Mammalian CDC14 phosphatases control exit from stemness in pluripotent cells.

Maintenance of stemness is tightly linked to cell cycle regulation through protein phosphorylation by cyclin-dependent kinases (CDKs). However, how this process is reversed during differentiation is unknown. We report here that exit from stemness and differentiation of pluripotent cells along the neural lineage are controlled by CDC14, a CDK-counteracting phosphatase whose function in mammals remains obscure. Lack of the two CDC14 family members, CDC14A and CDC14B, results in deficient development of the neural system in the mouse and impairs neural differentiation from embryonic stem cells (ESCs). Mechanistically, CDC14 directly dephosphorylates specific proline-directed Ser/Thr residues of undifferentiated embryonic transcription Factor 1 (UTF1) during the exit from stemness, triggering its proteasome-dependent degradation. Multiomic single-cell analysis of transcription and chromatin accessibility in differentiating ESCs suggests that increased UTF1 levels in the absence of CDC14 prevent the proper firing of bivalent promoters required for differentiation. CDC14 phosphatases are dispensable for mitotic exit, suggesting that CDC14 phosphatases have evolved to control stemness rather than cell cycle exit and establish the CDK-CDC14 axis as a critical molecular switch for linking cell cycle regulation and self-renewal.

Contingency plan of the Clinical Management Unit for Psychiatry and Mental Health (CMUPMH) of the Infanta Cristina University Hospital (ICUH) for the COVID-19 pandemic.

In recent decades, pandemics and health catastrophes have caused disorders in part of the population with quite diverse consequences (SARS in 2002-2003, Ebola in 2014- 2015) showing a tendency to create generalised fear in the population, stigmatisation of the sufferers and psychological effects in health-care staff themselves.

Optimal Fast Integral Decontamination of Bacillus thuringiensis Aerosols and Fast Disinfection of Contaminated Surfaces.

Aerosolized anthrax (Bacillus anthracis) spores are of extreme health concern and can remain airborne for hours and contaminate all kinds of surfaces, constituting reservoirs from which resuspension is easily produced. The assessment of decontamination techniques must therefore consider both air and surfaces. In the present study, several kinds of disinfecting fogs were experimentally tested against Bacillus thuringiensis spores, which served as a surrogate for Bacillus anthracis, both as aerosols released into the air and spread on porous and non-porous surfaces with different positions and orientations. This technology removed Bacillus thuringiensis spores from the air in 20 min with just a 1 min application of fog. The dynamics and characteristics of the fog, related to aerosol and surface interactions, proved to be critical for optimal performance and decontamination. An optimal configuration could provide effective disinfection even on indirectly reached surfaces. In all cases, 8% hydrogen peroxide (H2O2) provided a higher disinfection rate than 2% glutaraldehyde.

Assessment of Surface Disinfection Effectiveness of Decontamination System COUNTERFOG® SDR-F05A+ Against Bacteriophage ɸ29.

The experience of COVID19 pandemic has demonstrated the real concern of biological agents dispersed in the air and surfaces environments. Therefore, the need of a fast and large-scale disinfection method has arisen for prevention of contagion. COUNTERFOG® is an innovative technology developed for large-scale decontamination of air and surfaces. The objective of this study is to assess experimentally the effectiveness of COUNTERFOG® in disinfecting viral-contaminated surfaces. We also aim to measure the necessary time to disinfect said surfaces. Stainless steel surfaces were contaminated with bacteriophage φ29 and disinfected using COUNTERFOG® SDR-F05A+, which uses a sodium hypochlorite solution at different concentrations and for different exposure times. A log reduction over 6 logs of virus titer is obtained in 1 min with 1.2% sodium hypochlorite when the application is direct; while at a radial distance of 5 cm from the point of application the disinfection reaches a reduction of 5.5 logs in 8 min. In the same way, a higher dilution of the sodium hypochlorite concentration (0.7% NaOCl) requires more exposure time (16 min) to obtain the same log reduction (> 6 logs). COUNTERFOG® creates, in a short time and at a distance of 2 m from the point of application, a thin layer of disinfectant that covers the surfaces. The selection of the concentration and exposure time is critical for the efficacy of disinfection. These tests demonstrate that a concentration between 0.7- 1.2% sodium hypochlorite is enough for a fast and efficient ɸ29 phage inactivation. The fact that ɸ29 phage is more resistant to disinfection than SARS-CoV-2 sustains this disinfection procedure.

Fast Air-to-Liquid Sampler Detects Surges in SARS-CoV-2 Aerosol Levels in Hospital Rooms.

The COVID-19 pandemic highlighted the dangers of airborne pathogen transmission. SARS-CoV-2 is known to be transmitted through aerosols; however, little is known about the dynamics of these aerosols in real environments, the conditions, and the minimum viral load required for infection. Efficiently measuring and capturing pathogens present in the air would help to understand the infection process. Air samplers usually take several hours to obtain an air sample. In this work a fast (1-2 min) method for capturing bioaerosols into a liquid medium has been tested in hospital rooms with COVID-19 patients. This fast sampling allows detecting transient levels of aerosols in the air. SARS-CoV-2 RNA is detected in aerosols from several hospital rooms at different levels. Interestingly, there are sudden boosts of the SARS-CoV-2 load in the air, suggesting that SARS-CoV-2 could be released abundantly at certain moments. These results show that the distribution of SARS-CoV-2-containing aerosols is not homogeneous in the hospital room. This technology is a fast and effective tool for capturing airborne matter in a very short time, which allows for fast decision-making any kind of hazard in the air is detected. It is also useful for a better understanding of aerosols dynamics.

Randomized trial of clozapine vs. risperidone in treatment-naïve first-episode schizophrenia: results after one year.

In first-episode patients with psychosis, clozapine may be potentially valuable as an initial treatment seeking to limit early on clinical and cognitive deterioration. Nevertheless, until recently its restricted use has limited the study of this possibility. Our research group is developing a non-commercial, multicentric and open label study on the differential efficacy between clozapine and risperidone in first-episode schizophrenia. In this paper, we present the results related to clinical variables after a one-year follow-up. So far, we have recruited 30 patients diagnosed with schizophrenia or schizophreniform disorder with illness duration of less than two years. The patients had not received any previous treatment and they were randomized to treatment with clozapine or risperidone. Our results indicate that on average, patients on clozapine adhered to their original treatment for a longer time period than patients on risperidone. By last observation carried forward (LOCF) analysis, patients on clozapine and risperidone displayed similar clinical improvements, although marginally greater improvements in positive and total symptoms scores were found in the clozapine group. At the 12-month point we observed a marginal improvement in negative symptom scores in patients on clozapine. Subjective secondary effects, as measured with the Udvalg for KliniskeUndersøgelser (UKU) scale, correlated negatively with negative symptoms at follow-up. Our data, although preliminary, suggest that clozapine may have a slightly superior efficacy in the initial year of treatment of first-episode treatment-naïve patients with schizophrenia, and this can be explained for the most part by greater adherence to this treatment.