Diagnostic accuracy of uroflowmetry parameters to predict infravesical obstruction / Exactitud diagnóstica de los parámetros de la flujometría para predecir la obstrucción infravesical

Objective: to evaluate the performance statistics of average flow (Qave), voiding time (Vtime), and time to maximum flow (TQmax), in addition to maximum flow (Qmax), for diagnosis of infravesical obstruction. Methods: we reviewed urodynamic studies performed in men > 40 years. Obstruction was considered a grade 3-6 in the Schäfer nomogram. Sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and the receiver operator characteristic (ROC) curve were calculated for the different components of free uroflowmetry. Results: we analyzed 432 studies. Patients with obstruction had lower values of Qmax and Qave, and higher values of Vtime and TQmax. Considering different thresholds, Qmax had sensitivity, specificity, LR + and LR- values of 12-83%, 50-97%, 1.7-4.46 and 0.32-0.9, respectively; Qave had sensitivity, specificity, LR + and LR- values of 65-95%, 21-66%, 1.22-1.94 and 0.19-0.53, respectively; Vtime had sensitivity, specificity, LR + and LR- values of 49-85%, 26-67%, 1.15-1.54, and 0.57-0.74, respectively; TQmax had a sensitivity, specificity, LR + and LR- of 36-81%, 22-72%, 1.04-1.33 and 0.85-0.87, respectively. The areas under the ROC curves for Qmax, Qave, Vtime and TQmax were 0.75 (95% CI = 0.71-0.79, p < 0.001), 0.71 (95% CI = 0.66-0.75, p < 0.001), 0.62 (95% CI = 0.57-0.67, p < 0.001) and 0.55 (95% CI = 0.5-0.6, p = 0.03), respectively. Conclusions: Qave, Vtime, and TQmax showed a statistically significant discriminatory capacity to predict infravesical obstruction, and therefore they have clinical value as a complement to the information provided by Qmax.

Objetivo: evaluar las estadísticas de desempeño del flujo promedio (Qave), el tiempo de evacuación (Vtime) y el tiempo hasta el flujo máximo (TQmax), además del flujo máximo (Qmax), para el diagnóstico de obstrucción infravesical. Métodos: revisamos urodinamias realizadas en hombres > 40 años. La obstrucción se consideró un grado 3-6 en el nomograma de Schäfer. Se calcularon la sensibilidad, la especificidad, la razón de verosimilitud positiva (LR +), la razón de verosimilitud negativa (LR-) y la curva característica operativa del receptor (ROC) para los diferentes componentes de la flujometría libre. Resultados: analizamos 443 estudios. Los pacientes con obstrucción tenían valores más bajos de Qmax y Qave, y valores más altos de Vtime y TQmax. Considerando diferentes umbrales, el Qmax tuvo valores de sensibilidad, especificidad, LR + y LR- de 12-83%, 50-97%, 1.7-4.46 y 0.32-0.9, respectivamente; Qave tuvo valores de sensibilidad, especificidad, LR + y LR- de 65-95%, 21-66%, 1.22-1.94 y 0.19-0.53, respectivamente; Vtime tuvo valores de sensibilidad, especificidad, LR + y LR- de 49-85%, 26-67%, 1.15-1.54 y 0.57-0.74, respectivamente; TQmax tuvo una sensibilidad, especificidad, LR + y LR- de 36-81%, 22-72%, 1.04-1.33 y 0.85-0.87, respectivamente. Las áreas bajo las curvas ROC para Qmax, Qave, Vtime y TQmax fueron 0,75 (95% CI = 0.71-0.79, p < 0,001), 0.71 (95% CI = 0.66-0.75, p < 0,001), 0.62 (95% CI = 0.57-0.67, p < 0,001) y 0.55 (95% CI = 0.5-0.6, p = 0.03), respectivamente. Conclusiones: Qave, Vtime y TQmax mostraron una capacidad discriminatoria estadísticamente significativa para predecir la obstrucción infravesical, por lo que tienen valor clínico como complemento de la información proporcionada por el Qmax.

Dorsal Vascular Complex Nonligation Method and Preservation of Puboprostatic Ligaments and Endopelvic Fascia During Laparoscopic Radical Prostatectomy: Effect on Continence.

