Chronic toxicity and environmental risk assessment of antivirals in Ceriodaphnia dubia and Raphidocelis subcapitata.

Antiviral drugs are a class of medications used for treating viral infections. Due to their widespread use, especially in cases of pandemics and limited human metabolism, antivirals have been detected in multiple environmental matrices. This study aims to evaluate the chronic effects of acyclovir, efavirenz, lamivudine and zidovudine using Ceriodaphnia dubia and Raphidocelis subcapitata. The results with R. subcapitata showed the following toxicities: zidovudine (IC50 = 5.442 mg L-1) < acyclovir (IC50 = 3.612 mg L-1) < lamivudine (IC50 = 3.013 mg L-1) < efavirenz (IC50 = 0.034 mg L-1). The results of the chronic bioassay with C. dubia demonstrated that zidovudine is the least toxic (EC50 = 5.671 mg L-1), followed by acyclovir (EC50 = 3.062 mg L-1), lamivudine (EC50 = 1.345 mg L-1) and efavirenz (EC50 = 0.026 mg L-1). Both species have been shown to be sensitive to efavirenz. A risk quotient (RQ) was calculated, and efavirenz had an RQ greater than 1 for both species, and lamivudine had an RQ greater than 1 for C. dubia, representing a high ecological risk for these organisms. Antivirals pose a significant environmental risk to aquatic organisms and should be taken into consideration in future monitoring of water sources.

Blood pressure control in a registry of clinical practice, PINNACLEBRAZIL REGISTRY

INTRODUCTION: The prevalence of hypertension is estimated to be nearly 50% among Brazilian adults. Achieving an adequate control of this CVD risk factor is challenging but truly relevant on a public health perspective, as this is the top ranking cause of all deaths globally. PURPOSE: We aimed to describe crude and simple metrics of blood pressure management (including its control), as based on current guidelinederived recommendations, after one year of the clinical practice registry METHODS: Patients with documented Hypertension were included by using electronic case report form based on the ACC PINNACLE Registry. The registry has been enrolling patients from general practitioners and specialists. The main goal of the PINNACLE program is to improve the quality of care in "real world" clinical practice. Patients data were evaluated after 01 year of follow-up on regular clinical appointments and the differences on clinical practice were evaluated RESULTS: Currently, PINNACLEBrazil has enrolled 7598 patients, with 87% of diagnosed hypertension. Percentage of patients with a diagnosis of hypertension who had a blood pressure measurement <140/90 mmHg was 47.9%(baseline) and 57.3% (followup). Percentage of patients who had a blood pressure < 140/90 mm Hg, or who had a blood pressure >= 140/90 mm Hg and were prescribed >= 2 antihypertensive medications were 67.1% on baseline and 71.2% after 1 year. CONCLUSION: The preliminary data of PINNACLE Registry in Brazil shows that a significant proportion of hypertensive patients (nearly half) have not presented with adequate control of blood pressure levels and, moreover, a large proportion have not been treated with recommended combination of 02 or more antihypertensive medications to reach targeted BP levels the quality of care was improving after 01 year of registry. (AU)

Histopathologic Findings on Implantation Renal Allograft Biopsies Correlate With Kidney Donor Profile Index and 30-Day Serum Creatinine.

BACKGROUND: The Kidney Donor Profile Index (KDPI) provides a numerical estimate of deceased donor kidney quality. The KDPI uses 10 donor factors but it does not consider histopathologic findings. We examined whether the KDPI and its component donor factors correlate with the degree of histopathologic changes seen in implantation renal allograft biopsies. METHODS: All deceased donor kidney transplants at our institution from July 1, 2016 to March 15, 2017 that had an implantation biopsy were included. The biopsies were graded based on the Banff criteria for interstitial fibrosis, tubular atrophy, arterial intimal fibrosis, and arteriolar hyalinosis, as well as percent glomerulosclerosis. Linear and logistic regression were used to assess the correlation between histopathologic findings and KDPI and the ability of these variables to predict 30-day serum creatinine (SCr) and delayed graft function (DGF). RESULTS: One hundred thirty-four recipients from 107 donors were included. All histopathologic features examined correlated significantly with KDPI, with arteriolar hyalinosis correlating most strongly. Arteriolar hyalinosis was also associated with the most component donor factors of the KDPI. Histopathologic findings alone or in combination with KDPI predicted 30-day SCr but not DGF. Using the KDPI in combination with degree of interstitial fibrosis and tubular atrophy was the best predictor of 30-day SCr. CONCLUSION: Histopathologic changes seen in implantation renal allograft biopsies correlate with KDPI and predict 30-day SCr. Using a combination of donor histopathologic findings and KDPI may be the best predictor of short-term graft function.

