Measuring Adherence to Antiretroviral Treatment: The Role of Pharmacy Records of Drug Withdrawals

This study aimed to evaluate adherence to anti-retroviral treatment (ART) among HIV + adults, assess its association with HIV viral load (VL) and identify factors associated to adherence. A survey involving a random sample of adults followed at a HIV/AIDS reference center in Sao Paulo city, Brazil, from 2007 to 2009 was done. A questionnaire was applied and data were retrieved from the pharmacy and medical records. The study involved 292 subjects: 70.2% men; median age: 43 years; median duration of ART: 8 years. 89.3% self-reported taken all prescribed pills in the last 3 days but only 39.3% picked up >= 95% of the prescribed ART from the pharmacy in the last 12 months. At the multivariate analysis having symptoms prior to ART, taking fewer ART pills, and not missing medical appointments were independently associated to higher adherence. Adherence was strongly associated with undetectable HIV VL. Rates of undetectable HIV VL did not differ from 80 to >= 95% of adherence.

Impact of Glucocorticoid Receptor Gene Polymorphisms on the Metabolic Profile of Adult Patients with the Classical Form of 21-Hydroxylase Deficiency

Background: CAH patients have an increased risk of cardiovascular disease, and it remains unknown if lifelong glucocorticoid (GC) treatment is a contributing factor. In the general population, glucocorticoid receptor gene (NR3C1) polymorphisms are associated with an adverse metabolic profile. Our aim was to analyze the association between the NR3C1 polymorphisms and the metabolic profile of CAH patients. Methodology: Sixty-eight adult patients (34SV/34SW) with a mean age of 28.4 +/- 9 years received dexamethasone (mean 0.27 +/- 0.11 mg/day) to obtain normal androgen levels. SW patients also received fludrocortisone (50 mu g/day). Metabolic syndrome (MetS) was defined by the NCEP ATPIII criteria and obesity by BMI >= 30 kg/m(2). NR3C1 alleles were genotyped, and association analyses with phenotype were carried out with Chi-square, t-test and regression analysis. Results: Obesity and MetS were observed in 23.5% and 7.3% of patients, respectively, and were not correlated with GC doses and treatment duration. BMI was positively correlated with blood pressure (BP), triglycerides (TG), LDL-c levels and HOMA-IR and inversely correlated with HDL-c levels. BclI and A3669G variants were found in 26.4% and 9.6% of alleles, respectively. Heterozygotes for the BclI polymorphism presented with higher BMI (29 kg/m(2) +/- 5.3 vs. 26 kg/m(2) +/- 5.3, respectively) and waist circumference (89 cm +/- 12.7 vs. 81 cm +/- 13, respectively) compared to wild-type subjects. Hypertension was found in 12% of patients and heterozygotes for the BclI polymorphism presented higher systolic BP than wild type subjects. Low HDL-c and high TG levels were identified in 30% and 10% of patients, respectively, and were not associated with the NR3C1 polymorphisms. A3669G carriers and non-carriers did not differ. Conclusion: In addition to GC therapy, the BclI GR variant might play an important role in obesity susceptibility in CAH patients. Genotyping of GR polymorphisms could result in the identification of a subgroup at risk patients, allowing for the establishment of personalized treatment and the avoidance of long-term adverse consequences.

Differentiating between tuberculosis-related and lymphoma-related lymphocytic pleural effusions by measuring clinical and laboratory variables: Is it possible?