OBJECTIVE: To evaluate the impact on continence rate during 1-year follow-up of a preservation technique that included nonligation of the dorsal vascular complex and sparing of the puboprostatic ligaments and the endopelvic fascia during laparoscopic radical prostatectomy. MATERIAL AND METHODS: Information from 30 patients who underwent the preservation technique was prospectively collected and compared with data from 60 patients who underwent the nonpreservation traditional technique. A single surgeon performed all procedures. RESULTS: Demographic and preoperative characteristics were similar. The mean patient age was 59 years in both groups. All patients were stage cT1c or cT2. Operative time was significantly lower in the preservation technique group (229.6 vs. 262.7 minutes, P < .001). There were no significant differences in intraoperative bleeding, discharge hemoglobin level, blood transfusion rate, length of hospitalization, and drop in the hemoglobin level. The probability of continence recovery was significantly higher in the preservation technique group than in the traditional technique group (hazard ratio = 0.50, 95% CI = 0.31-0.81). The continence rate (0 pads/day) for the preservation technique group versus the traditional technique group at 1, 3, 6, and 12 months was, respectively, 53.3% versus 30% (P = .031), 90% versus 45% (P < .001), 90% versus 63.3% (P = .008), and 96.6% versus 78.3% (P = .024). There were no significant differences between the groups regarding potency and oncologic outcomes. CONCLUSION: Nonligation of the dorsal vascular complex and preservation of the puboprostatic ligaments and the endopelvic fascia improved urinary continence compared with the traditional nonpreservation technique, with no impact in terms of bleeding and oncologic outcomes.

Side-effects of pesticides on non-target insects in agriculture: a mini-review.

Climate change mediated by anthropogenic activity induces significant alterations on pest abundance and behavior and a potential increase in the use of agrochemicals for crop protection. Pesticides have been a tool in the control of pests, diseases, and weeds of agricultural systems. However, little attention has been given to their toxic effects on beneficial insect communities that contribute to the maintenance and sustainability of agroecosystems. In addition to pesticide-induced direct mortality, their sublethal effects on arthropod physiology and behavior must be considered for a complete analysis of their impact. This review describes the sublethal effects of pesticides on agriculturally beneficial insects and provides new information about the impacts on the behavior and physiology of these insects. The different types of sublethal effects of pesticides used in agriculture on pollinators, predators, parasitoids, and coprophagous insects were detailed.

Frequentist and Bayesian Hypothesis Testing: An Intuitive Guide for Urologists and Clinicians / Pruebas de hipótesis frecuentista y bayesiana: Una Guía intuitiva para urólogos y clínicos

Given the limitations of frequentist method for null hypothesis significance testing, different authors recommend alternatives such as Bayesian inference. A poor understanding of both statistical frameworks is common among clinicians. The present is a gentle narrative review of the frequentist and Bayesian methods intended for physicians not familiar with mathematics. The frequentist p-value is the probability of finding a value equal to or higher than that observed in a study, assuming that the null hypothesis (H0) is true. The H0 is rejected or not based on a p threshold of 0.05, and this dichotomous approach does not express the probability that the alternative hypothesis (H1) is true. The Bayesian method calculates the probability of H1 and H0 considering prior odds and the Bayes factor (Bf). Prior odds are the researcher's belief about the probability of H1, and the Bf quantifies how consistent the data is concerning H1 and H0. The Bayesian prediction is not dichotomous but is expressed in continuous scales of the Bf and of the posterior odds. The JASP software enables the performance of both frequentist and Bayesian analyses in a friendly and intuitive way, and its application is displayed at the end of the paper. In conclusion, the frequentist method expresses how consistent the data is with H0 in terms of p-values, with no consideration of the probability of H1. The Bayesian model is a more comprehensive prediction because it quantifies in continuous scales the evidence for H1 versus H0 in terms of the Bf and the

