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.

Aldosterone-Induced Sarco/Endoplasmic Reticulum Ca2+ Pump Upregulation Counterbalances Cav1.2-Mediated Ca2+ Influx in Mesenteric Arteries.

In mesenteric arteries (MAs), aldosterone (ALDO) binds to the endogenous mineralocorticoid receptor (MR) and increases the expression of the voltage-gated L-type Cav1.2 channel, an essential ion channel for vascular contraction, sarcoplasmic reticulum (SR) Ca2+ store refilling, and Ca2+ spark generation. In mesenteric artery smooth muscle cells (MASMCs), Ca2+ influx through Cav1.2 is the indirect mechanism for triggering Ca2+ sparks. This process is facilitated by plasma membrane-sarcoplasmic reticulum (PM-SR) nanojunctions that drive Ca2+ from the extracellular space into the SR via Sarco/Endoplasmic Reticulum Ca2+ (SERCA) pump. Ca2+ sparks produced by clusters of Ryanodine receptors (RyRs) at PM-SR nanodomains, decrease contractility by activating large-conductance Ca2+-activated K+ channels (BKCa channels), which generate spontaneous transient outward currents (STOCs). Altogether, Cav1.2, SERCA pump, RyRs, and BKCa channels work as a functional unit at the PM-SR nanodomain, regulating intracellular Ca2+ and vascular function. However, the effect of the ALDO/MR signaling pathway on this functional unit has not been completely explored. Our results show that short-term exposure to ALDO (10 nM, 24 h) increased the expression of Cav1.2 in rat MAs. The depolarization-induced Ca2+ entry increased SR Ca2+ load, and the frequencies of both Ca2+ sparks and STOCs, while [Ca2+]cyt and vasoconstriction remained unaltered in Aldo-treated MAs. ALDO treatment significantly increased the mRNA and protein expression levels of the SERCA pump, which counterbalanced the augmented Cav1.2-mediated Ca2+ influx at the PM-SR nanodomain, increasing SR Ca2+ content, Ca2+ spark and STOC frequencies, and opposing to hyperpolarization-induced vasoconstriction while enhancing Acetylcholine-mediated vasorelaxation. This work provides novel evidence for short-term ALDO-induced upregulation of the functional unit comprising Cav1.2, SERCA2 pump, RyRs, and BKCa channels; in which the SERCA pump buffers ALDO-induced upregulation of Ca2+ entry at the superficial SR-PM nanodomain of MASMCs, preventing ALDO-triggered depolarization-induced vasoconstriction and enhancing vasodilation. Pathological conditions that lead to SERCA pump downregulation, for instance, chronic exposure to ALDO, might favor the development of ALDO/MR-mediated augmented vasoconstriction of mesenteric arteries.

Non-proteinaceous salivary compounds of a predatory bug cause histopathological and cytotoxic effects in prey.

N,N-dimethylaniline and 1,2,5-trithiepane, present in the salivary glands of Podisus nigrispinus Dallas (Heteroptera: Pentatomidae), are toxic compounds which kill prey. The insecticidal activity and midgut cytotoxicity in Spodoptera frugiperda (J. E. Smith (Lepidoptera: Noctuidae) caterpillars fed on a diet with lethal concentrations of N,N-dimethylaniline and 1,2,5-trithiepane were evaluated. Midgut cell damage was evaluated with both light and transmission electron microscopy. The LC50 and LC90 of N,N-dimethylaniline were 0.611 and 0.818 µg L-1, respectively, and for 1,2,5-trithiepane they were 0.671 and 0.885 µg L-1, respectively. Vacuolization in the digestive and goblet cells occurred after 1 h of exposure in the midgut of the insects treated with either N,N-dimethylaniline and 1,2,5-trithiepane. Changes caused by N,N-dimethylaniline and 1,2,5-trithiepane in the midgut of S. frugiperda caterpillars may affect digestion and nutrient absorption with negative impacts on the insect's development and survival. The non-proteinaceous N,N-dimethylaniline and 1,2,5-trithiepane compounds have insecticidal effects, confirming the potential use on S. frugiperda caterpillars through oral administration.

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.

Indoxacarb effects on non-target predator, Podisus distinctus (Hemiptera: Pentatomidae).

