Chemometric analysis of Hymenoptera toxins and defensins: A model for predicting the biological activity of novel peptides from venoms and hemolymph

When searching for prospective novel peptides, it is difficult to determine the biological activity of a peptide based only on its sequence. The trial and error approach is generally laborious, expensive and time consuming due to the large number of different experimental setups required to cover a reasonable number of biological assays. To simulate a virtual model for Hymenoptera insects, 166 peptides were selected from the venoms and hemolymphs of wasps, bees and ants and applied to a mathematical model of multivariate analysis, with nine different chemometric components: GRAVY, aliphaticity index, number of disulfide bonds, total residues, net charge, pI value, Boman index, percentage of alpha helix, and flexibility prediction. Principal component analysis (PCA) with non-linear iterative projections by alternating least-squares (NIPALS) algorithm was performed, without including any information about the biological activity of the peptides. This analysis permitted the grouping of peptides in a way that strongly correlated to the biological function of the peptides. Six different groupings were observed, which seemed to correspond to the following groups: chemotactic peptides, mastoparans, tachykinins, kinins, antibiotic peptides, and a group of long peptides with one or two disulfide bonds and with biological activities that are not yet clearly defined. The partial overlap between the mastoparans group and the chemotactic peptides, tachykinins, kinins and antibiotic peptides in the PCA score plot may be used to explain the frequent reports in the literature about the multifunctionality of some of these peptides. The mathematical model used in the present investigation can be used to predict the biological activities of novel peptides in this system, and it may also be easily applied to other biological systems. © 2011 Elsevier Inc.

Efficacy of antibiotic therapy for peritoneal dialysis-associated peritonitis: a proportional meta-analysis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Early loading of 6-mm-short implants with a moderately rough surface supporting single crowns: a prospective 5-year cohort study

AimTo evaluate prospectively the clinical and radiographic outcomes after 5years of early loading of 6-mm implants with a moderately rough (SLActive((R))) surface supporting single crowns in the posterior regions.Material and methodsThirty-five consecutive patients received 40 SLActive((R)) (Straumann) 6-mm implants with a diameter of 4.1mm (n=19) or 4.8mm (n=21). Insertion torque and resonance frequency analysis (RFA) were measured at implant installation. RFA was also measured at abutment connection. SynOcta abutments were tightened with 35Ncm after 6weeks of healing, and single porcelain fuse to metal crowns was cemented within 1week. Implant survival rate and marginal bone loss were evaluated at various time intervals until 5years after loading. The clinical crown/implant ratio was calculated as well.ResultsTwo of 40 implants were lost before loading (incorporation rate 95%), and no further implant loss or technical complications were encountered during the 5-year follow-up period. A mean marginal bone loss of 0.70.6mm was found after 5years of function. The clinical crown/implant ratio increased with time from 1.6 at the delivery of the prosthesis to 2 after 5years of loading.ConclusionSix millimeter implants with a SLActive((R)) moderately rough surface supporting single crowns in the posterior region and loaded after 6-7weeks maintained full function for at least 5year with low marginal bone resorption.

Behavioral measures to reduce non-adherence in renal transplant recipients: a prospective randomized controlled trial

Solid-organ transplant recipients present a high rate of non-adherence to drug treatment. Few interventional studies have included approaches aimed at increasing adherence. The objective of this study was to evaluate the impact of an educational and behavioral strategy on treatment adherence of kidney transplant recipients. In a randomized prospective study, incident renal transplant patients (n = 111) were divided into two groups: control group (received usual transplant patient education) and treatment group (usual transplant patient education plus ten additional weekly 30-min education/counseling sessions about immunosuppressive drugs and behavioral changes). Treatment adherence was assessed using ITAS adherence questionnaire after 3 months. Renal function at 3, 6, and 12 months, and the incidence of transplant rejection were evaluated. The non-adherence rates were 46.4 and 14.5 % in the control and treatment groups (p = 0.001), respectively. The relative risk for non-adherence was 2.59 times (CI 1.38-4.88) higher in the control group. Multivariate analysis demonstrated a 5.84 times (CI 1.8-18.8, p = 0.003) higher risk of non-adherence in the control group. There were no differences in renal function and rejection rates between groups. A behavioral and educational strategy addressing the patient's perceptions and knowledge about the anti-rejection drugs significantly improved the short-term adherence to immunosuppressive therapy.