Objective: To describe clinical and laboratory characteristics in patients with tuberculosis-related or lymphoma-related lymphocytic pleural effusions, in order to identify the variables that might contribute to differentiating between these diseases. Methods: This was a retrospective study involving 159 adult HIV-negative patients with tuberculosis-related or lymphoma-related lymphocytic effusions (130 and 29 patients, respectively), treated between October of 2008 and March of 2010 at the Pleural Diseases Outpatient Clinic of the University of Sao Paulo School of Medicine Hospital das Clinicas Heart Institute, in the city of Sao Paulo, Brazil. Results: Mean age and the mean duration of symptoms were lower in the tuberculosis group than in the lymphoma group. The levels of proteins, albumin, cholesterol, amylase, and adenosine deaminase (ADA) in pleural fluid, as well as the serum levels of proteins, albumin, and amylase, were higher in the tuberculosis group, whereas serum cholesterol and triglycerides were higher in the lymphoma group. Pleural fluid leukocyte and lymphocyte counts were higher in the tuberculosis group. Of the tuberculosis group patients, none showed malignant cells; however, 4 showed atypical lymphocytes. Among the lymphoma group patients, cytology for neoplastic cells was positive, suspicious, and negative in 51.8%, 24.1%, and 24.1%, respectively. Immunophenotyping of pleural fluid was conclusive in most of the lymphoma patients. Conclusions: Our results demonstrate clinical and laboratory similarities among the patients with tuberculosis or lymphoma. Although protein and ADA levels in pleural fluid tended to be higher in the tuberculosis group than in the lymphoma group, even these variables showed an overlap. However, none of the tuberculosis group patients had pleural fluid ADA levels below the 40-U/L cut-off point.

Manipulation effects of prior exercise intensity feedback by the Borg scale during open-loop cycling

Objective To verify the effects of exercise intensity deception by the Borg scale on the ratings of perceived exertion (RPE), heart rate (HR) and performance responses during a constant power output open-loop exercise. Methods Eight healthy men underwent a maximal incremental test on a cycle ergometer to identify the peak power output (PPO) and heart rate deflection point (HRDP). Subsequently, they performed a constant power output trial to exhaustion set at the HRDP intensity, in deception (DEC) and informed (INF) conditions: DEC-subjects were told that they would be cycling at an intensity corresponding to two categories below the RPE quantified at the HRDP; INF-subjects were told that they would cycle at the exact intensity corresponding to the RPE quantified at the HRDP. Results The PPO and power output at the HRDP obtained in maximal incremental tests were 247.5 +/- 32.1 W and 208.1 +/- 27.1 W, respectively. No significant difference in the time to exhaustion was found between DEC (525 +/- 244 s) or INF (499 +/- 224 s) trials. The slope and the first and second measurements of the RPE and HR parameters showed no significant difference between trials. Conclusions Psychophysiological variables such as RPE and HR as well as performance were not affected when exercise intensity was deceptively manipulated via RPE scores. This may suggest that unaltered RPE during exercise is a regulator of performance in this open-loop exercise.

Metformin versus lifestyle changes in treating women with polycystic ovary syndrome

Objective: To compare the efficacy of metformin with that of lifestyle changes in patients with polycystic ovary syndrome (PCOS). Design: Prospective, randomized clinical trial of 40 women with PCOS to analyze the effects of metformin and lifestyle intervention treatments on menstrual pattern and hormone and metabolic profile. The duration of treatment was 6 months. Statistical analysis was done using Student's t-test. Results: Fifteen women in the metformin group and 12 in the lifestyle changes group completed the study. The menstrual pattern improved by similar to 67% in both groups. There was a significant decrease in waist circumference in the lifestyle changes group (101.8 +/- 3.9 and 95.1 +/- 3.6, at baseline and at 6 months of treatment, respectively; p<0.001) and in body mass index (BMI) in both groups. The predictor of menstrual pattern improvement was BMI. Conclusions: Both metformin and lifestyle changes may increase the number of menstrual cycles in PCOS. This effect was related to a decrease in BMI.

