The Molecular Basis of Resistance Antiretroviral Markers and Polymorphisms of the Human Immunodeficiency Virus-1 Subtype Crf01-ae Protease Gene in Naïve and Treatment Failure Patients in Bali

Application of antiretrovirals (ARVs) in patients with Human Immunodeficiency Virus (HIV) infection has proven to reduce mortality rates and prolong life expectancy. On the other hand, the use of antiretroviral drugs has incited the emergence of HIVDR. The resistance is due to mutation at genes associated with drug resistance. Nowadays, the determination of resistance markers mutations are based on HIV-1 subtype B. However, the majority of HIV in Indonesia, particularly in Bali are of subtype CRF01_AE. Genetic variation between HIV viruses has led to variations in subtypes; therefore, resistance markers of subtype B could be polymorphisms of non-B subtypes. This study aims to determine the number and types of the resistance markers mutations and polymorphisms that occur on the PR gene of HIV-1 subtype CRF01_AE of naïve and treatment failure patients in Bali. This is an observational cross-sectional analytical study, conducted at two VCT clinics in Denpasar, during the period of April 2010 until October 2011. Samples consist of 18 HIV patients with treatment failure and 30 naïve HIV patients. Mutations were evaluated using PCR, sequenced and aligned were carried out using MEGA4. Interpretations of the mutations were made based on the Stanford HIV database. Hypothesis tests used were Mann-Whitney because of abnormal distribution of data. Hypothesis was accepted if the significant level p<0.05. This study found that of the demographic data, only the predisposing factors of the two groups were significantly different (p<0.05). Two patients with treatment failure and 5 naïve patients were found to have L10LV/I mutations. Only one patient with treatment failure had the I54FI mutation. No major mutations were found among the two study groups. The number and types of minor mutations were not significantly different (p>0.05) between the naïve group and treatment failure group. M36I and H69K polymorphisms of the PR gene were found in all the study samples. In conclusion of this study, two types of major mutations were found, L10LV/I and I54FI. The number and types of the resistance markers mutations towards the protease inhibitor (PI) group were not significantly different between the two study groups. M36I, H69K mutations of the PR gene are markers of polymorphisms of HIV-1 subtype CRF01_AE

Tracheotomy care simulation training program for inpatient providers

Objectives: Tracheotomy complications can be life-threatening. Many of these complications may be avoided with proper education of health care providers. Unfortunately, access to high-quality tracheotomy care curricula is limited. We developed a program to address this gap in tracheotomy care education for inpatient providers. This study aimed to assess the efficacy of this training program in improving trainee knowledge and comfort with tracheotomy care. Methods: The curriculum includes asynchronous online modules coupled with a self-directed hands-on simulation activity using a low-cost tracheotomy care task trainer. The program was offered to inpatient providers including medical students, residents, medical assistants, nurses, and respiratory therapists. Efficacy of the training was assessed using pre-training and post-training surveys of learner comfort, knowledge, and qualitative feedback. Results: Data was collected on 41 participants. After completing the program, participants exhibited significantly improved comfort in performing tracheotomy care activities and 15% improvement in knowledge scores, with large effect sizes respectively and greater gains among those with little prior tracheotomy care experience. Conclusion: This study has demonstrated that completion of this integrated online and hands-on tracheotomy simulation curriculum training increases comfort and knowledge, especially for less-experienced learners. This training addresses an important gap in tracheotomy care education among health care professionals with low levels of tracheotomy care experience and ultimately aims to improve patient safety and quality of care. This curriculum is easily transferrable as it requires only access to the online modules and low-cost simulation materials and could be used in other hospitals, long-term care facilities, outpatient clinics, and home settings

A triple action CDK4/6-PI3K-BET inhibitor with augmented cancer cell cytotoxicity

National Institutes of Health GM125195, GM135671, CA192656, FD00511

Loss to Followup in HIV-Infected Patients from Asia-Pacific Region: Results from TAHOD

This study examined characteristics of HIV-infected patients in the TREAT Asia HIV Observational Database who were lost to follow-up (LTFU) from treatment and care. Time from last clinic visit to 31 March 2009 was analysed to determine the interval that best classified LTFU. Patients defined as LTFU were then categorised into permanently LTFU (never returned) and temporary LTFU (re-entered later), and these groups compared. A total of 3626 patients were included (71% male). No clinic visits for 180 days was the best-performing LTFU definition (sensitivity 90.6%, specificity 92.3%). During 7697 person-years of follow-up, 1648 episodes of LFTU were recorded (21.4 per 100-person-years). Patients LFTU were younger (P = 0.002), had HIV viral load ≥500 copies/mL or missing (P = 0.021), had shorter history of HIV infection (P = 0.048), and received no, single- or double-antiretroviral therapy, or a triple-drug regimen containing a protease inhibitor (P < 0.001). 48% of patients LTFU never returned. These patients were more likely to have low or missing haemoglobin (P < 0.001), missing recent HIV viral load (P < 0.001), negative hepatitis C test (P = 0.025), and previous temporary LTFU episodes (P < 0.001). Our analyses suggest that patients not seen at a clinic for 180 days are at high risk of permanent LTFU, and should be aggressively traced

Regular use of aspirin and pancreatic cancer risk

BACKGROUND: Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been consistently associated with reduced risk of colorectal cancer and adenoma, and there is some evidence for a protective effect for other types of cancer. As experimental studies reveal a possible role for NSAIDs is reducing the risk of pancreatic cancer, epidemiological studies examining similar associations in human populations become more important. METHODS: In this hospital-based case-control study, 194 patients with pancreatic cancer were compared to 582 age and sex-matched patients with non-neoplastic conditions to examine the association between aspirin use and risk of pancreatic cancer. All participants received medical services at the Roswell Park Cancer Institute in Buffalo, NY and completed a comprehensive epidemiologic questionnaire that included information on demographics, lifestyle factors and medical history as well as frequency and duration of aspirin use. Patients using at least one tablet per week for at least six months were classified as regular aspirin users. Unconditional logistic regression was used to compute crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Pancreatic cancer risk in aspirin users was not changed relative to non-users (adjusted OR = 1.00; 95% CI 0.72–1.39). No significant change in risk was found in relation to greater frequency or prolonged duration of use, in the total sample or in either gender. CONCLUSIONS: These data suggest that regular aspirin use may not be associated with lower risk of pancreatic cancer

Acoustic emission signal processing framework to identify fracture in aluminum alloys

Acoustic emission (AE) is a common nondestructive evaluation tool that has been used to monitor fracture in materials and structures. The direct connection between AE events and their source, however, is difficult because of material, geometry and sensor contributions to the recorded signals. Moreover, the recorded AE activity is affected by several noise sources which further complicate the identification process. This article uses a combination of in situ experiments inside the scanning electron microscope to observe fracture in an aluminum alloy at the time and scale it occurs and a novel AE signal processing framework to identify characteristics that correlate with fracture events. Specifically, a signal processing method is designed to cluster AE activity based on the selection of a subset of features objectively identified by examining their correlation and variance. The identified clusters are then compared to both mechanical and in situ observed microstructural damage. Results from a set of nanoindentation tests as well as a carefully designed computational model are also presented to validate the conclusions drawn from signal processing

Risk and prognostic significance of tuberculosis in patients from The TREAT Asia HIV Observational Database

10.1186/1471-2334-9-46BMC Infectious Diseases94