Automated peritoneal dialysis is associated with better survival rates compared to continuous ambulatory peritoneal dialysis: a propensity score matching analysis

The impact of peritoneal dialysis modality on patient survival and peritonitis rates is not fully understood, and no large-scale randomized clinical trial (RCT) is available. In the absence of a RCT, the use of an advanced matching procedure to reduce selection bias in large cohort studies may be the best approach. The aim of this study is to compare automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD) according to peritonitis risk, technique failure and patient survival in a large nation-wide PD cohort. This is a prospective cohort study that included all incident PD patients with at least 90 days of PD recruited in the BRAZPD study. All patients who were treated exclusively with either APD or CAPD were matched for 15 different covariates using a propensity score calculated with the nearest neighbor method. Clinical outcomes analyzed were overall mortality, technique failure and time to first peritonitis. For all analysis we also adjusted the curves for the presence of competing risks with the Fine and Gray analysis. After the matching procedure, 2,890 patients were included in the analysis (1,445 in each group). Baseline characteristics were similar for all covariates including: age, diabetes, BMI, Center-experience, coronary artery disease, cancer, literacy, hypertension, race, previous HD, gender, pre-dialysis care, family income, peripheral artery disease and year of starting PD. Mortality rate was higher in CAPD patients (SHR1.44 CI95%1.21-1.71) compared to APD, but no difference was observed for technique failure (SHR0.83 CI95%0.69-1.02) nor for time till the first peritonitis episode (SHR0.96 CI95%0.93-1.11). In the first large PD cohort study with groups balanced for several covariates using propensity score matching, PD modality was not associated with differences in neither time to first peritonitis nor in technique failure. Nevertheless, patient survival was significantly better in APD patients.

A comparative, prospective and randomized evaluation of roux-en-y gastric bypass with and without the silastic ring: a 2-year follow up preliminary report on weight loss and quality of life

Currently, Roux-en-Y gastric bypass (RYGB) is one of the most widely used bariatric surgeries. Banding the pouch forms a banded gastric bypass operation, an accepted and frequently used variant. Placing a silastic ring around the pouch to band the gastric bypass operation increases the restriction mechanism. However, the ubiquitous use of the banded gastric bypass remains controversial. One of the controversies is the effect of the silastic ring on patients' perception of their well being after surgery because of the frequency of vomiting. A prospective, blindly randomized, comparative trial was undertaken to resolve this controversy. Four hundred subjects scheduled for gastric bypass surgery were randomized into two arms of the trial, 200 with a silastic ring (WR) and 200 without (NR). After 2-year follow-up, the variables associated with the scores of Bariatric Analysis and Reporting Outcome System (BAROS) were analyzed. The initial median weight (125 kg), BMI (47), and age (36 years) were the same in both the NR and WR groups. The median excess weight loss, weight regain, and incidence of vomiting were 71, 10.5, and 7.75 %, respectively, in the NR group vs. 75.4 and 1.1, and 24.4 % in the WR group. The mean QOL score was 79 % in the NR group vs. 80 % in the WR group. After 2-year follow-up, silastic ring placement in the RYGB resulted in greater weight loss and weight stability and a threefold greater incidence of vomiting. There was no difference in the scores in the quality of life analysis.

Blood transfusions increase circulating plasma free hemoglobin levels and plasma nitric oxide consumption: a prospective observational pilot study

Introduction: The increasing number of reports on the relation between transfusion of stored red blood cells (RBCs) and adverse patient outcome has sparked an intense debate on the benefits and risks of blood transfusions. Meanwhile, the pathophysiological mechanisms underlying this postulated relation remain unclear. The development of hemolysis during storage might contribute to this mechanism by release of free hemoglobin (fHb), a potent nitric oxide (NO) scavenger, which may impair vasodilation and microcirculatory perfusion after transfusion. The objective of this prospective observational pilot study was to establish whether RBC transfusion results in increased circulating fHb levels and plasma NO consumption. In addition, the relation between increased fHb values and circulating haptoglobin, its natural scavenger, was studied. Methods: Thirty patients electively received 1 stored packed RBC unit (n = 8) or 2 stored packed RBC units (n = 22). Blood samples were drawn to analyze plasma levels of fHb, haptoglobin, and NO consumption prior to transfusion, and 15, 30, 60 and 120 minutes and 24 hours after transfusion. Differences were compared using Pearson's chi-square test or Fisher's exact test for dichotomous variables, or an independent-sample t test or Mann-Whitney U test for continuous data. Continuous, multiple-timepoint data were analyzed using repeated one-way analysis of variance or the Kruskall-Wallis test. Correlations were analyzed using Spearman or Pearson correlation. Results: Storage duration correlated significantly with fHb concentrations and NO consumption within the storage medium (r = 0.51, P < 0.001 and r = 0.62, P = 0.002). fHb also significantly correlated with NO consumption directly (r = 0.61, P = 0.002). Transfusion of 2 RBC units significantly increased circulating fHb and NO consumption in the recipient (P < 0.001 and P < 0.05, respectively), in contrast to transfusion of 1 stored RBC unit. Storage duration of the blood products did not correlate with changes in fHb and NO consumption in the recipient. In contrast, pre-transfusion recipient plasma haptoglobin levels inversely influenced post-transfusion fHb concentrations. Conclusion: These data suggest that RBC transfusion can significantly increase post-transfusion plasma fHb levels and plasma NO consumption in the recipient. This finding may contribute to the potential pathophysiological mechanism underlying the much-discussed adverse relation between blood transfusions and patient outcome. This observation may be of particular importance for patients with substantial transfusion requirements.