Age-Related Expansion of Tim-3 Expressing T Cells in Vertically HIV-1 Infected Children

As perinatally HIV-1-infected children grow into adolescents and young adults, they are increasingly burdened with the long-term consequences of chronic HIV-1 infection, with long-term morbidity due to inadequate immunity. In progressive HIV-1 infection in horizontally infected adults, inflammation, T cell activation, and perturbed T cell differentiation lead to an "immune exhaustion'', with decline in T cell effector functions. T effector cells develop an increased expression of CD57 and loss of CD28, with an increase in co-inhibitory receptors such as PD-1 and Tim-3. Very little is known about HIV-1 induced T cell dysfunction in vertical infection. In two perinatally antiretroviral drug treated HIV-1-infected groups with median ages of 11.2 yr and 18.5 yr, matched for viral load, we found no difference in the proportion of senescent CD28(-)CD57(+)CD8(+) T cells between the groups. However, the frequency of Tim-3(+)CD8(+) and Tim-3(+)CD4(+) exhausted T cells, but not PD-1(+) T cells, was significantly increased in the adolescents with longer duration of infection compared to the children with shorter duration of HIV-1 infection. PD-1(+)CD8(+) T cells were directly associated with T cell immune activation in children. The frequency of Tim-3(+)CD8(+) T cells positively correlated with HIV-1 plasma viral load in the adolescents but not in the children. These data suggest that Tim-3 upregulation was driven by both HIV-1 viral replication and increased age, whereas PD-1 expression is associated with immune activation. These findings also suggest that the Tim-3 immune exhaustion phenotype rather than PD-1 or senescent cells plays an important role in age-related T cell dysfunction in perinatal HIV-1 infection. Targeting Tim-3 may serve as a novel therapeutic approach to improve immune control of virus replication and mitigate age related T cell exhaustion.

Experimental Assessment of the Sensitiveness of an Electrochemical Oscillator towards Chemical Perturbations

In this study we address the problem of the response of a (electro)chemical oscillator towards chemical perturbations of different magnitudes. The chemical perturbation was achieved by addition of distinct amounts of trifluoromethanesulfonate (TFMSA), a rather stable and non-specifically adsorbing anion, and the system under investigation was the methanol electro-oxidation reaction under both stationary and oscillatory regimes. Increasing the anion concentration resulted in a decrease in the reaction rates of methanol oxidation and a general decrease in the parameter window where oscillations occurred. Furthermore, the addition of TFMSA was found to decrease the induction period and the total duration of oscillations. The mechanism underlying these observations was derived mathematically and revealed that inhibition in the methanol oxidation through blockage of active sites was found to further accelerate the intrinsic non-stationarity of the unperturbed system. Altogether, the presented results are among the few concerning the experimental assessment of the sensitiveness of an oscillator towards chemical perturbations. The universal nature of the complex chemical oscillator investigated here might be used for reference when studying the dynamics of other less accessible perturbed networks of (bio)chemical reactions.

Biological and behavioral parameters of the parasitoid Cotesia flavipes (Hymenoptera: Braconidae) are altered by the pathogen Nosema sp (Microsporidia: Nosematidae)

A major issue for mass rearing of insects concerns sanitary conditions and disease. Microsporidian infection (Nosema sp.) in laboratory colonies of Diatraea saccharalis (Fabr.) (Lepidoptera: Crambidae), used in producing the parasitoid. Cotesia flavipes Cameron (Hymenoptera: Braconidae), is representative of the problems faced by growers and industry. Although C. flavipes has been produced for several years in Brazil for biological control of D. saccharalis, we have only recently observed that the parasitoid becomes infected when developing inside hosts infected with Nosema sp. We assessed the effects of Nosema sp. on C. flavipes, including the ability to locate and select hosts, and evaluated pathogen transmission. Third instar larvae of D. saccharalis were inoculated with Nosema sp. spores at different concentrations and were parasitized when larvae reached fifth instar. Heavily infected D. saccharalis larvae did not support parasitism. Parasitoids that developed in infected D. saccharalis larvae exhibited increased duration of larval and pupal stages, decreased adult longevity and number of offspring, and reduced tibia size compared to parasitoids developing in uninfected D. saccharalis larvae. Infection by Nosema sp. reduced the ability of the C. flavipes parasitoid to distinguish between volatiles released by the sugarcane infested by healthy larvae and pure air. Uninfected parasitoids preferred plants infested with uninfected hosts. But infected C. flavipes did not differentiate between uninfected hosts and those infected with Nosema sp. The pathogen is transmitted from host to parasitoids and parasitoids to hosts. Pathogenic effects of the microsporidium in C. flavipes are sufficiently severe to justify disease management efforts, particularly considering the importance of C. flavipes as a biological control agent in sugarcane. (C) 2012 Elsevier Inc. All rights reserved.

