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Verma S.C.,National Center
Journal of Nepal Health Research Council

Tuberculosis (TB) is a major public health problem in Nepal. HIV co-infection has further added a serious challenge to control TB. An early diagnosis and treatment of TB in HIV infected individuals can help reduce not only the morbidity and mortality associated in this high risk group but also to control the TB burden in Nepal. Clinical and bacteriological examination for pulmonary TB was carried out in 184 HIV positive persons from the community in Pokhara. Questionnaire was used to screen for symptoms and collect participants' demographic information and potential risk factors for TB. Eighty (43.5%) sero-positive participants were young adult (21-30 years), followed by 71 (38.6%) middle aged (31-40 years) persons. Eleven participants were found to have Mycobacterium tuberculosis in their sputum, giving an overall prevalence of tuberculosis of 5.97%. All 11 cases were detected by Acid Fast Bacilli (AFB) culture, of which only three cases were detected by direct microscopy of AFB stained sputum smear. The majority of TB/HIV patients were asymptomatic with low AFB smear positivity. No significant association was found between TB and risk factors like ARV status, common clinical features of tuberculosis and smoking habit. However, significant association was found between the alcohol consumption and TB (X2=4.11, p<0.05). High prevalence of tuberculosis (5.97%) was found among HIV infected persons. Alcohol consumption was associated with the development of tuberculosis. Majority of the studied subjects were asymptomatic for common signs and symptoms of TB. Weight loss was observed in 43% of the studied subjects followed by chest pain (39.2%), loss of appetite (34.8%), fever (34.8%) and night sweat (26.1%). Only 27% of the TB cases were found to be smear-positive. Source

Murfuni I.,Section of Experimental and Computational Carcinogenesis | De Santis A.,Section of Molecular Epidemiology | Federico M.,National Center | Bignami M.,Section of Experimental and Computational Carcinogenesis | And 2 more authors.

The Werner syndrome protein (WRN) is a member of the RecQ helicase family. Loss of WRN results in a human disease, the Werner syndrome (WS), characterized by high genomic instability, elevated cancer risk and premature aging. WRN is crucial for the recovery of stalled replication forks and possesses both helicase and exonuclease enzymatic activities of uncertain biological significance. Previous work revealed that WRN promotes formation of MUS81-dependent double strand breaks (DSBs) at HU-induced stalled forks, allowing replication restart at the expense of chromosome stability. Here, using cells expressing the helicase- or exonuclease-dead WRN mutant, we show that both activities of WRN are required to prevent MUS81-dependent breakage after HU-induced replication arrest. Moreover, we provide evidence that, in WS cells, DSBs generated by MUS81 do not require RAD51 activity for their formation. Surprisingly, when replication is specifically perturbed at common fragile sites (CFS) by aphidicolin, WRN limits accumulation of ssDNA gaps and no MUS81-dependent DSBs are detected. However, in both cases, RAD51 is essential to ensure viability of WS cells, although by different mechanisms. Thus, the role of WRN in response to perturbation of replication along CFS is functionally distinct from that carried out at stalled forks genome wide. Our results contribute to unveil two different mechanisms used by the cell to overcome the absence of WRN. © The Author 2012. Published by Oxford University Press. All rights reserved. Source

Hanson L.C.,University of North Carolina at Chapel Hill | Ersek M.,Center for Health Equity Research and Promotion Philadelphia Veterans Affairs Medical Center | Ersek M.,National Center | Ersek M.,University of Pennsylvania | And 2 more authors.
Journal of the American Geriatrics Society

Objectives To describe quality of care for feeding problems in advanced dementia and probability and predictors of weight loss and mortality. Design Prospective cohort. Setting Twenty-four nursing homes (NHs). Participants Nursing home residents with advanced dementia and feeding problems and family surrogates (N = 256). Measurements Family reported on quality of feeding care at enrollment and 3 months. Chart reviews at enrollment and 3, 6, and 9 months provided data on feeding problems, treatments, weight loss of more than 5% in 30 days or more than 10% in 6 months, and mortality. Organizational variables were obtained from administrator surveys and publically reported data. Results Residents with advanced dementia and feeding problems had an average age of 85; 80% had chewing and swallowing problems, 11% weight loss, and 48% poor intake. Family reported feeding assistance of moderate quality; 23% felt the resident received less assistance than needed. Mortality risk was significant; 8% died within 3 months, 17% within 6 months, and 27% within 9 months. Residents with advanced dementia who had stable weight over 3 months had a 5.4% rate of significant weight loss and a 2.1% risk of death over the next 3 months. Residents with advanced dementia and weight loss over 3 months had a 38.9% chance of stabilizing weight over the next 3 months but also had a 19.2% chance of dying. Weight loss was the only independent predictor of death. Conclusion Weight loss is a predictor of death in advanced dementia. Treatments can often stabilize weight, but weight loss should be used to trigger discussion of goals of care and treatment options. © 2013, The American Geriatrics Society. Source

Muratori C.,National Center
Methods in molecular biology (Clifton, N.J.)

Virus Like Particles (VLPs) are self-assembling, nonreplicating, nonpathogenic, genomeless particles similar in size and conformation to intact infectious virions. The possibility of engineering VLPs to incorporate heterologous polypeptides/proteins renders VLPs attractive candidates for vaccine strategies, as well as for protein delivery for basic science. Among the wide number of VLP types, our expertise focused on both retro- and lentivirus based VLPs as protein delivery tools. In particular, here we describe a system relying on the finding that some HIV-1 Nef mutants are incorporated at high levels into both Human Immunodeficiency virus (HIV)-1 and Moloney Leukemia Virus (MLV)-based VLPs. Most importantly, these Nef mutants can efficiently act as anchoring proteins upon fusion with heterologous proteins up to 630 amino acids in length. This chapter describes the preparation of prototypic HIV-1 based VLPs incorporating Nef mutant-GFP fusion molecules. Besides having potential utility in the field of basic virology, these VLPs represent a useful reference model for recovering alternative retro- or lentiviral based VLPs for the cell delivery of polypeptides/proteins of interest. Source

MacLean R.,National Center
Nursing standard (Royal College of Nursing (Great Britain) : 1987)

This article provides a brief overview of the pathophysiology of multiple sclerosis (MS). The symptoms experienced, including their management and treatment by members of the multidisciplinary team, are discussed, with a particular focus on the role of the nurse. Promoting and/or enabling self-management is an integral part of the nurse's role. Although there is no cure for MS, good management can enable all people affected by the condition to come to terms with their diagnosis and have a positive outlook for the future. Source

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