Forestry pest management includes biological and chemical methods of pest control. Using insecticides and natural enemies can be compatible in forest pest management programs. The compatibility of the predatory stink bug Podisus distinctus with the insecticide indoxacarb, used in forestry, needs to be evaluated in Brazil. This study investigated the mortality, survival, respiration, preference, prey consumption, and locomotor activity of P. distinctus adults exposed to indoxacarb. In concentration-mortality bioassays, the lethality of indoxacarb (LC50 = 2.62 g L-1 and LC90 = 6.11 g L-1) was confirmed in P. distinctus adults. The survival rate was 100% in predator insects not exposed to indoxacarb, declining to 40.7% in predator insects exposed to 2.62 g L-1 and 0.1% in predators treated with 6.11 g L-1. Indoxacarb reduced the respiration of P. distinctus from 18.45 to 14.41 µL CO2 h-1 at 2.62 g L-1 for up to 3 h after insecticide exposure, inhibiting food consumption and displaying hyperexcitation. The harmful effects of indoxacarb to the natural enemy suggest that it should be better assessed for use with P. distinctus for pest management in forestry.

Susceptibility of Demotispa neivai (Coleoptera: Chrysomelidae) to Beauveria bassiana and Metarhizium anisopliae entomopathogenic fungal isolates.

BACKGROUND: The potential of Beauveria bassiana and Metarhizium anisopliae isolates obtained from naturally infected oil palm pests was evaluated to control Demotispa neivai as an alternative for organophosphate insecticide use in oil palm crops in Latin America. Two B. bassiana (Bb-0018 and Bb-0025) and two M. anisopliae (Ma-0002 and Ma-0003) isolates were tested against D. neivai adults for hydrophobicity, virulence, survival, adhesion to host cuticle, and mortality in semi-field conditions. RESULTS: Concentration-mortality bioassays demonstrate that isolates had lethal effect on D. neivai adults with Bb-0025 [median lethal concentration (LC50 ) = 3.45 × 107 conidia mL-1 ] and Bb-0018 (LC50  = 3.75 × 107 conidia mL-1 ) being the most effective followed by Ma-0003 (LC50  = 3.38 × 108 conidia mL-1 ) and Ma-0002 (5.33 × 108 conidia mL-1 ). Adult survival was 99% without exposure to fungal isolates, decreasing to 21.65% in insects exposed to Ma-0002, 19.41% with Ma-0003, 20.13% with Bb-0018, and 0.17% with Bb-0025. Mortality of D. neivai adults caused by the entomopathogenic fungal isolates was similar in both laboratory and semi-field conditions. Also, vegetative growth of the entomopathogenic fungal isolates was found in infected D. neivai adults in the field. CONCLUSION: Our data suggest that the tested entomopathogenic fungal isolates are effective against D. neivai with potential to be used as biological control agents contributing to the decrease of the use of chemical insecticides to control this oil palm pest. © 2021 Society of Chemical Industry.

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.

Tale of two kinases: Protein kinase A and Ca2+/calmodulin-dependent protein kinase II in pre-diabetic cardiomyopathy.

Metabolic syndrome is a pre-diabetic state characterized by several biochemical and physiological alterations, including insulin resistance, visceral fat accumulation, and dyslipidemias, which increase the risk for developing cardiovascular disease. Metabolic syndrome is associated with augmented sympathetic tone, which could account for the etiology of pre-diabetic cardiomyopathy. This review summarizes the current knowledge of the pathophysiological consequences of enhanced and sustained ß-adrenergic response in pre-diabetes, focusing on cardiac dysfunction reported in diet-induced experimental models of pre-diabetic cardiomyopathy. The research reviewed indicates that both protein kinase A and Ca2+/calmodulin-dependent protein kinase II play important roles in functional responses mediated by ß1-adrenoceptors; therefore, alterations in the expression or function of these kinases can be deleterious. This review also outlines recent information on the role of protein kinase A and Ca2+/calmodulin-dependent protein kinase II in abnormal Ca2+ handling by cardiomyocytes from diet-induced models of pre-diabetic cardiomyopathy.

Deltamethrin-Mediated Effects on Locomotion, Respiration, Feeding, and Histological Changes in the Midgut of Spodoptera frugiperda Caterpillars.

Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) is the main pest of maize crops, and effective methods for pest management are needed. The insecticidal efficacy of deltamethrin was evaluated against S. frugiperda for toxicity, survival, locomotion, anti-feeding, and histological changes in the midgut. Concentration-mortality bioassays confirmed that deltamethrin (LC50 = 3.58 mg mL-1) is toxic to S. frugiperda caterpillars. The survival rate was 99.7% in caterpillars not exposed to deltamethrin, decreasing to 50.3% in caterpillars exposed to LC50, and 0.1% in caterpillars treated with LC90. Spodoptera frugiperda demonstrated reduced mobility on deltamethrin-treated surfaces. Deltamethrin promoted a low respiration rate of S. frugiperda for up to 3 h after insecticide exposure, displaying immobilization and inhibiting food consumption. Deltamethrin induces histological alterations (e.g., disorganization of the striated border, cytoplasm vacuolization, and cell fragmentation) in the midgut, damaging the digestive cells and peritrophic matrix, affecting digestion and nutrient absorption.