Maternal Moderate Physical Training during Pregnancy Attenuates the Effects of a Low-Protein Diet on the Impaired Secretion of Insulin in Rats: Potential Role for Compensation of Insulin Resistance and Preventing Gestational Diabetes Mellitus

The effects of pregestational and gestational low-to-moderate physical training on insulin secretion in undernourished mothers were evaluated. Virgin female Wistar rats were divided into four groups as follows: control (C, n = 5); trained (T, n = 5); low-protein diet (LP, n = 5); trained with a low-protein diet (T + LP, n = 5). Trained rats ran on a treadmill over a period of 4 weeks before mate (5 days week(-1) and 60 min day(-1), at 65% of VO2max). At pregnancy, the intensity and duration of the exercise were reduced. Low-protein groups were provided with an 8% casein diet, and controls were provided with a 17% casein diet. At third day after delivery, mothers and pups were killed and islets were isolated by collagenase digestion of pancreas and incubated for a further 1 h with medium containing 5.6 or 16.7 mM glucose. T mothers showed increased insulin secretion by isolated islets incubated with 16.7 mM glucose, whereas LP group showed reduced secretion of insulin by isolated islets when compared with both C and LP + T groups. Physical training before and during pregnancy attenuated the effects of a low-protein diet on the secretion of insulin, suggesting a potential role for compensation of insulin resistance and preventing gestational diabetes mellitus.

Assessment of "non-recordable" electroretinograms by 9 Hz flicker stimulation under scotopic conditions

To refine methods of electroretinographical (ERG) recording for the analysis of low retinal potentials under scotopic conditions in advanced retinal degenerative diseases. Standard Ganzfeld ERG equipment (Diagnosys LLC, Cambridge, UK) was used in 27 healthy volunteers (mean age 28 +/- A SD 8.5 years) to define the stimulation protocol. The protocol was then applied in clinical routine and 992 recordings were obtained from patients (mean age 40.6 +/- A 18.3 years) over a period of 5 years. A blue stimulus with a flicker frequency of 9 Hz was specified under scotopic conditions to preferentially record rod-driven responses. A range of stimulus strengths (0.0000012-6.32 scot. cd s/mA(2) and 6-14 ms flash duration) was tested for maximal amplitudes and interference between rods and cones. Analysis of results was done by standard Fourier Transformation and assessment of signal-to-noise ratio. Optimized stimulus parameters were found to be a time-integrated luminance of 0.012 scot. cd s/mA(2) using a blue (470 nm) flash of 10 ms duration at a repetition frequency of 9 Hz. Characteristic stimulus strength versus amplitude curves and tests with stimuli of red or green wavelength suggest a predominant rod-system response. The 9 Hz response was found statistically distinguishable from noise in 38% of patients with otherwise non-recordable rod responses according to International Society for Clinical Electrophysiology of Vision standards. Thus, we believe this protocol can be used to record ERG potentials in patients with advanced retinal diseases and in the evaluation of potential treatments for these patients. The ease of implementation in clinical routine and of statistical evaluation providing an observer-independent evaluation may further facilitate its employment.

