A primary microcephaly-associated sas-6 mutation perturbs centrosome duplication, dendrite morphogenesis, and ciliogenesis in Caenorhabditis elegans.

The human SASS6(I62T) missense mutation has been linked with the incidence of primary microcephaly in a Pakistani family, although the mechanisms by which this mutation causes disease remain unclear. The SASS6(I62T) mutation corresponds to SAS-6(L69T) in Caenorhabditis elegans. Given that SAS-6 is highly conserved, we modeled this mutation in C. elegans and examined the sas-6(L69T) effect on centrosome duplication, ciliogenesis, and dendrite morphogenesis. Our studies revealed that all the above processes are perturbed by the sas-6(L69T) mutation. Specifically, C. elegans carrying the sas-6(L69T) mutation exhibit an increased failure of centrosome duplication in a sensitized genetic background. Further, worms carrying this mutation also display shortened phasmid cilia, an abnormal phasmid cilia morphology, shorter phasmid dendrites, and chemotaxis defects. Our data show that the centrosome duplication defects caused by this mutation are only uncovered in a sensitized genetic background, indicating that these defects are mild. However, the ciliogenesis and dendritic defects caused by this mutation are evident in an otherwise wild-type background, indicating that they are stronger defects. Thus, our studies shed light on the novel mechanisms by which the sas-6(L69T) mutation could contribute to the incidence of primary microcephaly in humans.

The retromer complex regulates C. elegans development and mammalian ciliogenesis.

The mammalian retromer consists of subunits VPS26 (either VPS26A or VPS26B), VPS29 and VPS35, and a loosely associated sorting nexin (SNX) heterodimer or a variety of other SNX proteins. Despite involvement in yeast and mammalian cell trafficking, the role of retromer in development is poorly understood, and its impact on primary ciliogenesis remains unknown. Using CRISPR/Cas9 editing, we demonstrate that vps-26-knockout worms have reduced brood sizes, impaired vulval development and decreased body length, all of which have been linked to ciliogenesis defects. Although preliminary studies did not identify worm ciliary defects, and impaired development limited additional ciliogenesis studies, we turned to mammalian cells to investigate the role of retromer in ciliogenesis. VPS35 localized to the primary cilium of mammalian cells, and depletion of VPS26, VPS35, VPS29, SNX1, SNX2, SNX5 or SNX27 led to decreased ciliogenesis. Retromer also coimmunoprecipitated with the centriolar protein, CP110 (also known as CCP110), and was required for its removal from the mother centriole. Herein, we characterize new roles for retromer in C. elegans development and in the regulation of ciliogenesis in mammalian cells, suggesting a novel role for retromer in CP110 removal from the mother centriole.

The hemodynamic effects of diazepam versus dexmedetomidine in the treatment of alcohol withdrawal syndrome: A randomized clinical trial.

BACKGROUND: Dexmedetomidine (DEX) is an alpha-2 adrenergic drug used for short sedation and as an alternative to diazepam (DZP) in the treatment of alcohol withdrawal syndrome (AWS). PURPOSE: This study aims to compare the hemodynamic effect of DZP versus DEX on heart rate (HR) and blood pressure in patients with AWS. METHODS: Prospective randomized clinical trial that includes 40 patients with AWS from Mérida, Yucatán, México. RESULTS: Forty patients were randomly divided into two groups: one group DZP (n=20) patients received diazepam (doses 5-20mg IV) and the other group (n=20) received DEX (dexmedetomidine infusion .2-.7mcg/kg/min). We obtained statistical significance in sedation with the DEX group in the degree of traumatic brain injury I/II (p=.003). The DEX group remained haemodynamically stable in the first 24h, the mean HR (73.85±8.39) was significant comparing both groups (p=.002). In the comparison of the figures for the DEX group with the DZP (143.85±2.30-137.95±5.62) the SBP was significant with a (p=.0001). Furthermore, DEX treatment was shorter. CONCLUSION: Although DEX is not indicated for the routine treatment of AWS, this study proposes a positive effect on HR, SBP and fewer days of treatment compared to the standard DZP treatment for AWS. Clinical Trials.gov ID: NCT03877120-https://clinicaltrials.gov/ct2/show/NCT03877120.

Application of NMR Spectroscopy for the Detection of Equilibrating E-Z Diastereomers.

Conjugation can lower the energy barrier for unsaturated C-C bond rotations, resulting in a mixture of equilibrating diastereomers at room temperature. Therefore, methods claiming diastereoselective synthesis of conjugated double bonds often require proof that the observed diastereomeric ratio is not because of the diastereomeric equilibration of the product. Variable-temperature (VT) NMR experiments are commonly used to distinguish between the two possibilities. However, the VT technique requires accessories for the NMR spectrometer and more setup time. Here, we show that the rarely used application of 1-D and 2-D nuclear Overhauser effect spectroscopy experiments for the detection of the equilibrating diastereomers is a convenient alternative to the VT technique.

