口唇トレーニングの多方位口唇閉鎖力に対する影響─健常若年成人および健常高齢者を対象として─

The topical application of sunscreen and cosmetic products that afford protection from terrestrial ultraviolet radiation to reduce the risk of developing skin cancer is an integral part of modern sun protection. The current sunscreen formulations use inorganic zinc oxide (ZnO) and titanium dioxide (TiO ), that are highly photocatalytic, with the ability to penetrate the skin, and exhibit potential toxicity. In this study, we demonstrate a novel methodology to increase the sun protection factor (SPF) of encapsulated metal oxide (Fe O ) nanoparticles in poly(lactic acid) (PLA) microspheres as ultraviolet filters for sunscreen applications. The combination of these two materials results in a nanocomposite with increased UV attenuation and without significant cytotoxic effects during in vitro evaluation. A commercial sunscreen formulation was used to show the benefits of the developed nanocomposites by replacing the harmful ZnO particles by the Fe O -PLA ones, and a throughout comparison between commercial and the new sunscreen formulation was performed. By adding a small amount of the novel Fe O -PLA particles, a remarkable increase in the SPF performance, from 40 (commercial ZnO formulation) to 50 was achieved just by replacing the ZnO particles with 5 wt% of Fe O -PLA ones, resulting in a high level of UV protection, coupled with lower dangerous photocatalytic activity when compared with commercial ZnO nanoparticles. The encapsulation of metal oxide nanoparticles by PLA could provide a route to improve the sunscreen efficacy and enhance its SPF by using more environmentally friendly materials. 2 2 3 2 3 2 3 2

Opportunities and Challenges in Developing a Cryptosporidium Controlled Human infection Model For Testing antiparasitic agents

Cryptosporidiosis is a leading cause of moderate-to-severe diarrhea in low- and middle-income countries, responsible for high mortality in children younger than two years of age, and it is also strongly associated with childhood malnutrition and growth stunting. There is no vaccine for cryptosporidiosis and existing therapeutic options are suboptimal to prevent morbidity and mortality in young children. Recently, novel therapeutic agents have been discovered through high-throughput phenotypic and target-based screening strategies, repurposing malaria hits, etc., and these agents have a promising preclinical in vitro and in vivo anti

Mitral valve endocardiosis in Cavalier King Charles spaniels in France: epidemiological, clinical and echo-Doppler study of 451 cases

A retrospective study was performed in the Cardiology Unit of Alfort in 451 Cavalier King Charles (CKC) spaniels. A left apical systolic murmur was detected in 183 of them (40.6 %). The prevalence of the murmur increased with age (18.8 % for CKC 11 years old). Mitral valve endocardiosis represented 93.3 % of the ultrasound anomalies. There was a positive correlation between age and several echo-Doppler parameters (P<0.01): atrium/aorta ratio, diastolic left ventricular diameter, thickness of the mitral valve leaflets, and mitral regurgitant mapping area. A positive correlation was also noted between the intensity of the murmur and these echo- Doppler parameters (P<0.0001). In conclusion, mitral valve endocardiosis is a frequent valvulopathy which occurs at an early age in CKC spaniels in France. Several clinical and echo-Doppler parameters have a predictive value for the severity of the disease.Une étude rétrospective a été menée dans l'Unité de Cardiologie d'Alfort chez 451 Cavaliers King Charles (CKC). Un souffle systolique apexien gauche a été détecté chez 183 d'entre eux (40,6 %). La prévalence de ce souffle augmentait avec l'âge (18,8 % pour les CKC 11 ans). L'endocardiose valvulaire mitrale a représenté 93,3 % des anomalies diagnostiquées à l'échocardiographie. Une corrélation positive a été observée entre l'âge et différents paramètres échographiques (P<0,01): le rapport atrium/aorte, le diamètre diastolique ventriculaire gauche, l'épaisseur des feuillets mitraux et la surface colorimétrique du reflux mitral. Une corrélation positive a aussi été observée entre l'intensité du souffle et ces paramètres échographiques (P<0,0001). En conclusion, l'endocardiose mitrale est une valvulopathie à la fois précoce et fréquente chez le CKC en France. Certains paramètres cliniques et écho-Doppler ont une valeur prédictive de la gravité de la maladie

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

Phosphorothioate antisense oligonucleotides induce the formation of nuclear bodies

