Experimental and computational evidence that Calpain-10 binds to the carboxy terminus of NaV1.2 and NaV1.6.

Voltage-gated sodium channels (NaV) are pivotal proteins responsible for initiating and transmitting action potentials. Emerging evidence suggests that proteolytic cleavage of sodium channels by calpains is pivotal in diverse physiological scenarios, including ischemia, brain injury, and neuropathic pain associated with diabetes. Despite this significance, the precise mechanism by which calpains recognize sodium channels, especially given the multiple calpain isoforms expressed in neurons, remains elusive. In this work, we show the interaction of Calpain-10 with NaV's C-terminus through a yeast 2-hybrid assay screening of a mouse brain cDNA library and in vitro by GST-pulldown. Later, we also obtained a structural and dynamic hypothesis of this interaction by modeling, docking, and molecular dynamics simulation. These results indicate that Calpain-10 interacts differentially with the C-terminus of NaV1.2 and NaV1.6. Calpain-10 interacts with NaV1.2 through domains III and T in a stable manner. In contrast, its interaction with NaV1.6 involves domains II and III, which could promote proteolysis through the Cys-catalytic site and C2 motifs.

Pre-operative factors associated with short- and long-term outcomes in the patient with inguinal hernia: What does the current evidence say?

Hernia repair is one of the most frequent interventions in surgery worldwide. The approach to abdominal wall and inguinal hernias remains a challenge due to emerging evidence on aspects such as timely diagnosis, use of innovative techniques or post-surgical care. However, pre-operative preparation is also a factor that substantially affects the absolute success rate of this type of condition. Time management between diagnosis and intervention, control of diseases that increase intra-abdominal pressure, weight and nutritional status, are some of the many elements to be considered in this type of patients before surgery. Considering that this condition carries high health care costs, especially in case of recurrence, has a risk of complications and affects the individual's functional capacity, the objective of this review is to synthesize evidence on the role of these factors on the short- and long-term outcome of inguinal hernia management, and to make suggestions on the general approach to this type of patients.

Synthesis of flutamide-conjugates.

In this paper, we designed and extended modification basing on the flutamide structure. A series of flutamide-conjugates were obtained with methyl bromoacetate and ethylenediamine. Through the synthesis of two conjugates with 3,5-bis(dodecyloxy)benzoate derivatives, these flutamide conjugates were tested for anticancer activity. Among the compounds tested, the flutamide-conjugates showed good inhibition activity against cancer cell lines U-251, PC-3 and K-562. The conjugates showed a better inhibitory effect than free flutamide and did not show activity against normal COS-7 monkey kidney fibroblast cells. It was also observed that the flutamide conjugates had an inhibitory effect against human colorectal adenocarcinoma HCT-15.

Factores de riesgo de infección puerperal en el Hospital General Docente Dr Agostinho Neto, Guantánamo 2016-2018 / Facores de risco de infecção puerperal no Hospital Geral Universitario Agostinho Neto, Guantánamo 2016-2018 / Risk factors of puerperal infection in the Teaching General Hospital Agostinho Neto, Guantánamo 2016-2018

Introducción: la prevención de la infección puerperal es una exigencia social. Objetivo: precisar la asociación entre rotura de membranas ovulares, infección cervicovaginal y corioamnionitis, y presentación de infección puerperal en puérperas atendidas en el servicio de Obstetriciadel Hospital General Docente Dr Agostinho Neto durante los años 2016-2018. Método: se realizó un estudio de casos y controles. El universo se conformó por todas las puérperas con infección puerperal (n=622) y de estas últimas se seleccionó una muestra por conveniencia de 60 pacientes, las que constituyeron el grupo de casos y se eligió un grupo de pacientes sin infección puerperal (n=120) que conformaron el grupo control. Se estudiaron las siguientes variables: edad en años, tiempo de rotura de membranas ovulares, diagnóstico de infección cervicovaginal y corioamnionitis y vía del parto. Resultados: predominaron las edades entre 20 y 29 años en los casos (41,7 por ciento) y controles (48,3 por ciento). Existieron evidencias estadísticamente significativas, con una confiabilidad del 95 por ciento, de que la rotura de membranas de más de 24 horas, la infección cervicovaginal y la corioamnionitis fueron factores de riesgo de infección puerperal. Predominó la vía vaginal en los casos (60 por ciento) y controles (61,7 por ciento), que no resultó estadísticamente significativa asociada a la infección puerperal. Conclusiones: las puérperas con rotura de membranas ovulares de más de 24 horas, infección cervicovaginal y corioamnionitis presentaron mayor riesgo de infección puerperal(AU)

Introduction: the prevention of puerperal infection is a social requirement. Objective: to specify the association between rupture of ovular membranes, cervicovaginal infection and chorioamnionitis and the presentation of puerperal infection in puerperal women attended in the Obstetrics Service of the Hospital Dr. Agostinho Neto during the years 2016-2018. Method: a study was conducted of cases and controls. The universe was formed by all puerperal puerperal infections (n=622), and of the latter a sample was selected for convenience of 60 patients, which constituted the group of cases; a group of patients without puerperal infection (n=120) who formed the control group was chosen. The following variables were studied: age in years, time of rupture of ovular membranes, diagnosis of cervicovaginal infection and chorioamnionitis and birth pathway. Results: ages between 20 and 29 years predominated in cases (41.7 per cent) and controls (48.3per cent). There was statistically significant evidence, with a reliability of 95per cent, that the rupture of membranes over 24 hours, cervicovaginal infection and chorioamnionitis were risk factors for puerperal infection. The vaginalroute predominated in the cases (60per cent) and controls (61.7per cent), which was not statistically significant associated with puerperal infection. Conclusions: puerperal women with ruptured ovular membranes over 24 hours, cervicovaginal infection and chorioamnionitis presented a higher risk of puerperal infection(AU)

