for comprehensive HCV care services among key populations like drug users and prisoners in Yangon and Dawei.

Yeast Rgd3 is a phospho-regulated F-BAR-containing RhoGAP involved in the regulation of Rho3 distribution and cell morphology.

Polarized growth requires the integration of polarity pathways with the delivery of exocytic vesicles for cell expansion and counterbalancing endocytic uptake. In budding yeast, the myosin-V Myo2 is aided by the kinesin-related protein Smy1 in carrying out the essential Sec4-dependent transport of secretory vesicles to sites of polarized growth. Overexpression suppressors of a conditional myo2 smy1 mutant identified a novel F-BAR (Fes/CIP4 homology-Bin-Amphiphysin-Rvs protein)-containing RhoGAP, Rgd3, that has activity primarily on Rho3, but also Cdc42. Internally tagged Rho3 is restricted to the plasma membrane in a gradient corresponding to cell polarity that is altered upon Rgd3 overexpression. Rgd3 itself is localized to dynamic polarized vesicles that, while distinct from constitutive secretory vesicles, are dependent on actin and Myo2 function. In vitro Rgd3 associates with liposomes in a PIP2-enhanced manner. Further, the Rgd3 C-terminal region contains several phosphorylatable residues within a reported SH3-binding motif. An unphosphorylated mimetic construct is active and highly polarized, while the phospho-mimetic form is not. Rgd3 is capable of activating Myo2, dependent on its phospho state, and Rgd3 overexpression rescues aberrant Rho3 localization and cell morphologies seen at the restrictive temperature in the myo2 smy1 mutant. We propose a model where Rgd3 functions to modulate and maintain Rho3 polarity during growth.

Chromosomal breaks at FRA18C: association with reduced DOK6 expression, altered oncogenic signaling and increased gastric cancer survival.

Chromosomal rearrangements are common in cancer. More than 50% occur in common fragile sites and disrupt tumor suppressors. However, such rearrangements are not known in gastric cancer. Here we report recurrent 18q2 breakpoints in 6 of 17 gastric cancer cell lines. The rearranged chromosome 18, t(9;18), in MKN7 cells was flow sorted and identified by reverse chromosome painting. High-resolution tiling array hybridization mapped breakpoints to DOK6 (docking protein 6) intron 4 in FRA18C (18q22.2) and an intergenic region in 9q22.2. The same rearrangement was detected by FISH in 22% of 99 primary gastric cancers. Intron 4 truncation was associated with reduced DOK6 transcription. Analysis of The Cancer Genome Atlas stomach adenocarcinoma cohort showed significant correlation of DOK6 expression with histological and molecular phenotypes. Multiple oncogenic signaling pathways (gastrin-CREB, NGF-neurotrophin, PDGF, EGFR, ERK, ERBB4, FGFR1, RAS, VEGFR2 and RAF/MAP kinase) known to be active in aggressive gastric cancers were strikingly diminished in gastric cancers with low DOK6 expression. Median survival of patients with low DOK6-expressing tumors was 2100 days compared with 533 days in patients with high DOK6-expressing tumors (log-rank P = 0.0027). The level of DOK6 expression in tumors predicted patient survival independent of TNM stage. These findings point to new functions of human DOK6 as an adaptor that interacts with diverse molecular components of signaling pathways. Our data suggest that DOK6 expression is an integrated biomarker of multiple oncogenic signals in gastric cancer and identify FRA18C as a new cancer-associated fragile site.

Kinesin-related Smy1 enhances the Rab-dependent association of myosin-V with secretory cargo.

The mechanisms by which molecular motors associate with specific cargo is a central problem in cell organization. The kinesin-like protein Smy1 of budding yeast was originally identified by the ability of elevated levels to suppress a conditional myosin-V mutation (myo2-66), but its function with Myo2 remained mysterious. Subsequently, Myo2 was found to provide an essential role in delivery of secretory vesicles for polarized growth and in the transport of mitochondria for segregation. By isolating and characterizing myo2 smy1 conditional mutants, we uncover the molecular function of Smy1 as a factor that enhances the association of Myo2 with its receptor, the Rab Sec4, on secretory vesicles. The tail of Smy1-which binds Myo2-its central dimerization domain, and its kinesin-like head domain are all necessary for this function. Consistent with this model, overexpression of full-length Smy1 enhances the number of Sec4 receptors and Myo2 motors per transporting secretory vesicle. Rab proteins Sec4 and Ypt11, receptors for essential transport of secretory vesicles and mitochondria, respectively, bind the same region on Myo2, yet Smy1 functions selectively in the transport of secretory vesicles. Thus a kinesin-related protein can function intimately with a myosin-V and its receptor in the transport of a specific cargo.

Prostate cancer educational intervention among men in western Jamaica.