Impaired lung function in individuals chronically exposed to biomass combustion

Background: The use of biomass for cooking and heating is considered an important factor associated with respiratory diseases. However, few studies evaluate the amount of particulate matter less than 2.5 mu in diameter (PM2.5), symptoms and lung function in the same population. Objectives: To evaluate the respiratory effects of biomass combustion and compare the results with those of individuals from the same community in Brazil using liquefied petroleum gas (Gas). Methods: 1402 individuals in 260 residences were divided into three groups according to exposure (Gas, Indoor-Biomass, Outside-Biomass). Respiratory symptoms were assessed using questionnaires. Reflectance of paper filters was used to assess particulate matter exposure. In 48 residences the amount of PM2.5 was also quantified. Pulmonary function tests were performed in 120 individuals. Results: Reflectance index correlated directly with PM2.5 (r=0.92) and was used to estimate exposure (ePM2.5). There was a significant increase in ePM2.5 in Indoor-Biomass and Outside-Biomass, compared to Gas. There was a significantly increased odds ratio (OR) for cough, wheezing and dyspnea in adults exposed to Indoor-Biomass (OR=2.93, 2.33, 2.59, respectively) and Outside-Biomass (OR=1.78, 1.78, 1.80, respectively) compared to Gas. Pulmonary function tests revealed both Non-Smoker-Biomass and Smoker-Gas individuals to have decreased %predicted-forced expiratory volume in the first second (FEV1) and FEV1/forced vital capacity (FVC) as compared to Non-Smoker-Gas. Pulmonary function tests data was inversely correlated with duration and ePM2.5. The prevalence of airway obstruction was 20% in both Non-Smoker-Biomass and Smoker-Gas subjects. Conclusion: Chronic exposure to biomass combustion is associated with increased prevalence of respiratory symptoms, reduced lung function and development of chronic obstructive pulmonary disease. These effects are associated with the duration and magnitude of exposure and are exacerbated by tobacco smoke. (C) 2011 Elsevier Inc. All rights reserved.

Low pressure support changes the rapid shallow breathing index (RSBI) in critically ill patients on mechanical ventilation

Background: The rapid shallow breathing index (RSBI) is the most widely used index within intensive care units as a predictor of the outcome of weaning, but differences in measurement techniques have generated doubts about its predictive value. Objective: To investigate the influence of low levels of pressure support (PS) on the RSBI value of ill patients. Method: Prospective study including 30 patients on mechanical ventilation (MV) for 72 hours or more, ready for extubation. Prior to extubation, the RSBI was measured with the patient connected to the ventilator (Drager (TM) Evita XL) and receiving pressure support ventilation (PSV) and 5 cmH(2)O of positive end expiratory pressure or PEEP (RSBI_MIN) and then disconnected from the VM and connected to a Wright spirometer in which respiratory rate and exhaled tidal volume were recorded for 1 min (RSBI_ESP). Patients were divided into groups according to the outcome: successful extubation group (SG) and failed extubation group (FG). Results: Of the 30 patients, 11 (37%) failed the extubation process. In the within-group comparison (RSBI_MIN versus RSBI_ESP), the values for RSBI_MIN were lower in both groups: SG (34.79 +/- 4.67 and 60.95 +/- 24.64) and FG (38.64 +/- 12.31 and 80.09 +/- 20.71; p<0.05). In the between-group comparison, there was no difference in RSBI_MIN (34.79 +/- 14.67 and 38.64 +/- 12.31), however RSBI_ESP was higher in patients with extubation failure: SG (60.95 +/- 24.64) and FG (80.09 +/- 20.71; p<0.05). Conclusion: In critically ill patients on MV for more than 72h, low levels of PS overestimate the RSBI, and the index needs to be measured with the patient breathing spontaneously without the aid of pressure support.

Early Rheumatoid Arthritis in Latin America: Low Socioeconomic Status Related to High Disease Activity at Baseline