Behavioral and ultrastructural effects of novaluron on Aedes aegypti larvae.

Chitin synthesis inhibitors (CSI) are supposed to inhibit formation of chitin microfibrils in newly synthesized cuticle during molting process. Conversely, there has been comparatively few data on morphological effects of CSI on non-target insect organs. In this work, the effects of the CSI novaluron on behavior and midgut of A. aegypti were evaluated. Toxicity bioassays revealed that novaluron is toxic to A. aegypti larva with LC50 = 18.57 mg L-1 when exposed in aqueous solution for 24 h. Novaluron treated larvae were less active and spent more time resting compared to the control group. Histopathology showed that midguts of novaluron-treated larvae had cytoplasm vacuolization and damaged brush border. Cytotoxic effects in midguts of treated larvae induced necrosis, autophagy and damage to mitochondria. Despite being chitin synthesis inhibitor, novaluron did not induce alterations in the integument of A. aegypti larvae. Fluorescence microscopy revealed that the number of digestive cells were higher in novaluron-treated larvae than in control, in response to digestive cell apoptosis. The present study highlights the importance of novaluron against A. aegypti larvae by causing injuries to non-target organs, altering behaviors, inducing cell death and inhibiting cell proliferation.

Exposure to insecticides causes effects on survival, prey consumption, and histological changes in the midgut of the predatory bug, Podisus nigrispinus (Hemiptera: Pentatomidae).

The control of defoliating caterpillars in forestry includes the use of insecticides and releases of the predatory bug Podisus nigrispinus, but some compounds may affect non-target natural enemies, which need evaluation of risk assessment. This research investigates the survival, preference, and prey consumption of P. nigrispinus adults fed with prey treated with the lethal concentration (LC50) of Bacillus thuringiensis (Bt), permethrin, tebufenozide, and thiamethoxam. Moreover, midgut histopathology of P. nigrispinus fed with preys treated with LC50 of each insecticide was investigated. The insecticides Bt, permethrin, and thiamethoxam reduce the survival and the prey consumption in P. nigrispinus fed with preys contaminate with these chemicals. However, the four tested insecticides, including tebufenozide, cause histological changes such as irregular epithelial architecture, cytoplasm vacuolization, and release of cell fragments in the midgut lumen of P. nigrispinus. The sublethal effects of Bt, permethrin, tebufenozide, and thiamethoxam to the natural enemy suggest that they should be better evaluated to be used together with P. nigrispinus for integrated pest management in forestry.

Ca2+ mishandling in heart failure: Potential targets.

Ca2+ mishandling is a common feature in several cardiovascular diseases such as heart failure (HF). In many cases, impairment of key players in intracellular Ca2+ homeostasis has been identified as the underlying mechanism of cardiac dysfunction and cardiac arrhythmias associated with HF. In this review, we summarize primary novel findings related to Ca2+ mishandling in HF progression. HF research has increasingly focused on the identification of new targets and the contribution of their role in Ca2+ handling to the progression of the disease. Recent research studies have identified potential targets in three major emerging areas implicated in regulation of Ca2+ handling: the innate immune system, bone metabolism factors and post-translational modification of key proteins involved in regulation of Ca2+ handling. Here, we describe their possible contributions to the progression of HF.

The salivary glands of Brontocoris tabidus (Heteroptera: Pentatomidae): Morphology and secretory cycle.

Brontocoris tabidus (Signoret) (Heteroptera: Pentatomidae) is a zoophytophagous insect used for biological control in agriculture and forest systems because its nymphs and adults feed on insects and plants. The predatory Pentatomidae insert the mouthparts into the prey, releasing saliva to paralysis and kills the insect, as well as digest body parts to be sucked in a preliminary extra-oral digestion. In a short period of time, this insect shows the ability to feed again, suggesting the existence of a constant and abundant secretory cycle in the salivary glands. This study evaluated the morphological, histochemical and ultrastructural changes of the salivary glands of B. tabidus in fed and starved insects. The salivary complex of this predatory bug has a pair of bilobed salivary glands and a pair of tubular accessory salivary glands. The accessory glands have the lumen lined by a thick non-cuticular layer rich in glycoproteins. The secretory cells of the B. tabidus principal salivary glands have constant secretory activity, with each lobe producing different substances. The physiological processes that occur in the salivary gland of B. tabidus indicate that the insect needs to feed constantly, corroborating the potential of this insect to be used in biological control programs.