Tele-obstetric ultrasound: analysis of first-trimester ultrasound images transmitted in realtime

We evaluated the diagnostic quality of first-trimester ultrasound images transmitted in realtime using low-cost telecommunications. A prospective sample of fetal ultrasound images from 11 weeks to 13 weeks and six days of pregnancy was obtained from pregnant women over 18 years old. The examinations were transmitted in realtime to three independent examiners who carried out a qualitative assessment based on parameters established by the Fetal Medicine Foundation. All fetal structures could be viewed and the quality of images received by the examiners was considered normal. There were significant differences for crown-rump length and nuchal translucency in the transmitted images but the loss in definition was acceptable. Thus the quality of images transmitted via the Internet through the use of low-cost software appeared suitable for screening for chromosomal abnormalities in the first trimester of pregnancy.

Nebulized 0.5, 2.5 and 5 ml L-epinephrine for post-extubation stridor in children: a prospective, randomized, double-blind clinical trial

Nebulized l-epinephrine has been recommended for the treatment of viral croup. However, the few studies assessing its effect on post-extubation stridor (PES) have shown conflicting results. We compared the efficacy and safety of nebulized l-epinephrine at three different doses for the treatment of PES. We conducted a prospective, randomized, double-blind trial including all consecutive children with a PES score of a parts per thousand yen4 (Westley score). The primary efficacy outcome was change in PES score at 40 min. A reduction of a parts per thousand yen2 points in stridor score was defined as clinically significant. A total of 96 patients were randomly assigned to receive one of three doses of nebulized l-epinephrine upon achieving a PES score of 4 or more following extubation. Stridor score and vital signs were recorded before treatment, and at 20, 40, 60 and 180 min after nebulization. Baseline characteristics were similar among all study groups. No significant difference was detected among the treatments based on change in Westley score by intent-to-treat analysis. In addition, the difference in the number of patients who clinically improved among the treatment groups was not significant (p = 0.54). Patients receiving 5 ml nebulized epinephrine had a significant increase of systolic and diastolic blood pressure at 40 and 180 min. Nebulized l-epinephrine at doses of 0.5, 2.5 and 5 ml demonstrated a lack of dose response in effect on PES and a modestly clinically significant increase in undesired side effects (heart rate and blood pressure) at higher doses.

HIGH VOLTAGE PULSED CURRENT STIMULATION OF THE SCIATIC NERVE IN RATS: ANALYSIS BY THE SFI

Objective: To analyze the efficiency of high voltage pulsed current (HVPC) with early application in three different sites, in the regeneration of the sciatic nerve in rats submitted to crush injury, the sciatic functional index (SFI) was used to assess the functional recovery. Methods: After crushing of the nerve, 57 animals were submitted to cathodal HVPC at frequency of 50Hz and voltage of 100V, 20 minutes per day, 5 days per week. The rats were divided into five groups: control group; ganglion group; ganglion + muscle group; muscle group; and sham group. The SFI was determined weekly for seven weeks, from the preoperative period to the 6th postoperative week. Results: Compared with the control group, the results showed a significantly better performance of group 2 for the first 3 weeks; group 3 showed significantly better performance in the third week; and group 4 showed a significantly negative performance during the 481 and 6th weeks. Conclusion: Early application of HVPC had a positive effect in the treatment of the spinal cord region and the sciatic nerve root ganglion with a dispersive electrode on the contralateral lumbar region or on the gastrocnemius. However, HVPC had a negative effect in the treatment with an active electrode on the gastrocnemius and a dispersive electrode on the contralateral thigh. Level of evidence II, Prospective comparative study.