Transient Elastography vs. Aspartate Aminotransferase to Platelet Ratio Index in Hepatitis C: A Meta-Analysis.

BACKGROUND AND RATIONALE: Many different non-invasive methods have been studied with the purpose of staging liver fibrosis. The objective of this study was verifying if transient elastography is superior to aspartate aminotransferase to platelet ratio index for staging fibrosis in patients with chronic hepatitis C. MATERIAL AND METHODS: A systematic review with meta-analysis of studies which evaluated both non-invasive tests and used biopsy as the reference standard was performed. A random-effects model was used, anticipating heterogeneity among studies. Diagnostic odds ratio was the main effect measure, and summary receiver operating characteristic curves were created. A sensitivity analysis was planned, in which the meta-analysis would be repeated excluding each study at a time. RESULTS: Eight studies were included in the meta-analysis. Regarding the prediction of significant fibrosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 11.70 (95% confidence interval = 7.13-19.21) and 8.56 (95% confidence interval = 4.90-14.94) respectively. Concerning the prediction of cirrhosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 66.49 (95% confidence interval = 23.71-186.48) and 7.47 (95% confidence interval = 4.88-11.43) respectively. CONCLUSION: In conclusion, there was no evidence of significant superiority of transient elastography over aspartate aminotransferase to platelet ratio index regarding the prediction of significant fibrosis, but the former proved to be better than the latter concerning prediction of cirrhosis.

Cow's milk-based beverage consumption in 1- to 4-year-olds and allergic manifestations: an RCT.

BACKGROUND: Nutrients such as docosahexaenoic acid (DHA), prebiotics and ß-glucan have been associated with reduced incidence of respiratory illnesses and allergic manifestations (AM). Our objective was to assess if consumption of a cow's milk-based beverage with these and other nutrients supports respiratory, gastrointestinal, and skin health in otherwise well-nourished, healthy children. METHODS: In this double-blind, randomized, controlled trial, healthy children (1-4 years of age) from two daycare centers in Brazil were fed three servings/day of a cow's milk-based beverage (CMBB; n = 125) containing DHA, the prebiotics polydextrose (PDX) and galactooligosaccharides (GOS), ß-glucan, and other key nutrients, or a control cow's milk-based beverage (control; n = 131) for up to 28 weeks. Occurrence of respiratory infections, diarrheal disease and AM was assessed by study pediatricians and the number of episodes were analyzed with the Cochran-Mantel-Haenszel test and the Andersen-Gill model. RESULTS: The CMBB group had fewer episodes of AM, which included allergic rhinitis or conjunctivitis, wheezing, allergic cough, eczema and urticaria, compared to the control group (p = 0.021). The hazard ratio for increased number of episodes of AM was lower in the CMBB group compared to control (HR, 0.64; 95 % CI 0.47-0.89; p = 0.007). There was no difference in the incidence of respiratory infections and diarrheal disease between groups. CONCLUSION: A cow's milk-based beverage containing DHA, PDX/GOS, and yeast ß-glucan, and supplemented with micronutrients, including zinc, vitamin A and iron, when consumed 3 times/day for 28 weeks by healthy 1- to 4-year-old children was associated with fewer episodes of allergic manifestations in the skin and the respiratory tract. TRIAL REGISTRATION: registration number: NCT01431469.

Overnourishment during lactation induces metabolic and haemodynamic heart impairment during adulthood.

