Synthesis, leishmanicidal and cytotoxic activity of triclosan-chalcone, triclosan-chromone and triclosan-coumarin hybrids.

Twelve hybrids derived from triclosan were obtained via Williamson etherification of O-triclosan alkyl bromide plus chalcone and O-coumarin or O-chromone alkyl bromide plus triclosan, respectively. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against L. (V) panamensis amastigotes. Cytotoxic activity was also evaluated against mammalian U-937 cells. Compounds 7-9 and 17, were active against Leishmania parasites (EC50=9.4; 10.2; 13.5 and 27.5 µg/mL, respectively) and showed no toxicity toward mammalian cells (>200 µg/mL). They are potential candidates for antileishmanial drug development. Compounds 25-27, were active and cytotoxic. Further studies using other cell types are needed in order to discriminate whether the toxicity shown by these compounds is against tumor or non-tumor cells. The results indicate that compounds containing small alkyl chains show better selectivity indices. Moreover, Michael acceptor moieties may modify both the leishmanicidal activity and cytotoxicity. Further studies are required to evaluate if the in vitro activity against Leishmania panamensis demonstrated here is also observed in vivo.

Comparison of social isolation in autistic children and adolescents according to age, marital status and number of siblings.

BACKGROUND: Children and adolescents with autism spectrum disorder (ASD) have difficulties that limit their opportunities to interact with peers and family members. These behaviors can lead to social exclusion, and consequently social isolation. The aim was to compare social isolation of children and adolescents with ASD according to age, marital status, and number of siblings. MATERIALS AND METHODS: Cross-sectional descriptive study in 37 subjects with ASD. Social isolation was assessed using a 6-item scale (with five alternatives). The sociodemographic variables were age, sex, marital status of parents, and number of siblings. Two groups were formed according to age (children from 4 to 10 years old and adolescents from 11 to 20 years old). RESULTS: For the total score of the social isolation scale, children showed a higher score (21.1 ± 4.7) than adolescents (17.7 ± 5.7). Children living with divorced parents had lower scores (16.2 ± 3.6), compared to married (22.2 ± 4.5) and cohabiting (22.8) children. For the number of siblings, with no siblings 17.2 ± 3.1 points, one sibling 22.2 ± 3.5 points, two siblings 22.1 ± 3.1 points, and three siblings 22.4 ± 3.2 points (P < 0.05). Age was related to social isolation (r = -0.30, P < 0.05). CONCLUSION: Children who live with divorced parents and have no siblings presented a higher degree of isolation in relation to their counterparts who live with both parents and have at least one sibling. Age plays a relevant role, with children aged 4-10 years presenting a lower degree of isolation than the adolescent group. It is suggested that the preservation of a functional family and the presence of siblings could contribute to improving social isolation.

Knockin' on Egg's Door: Maternal Control of Egg Activation That Influences Cortical Granule Exocytosis in Animal Species.

Fertilization by multiple sperm leads to lethal chromosomal number abnormalities, failed embryo development, and miscarriage. In some vertebrate and invertebrate eggs, the so-called cortical reaction contributes to their activation and prevents polyspermy during fertilization. This process involves biogenesis, redistribution, and subsequent accumulation of cortical granules (CGs) at the female gamete cortex during oogenesis. CGs are oocyte- and egg-specific secretory vesicles whose content is discharged during fertilization to block polyspermy. Here, we summarize the molecular mechanisms controlling critical aspects of CG biology prior to and after the gametes interaction. This allows to block polyspermy and provide protection to the developing embryo. We also examine how CGs form and are spatially redistributed during oogenesis. During egg activation, CG exocytosis (CGE) and content release are triggered by increases in intracellular calcium and relies on the function of maternally-loaded proteins. We also discuss how mutations in these factors impact CG dynamics, providing unprecedented models to investigate the genetic program executing fertilization. We further explore the phylogenetic distribution of maternal proteins and signaling pathways contributing to CGE and egg activation. We conclude that many important biological questions and genotype-phenotype relationships during fertilization remain unresolved, and therefore, novel molecular players of CG biology need to be discovered. Future functional and image-based studies are expected to elucidate the identity of genetic candidates and components of the molecular machinery involved in the egg activation. This, will open new therapeutic avenues for treating infertility in humans.

Occupational therapy for delirium management in elderly patients without mechanical ventilation in an intensive care unit: A pilot randomized clinical trial.

PURPOSE: Delirium has negative consequences such as increased mortality, hospital expenses and decreased cognitive and functional status. This research aims to determine the impact of occupational therapy intervention in duration, incidence and severity of delirium in elderly patients in the intensive care unit; secondary outcome was to assess functionality at hospital discharge. METHODS: This is a pilot randomized clinical trial of patients without mechanical ventilation for 60 years. Patients were assigned to a control group that received standard strategies of prevention (n=70) or to an experimental group that received standard strategies plus occupational therapy twice a day for 5 days (n=70). Delirium was valued with Confusion Assessment Method and Delirium Rating Scale, and functional outcomes at discharge with Functional Independence Measure, Hand Dynamometer, and Mini-Mental State Examination. RESULTS: A total of 140 participants were recruited. The experimental group had lower duration (risk incidence ratios, 0.15 [P=.000; 95% confidence interval, 0.12-0.19] vs 6.6 [P=.000, 95% confidence interval, 5.23-8.3]) and incidence of delirium (3% vs 20%, P=.001), and had higher scores in Motor Functional Independence Measure (59 vs 40 points, P<.0001), cognitive state (MMSE: 28 vs 26 points, P<.05), and grip strength in the dominant hand (26 vs 18 kg, P<.05), compared with the control group. CONCLUSIONS: Occupational therapy is effective in decreasing duration and incidence of delirium in nonventilated elderly patients in the intensive care unit and improved functionality at discharge.