Dadas las limitaciones del método de significancia frecuentista basado en la hipótesis nula, diferentes autores recomiendan alternativas como la inferencia bayesiana. Es común entre los médicos una comprensión deficiente de ambos marcos estadísticos. Esta es una revisión narrativa amigable de los métodos frecuentista y bayesiano dirigida quienes no están familiarizados con las matemáticas. El valor de p frecuentista es la probabilidad de encontrar un valor igual o superior al observado en un estudio, asumiendo que la hipótesis nula (H0) es cierta. La H0 se rechaza o no con base en un umbral p de 0.05, y este enfoque dicotómico no expresa la probabilidad de que la hipótesis alternativa (H1) sea verdadera. El método bayesiano calcula la probabilidad de H1 y H0 considerando las probabilidades a priori y el factor de Bayes (fB). Las probabilidades a priori son la creencia del investigador sobre la probabilidad de H1, y el fB cuantifica cuán consistentes son los datos con respecto a H1 y H0. La predicción bayesiana no es dicotómica, sino que se expresa en escalas continuas del fB y de las probabilidades a posteriori. El programa JASP permite realizar análisis frecuentista y bayesiano de una forma simple e intuitiva, y su aplicación se muestra al final del documento. En conclusión, el método frecuentista expresa cuán consistentes son los datos con H0 en términos de valores p, sin considerar la probabilidad de H1. El modelo bayesiano es una predicción más completa porque cuantifica en escalas continuas la evidencia de H1 versus H0 en términos del fB y de las probabilidades a posteriori.

Origanum vulgare Essential Oil against Tenebrio molitor (Coleoptera: Tenebrionidae): Composition, Insecticidal Activity, and Behavioral Response.

Tenebrio molitor is one of the main stored product pests. This study characterized oregano essential oil (OEO) by gas chromatography (GC/FID and GC/MS) and assessed its insecticidal properties against T. molitor. Mortality, survival, respiration, and behavioral response in larva, pupa, and adult of this insect were determined. The major components of OEO were carvacrol (25.6%), p-cymene (12.3%), linalool (8.71%), thymol (7.22%), γ-terpinene (7.21%), caryophyllene oxide (4.67%), α-pinene (2.71%), and eucalyptol (2.69%). OEO caused high contact toxicity in larvae (LD50 = 3.03 µg insect-1), pupae (LD50 = 5.01 µg insect-1), and adults (LD50 = 5.12 µg insect-1) of T. molitor. Survival rates were 100% in larvae, pupae, and adults of T. molitor not treated with OEO, declining to 65-54%, 38-44%, 30-23%, and 6-2% in insects treated with LD25, LD50, LD75, and LD90, respectively. Low respiration rates of T. molitor at different developmental stages was observed after OEO exposure. Additionally, OEO exposure affects behavioral avoidance response and causes repellency in larvae and adults. These findings show that OEO exerts insecticidal and repellent effects against T. molitor, suggesting a potent alternative to synthetic insecticides for controlling the beetle.

TRPV4 activity regulates nuclear Ca2+ and transcriptional functions of ß-catenin in a renal epithelial cell model.

TRPV4 is a nonselective cationic channel responsive to several physical and chemical stimuli. Defects in TRPV4 channel function result in human diseases, such as skeletal dysplasias, arthropathies, and peripheral neuropathies. Nonetheless, little is known about the role of TRPV4 in other cellular functions, such as nuclear Ca2+ homeostasis or Ca2+ -regulated transcription. Here, we confirmed the presence of the full-length TRPV4 channel in the nuclei of nonpolarized Madin-Darby canine kidney cells. Confocal Ca2+ imaging showed that activation of the channel increases cytoplasmic and nuclear Ca2+ leading to translocation of TRPV4 out of the nucleus together with ß-catenin, a transcriptional regulator in the Wnt signaling pathway fundamental in embryogenesis, organogenesis, and cellular homeostasis. TRPV4 inhibits ß-catenin transcriptional activity through a direct interaction dependent upon channel activity. This interaction also occurs in undifferentiated osteoblastoma and neuroblastoma cell models. Our results suggest a mechanism in which TRPV4 may regulate differentiation in several cellular contexts.

Autonomous activation of CaMKII exacerbates diastolic calcium leak during beta-adrenergic stimulation in cardiomyocytes of metabolic syndrome rats.

