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

Pin-point effect determination using a rigorous approach

A new method for evaluating the pin-point effect of pile yarn of carpets before weaving has been introduced. The method has been initially accomplished by presenting a standard method for bundle preparation and consequently the pin-point index is presented by image analysis technique. To this end, yarns with different twists are heat set at various times and temperatures. Comparison of the results shows that increasing the twist, time and temperature positively contribute to the pin-point index. In the last section, an adaptive neuro fuzzy model (ANFIS) and an artificial neural network model (ANN) have been designed to predict the pin-point index of the heat set yarns based on training with the experimental data.  The input parameters are twist, time and temperature, and the output is the pin-point index. The results illustrate that the learning capability of the ANFIS model is superior and its generalization ability is slightly better than that of a standalone ANN model

Complexity analysis of surface electromyography for assessing the myoelectric manifestation of muscle fatigue: A review

The surface electromyography (sEMG) records the electrical activity of muscle fibers during contraction: one of its uses is to assess changes taking place within muscles in the course of a fatiguing contraction to provide insights into our understanding of muscle fatigue in training protocols and rehabilitation medicine. Until recently, these myoelectric manifestations of muscle fatigue (MMF) have been assessed essentially by linear sEMG analyses. However, sEMG shows a complex behavior, due to many concurrent factors. Therefore, in the last years, complexity-based methods have been tentatively applied to the sEMG signal to better individuate the MMF onset during sustained contractions. In this review, after describing concisely the traditional linear methods employed to assess MMF we present the complexity methods used for sEMG analysis based on an extensive literature search. We show that some of these indices, like those derived from recurrence plots, from entropy or fractal analysis, can detect MMF efficiently. However, we also show that more work remains to be done to compare the complexity indices in terms of reliability and sensibility; to optimize the choice of embedding dimension, time delay and threshold distance in reconstructing the phase space; and to elucidate the relationship between complexity estimators and the physiologic phenomena underlying the onset of MMF in exercising muscles

Predictors of Loss to Follow Up and Mortality Among Children ?12 Years Receiving Anti Retroviral Therapy During the First Year at a Referral Hospital in Bali

Background and purpose: Many HIV-infected children in Bali have started antiretroviral therapy (ART), but loss to follow up (LTFU) is a continuing concern, and the issue of childhood adherence is more complex compared to adults.Methods: This was a retrospective study among cohort of 138 HIV+ children on ART in Sanglah General Hospital, Denpasar, Bali from January 2010 to December 2015. Kaplan-Meier analysis was used to describe incidence and median time to LTFU/mortality and Cox Proportional Hazard Model was used to identify predictors. Variables which were analysed were socio-demographic characteristics, birth history, care giver and clinical condition of the children.Results: Mean age when starting ARV therapy was 3.21 years. About 25% experienced LTFU/death by 9.1 month resulting in an incidence rate of 3.28 per 100 child month. The higher the WHO stage, the higher the risk for LTFU/mortality along with low body weight (AHR=0.90; 95%CI: 0.82-0.99).Conclusion: Clinical characteristics were found as predictors for LTFU/mortality among children on ART

Dynamics of myocardial adaptation to low-flow ischemia and hypoxemia

We investigated whether one or more factors control performance in O2- limited hearts. For this purpose, we measured the dynamics of myocardial adaptation to reduced O2 supply with a specially designed setup, analyzing early changes after reduction in either flow of the perfusion medium or its PO2. For 10 min, 38 isolated rat hearts underwent low-flow ischemia or hypoxemia, matched for O2 supply. Early during ischemia, developed pressure declined at a rate of 311 \ub1 25 mmHg/s; lactate release increased and then leveled off to 3.4 \ub1 0.7 \u3bcmol/min within 2 min. During hypoxemia, pressure dropped initially, as observed during ischemia. However, it then increased before slowly decreasing. Lactate release during hypoxemia peaked at 13.0 \ub1 2.3 \u3bcmol/min after 2 min, leveling off to 3.5 \ub1 1.3 \u3bcmol/min. Glycogen decreased by 52 and 81% in ischemic and hypoxemic hearts, respectively (P < 0.05). Reexposure to ischemia or hypoxemia induced comparable changes in both groups. We conclude that, at the beginning of ischemia, a single factor does limit myocardial performance. This variable, which remains undisturbed for 10 min, is presumably O2 availability. In contrast, 20 s after induction of hypoxemia, glycolytic ATP production can partially override low O2 availability by providing most of the energy needed. During repeated restriction of O2 supply, O2 availability alone limits performance during both ischemia and hypoxemia

High-Intensity Exercise Mitigates Cardiovascular Deconditioning During Long-Duration Bed Rest