AIM: In this study, the effects of postnatal overfeeding on heart energy homoeostasis and cardiac haemodynamics in adult male Swiss mice were examined. METHODS AND RESULTS: During the suckling period, the mice were divided into four groups of control or overfed pups in combination with baseline or ischaemia/reperfusion treatments (control group baseline, CGBL; overfed group baseline, OGBL; control group ischaemia/reperfusion, CGIR; and overfed group ischaemia/reperfusion, OGIR). End diastolic pressure (EDP), heart contraction speed (Max dP/dt), relaxation speed (Min dP/dt), isovolumetric relaxation time (Tau) and frequency by beats per minute (BPM) were measured. During baseline and ischaemia/reperfusion, key proteins such as AKT1, AKT2, AKT3, pAKT, adenosine monophosphate-activated protein kinase (AMPK), pAMPK, insulin receptor beta (IRß), protein tyrosine phosphatase 1B (PTP1B), insulin receptor substrate 1 (IRS1), fatty acid binding protein (FABP), CD36, phosphoinositide 3-kinase (PI3K) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) were studied. The expression of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), carnitine palmitoyltransferase 1 (CPT1) and uncoupling protein 3 (UCP3) was studied as a marker of cardiac hypertrophy and energetic metabolism. Cardiac fibrosis was analyzed by quantifying collagen deposition, which is increased in the OGBL and OGIR groups compared with the control groups. CONCLUSIONS: The OGBL group showed reduced EDP compared with the CGBL group and high Max dP/dt compared with the OGBL group. Ischaemia/reperfusion increased EDP and Min dP/dt in the intragroup comparison. By contrast, Tau and frequency were not significantly different among groups. The OGIR mice showed significant alterations in heart metabolism proteins, including AKT2, pAKT/AKT1, pAKT/AKT2, AMPK, pAMPK/AMPK, PTP1B, IRS1, FABP and CD36. Furthermore, alterations in ANP, BNP, CPT1 and UCP3 messenger RNA (mRNA) expression indicated hypertrophy and reduction in their efficiency, such that exclusive overnutrition in childhood induces a long-term effect on haemodynamics, metabolism and heart remodelling.

Bonding durability of silorane and methacrylate-based resins to enamel.

AIM: Few studies compared the silorane and mechacrylate based resins bonded to enamel. The aim of this study was to evaluate the bonding durability of silorane and methacrylate-based resins to enamel. METHODS: Twenty seven molars were divided into G1 Clearfil SE Bond/Filtek Z350; G2 Adper Easy One/Filtek Z350; and G3 P90 Adhesive System/Filtek P90 groups. Following application of adhesive systems, blocks of composites were built, samples were stored in water (24 hours/37 ºC), sectioned (0.8 mm²) and tested in tensile (24 hours and 6 months). Fractures were observed (40×). Bond strength (in MPa) was analysed by MANOVA General Linear Model and Tukey's post-hoc test at 5%. The power test was calculated. The etching pattern was observed. RESULTS: There were differences for material (P=0.029), storage time (P=0.012) and their interaction (P=0.000). Similar bond strengths were found at 24 h for all. The bond strength of G1 decreased after 6 months. At 6 months, G2 showed higher bond strength than G1 and G3, that were similar. The power-test value was 0.87. Mixed fractures and enamel rods were observed. CONCLUSION: Bond strength varied over time depending on the restorative system.

Randomized trial of benznidazole for chronic Chagas' cardiomyopathy

BACKGROUND:The role of trypanocidal therapy in patients with established Chagas' cardiomyopathy is unproven.METHODS:We conducted a prospective, multicenter, randomized study involving 2854 patients with Chagas' cardiomyopathy who received benznidazole or placebo for up to 80 days and were followed for a mean of 5.4 years. The primary outcome in the time-to-event analysis was the first event of any of the components of the composite outcome of death, resuscitated cardiac arrest, sustained ventricular tachycardia, insertion of a pacemaker or implantable cardioverter-defibrillator, cardiac transplantation, new heart failure, stroke, or other thromboembolic event.RESULTS:The primary outcome occurred in 394 patients (27.5%) in the benznidazole group and in 414 (29.1%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.07; P=0.31). At baseline, a polymerase-chain-reaction (PCR) assay was performed on blood samples obtained from 1896 patients; 60.5% had positive results for Trypanosoma cruzi on PCR. The rates of conversion to negative PCR results (PCR conversion) were 66.2% in the benznidazole group and 33.5% in the placebo group at the end of treatment, 55.4% and 35.3%, respectively, at 2 years, and 46.7% and 33.1%, respectively, at 5 years or more (P<0.001 for all comparisons)...