Autonomous Ca2+/calmodulin-dependent protein kinase II (CaMKII) activation induces abnormal diastolic Ca2+ leak, which leads to triggered arrhythmias in a wide range of cardiovascular diseases, including diabetic cardiomyopathy. In hyperglycemia, Ca2+ handling alterations can be aggravated under stress conditions via the ß-adrenergic signaling pathway, which also involves CaMKII activation. However, little is known about intracellular Ca2+ handling disturbances under ß-adrenergic stimulation in cardiomyocytes of the prediabetic metabolic syndrome (MetS) model with obesity, and the participation of CaMKII in these alterations. MetS was induced in male Wistar rats by administering 30 % sucrose in drinking water for 16 weeks. Fluo 3-loaded MetS cardiomyocytes exhibited augmented diastolic Ca2+ leak (in the form of spontaneous Ca2+ waves) under basal conditions and that Ca2+ leakage was exacerbated by isoproterenol (ISO, 100 nM). At the molecular level, [3H]-ryanodine binding and basal phosphorylation of cardiac ryanodine receptor (RyR2) at Ser2814, a CaMKII site, were increased in heart homogenates of MetS rats with no changes in RyR2 expression. These alterations were not further augmented by Isoproterenol. SERCA pump activity was augmented 48 % in MetS hearts before ß-adrenergic stimuli, which is associated to augmented PLN phosphorylation at T17, a target of CaMKII. In MetS hearts. CaMKII auto-phosphorylation (T287) was increased by 80 %. The augmented diastolic Ca2+ leak was prevented by CaMKII inhibition with AIP. In conclusion, CaMKII autonomous activation in cardiomyocytes of MetS rats with central obesity significantly contributes to abnormal diastolic Ca2+ leak, increasing the propensity for ß-adrenergic receptor-driven lethal arrhythmias.

Acute Toxicity and Sublethal Effects of Lemongrass Essential Oil and Their Components against the Granary Weevil, Sitophilus granarius.

In the present work, we evaluate the toxic and repellent properties of lemongrass (Cymbopogon citratus (DC. ex Nees) Stapf.) essential oil and its components against Sitophilus granarius Linnaeus as an alternative to insecticide use. The lethal dose (LD50 and LD90), survivorship, respiration rate, and repellency on adults of S. granarius exposed to different doses of lemongrass oil and some of its components were evaluated. The chemical composition of the essential oil was found to have the major components of neral (24.6%), citral (18.7%), geranyl acetate (12.4%), geranial (12.3%), and limonene (7.55%). Lemongrass essential oil (LD50 = 4.03 µg·insect-1), citral (LD50 = 6.92 µg·insect-1), and geranyl acetate (LD50 = 3.93 µg·insect-1) were toxic to S. granarius adults. Survivorship was 99.9% in insects not exposed to lemongrass essential oil, decreasing to 57.6%, 43.1%, and 25.9% in insects exposed to LD50 of essential oil, citral, and geranyl acetate, respectively. The insects had low respiratory rates and locomotion after exposure to the essential oil, geranyl acetate, and citral. Our data show that lemongrass essential oils and their components have insecticidal and repellent activity against S. granarius and, therefore, have the potential for application in stored grain pest management schemes.

Metabolic syndrome diminishes insulin-induced Akt activation and causes a redistribution of Akt-interacting proteins in cardiomyocytes.

Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors, with insulin resistance as a critical component for its development. Insulin signaling in the heart leads to Akt (also known as PKB) activation, a serine/threonine protein kinase, which regulates cardiac glucose metabolism and growth. Cardiac metabolic inflexibility, characterized by impaired insulin-induced glucose uptake and oxidation, has been reported as an early and consistent change in the heart of different models of MetS and diabetes; however, the evaluation of Akt activation has yielded variable results. Here we report in cardiomyocytes of MetS rats, diminished insulin-induced glucose uptake and Akt activation, evaluated by its impaired mobilization towards the plasma membrane and phosphorylation, and reflected in a re-distribution of its interacting proteins, assessed by label-free mass spectrometry (data are available via ProteomeXchange with identifier PXD013260). We report 45 proteins with diminished abundance in Akt complex of MetS cardiomyocytes, mainly represented by energy metabolism-related proteins, and also, 31 Akt-interacting proteins with increased abundance, which were mainly related to contraction, endoplasmic reticulum stress, and Akt negative regulation. These results emphasize the relevance of Akt in the regulation of energy metabolism in the heart and highlight Akt-interacting proteins that could be involved in the detrimental effects of MetS in the heart.

Basic and clinical insights in catecholaminergic (familial) polymorphic ventricular tachycardia

Abstract Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal disease, whose characteristic ventricular tachycardias are adrenergic-dependent. Although rare, CPVT should be considered in the differential diagnosis of young individuals with exercise-induced syncope. Mutations in five different genes (RYR2, CASQ2, CALM1, TRDN, and TECRL) are associated with the CPVT phenotype, although RYR2 missense mutations are implicated in up to 60 % of all CPVT cases. Genetic testing has an essential role in the diagnosis, management, pre-symptomatic diagnosis, counseling, and treatment of the proband; furthermore, genetic information can be useful for offspring and relatives. By expert consensus, CPVT gene testing is a Class I recommendation for patients with suspected CPVT. Beta-adrenergic and calcium-channel blockers are the cornerstones of treatment due to the catecholaminergic dependence of the arrhythmias. Unresponsive patients are treated with an implantable cardioverter-defibrillator to reduce the risk of sudden cardiac death. In the present article, a brief review of the genetic and molecular mechanisms of this intriguing disease is provided.