HIV-1 tropism and CD4 T lymphocyte recovery in a prospective cohort of patients initiating HAART in Ribeirao Preto, Brazil

While human immunodeficiency virus (HIV)-1 chemokine co-receptors 5 tropism and the GWGR motif in the envelope third variable region (V3 loop) have been associated with a slower disease progression, their influence on antiretroviral response remains unclear. The impact of baseline V3 characteristics on treatment response was evaluated in a randomised, double blind, prospective cohort study with patients initiating highly active antiretroviral therapy with lopinavir or efavirenz plus azithothymidine/3TC (1:1) over 48 weeks. Similar virological and immunological responses were observed for both treatment regimens. The 43 individuals had a mean baseline CD4 T cell count of 119 cells/mm(3) [standard deviation (SD) = 99] and a mean viral load of 5.09 log(10) copies/mL (SD = 0.49). The GWGR motif was not associated with a CD4 T cell response, but predicted R5 tropism by the geno2pheno([clinical20%]) algorithm correlated with higher CD4 T cell levels at all monitoring points (p < 0.05). Moreover, higher false-positive rates (FPR) values from this analysis revealed a strong correlation with CD4 T cell recovery (p < 0.0001). Transmitted drug resistance mutations, documented in 3/41 (7.3%) cases, were unrelated to the assigned antiretroviral regimen and had no impact on patient outcomes. In conclusion, naive HIV-1 R5 infected patients exhibited higher CD4 T cell counts at baseline; this difference was sustained throughout therapy. The geno2pheno[clinical] option FPR positively correlated with CD4 T cell gain and may be useful in predicting CD4 T cell recovery.

Long-Term Prospective Study of the Influence of Estrone Levels on Events in Postmenopausal Women with or at High Risk for Coronary Artery Disease

Background. The link between endogenous estrogen, coronary artery disease (CAD), and death in postmenopausal women is uncertain. We analyzed the association between death and blood levels of estrone in postmenopausal women with known coronary artery disease (CAD) or with a high-risk factor score for CAD. Methods. 251 postmenopausal women age 50-90 years not on estrogen therapy. Fasting blood for estrone and heart disease risk factors were collected at baseline. Women were grouped according to their estrone levels (<15 and >= 15 pg/mL). Fatal events were recorded after 5.8 perpendicular to 1.4 years of followup. Results. The Kaplan-Meier survival curve showed a significant trend (P = 0.039) of greater all-cause mortality in women with low estrone levels (< 15 pg/mL). Cox multivariate regression analysis model adjusted for body mass index, diabetes, dyslipidemia, family history, and estrone showed estrone (OR = 0.45; P = 0.038) as the only independent variable for all-cause mortality. Multivariate regression model adjusted for age, body mass index, hypertension, diabetes, dyslipidemia, family history, and estrone showed that only age (OR = 1.06; P = 0.017) was an independent predictor of all-cause mortality. Conclusions. Postmenopausal women with known CAD or with a high-risk factor score for CAD and low estrone levels (< 15 pg/mL) had increased all-cause mortality.

Ankle-Brachial Index: A Simple Way to Predict Mortality among Patients on Hemodialysis - A Prospective Study

Background: Ankle-brachial index (ABI) can access peripheral artery disease and predict mortality in prevalent patients on hemodialysis. However, ABI has not yet been tested in incident patients, who present significant mortality. Typically, ABI is measured by Doppler, which is not always available, limiting its use in most patients. We therefore hypothesized that ABI, evaluated by a simplified method, can predict mortality in an incident hemodialysis population. Methodology/Principal Findings: We studied 119 patients with ESRD who had started hemodialysis three times weekly. ABI was calculated by using two oscillometric blood pressure devices simultaneously. Patients were followed until death or the end of the study. ABI was categorized in two groups normal (0.9-1.3) or abnormal (<0.9 and >1.3). There were 33 deaths during a median follow-up of 12 months (from 3 to 24 months). Age (1 year) (hazard of ratio, 1.026; p = 0.014) and ABI abnormal (hazard ratio, 3.664; p = 0.001) were independently related to mortality in a multiple regression analysis. Conclusions: An easy and inexpensive technique to measure ABI was tested and showed to be significant in predicting mortality. Both low and high ABI were associated to mortality in incident patients on hemodialysis. This technique allows nephrologists to identify high-risk patients and gives the opportunity of early intervention that could alter the natural progression of this population.