OBJECTIVE: To conduct and evaluate the impact of a theory-based health education intervention on awareness of prostate cancer and intention to screen among men in Western Jamaica and determine screening rates of men participating in the intervention at 6 months post-intervention. MATERIALS AND METHODS: 454 men utilizing various clinics and hospitals in Western Jamaica completed an interviewer-administered pretest survey on general prostate cancer knowledge and intention to screen. Upon completing the pretest, participants observed a prostate cancer health education intervention and immediately completed a posttest survey. RESULTS: Statistically significant improvements in the percentage of correct responses between the pretest and posttest were evident. (p < 0.05). Additionally, screening rates increased dramatically by 6 months post-intervention with over 33% of men receiving a prostate exam after participating the in the educational intervention. CONCLUSION: The theory-based educational intervention increased participants' knowledge of prostate cancer, types of screening tests, frequency of screenings and risk factors and symptoms, and was effective in increasing screening rates among the men in Western Jamaica within 6 months post- intervention. This theory-based educational intervention may be replicated to promote awareness of prostate cancer and further increase screening rates in other areas of Jamaica and other developing countries.

Diabetes Mellitus Care Provided by Nurse Practitioners vs Primary Care Physicians.

OBJECTIVES: To compare processes and cost of care of older adults with diabetes mellitus cared for by nurse practitioners (NPs) with processes and cost of those cared for by primary care physicians (PCPs). DESIGN: Retrospective cohort study. SETTING: Primary care in communities. PARTICIPANTS: Individuals with a diagnosis of diabetes mellitus in 2009 who received all their primary care from NPs or PCPs were selected from a national sample of Medicare beneficiaries (N = 64,354). MEASUREMENTS: Propensity score matching within each state was used to compare these two cohorts with regard to rate of eye examinations, low-density lipoprotein cholesterol (LDL-C) and glycosylated hemoglobin (HbA1C) testing, nephropathy monitoring, specialist consultation, and Medicare costs. The two groups were also compared regarding medication adherence and use of statins, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (for individuals with a diagnosis of hypertension), and potentially inappropriate medications (PIMs). RESULTS: Nurse practitioners and PCPs had similar rates of LDL-C testing (odds ratio (OR) = 1.01, 95% confidence interval (CI) = 0.94-1.09) and nephropathy monitoring (OR = 1.05, 95% CI = 0.98-1.03), but NPs had lower rates of eye examinations (OR = 0.89, 95% CI = 0.84-0.93) and HbA1C testing (OR = 0.88, 95% CI = 0.79-0.98). NPs were more likely to have consulted cardiologists (OR = 1.29, 95% CI = 1.21-1.37), endocrinologists (OR = 1.64, 95% CI = 1.48-1.82), and nephrologists (OR = 1.90, 95% CI = 1.67-2.17) and more likely to have prescribed PIMs (OR = 1.07, 95% CI = 1.01-1.12). There was no statistically significant difference in adjusted Medicare spending between the two groups (P = .56). CONCLUSION: Nurse practitioners were similar to PCPs or slightly lower in their rates of diabetes mellitus guideline-concordant care. NPs used specialist consultations more often but had similar overall costs of care to PCPs.

Not just another cause of dyspnea: common complaint leads to a rare diagnosis.

A 62-year-old man with past medical history of type 2 diabetes mellitus (DM-2) and hypertension presented with progressive shortness of breath since three months. He was diagnosed with diabetic polyradiculopathy with diaphragmatic involvement and was started on intravenous immunoglobulin (IVIg) therapy. Rapid improvement was seen as evidenced by increased vital capacity and other pulmonary function parameters. Considering the patient's positive response to intravenous immunoglobulins (IVIg), this case strengthens the fact that diaphragmatic involvement in Type 2 Diabetes Mellitus can be a part of focal or polyneuropathy and that the pathogenesis is immune mediated.

BCG vaccination of children against leprosy: fourteen-year findings of the trial in Burma

The value of BCG vaccination in preventing leprosy among children was studied in an area of high leprosy endemicity in Burma through a controlled trial; one group of 13066 children received BCG and another group of 13176 served as controls. The overall protective effect of BCG, which was only about 20% over the 14-year period, was found to vary with the batch of vaccine, as well as age, sex, and contacts status the children. The protective effect of BCG against the lepromatous type of leprosy could not be measured because of the low incidence. Protection was observed throught the fourteen years of the study except for the firts year. The results are compared with those of three other major BCG trials in leprosy. The trial has shown that BCG provides only a very modest level of protection and that BCG vaccination is not likely to be an important solution for leprosy control.

The efficacy and tolerability of rifampicin Burmese patients with lepromatous leprosy

Seventy-one Burnese adult patients with lepromatous leprosy were treated with regimens of rifampicin monotherapy, 450 mg daily for 60 days or relapsed after stopping DDS therapy, 20 were intolerant of DDS, 18 were DDS resistant and 15 had received no previous treatment. Rifampicin produced a 75 por cento reduction in the size of skin nodules in two thirds of the patients and a complete disappearance of nodules in the others. After one month drug treatment the MI fell to zero but the BI remained unchanged. the once weekly regimen was as effective as the daily treatment. Four patients had to be withdrawn due to ENL reactions.