Bioactivity of the Cymbopogon citratus (Poaceae) essential oil and its terpenoid constituents on the predatory bug, Podisus nigrispinus (Heteroptera: Pentatomidae).

Podisus nigrispinus Dallas (Heteroptera: Pentatomidae), released in biological control programs, is a predator of Lepidopteran and Coleopteran species. Lemongrass essential oil and its constituents can be toxic to this natural enemy. The major constituents of lemongrass essential oil are neral (31.5%), citral (26.1%), and geranyl acetate (2.27%). Six concentrations of lemongrass essential oil and of its citral and geranyl acetate constituents were applied to the thorax of P. nigrispinus nymphs and adults. The walking and respiratory behavior of the P. nigrispinus third-instar nymphs, treated with citral and geranyl acetate at the LD50 and LD90 doses, were analyzed with video and respirometer. The lemongrass essential oil toxicity increased from first- to fifth-instar P. nigrispinus nymphs. The P. nigrispinus respiration rates (µL de CO2 h-1/insect) with citral and geranyl acetate in the LD50 and LD90 differed. Nymphs exposed to the lemongrass essential oil and its constituents on treated surfaces presented irritability or were repelled. Podisus nigrispinus adults were tolerant to the lemongrass essential oil and its constituents, geranyl acetate and citral. The altered respiratory activity with geranyl acetate and the fact that they were irritated and repelled by citral suggest caution with regard to the use of the lemongrass essential oil and its constituents in integrated pest management incorporating this predator, in order to avoid diminishing its efficiency against the pests.

Exposure to Insecticides Reduces Populations of Rhynchophorus palmarum in Oil Palm Plantations with Bud Rot Disease.

The South American palm weevil (SAPW), Rhynchophorus palmarum Linnaeus (Coleoptera: Curculionidae) is the main pest of Elaeis guineensis and damages palm trees with bud rot disease in the Americas. The effects of six neurotoxic insecticides (abamectin, carbaryl, deltamethrin, fipronil, imidacloprid and spinosad) were evaluated against SAPW for toxicity, survival, reproduction, and mortality. Abamectin (LC50 = 0.33 mg mL-1), Carbaryl (LC50 = 0.24 mg mL-1), deltamethrin (LC50 = 0.17 mg mL-1), and fipronil (LC50 = 0.42 mg mL-1) were the most toxic to SAPW. Adult survival was 95% without exposure to insecticides, decreasing to 78-65% in insects treated with the LC25 and 49-35% in insects exposed to LC50. Sublethal doses of carbaryl, fipronil and imidacloprid showed significant effect on the reproduction of this insect. Mortality of SAPW populations caused by insecticides had similar effects in the laboratory and field conditions. The results suggest that carbaryl, deltamethrin, fipronil, and imidacloprid caused significantly higher mortality as compared to the control in SAPW and may be used to control its populations in oil palm trees where bud rot appears as the key disease for SAPW attraction and infestation.

Lasioderma serricorne (Coleoptera: Anobiidae): First Report on Black Sesame (Sesamum indicum).

Insect pests may make food products and by-products unfit for human consumption. This study reports the occurrence of Lasioderma serricorne (Coleoptera: Anobiidae) in packaged seeds of black Sesamum indicum. An intact plastic pot of S. indicum seeds was purchased by a consumer in a supermarket in Divinópolis, Minas Gerais state, Brazil, in April 2014 and was kept at his home for 3 months. Two hundred adults of this insect (196 dead and 4 alive) were counted in the pot with the seeds, besides three live larvae. This insect fed on S. indicum seeds, making them unfit for consumption. L. serricorne feed on and reproduce in S. indicum seeds stored in plastic packaging.

Insecticidal activity of garlic essential oil and their constituents against the mealworm beetle, Tenebrio molitor Linnaeus (Coleoptera: Tenebrionidae).