Incidence and Predictors of Adverse Drug Reactions Caused by Drug-Drug Interactions in Elderly Outpatients: A Prospective Cohort Study

Purpose. The primary objective of this study was to investigate the incidence of drug-drug interactions (DDIs) related to adverse drug reactions (ADRs) in elderly outpatients who attended public primary healthcare units in a southeastern region of Brazil. The secondary objective was to investigate the possible predictors of DDI-related ADRs. Methods. A prospective cohort study was conducted between November 1, 2010, and November 31, 2011, in the primary public healthcare system in the Ourinhos micro-region in Brazil. Patients who were at least 60 years old, with at least one potential DDI, were eligible for inclusion in the study. Eligible patients were assessed by clinical pharmacists for DDI-related ADRs for 4 months. The causality of DDI-related ADRs was assessed independently by four clinicians using three decisional algorithms. The incidence of DDI-related ADRs during the study period was calculated. Logistic regression analysis was used to study DDI-related ADR predictors. Results. A total of 433 patients completed the study. The incidence of DDI-related ADRs was 6.5%. A multivariate analysis indicated that the adjusted odds ratios (ORs) rose from 0.91 (95% confidence interval [CI] = 0.75-1.12, p = 0.06) in patients aged 65-69 years to 4.40 (95% CI = 3.00-6.12, p < 0.01) in patients aged 80 years or older. Patients who presented two to three diagnosed diseases presented lower adjusted ORs (OR = 0.93 [95% CI = 0.68-1.18, p = 0.08]) than patients who presented six or more diseases (OR = 1.12 [95% CI = 1.02-2.01, p < 0.01]). Elderly patients who took five or more drugs had a significantly higher risk of DDI-related ADRs (OR = 2.72 [95% CI = 1.92-3.12, p < 0.01]) than patients who took three to four drugs (OR = 0.93 [95% CI = 0.74-1.11, p = 0.06]). No significant difference was found with regard to sex (OR = 1.08 [95% CI 0.48-2.02, p = 0.44]). Conclusion. The incidence of DDI-related ADRs in elderly outpatients was significant, and most of the events presented important clinical consequences. Because clinicians still have difficulty managing this problem, highlighting the factors that increase the risk of DDI-related ADRs is essential. Polypharmacy was found to be a significant predictor of DDI-related ADRs in our sample.

Adverse drug reactions caused by drug-drug interactions in elderly outpatients: a prospective cohort study

Although the prevalence of drug-drug interactions (DDIs) in elderly outpatients is high, many potential DDIs do not have any actual clinical effect, and data on the occurrence of DDI-related adverse drug reactions (ADRs) in elderly outpatients are scarce. This study aimed to determine the incidence and characteristics of DDI-related ADRs among elderly outpatients as well as the factors associated with these reactions. A prospective cohort study was conducted between 1 November 2010 and 31 November 2011 in the primary public health system of the Ourinhos micro-region, Brazil. Patients aged a parts per thousand yen60 years with at least one potential DDI were eligible for inclusion. Causality, severity, and preventability of the DDI-related ADRs were assessed independently by four clinicians using validated methods; data were analysed using descriptive analysis and multiple logistic regression. A total of 433 patients completed the study. The incidence of DDI-related ADRs was 6 % (n = 30). Warfarin was the most commonly involved drug (37 % cases), followed by acetylsalicylic acid (17 %), digoxin (17 %), and spironolactone (17 %). Gastrointestinal bleeding occurred in 37 % of the DDI-related ADR cases, followed by hyperkalemia (17 %) and myopathy (13 %). The multiple logistic regression showed that age a parts per thousand yen80 years [odds ratio (OR) 4.4; 95 % confidence interval (CI) 3.0-6.1, p < 0.01], a Charlson comorbidity index a parts per thousand yen4 (OR 1.3; 95 % CI 1.1-1.8, p < 0.01), consumption of five or more drugs (OR 2.7; 95 % CI 1.9-3.1, p < 0.01), and the use of warfarin (OR 1.7; 95 % CI1.1-1.9, p < 0.01) were associated with the occurrence of DDI-related ADRs. With regard to severity, approximately 37 % of the DDI-related ADRs detected in our cohort necessitated hospital admission. All DDI-related ADRs could have been avoided (87 % were ameliorable and 13 % were preventable). The incidence of ADRs not related to DDIs was 10 % (n = 44). The incidence of DDI-related ADRs in elderly outpatients is high; most events presented important clinical consequences and were preventable or ameliorable.