Impacto poblacional de un programa de salud escolar podológica / Population impact of a podiatric school health programme

Este trabajo presenta un resumen de lo realizado en los últimos 12 años de colaboración entre la comunidad escolar de varios centros de enseñanza primaria y secundaria y los/las responsables de las prácticas de la asignatura Podología Preventiva y Comunitaria del Grado en Podología, que se imparte en la Universidad de Sevilla. Se muestran diferentes estrategias llevadas a cabo desde las líneas de investigación Salud Podológica para Todos y Podología Preventiva y Comunitaria, integradas en el Grupo de Investigación Hermes (CTS-601), dirigidas a promocionar la salud podológica en general. Se ha explorado un total de 4630 escolares y se han confirmado alteraciones podológicas en 677. También se han beneficiado 7145 miembros de la comunidad escolar a quienes se ha llegado a través de actividades educativas sobre el cuidado de los pies. Su desarrollo trata de impedir que se generen lesiones, en la edad adulta, que perjudiquen la calidad de vida

This article presents an overview of the work done over the past 12 years in a collaboration between the school communities at various primary and secondary schools and the practical experience managers working in the Preventive and Community Podiatry area of the Podiatry degree at the University of Seville (Spain). The article presents several strategies, which were carried out in the fields of Foot Health for All and Preventive and Community Podiatry as part of the Hermes Research Group (CTS-601) aimed at promoting general foot health. Foot examinations were conducted in a total of 4,630 school pupils, with foot problems being confirmed in 677 of them. Some 7,145 members of the school community were also helped, with these people being reached through educational activities around foot care. The aim of the initiative was to prevent foot damage among children, which could have a harmful impact on their quality of life as adults

[Population impact of a podiatric school health programme]. / Impacto poblacional de un programa de salud escolar podológica.

This article presents an overview of the work done over the past 12 years in a collaboration between the school communities at various primary and secondary schools and the practical experience managers working in the Preventive and Community Podiatry area of the Podiatry degree at the University of Seville (Spain). The article presents several strategies, which were carried out in the fields of Foot Health for All and Preventive and Community Podiatry as part of the Hermes Research Group (CTS-601) aimed at promoting general foot health. Foot examinations were conducted in a total of 4,630 school pupils, with foot problems being confirmed in 677 of them. Some 7,145 members of the school community were also helped, with these people being reached through educational activities around foot care. The aim of the initiative was to prevent foot damage among children, which could have a harmful impact on their quality of life as adults.

Experimental demonstration of a cognitive quality of transmission estimator for optical communication systems.

The impact of physical layer impairments in optical network design and operation has received significant attention in the last years, thereby requiring estimation techniques to predict the quality of transmission (QoT) of optical connections before being established. In this paper, we report on the experimental demonstration of a case-based reasoning (CBR) technique to predict whether optical channels fulfill QoT requirements, thus supporting impairment-aware networking. The validation of the cognitive QoT estimator is performed in a WDM 80 Gb/s PDM-QPSK testbed, and we demonstrate that even with a very small and not optimized underlying knowledge base, it achieves between 79% and 98.7% successful classifications based on the error vector magnitude (EVM) parameter, and approximately 100% when the classification is based on the optical signal to noise ratio (OSNR).

Man-machine interface system for neuromuscular training and evaluation based on EMG and MMG signals.

This paper presents the UVa-NTS (University of Valladolid Neuromuscular Training System), a multifunction and portable Neuromuscular Training System. The UVa-NTS is designed to analyze the voluntary control of severe neuromotor handicapped patients, their interactive response, and their adaptation to neuromuscular interface systems, such as neural prostheses or domotic applications. Thus, it is an excellent tool to evaluate the residual muscle capabilities in the handicapped. The UVa-NTS is composed of a custom signal conditioning front-end and a computer. The front-end electronics is described thoroughly as well as the overall features of the custom software implementation. The software system is composed of a set of graphical training tools and a processing core. The UVa-NTS works with two classes of neuromuscular signals: the classic myoelectric signals (MES) and, as a novelty, the myomechanic signals (MMS). In order to evaluate the performance of the processing core, a complete analysis has been done to classify its efficiency and to check that it fulfils with the real-time constraints. Tests were performed both with healthy and selected impaired subjects. The adaptation was achieved rapidly, applying a predefined protocol for the UVa-NTS set of training tools. Fine voluntary control was demonstrated to be reached with the myoelectric signals. And the UVa-NTS demonstrated to provide a satisfactory voluntary control when applying the myomechanic signals.

Prostatic aspergillosis in a heart transplant recipient: case report and review.

In this study we report the first case of invasive prostatic aspergillosis (IPRA) in a heart recipient with post-transplantation antibody deficiency, and review the other 11 cases described in the medical literature. Seven patients were immunocompromised and 6 had dissemination to other sites. Examination of the prostate usually revealed enlargement, with or without nodular lesions. Transrectal ultrasonography or computed tomography scan can provide the diagnosis, although this should be confirmed with biopsy and culture of the lesion. Urine culture can be negative and treatment should include long-term systemic anti-fungal therapy and, in most cases, prostatectomy.