This study evaluated the insecticidal activity of garlic, Allium sativum Linnaeus (Amaryllidaceae) essential oil and their principal constituents on Tenebrio molitor. Garlic essential oil, diallyl disulfide, and diallyl sulfide oil were used to compare the lethal and repellent effects on larvae, pupae and adults of T. molitor. Six concentrations of garlic essential oil and their principal constituents were topically applied onto larvae, pupae and adults of this insect. Repellent effect and respiration rate of each constituent was evaluated. The chemical composition of garlic essential oil was also determined and primary compounds were dimethyl trisulfide (19.86%), diallyl disulfide (18.62%), diallyl sulfide (12.67%), diallyl tetrasulfide (11.34%), and 3-vinyl-[4H]-1,2-dithiin (10.11%). Garlic essential oil was toxic to T. molitor larva, followed by pupa and adult. In toxic compounds, diallyl disulfide was the most toxic than diallyl sulfide for pupa > larva > adult respectively and showing lethal effects at different time points. Garlic essential oil, diallyl disulfide and diallyl sulfide induced symptoms of intoxication and necrosis in larva, pupa, and adult of T. molitor between 20-40 h after exposure. Garlic essential oil and their compounds caused lethal and sublethal effects on T. molitor and, therefore, have the potential for pest control.

Toxic effects of the neem oil (Azadirachta indica) formulation on the stink bug predator, Podisus nigrispinus (Heteroptera: Pentatomidae).

This research investigated the effects of neem oil on mortality, survival and malformations of the non-target stink bug predator, Podisus nigrispinus. Neurotoxic and growth inhibitor insecticides were used to compare the lethal and sublethal effects from neem oil on this predator. Six concentrations of neem oil were topically applied onto nymphs and adults of this predator. The mortality rates of third, fourth, and fifth instar nymphs increased with increasing neem oil concentrations, suggesting low toxicity to P. nigrispinus nymphs. Mortality of adults was low, but with sublethal effects of neem products on this predator. The developmental rate of P. nigrispinus decreased with increasing neem oil concentrations. Longevity of fourth instar nymphs varied from 3.74 to 3.05 d, fifth instar from 5.94 to 4.07 d and adult from 16.5 and 15.7 d with 0.5 and 50% neem doses. Podisus nigrispinus presented malformations and increase with neem oil concentrations. The main malformations occur in wings, scutellum and legs of this predator. The neem oil at high and sub lethal doses cause mortality, inhibits growth and survival and results in anomalies on wings and legs of the non-traget predator P. nigrispinus indicating that its use associated with biological control should be carefully evaluated.

Interactions Between the Bud Rot Disease of Oil Palm and Rhynchophorus palmarum (Coleoptera: Curculionidae).

Rhynchophorus palmarum (L.) causes great losses to the oil palm plantations, and therefore, the spatial and temporal distribution of this insect should be studied, to manage its populations. Insect sampling was done for 2 yr in an oil palm plantation from Colombia. In total, 60 pheromone traps were used in healthy palm trees and infected ones with the Bud Rot disease. On the other hand, developmental stages of this insect were quantified on healthy and diseased palms for two consecutive years. Number of adult R. palmarum per sampling was higher in the plantation with diseased palm trees, 3.85 and 74.7 insects per trap, than in those with healthy ones, 1.91 and 9.48 insects per trap, in the first and second years, respectively. After the integration of pheromone traps, there was a significant increase in the infestation level at all stages of development of the insect. For the first time, the presence of R. palmarum attracted to diseased palms is reported. The association between R. palmarum and the Bud Rot disease is a cause of death and great loss to the oil palm plantations.

Reconciling depressed Ca2+ sparks occurrence with enhanced RyR2 activity in failing mice cardiomyocytes.