Effect of Benzoylphenyl Ureas on Survival and Reproduction of the Lace Bug, Leptopharsa gibbicarina.

The lace bug, Leptopharsa gibbicarina is a vector of Pestalotiopsis fungal complex in oil palm crops in the Americas. The effects of four benzoylphenyl ureas (BPUs) (lufenuron, novaluron, teflubenzuron, and triflumuron) were evaluated against L. gibbicarina for toxicity, survival, reproduction, and mortality in semi-field conditions. Concentration-mortality bioassays demonstrated that novaluron (LC50 = 0.33 ppm), teflubenzuron (LC50 = 0.24 ppm), lufenuron (LC50 = 0.17 ppm), and triflumuron (LC50 = 0.42 ppm) are toxic to L. gibbicarina nymphs. The survival rate was 99% in control nymphs, decreasing to 50% in nymphs exposed to LC50 of triflumuron, 47% in nymphs treated with lufenuron, 43% in nymphs treated with teflubenzuron, and 43% in those treated with novaluron. Sublethal concentrations of BPUs showed detrimental effects on the adult emergence, longevity, fecundity, and fertility of this insect. The mortality of nymphs caused by these insecticides was similar in both laboratory and semi-field conditions. Our results suggest that novaluron, teflubenzuron, and triflumuron are highly effective against L. gibbicarina, and therefore, have potential applications for this oil palm pest.

Exposure to chlorantraniliprole reduces locomotion, respiration, and causes histological changes in the midgut of velvetbean caterpillar Anticarsia gemmatalis (Lepidoptera: Noctuidae).

The anthranilic diamide, chlorantraniliprole is a systemic insecticide affecting ryanodine receptors. This insecticide is used to control caterpillars in soybean crops because it has low toxicity to non-target organisms. The objective was to identify side-effects of chlorantraniliprole on midgut histopathology, respiration and behavior of the velvetbean caterpillar Anticarsia gemmatalis in laboratoty. Chlorantraniliprole has LC50 = 0.61 (0.58-0.64) mg mL-1 for A. gemmatalis fourth instar caterpillars after 96 h. The insecticide causes severe histopathological effects in the midgut with epithelial disorganization, microvilli degeneration, cytoplasm vacuolization, cell fragmentation, and peritrophic matrix disorganization. The respiratory rate and the walking speed decrease, whereas the resting period increase for caterpillars exposed to this insecticide. Chlorantraniliprole is toxic to A. gemmatalis at median lethal concentrations causing severe histological and ultrastructural changes with degeneration of the midgut epithelium, reduction of respiratory rates and inducing an arresting behavioral response of this insect.

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.

Genetic Deletion of NOD1 Prevents Cardiac Ca2+ Mishandling Induced by Experimental Chronic Kidney Disease.

Risk of cardiovascular disease (CVD) increases considerably as renal function declines in chronic kidney disease (CKD). Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) has emerged as a novel innate immune receptor involved in both CVD and CKD. Following activation, NOD1 undergoes a conformational change that allows the activation of the receptor-interacting serine/threonine protein kinase 2 (RIP2), promoting an inflammatory response. We evaluated whether the genetic deficiency of Nod1 or Rip2 in mice could prevent cardiac Ca2+ mishandling induced by sixth nephrectomy (Nx), a model of CKD. We examined intracellular Ca2+ dynamics in cardiomyocytes from Wild-type (Wt), Nod1-/- and Rip2-/- sham-operated or nephrectomized mice. Compared with Wt cardiomyocytes, Wt-Nx cells showed an impairment in the properties and kinetics of the intracellular Ca2+ transients, a reduction in both cell shortening and sarcoplasmic reticulum Ca2+ load, together with an increase in diastolic Ca2+ leak. Cardiomyocytes from Nod1-/--Nx and Rip2-/--Nx mice showed a significant amelioration in Ca2+ mishandling without modifying the kidney impairment induced by Nx. In conclusion, Nod1 and Rip2 deficiency prevents the intracellular Ca2+ mishandling induced by experimental CKD, unveiling new innate immune targets for the development of innovative therapeutic strategies to reduce cardiac complications in patients with CKD.