Objective. To determine the influence of socioeconomic factors on disease activity in a Latin American (LA) early rheumatoid arthritis (RA) multinational inception cohort at baseline. Methods. Clinical evaluation, ethnicity, socioeconomic status (SES), 4-variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR), Health Assessment Questionnaire (HAQ) disability index (DI), and erosions were recorded in 1,093 patients with early RA (<1 year from onset). Multivariate analyses evaluated influences of sex, age, marital status, education, medical coverage, SES, and ethnicity on HAQ DI, DAS28-ESR, and presence of erosions. Results. Ethnicities included 43% Mestizo, 31% Caucasian, 19% African LA, 4% Amerindian, and 3% other. Fifty-eight percent were of low/low-middle SES, 42% had <8 years of education, 21% had no medical coverage, median disease duration was 6 months (25th, 75th percentiles 4, 9 months), median HAQ DI score was 1.25 (25th, 75th percentiles 0.63, 2.00), median DAS28-ESR score was 6.2 (25th, 75th percentiles 4.9, 7.2), and 25% had erosions. Women and Mestizos, African LA, and Amerindians had earlier onset than men or Caucasians (P < 0.01). When adjusted by country, the analysis of covariance model showed that low/low-middle SES, female sex, partial coverage, and older age were associated with worse HAQ DI scores; only low/low-middle SES was associated with higher DAS28 scores. Statistically significant differences were found in HAQ DI and DAS28 scores between countries. When excluding country, low/low-middle SES, female sex, and no coverage were associated with worse HAQ DI and DAS28 scores, whereas separated/divorced/widowed status was associated with worse HAQ DI scores and age was associated with worse DAS28 scores. Logistic regression showed that older age, no coverage, and the Amerindian and other ethnic groups were associated with erosions. Conclusion. We compared early RA patients from the main LA ethnic groups. Our findings suggest that low/low-middle SES is important in determining disease activity. A more genetic-related background for erosions is possible.

Effects of Gastric Bypass Surgery in Patients With Type 2 Diabetes and Only Mild Obesity

OBJECTIVE-Roux-en-Y gastric bypass (RYGB) ameliorates type 2 diabetes in severely obese patients through mechanisms beyond just weight loss, and it may benefit less obese diabetic patients. We determined the long-term impact of RYGB on patients with diabetes and only class 1 obesity. RESEARCH DESIGN AND METHODS-Sixty-six consecutively selected diabetic patients with BMI 30-35 kg/m(2) underwent RYGB in a tertiary-care hospital and were prospectively studied for up to 6 years (median 5 years [range 1-6]), with 100% follow-up. Main outcome measures were safety and the percentage of patients experiencing diabetes remission (HbA(1c) <6.5% without diabetes medication). RESULTS-Participants had severe, longstanding diabetes, with disease duration 12.5 +/- 7.4 years and HbA(1c) 9.7 +/- 1.5%, despite insulin and/or oral diabetes medication usage in everyone. For up to 6 years following RYGB, durable diabetes remission occurred in 88% of cases, with glycemic improvement in 11%. Mean HbA(1c) fell from 9.7 +/- 1.5 to 5.9 +/- 0.1% (P < 0.001), despite diabetes medication cessation in the majority. Weight loss failed to correlate with several measures of improved glucose homeostasis, consistent with weight-independent antidiabetes mechanisms of RYGB. C-peptide responses to glucose increased substantially, suggesting improved beta-cell function. There was no mortality, major surgical morbidity, or excessive weight loss. Hypertension and dyslipidemia also improved, yielding 50-84% reductions in predicted 10-year cardiovascular disease risks of fatal and nonfatal coronary heart disease and stroke. CONCLUSIONS-This is the largest, longest-term study examining RYGB for diabetic patients without severe obesity. RYGB safely and effectively ameliorated diabetes and associated comorbidities, reducing cardiovascular risk, in patients with a BMI of only 30-35 kg/m(2).

Reproductive behavior of Acanthagrion truncatum Selys, 1876 (Odonata: Coenagrionidae)

Behavioral data on Neotropical coenagrionids is still scanty, with very few studies on their reproductive behavior. Here we present the first description of the reproductive behavior of A. truncatum in a high density population in the Brazilian Neotropical savanna. The observations were made at a pond in an ecological reserve. Males remain at the water searching for females. Females remain in the surrounding vegetation and only approach the water to mate and oviposit. The mean duration of copulation was 25.6 +/- 3.26 minutes. Copulations are concentrated between 12:00 and 14:00 h (71%). Females oviposit in tandem with males, sometimes submerging to oviposit. Oviposition took 43.08 +/- 22.17 minutes. Female underwater oviposition seems to disrupt male guarding and females emerge from the water by themselves. Malemale interactions usually consist of chases and facing off. This damselfly species is apparently non-territorial, since males did not defend resources and searched for females in the area.