Abnormalities in cardiomyocyte Ca2+ handling contribute to impaired contractile function in heart failure (HF). Experiments on single ryanodine receptors (RyRs) incorporated into lipid bilayers have indicated that RyRs from failing hearts are more active than those from healthy hearts. Here, we analyzed spontaneous Ca2+ sparks (brief, localized increased in [Ca2+]i) to evaluate RyR cluster activity in situ in a mouse post-myocardial infarction (PMI) model of HF. The cardiac ejection fraction of PMI mice was reduced to ∼30% of that of sham-operated (sham) mice, and their cardiomyocytes were hypertrophied. The [Ca2+]i transient amplitude and sarcoplasmic reticulum (SR) Ca2+ load were decreased in intact PMI cardiomyocytes compared with those from sham mice, and spontaneous Ca2+ sparks were less frequent, whereas the fractional release and the frequency of Ca2+ waves were both increased, suggesting higher RyR activity. In permeabilized cardiomyocytes, in which the internal solution can be controlled, Ca2+ sparks were more frequent in PMI cells (under conditions of similar SR Ca2+ load), confirming the enhanced RyR activity. However, in intact cells from PMI mice, the Ca2+ sparks frequency normalized by the SR Ca2+ load in that cell were reduced compared with those in sham mice, indicating that the cytosolic environment in intact cells contributes to the decrease in Ca2+ spark frequency. Indeed, using an internal "failing solution" with less ATP (as found in HF), we observed a dramatic decrease in Ca2+ spark frequency in permeabilized PMI and sham myocytes. In conclusion, our data show that, even if isolated RyR channels show more activity in HF, concomitant alterations in intracellular media composition and SR Ca2+ load may mask these effects at the Ca2+ spark level in intact cells. Nonetheless, in this scenario, the probability of arrhythmogenic Ca2+ waves is enhanced, and they play a potential role in the increase in arrhythmia events in HF patients.

Effects of vitamin D in the prevention of acute viral bronchiolitis: systematic review / Efeitos da vitamina D na prevenção da bronquiolite viral aguda: revisão sistemática

Aims: Published evidence suggests that Vitamin D supplementation may have a protective effect on infectious disease of the lower respiratory tract. The objective of this review was to critically appraise the effects of vitamin D intake in the prevention of acute viral bronchiolitis in children. Methods: We searched the databases Medline, EMBASE, Web of Science, LILACS, and Cochrane Central Register of Controlled Trials, until December 2014, using the keywords: "Vitamin D" or cholecalciferol or ergocalciferol and "bronchiolitis, viral" or "viral bronchiolitis" or "bronchiolitides, viral" or "viral bronchiolitides". Studies evaluating the effect of vitamin D intake in the prevention of acute viral bronchiolitis in young children were included. Studies with less than two weeks of intervention and review articles were excluded. Results: The search identified 241 articles, among which 20 articles were selected for full reading and two articles were included in the systematic review, comprising 296 children. No study measured serum levels of vitamin D. One of the included studies was a clinical trial, where the number of episodes of acute viral bronchiolitis was significantly lower in children supplemented with vitamin D (Group I: mean 0.6±0.7 Group II: mean 1.4±0.9; P=0.001). The other, a case-control study, did not find a significant relationship between the occurrence of acute viral bronchiolitis cases and the intake of vitamin D (odds ratio 1.7, 95% confidence interval 0.7-4.0). Conclusions: Current scientific evidence is insufficient to prove clinical benefits of vitamin D in preventing acute viral bronchiolitis.

Objetivos: Evidências publicadas sugerem que a suplementação da vitamina D pode ter efeito protetor nas infecções do trato respiratório inferior. O objetivo desta revisão foi avaliar os efeitos da ingestão de vitamina D na prevenção da bronquiolite viral aguda em crianças. Métodos: Foram feitas buscas nas bases de dados Medline, EMBASE, Web of Science, LILACS e Cochrane Central Register of Controlled Trials, até dezembro de 2014, usando os descritores "Vitamin D" ou cholecalciferol ou ergocalciferol e "bronchiolitis, viral" ou "viral bronchiolitis" ou "bronchiolitides, viral" ou "viral bronchiolitides". Foram incluídos estudos que avaliaram o efeito da ingesta da vitamina D na prevenção da bronquiolite viral aguda em crianças. Estudos com intervenção menor que duas semanas e artigos de revisão foram excluídos. Resultados: A busca identificou 241 artigos, entre os quais 20 artigos foram selecionados para leitura na íntegra e dois artigos foram incluídos na revisão sistemática, incluindo 296 crianças. Nenhum estudo mediu os níveis séricos de vitamina D. Um dos estudos incluídos foi um ensaio clinico, no qual o número de episódios de bronquiolite foi significativamente menor nas crianças suplementadas com vitamina D (Grupo I: média 0,6±0,7 Grupo II: média 1,4 ±0,9; P=0,001). No outro, um estudo de casos e controles, não se encontrou relação significativa entre casos de bronquiolite viral aguda e ingesta de vitamina D (odds ratio 1,7 ­ intervalo de confiança 95% 0,7-4,0). Conclusões: As evidências científicas atuais são insuficientes para comprovar os benefícios clínicos da vitamina D na prevenção da bronquiolite viral aguda.