Introdução: a prevenção da infecção puerperal é uma exigência social. Objetivo: Para esclarecer a associação entre a ruptura de membranas, infecção cérvico-vaginal e corioamnionite e apresentação de infecção puerperal em puérperas atendidas no Departamento de Obstetrícia Dr. Agostinho Neto Hospital durante os anos de 2016-2018. Método: foi realizado um estudo de casos e controles. O universo foi formado por todas as infecções puerperais no puerpério (n=622) e, deste último, uma amostra foi selecionada por conveniência de 60 pacientes, constituindo o grupo de casos; um grupo de pacientes sem infecção puerperal (n=120) que formou o grupo controle foi escolhido. As seguintes variáveis foram estudadas: idade em anos, tempo de ruptura das membranas ovulares, diagnóstico de infecção cervicovaginal e corioamnionite e via de nascimento. Resultados: as idades entre 20 e 29 anos predominaram nos casos (41,7por cento) e controles (48,3por cento). Houve evidência estatisticamente significativa, com uma confiança de 95por cento, que a ruptura das membranas durante mais de 24 horas, a infecção genital do corioamniotite e eram factores de risco infecção puerperal. A via vaginal predominou nos casos (60por cento) e controles (61,7por cento), o que não foi estatisticamente significante associado à infecção puerperal. Conclusões: puérperas com ruptura de membranas ovulares por 24 horas, infecção cervicovaginal e corioamnionite apresentaram maior risco de infecção puerperal(AU)

Species composition and seasonal abundance of sandflies (Diptera: Psychodidae: Phlebotominae) in coffee agroecosystems

The composition and seasonal occurrence of sandflies were investigated in coffee agroecosystems in the Soconusco region of Chiapas, Mexico. Insect sampling was performed on three plantations located at different altitudes: Finca Guadalupe Zajú [1,000 m above sea level (a.s.l.)], Finca Argovia (613 m a.s.l.) and Teotihuacán del Valle (429 m a.s.l.). Sandflies were sampled monthly from August 2007-July 2008 using three sampling methods: Shannon traps, CDC miniature light traps and Disney traps. Sampling was conducted for 3 h during three consecutive nights, beginning at sunset. A total of 4,387 sandflies were collected during the course of the study: 2,718 individuals in Finca Guadalupe Zajú, 605 in Finca Argovia and 1,064 in Teotihuacán del Valle. The Shannon traps captured 94.3% of the total sandflies, while the CDC light traps and Disney traps captured 4.9% and 0.8%, respectively. More females than males were collected at all sites. While the number of sandflies captured was positively correlated with temperature and relative humidity, a negative correlation was observed between sandfly numbers and rainfall. Five species of sandflies were captured: Lutzomyia cruciata , Lutzomyia texana , Lutzomyia ovallesi , Lutzomyia cratifer / undulata and Brumptomyia sp. Lu. cruciata , constituting 98.8% of the total, was the most abundant species. None of the captured sandflies was infected with Leishmania spp.

Species composition and seasonal abundance of sandflies (Diptera: Psychodidae: Phlebotominae) in coffee agroecosystems.

The composition and seasonal occurrence of sandflies were investigated in coffee agroecosystems in the Soconusco region of Chiapas, Mexico. Insect sampling was performed on three plantations located at different altitudes: Finca Guadalupe Zajú [1,000 m above sea level (a.s.l.)], Finca Argovia (613 m a.s.l.) and Teotihuacán del Valle (429 m a.s.l.). Sandflies were sampled monthly from August 2007-July 2008 using three sampling methods: Shannon traps, CDC miniature light traps and Disney traps. Sampling was conducted for 3 h during three consecutive nights, beginning at sunset. A total of 4,387 sandflies were collected during the course of the study: 2,718 individuals in Finca Guadalupe Zajú, 605 in Finca Argovia and 1,064 in Teotihuacán del Valle. The Shannon traps captured 94.3% of the total sandflies, while the CDC light traps and Disney traps captured 4.9% and 0.8%, respectively. More females than males were collected at all sites. While the number of sandflies captured was positively correlated with temperature and relative humidity, a negative correlation was observed between sandfly numbers and rainfall. Five species of sandflies were captured: Lutzomyia cruciata , Lutzomyia texana , Lutzomyia ovallesi , Lutzomyia cratifer / undulata and Brumptomyia sp. Lu. cruciata , constituting 98.8% of the total, was the most abundant species. None of the captured sandflies was infected with Leishmania spp.

Pharmacogenetics of oral anticoagulants.

The use of oral anticoagulants (OA) is problematic due to its association with hemorrhagic complications. OA metabolism relies on the CYP2C9 complex. Genetic variations compromising metabolic competence of this complex may explain the risk of excessive and hazardous anticoagulation. A pharmacogenetics-based approach to this issue could be beneficial for choosing adequate dose and duration of treatment, in addition to having a better understanding of pharmacological interactions to which OA are susceptible. However, evidence from several basic and clinical studies indicates that both a complicated system of regulation of expression of multiple genes and the influence of a wide variety of epigenetic factors could be responsible for adverse drug reactions associated with the use of OA. Emphasis on understanding the gene-environment interactions could attain new paths to facilitate the use of these important drugs in the quotidian clinical practice.