Head-down-tilt bed rest (HDT) mimics the changes in hemodynamics and autonomic cardiovascular control induced by weightlessness. However, the time course and reciprocal interplay of these adaptations, and the effective exercise protocol as a countermeasure need further clarification. The overarching aim of this work (as part of a European Space Agency sponsored long-term bed rest study) was therefore to evaluate the time course of cardiovascular hemodynamics and autonomic control during prolonged HDT and to assess whether high-intensity, short-duration exercise could mitigate these effects. A total of n = 23 healthy, young, male participants were randomly allocated to two groups: training (TRAIN, n = 12) and non-training (CTRL, n = 11) before undergoing a 60-day HDT. The TRAIN group underwent a resistance training protocol using reactive jumps (5–6 times per week), whereas the CTRL group did not perform countermeasures. Finger blood pressure (BP), heart rate (HR), and stroke volume were collected beat-by-beat for 10 min in both sitting and supine positions 7 days before HDT (BDC−7) and 10 days after HDT (R+10), as well as on the 2nd (HDT2), 28th (HDT28), and 56th (HDT56) day of HDT. We investigated (1) the isolated effects of long-term HDT by comparing all the supine positions (including BDC−7 and R+10 at 0 degrees), and (2) the reactivity of the autonomic response before and after long-term HDT using a specific postural stimulus (i.e., supine vs. sitting). Two-factorial linear mixed models were used to assess the time course of HDT and the effect of the countermeasure. Starting from HDT28 onwards, HR increased (p &lt; 0.02) and parasympathetic tone decreased exclusively in the CTRL group (p &lt; 0.0001). Moreover, after 60-day HDT, CTRL participants showed significant impairments in increasing cardiac sympathovagal balance and controlling BP levels during postural shift (supine to sitting), whereas TRAIN participants did not. Results show that a 10-day recovery did not compensate for the cardiovascular and autonomic deconditioning following 60-day HDT. This has to be considered when designing rehabilitation programs—not only for astronauts but also in general public healthcare. High-intensity, short-duration exercise training effectively minimized these impairments and should therefore deserve consideration as a cardiovascular deconditioning countermeasure for spaceflight

Moderate aerobic exercise (brisk walking) increases bone density in cART-treated persons

Moderate intensity aerobic activity reduces the risk of cardiovascular disease, diabetes and metabolic syndrome in the general population and has a potential in preventing bone loss. We evaluated the effects of brisk walking, with or without strength exercise, on bone mineral density in HIV-infected treated persons. Twenty-eight HIV-infected, cART-treated, sedentary subjects with VL&#60;50 c/mL were enrolled in a 12-week exercise program, consisting of 3 outdoor sessions/week of 60 min walking at 67&#x2013;70% of HR (heart rate) max&#x00B1;30 min circuit training at 65% of 1-RM (repetition maximum). Subjects were examined at baseline (BL) and 12 weeks (W12) by 6-minute walking test (6MWT) and by counting the number of repetitions for each strength exercise; and by dual energy X-ray absorptiometry (DEXA) to evaluate lumbar spine and femoral bone mineral density with t- and z-scores - in addition to morphometric (BMI, waist, hip and leg circumference) and blood examination (cytometry, fasting total, HDL and LDL cholesterol, triglycerides, glucose, insulin; AST/ALT, ALP, gGT, creatinine, CPK, HbA1c; CD4+ and CD8+, plasma HIV-RNA). Differences over time were tested by Wilcoxon-signed rank test and between groups by Mann-Whitney test. Twenty-seven (96%) participants (19M, 8F; median 48 y-o, IQR 43&#x2013;54; median CD4+624/&#x00B5;L, IQR 478&#x2013;708; ART with PI: 13 patients, with NNRTI: 7 patients, and including TDF: 15 patients) completed the 12-week program with a median adherence of 61% (IQR 50&#x2013;70): 18 in the &#x2018;walk only&#x2019; only group and 9 in the &#x2018;walk and strength&#x2019; group. At W12, participants showed significant improvement of distance by 6MWT (Table), and of performance in all strength exercises (crunch p=0.023, lat machine p=0.016, chest press p=0.016, leg extension p=0.016, sitting calf p=0.008, leg press p=0.016). DEXA spine z-score improved significantly in the whole group, and femoral z-scores in the &#x2018;walk only&#x2019; group. There was no z-score difference at BL between patients with/out PIs, NNRTIs or TDF. However, spine z-score improved significantly in patients receiving TDF. At W12 BMI, waist circumference, and LDL also improved significantly in the whole group, whereas no significant changes were observed for the other variables, The above 12-week program improved fitness and bone density in HIV-infected treated subjects, in addition to some morphometric variables and serum LDL. Brisk walking, with or without strength exercise, might help control the long-term consequences of cART

Waiting times for diagnosis of attention-deficit hyperactivity disorder in children and adolescents referred to Italian ADHD centers must be reduced

BACKGROUND: To investigate timely access to and the time needed to complete the diagnostic path of children and adolescents with suspected attention deficit hyperactivity disorder (ADHD) in the 18 Italian Lombardy Region ADHD reference centers. METHODS: Data of children and adolescents enrolled in the Regional ADHD disease-oriented Registry for suspected ADHD who requested their first visit in 2013-2017 were analyzed. RESULTS: The sample comprised 2262 children and adolescents aged 5-17\u2009years who accessed the ADHD centers for diagnostic classification and management. The median waiting time was of 177\u2009days (range 66-375) from the request for the initial appointment to the completion of the diagnostic path, with a three - fold difference between centers. In addition to the center, the strongest significant predictors of long waiting times were age comorbidities, the severity of the disorder, and having already completed some diagnostic procedures provided by the common standard path. CONCLUSIONS: To guarantee an equal standard of care in ADHD centers for all children and adolescents there is a pressing need to reduce the times to complete the diagnostic path. It is the task of both policymakers and each center to optimize the quality of the service and of the care delivered