Bioactivity of six plant extracts on adults of Demotispa neivai (Coleoptera: Chrysomelidae).

Demotispa neivai Bondar (Coleoptera: Chrysomelidae) damage oil palm fruits, which makes it necessary to develop products to control this insect. The mortality, repellency, and antifeeding effects on adults of D. neivai of six plant extracts of Azadirachta indica A. Juss. (Sapindales: Meliaceae), Ricinus communis (L.) (Malpighiaes: Euphorbiaceae), Citrus sinensis Oesbek (Sapindales: Rutaceae), Nicotiana tabacum (L.) (Slanales: Solanaceae), Capsicum annuum (L.) (Solanales: Solanaceae), and Artemisia absinthium (L.) (Asterales: Asteraceae) were determined: 1) the lethal concentration LC50-90, lethal time of D. neivai was evaluated after spraying the fruits of oil palm; 2) repellent effects of each ingredient were evaluated by calculating the index of repellency; 3) antifeeding effects with the rate of inhibition calculated between doses of 20 and 24 g/liter. The mortality of D. neivai was higher with the extracts Ci. sinensis, R. communis, N. tabacum, and Ca. annuum. The mortality of D. neivai increased in the first 72 hr in all treatments. The extracts of N. tabacum, Ca. annuum, and A. indica were more repellent to D. neivai that those of Ci. sinensis, Ar. Absinthium, and R. communis. Antifeeding effect was higher with Ci. sinensis and R. communis. The increased mortality of D. neivai by Ci. sinensis can be explained by the effect of this compound on the respiratory system of insects. Extracts of Ci. sinensis, R. communis, N. tabacum, and Ca. annuum repelled and caused mortality of D. neivai and, thus, can be used in integrate pest management programs of this pest in oil palm plantations.

Receptor de rianodina, fuga de calcio y arritmias / Ryanodine receptor, calcium leak and arrhythmias

La participación del canal de Ca2+/receptor de rianodina en el acoplamiento excitación-contracción cardiaco se conoce desde finales de los años ochenta, cuando en varios trabajos trascendentales se comunicó por primera vez su purificación y se encontró que correspondía a las estructuras conocidas como «pies¼ localizadas en las cisternas terminales del retículo sarcoplásmico. Adicionalmente a su papel como canal responsable del aumento global y transitorio de Ca2+ que activa a la maquinaria contráctil durante el ciclo cardiaco, el receptor de rianodina también libera Ca2+ durante la fase de relajación, dando lugar a la fuga de Ca2+ en la diástole que en condiciones fisiológicas regula el nivel de Ca2+ luminal, pero cuando se encuentra alterada participa en la generación de arritmias adquiridas o hereditarias. Recientemente, el esfuerzo de diversos grupos de investigación se ha enfocado en el desarrollo de herramientas farmacológicas para controlar la fuga diastólica de Ca2+ que se presenta alterada en algunas enfermedades cardiacas. En esta revisión nos enfocamos en describir la participación del receptor de rianodina cardiaco en la fuga diastólica de Ca2+ así como los diversos enfoques terapéuticos que se han implementado para controlar su actividad exacerbada en la diástole.

The participation of the ionic Ca2+ release channel/ryanodine receptor in cardiac excitation-contraction coupling is well known since the late '80s, when various seminal papers communicated its purification for the first time and its identity with the "foot" structures located at the terminal cisternae of the sarcoplasmic reticulum. In addition to its main role as the Ca2+ channel responsible for the transient Ca2+ increase that activates the contractile machinery of the cardiomyocytes, the ryanodine receptor releases Ca2+ during the relaxation phase of the cardiac cycle, giving rise to a diastolic Ca2+ leak. In normal physiological conditions, diastolic Ca2+ leak regulates the proper level of luminal Ca2+, but in pathological conditions it participates in the generation of both, acquired and hereditary arrhythmias. Very recently, several groups have focused their efforts into the development of pharmacological tools to control the altered diastolic Ca2+ leak via ryanodine receptors. In this review, we focus our interest on describing the participation of cardiac ryanodine receptor in the diastolic Ca2+ leak under physiological or pathological conditions and also on the therapeutic approaches to control its undesired exacerbated activity during diastole.