Antisense oligonucleotides are powerful tools for the in vivo regulation of gene expression. We have characterized the intracellular distribution of fluorescently tagged phosphorothioate oligodeoxynucleotides (PS-ONs) at high resolution under conditions in which PS-ONs have the potential to display antisense activity. Under these conditions PS-ONs predominantly localized to the cell nucleus where they accumulated in 20-30 bright spherical foci designated phosphorothioate bodies (PS bodies), which were set against a diffuse nucleoplasmic population excluding nucleoli. PS bodies are nuclear structures that formed in cells after PS-ON delivery by transfection agents or microinjection but were observed irrespectively of antisense activity or sequence. Ultrastructurally, PS bodies corresponded to electron-dense structures of 150-300 nm diameter and resembled nuclear bodies that were found with lower frequency in cells lacking PS-ONs. The environment of a living cell was required for the de novo formation of PS bodies, which occurred within minutes after the introduction of PS-ONs. PS bodies were stable entities that underwent noticeable reorganization only during mitosis. Upon exit from mitosis, PS bodies were assembled de novo from diffuse PS-ON pools in the daughter nuclei. In situ fractionation demonstrated an association of PS-ONs with the nuclear matrix. Taken together, our data provide evidence for the formation of a nuclear body in cells after introduction of phosphorothioate oligodeoxynucleotides

European registry of type A aortic dissection (ERTAAD) - rationale, design and definition criteria

Correction: Volume16 Issue1 Article Number225 DOI10.1186/s13019-021-01606-8Background: Acute Stanford type A aortic dissection (TAAD) is a life-threatening condition. Surgery is usually performed as a salvage procedure and is associated with significant postoperative early mortality and morbidity. Understanding the patient's conditions and treatment strategies which are associated with these adverse events is essential for an appropriate management of acute TAAD. Methods: Nineteen centers of cardiac surgery from seven European countries have collaborated to create a multicentre observational registry (ERTAAD), which will enroll consecutive patients who underwent surgery for acute TAAD from January 2005 to March 2021. Analysis of the impact of patient's comorbidities, conditions at referral, surgical strategies and perioperative treatment on the early and late adverse events will be performed. The investigators have developed a classification of the urgency of the procedure based on the severity of preoperative hemodynamic conditions and malperfusion secondary to acute TAAD. The primary clinical outcomes will be in-hospital mortality, late mortality and reoperations on the aorta. Secondary outcomes will be stroke, acute kidney injury, surgical site infection, reoperation for bleeding, blood transfusion and length of stay in the intensive care unit. Discussion: The analysis of this multicentre registry will allow conclusive results on the prognostic importance of critical preoperative conditions and the value of different treatment strategies to reduce the risk of early adverse events after surgery for acute TAAD. This registry is expected to provide insights into the long-term durability of different strategies of surgical repair for TAAD.Peer reviewe

Cysteine Redox Potential Determines Pro-Inflammatory IL-1β Levels

Cysteine (Cys) and its disulfide, cystine (CySS) represent the major extracellular thiol/disulfide redox control system. The redox potential (E(h)) of Cys/CySS is centered at approximately -80 mV in the plasma of healthy adults, and oxidation of E(h) Cys/CySS is implicated in inflammation associated with various diseases.The purpose of the present study was to determine whether oxidized E(h) Cys/CySS is a determinant of interleukin (IL)-1beta levels. Results showed a 1.7-fold increase in secreted pro-IL-1beta levels in U937 monocytes exposed to oxidized E(h) Cys/CySS (-46 mV), compared to controls exposed to a physiological E(h) of -80 mV (P<0.01). In LPS-challenged mice, preservation of plasma E(h) Cys/CySS from oxidation by dietary sulfur amino acid (SAA) supplementation, was associated with a 1.6-fold decrease in plasma IL-1beta compared to control mice fed an isonitrogenous SAA-adequate diet (P<0.01). Analysis of E(h) Cys/CySS and IL-1beta in human plasma revealed a significant positive association between oxidized E(h) Cys/CySS and IL-1beta after controlling for age, gender, and BMI (P<0.001).These data show that oxidized extracellular E(h) Cys/CySS is a determinant of IL-1beta levels, and suggest that strategies to preserve E(h) Cys/CySS may represent a means to control IL-1beta in inflammatory disease states