Tissue iron deficiency and adiposity-related inflammation in disadvantaged preschoolers from NE Brazil.

BACKGROUND/OBJECTIVES: Earlier we reported an association between iron deficiency and overweight in Brazilian preschoolers. Here, we investigate whether this is the result of adipose-related inflammation. SUBJECTS/METHODS: Fasting serum C-reactive protein, α-1-acid glycoprotein (AGP), hepcidin, interleukin-6 (IL-6) and leptin, together with two iron biomarkers (serum ferritin and transferrin receptor (sTfR)), were measured in 364 disadvantaged preschoolers with a mean BMIZ (standardised Z-score for BMI) of 0.015, aged 3-6 years and attending day care in Salvador, Brazil. The role of genetic haemoglobin (Hb) disorders, intestinal parasites and dietary iron supply (calculated from serving sizes of 20 weekday menus) were also examined. RESULTS: Forty-eight children (13%) were overweight (BMIZ >1). Prevalence of tissue iron deficiency (sTfR >113.3 nmol/l; 30.6 vs 12.5%; P=0.002) and chronic inflammation (AGP >25 µmol/l; 19 vs 10%; P=0.025) were higher in overweight than in normal-weight children. From multiple regression, BMIZ was a positive predictor of log serum sTfR, ferritin and leptin, but not of log hepcidin or IL-6. Instead, major positive predictors of log hepcidin were log IL-6, followed by an elevated AGP and sex (male), whereas for log IL-6 elevated AGP was the only significant predictor. Besides BMIZ, sex (female) was also a major positive predictor of leptin. Heterozygous variant of sickle cell Hb (n=20), but not helminths, was also a positive predictor of log sTfR. Median dietary iron supply (mg/day) was above the WHO Recommended Nutrient Intake assuming moderate bioavailability and appeared adequate. CONCLUSIONS: The role of adiposity-related inflammation in tissue iron deficiency should be considered even when the prevalence of overweight is relatively low.

Epidural methadone results in dose-dependent analgesia in cancer pain, further enhanced by epidural dexamethasone.

BACKGROUND: This study was designed to evaluate the role of epidural methadone-lidocaine in cancer pain combined or not to epidural dexamethasone. METHODS: In all, 72 cancer patients, 32- to 67-year-old were randomized to six groups (n=12) and prospectively studied to examine analgesia and adverse effects for 3 weeks. Patients received single-dose protocol epidural test drugs: Control group (CG) received epidural 40-mg lidocaine diluted to 10-ml volume with saline. Dexamethasone group (DG) 40-mg lidocaine plus 10-mg dexamethasone. The 2.5MetG 2.5-mg epidural methadone with 40-mg lidocaine; the 5MetG, 5-mg epidural methadone plus 40-mg lidocaine, the 7.5MetG, 7.5-mg epidural methadone plus 40-mg lidocaine and finally the 7.5Met-DexG, 7.5-mg methadone with 40-mg lidocaine and 10-mg dexamethasone. RESULTS: Groups CG, DG and 2.5MetG were similar regarding analgesia and side effects. Patients from 5MetG and 7.5MetG took 3 ± 1 and 5 ± 1 days, respectively, to restart oral morphine. Patients from 7.5MetDG took 14 ± 2 to restart oral morphine (P<0.001). Daily somnolence and appetite improved in the 7.5MetDG during 2-week evaluation (P<0.005). Fatigue improved for both DG and 7.5MetDG during 2-week evaluation (P<0.005). By the third week of evaluation, all patients were similar. CONCLUSIONS: Epidural methadone plus lidocaine resulted in dose-dependent analgesia, further improved by epidural dexamethasone, which also improved fatigue.

Interaction of Schistosoma mansoni Sporocysts and Hemocytes of Biomphalaria.

Human infection by Schistosoma mansoni affects more than 100 million people worldwide, most often in populations of developing countries of Africa, Asia, and Latin America. The transmission of S. mansoni in human populations depends on the presence of some species of Biomphalaria that act as an intermediate host. The compatibility between S. mansoni and its intermediate host is influenced by behavioral, physiological, and genetical factors of the mollusc and the parasite. The susceptibility level of the mollusc has been attributed to the capacity of internal defense system (IDS)-hemocytes and soluble components of the hemolymph-to recognize and destroy the parasite, and this will be the center of interest of this paper. The schistosome-resistant Biomphalaria can be an alternative strategy for the control of schistosomiasis.

Adeno-associated virus may play a protective role against human papillomavirus-induced cervical lesions independent of HIV serostatus.

This study investigated the prevalence of adeno-associated virus (AAV) and human papillomavirus (HPV) DNA in cervical samples of HIV-seropositive and -seronegative women attending a clinic in south-eastern Brazil. Both viruses were investigated by polymerase chain reaction (PCR) and cytological exams were performed. AAV was typed by PCR and restriction fragment length polymorphism analysis. AAV prevalence was 19.7% (56/284), with 18.7% (21/112) and 20.3% (35/172) in HIV-positive and -negative women, respectively. AAV type 2 was the single virus type detected. AAV was detected with higher frequency in HPV-infected women (P < 0.05) as was HPV in HIV-positive women (P < 0.05). The AAV-HPV co-infected women showed a lower rate of atypical squamous cells of undetermined significance or cervical intraepithelial neoplasia development compared with those infected only with HPV. The prevalence of AAV2 confirms this type as the most common in human samples. This is the first report examining AAV in cervical samples of HIV-infected women and indicates that HIV infection does not appear to influence AAV prevalence or AAV-HPV co-infection.

In vitro evaluation of the schistosomicidal potential of Eremanthus erythropappus (DC) McLeisch (Asteraceae) extracts.

Eremanthus erythropappus (DC) McLeisch, a plant popularly known as Candeia (Asteraceae), has high therapeutic potential. In this study, the in vitro schistosomicidal potentials of the ethanolic, dichloromethane and hexane extract of branches were evaluated. Couples of worms obtained from the infected mice were cultured in RPMI supplemented with foetal bovine serum and antibiotics. Four pairs of adult worms were exposed to increasing concentrations of each extract and examined by light microscope. The extracts at 100 and 200 µg mL(-1) had schistosomicidal activity, as demonstrated by the analysis of several aspects such as tegument darkening, absence of motility, incapacity of adhesion in culture plate and absence of egg in culture medium. At 50 and 75 µg mL(-1), the dichloromethane and hexane extracts were highly effective. The results suggest that these extracts could be useful in the development of new schistosomicidal drugs.

Use of fluorescent probes as a useful tool to identify resistant Schistosoma mansoni isolates to praziquantel.

The use of chemotherapy on a mass scale in endemic areas may lead to the appearance of resistant isolates through the mechanism of selective drug pressure. Studies have demonstrated that praziquantel (PZQ) is able to inhibit the excretory activity and to cause tegumental damage in Schistosoma mansoni adult worms. The use of the probe resorufin to evaluate excretory activity, as well as the probe Hoechst 33258 to detect tegumental damage in adult worms, may represent a method to identify resistant (or less susceptible) isolates. The purpose of the present work was to compare the changes caused by PZQ in the function of the excretory system and in the integrity of the tegument of adult worms from the LE isolate (susceptible to PZQ) and the LE-PZQ isolate (less susceptible to PZQ). Worms from the isolate LE-PZQ showed less severe tegumental lesions, in both in vitro and in vivo experiments, detected by labelling with Hoechst 33258 and continued to have a functional excretory system as shown by labelling with resorufin in vitro.

The effect of thyroid hormones on the white adipose tissue gene expression of PAI-1 and its serum concentration

Metabolic syndrome is associated with an increased risk of developing cardiovascular diseases and Plasminogen activator inhibitor 1 (PAI-1) overexpression may play a significant role in this process. A positive correlation between adipose tissue gene expression of PAI-1 and its serum concentration has been reported. Furthermore, high serum levels of thyroid hormones (T3 and T4) and PAI-1 have been observed in obese children. The present study evaluates the impact of thyroid hormone treatment on white adipose tissue PAI-1 gene expression and its serum concentration. Male Wistar rats (60 days old) were treated for three weeks with T4 (50 µg/day, Hyper) or with saline (control). Additionally, 3T3-L1 adipocytes were treated for 24 h with T4 (100 nM) or T3 (100 nM). PAI-1 gene expression was determined by real-time PCR, while the serum concentration of PAI-1 was measured by ELISA using a commercial kit (Innovative Research, USA). Both the serum concentration of PAI-1 and mRNA levels were similar between groups in retroperitoneal and epididymal white adipose tissue. Using 3T3-L1 adipocytes, in vitro treatment with T4 and T3 increased the gene expression of PAI-1, suggesting non-genomic and genomic effects, respectively. These results demonstrate that thyroid hormones have different effects in vitro and in vivo on PAI-1 gene expression in adipocytes.

The effect of thyroid hormones on the white adipose tissue gene expression of PAI-1 and its serum concentration.

Metabolic syndrome is associated with an increased risk of developing cardiovascular diseases and Plasminogen activator inhibitor 1 (PAI-1) overexpression may play a significant role in this process. A positive correlation between adipose tissue gene expression of PAI-1 and its serum concentration has been reported. Furthermore, high serum levels of thyroid hormones (T3 and T4) and PAI-1 have been observed in obese children. The present study evaluates the impact of thyroid hormone treatment on white adipose tissue PAI-1 gene expression and its serum concentration. Male Wistar rats (60 days old) were treated for three weeks with T4 (50 microg/day, Hyper) or with saline (control). Additionally, 3T3-L1 adipocytes were treated for 24 h with T4 (100 nM) or T3 (100 nM). PAI-1 gene expression was determined by real-time PCR, while the serum concentration of PAI-1 was measured by ELISA using a commercial kit (Innovative Research, USA). Both the serum concentration of PAI-1 and mRNA levels were similar between groups in retroperitoneal and epididymal white adipose tissue. Using 3T3-L1 adipocytes, in vitro treatment with T4 and T3 increased the gene expression of PAI-1, suggesting non-genomic and genomic effects, respectively. These results demonstrate that thyroid hormones have different effects in vitro and in vivo on PAI-1 gene expression in adipocytes.

Alpha coma pattern in a child.

Alpha coma, an EEG pattern characterized by diffuse or widespread rhythmic activity in the alpha frequency band, is typically recorded in patients with profound coma and is frequently associated with severe neurological conditions. The most common etiologic factors of this pattern are hypoxic-ischemic encephalopathy, encephalitis, head trauma, metabolic disorders, and drug overdose. Reports of alpha coma pattern in children are relatively common. Clinical significance, both in children and adults, is variable, and highly dependent on etiology. The objective of this article is to report a clinical case of alpha coma pattern in a child with neuroblastoma. The EEG pattern was recorded during the evolution of treatment, secondary to complicating septic encephalopathy. The alpha coma pattern was replaced by a normal trace following a favorable outcome after sepsis resolution.

Mammalian target of rapamycin inhibitor dyslipidemia in kidney transplant recipients.

The incidence, pathogenesis, consequences and treatment of mammalian target of rapamycin (mTOR) inhibitor dyslipidemia are not well described. We conducted a systematic review of randomized controlled trials reporting cholesterol and triglycerides in mTOR versus non-mTOR inhibitor immunosuppressive treatment regimens in kidney transplant recipients. All but one of 17 trials reported higher levels of cholesterol and triglycerides, or an increased prevalence of treatment with lipid-lowering agents. Approximately 60% of mTOR inhibitor-treated patients received lipid-lowering agents (2-fold higher than controls). There appeared to be little difference between dyslipidemias caused by sirolimus (14 trials) versus everolimus (3 trials). It was difficult to determine the extent to which declines in lipids over time posttransplant were due to lipid-lowering therapy, changes in doses and/or discontinuations of mTOR inhibitors. From the four trials that measured lipoproteins, it appeared that at least some of the increase in total cholesterol with mTOR inhibitors was due to increased low-density lipoprotein cholesterol. What direct or indirect effects mTOR inhibitors have on atherosclerotic cardiovascular disease in kidney transplant patients are unknown. However, in the absence of the necessary clinical trials, dyslipidemia should be managed, as it would be in nontransplant patients at high risk for cardiovascular disease.