Beierlundsgaard4752

In adult animals, acute viral infections only temporarily alter the composition of both respiratory and intestinal commensal microbiota, potentially due to the intrinsic stability of this microbial ecosystem. In stark contrast, commensal bacterial communities are rather vulnerable to perturbation in infancy. Animal models proved that disruption of a balanced microbiota development e.g., by antibiotics treatment early in life, increases the probability for metabolic disorders in adults. Importantly, infancy is also a phase in life with high incidence of acute infections. We postulated that acute viral infections in early life might pose a similarly severe perturbation and permanently shape microbiota composition with long-term physiological consequences for the adult host. As a proof of concept, we infected infant mice with a sub-lethal dose of influenza A virus. We determined microbiota composition up to early adulthood (63 days) from small intestine by 16S rRNA gene-specific next-generation sequencing. Infected mice underwent long-lasting changes in microbiota composition, associated with increase in fat mass. High-fat-high-glucose diet promoted this effect while co-housing with mock-treated animals overwrote the weight gain. Our data suggest that in the critical phase of infancy even a single silent viral infection could cast a long shadow and cause long-term microbiota perturbations, affecting adult host physiology.

Glutamate signaling activates MAPK and PI3K/AKT pathways in tumor cells. Treatment with riluzole, a glutamate release inhibitor, has been previously shown to be safe in melanoma patients and produced biologic effects, but did not lead to radiographic responses, possibly due to poor pharmacokinetic properties. Therefore, we conducted a phase Ib trial to determine the safety and tolerability of the combination of the riluzole prodrug troriluzole (BHV-4157, trigriluzole) and the PD-1 antibody nivolumab in patients with advanced solid tumors.

Patients with advanced or refractory solid tumors and measurable disease per RECIST 1.1 were treated with increasing doses of troriluzole using a semi-Bayesian modified toxicity probability interval dose escalation procedure. Troriluzole monotherapy was orally self-administered for a 14-day lead-in period followed by continuation of troriluzole in combination with nivolumab 240mg IV every 2weeks. Endpoints included safety, pharmacokinetics (PK) and efficacy.

We enrollembination of troriluzole and nivolumab was safe and well-tolerated. selleck products The MTD of troriluzole was determined to be 420mg total daily dose. The observed antitumor activity, primarily disease stabilization, is of interest in patients with PD-1 resistant tumors. Trial Registration ClinicalTrials.gov Identifier NCT03229278.

The combination of troriluzole and nivolumab was safe and well-tolerated. The MTD of troriluzole was determined to be 420 mg total daily dose. The observed antitumor activity, primarily disease stabilization, is of interest in patients with PD-1 resistant tumors. Trial Registration ClinicalTrials.gov Identifier NCT03229278.Planar spiral spring is important for the dimensional miniaturisation of motor-based elastic actuators. However, when the stiffness calculation of the spring arm is based on simple beam bending theory, the results possess substantial errors compared with the stiffness obtained from finite-element analysis (FEA). It deems that the errors arise from the spiral length term in the calculation formula. Two Gaussian process regression models are trained to amend this term in the stiffness calculation of spring arm and complete spring. For the former, 216 spring arms' data sets, including different spiral radiuses, pitches, wrap angles and the stiffness from FEA, are employed for training. The latter engages 180 double-arm springs' data sets, including widths instead of wrap angles. The simulation of five spring arms and five planar spiral springs with arbitrary dimensional parameters verifies that the absolute values of errors between the predicted stiffness and the stiffness from FEA are reduced to be less than 0.5% and 2.8%, respectively. A planar spiral spring for a powered ankle-foot prosthesis is designed and manufactured to verify further, of which the predicted value possesses a 3.25% error compared with the measured stiffness. Therefore, the amendment based on the prediction of trained models is available.

We conducted a single-centered randomized controlled single-blinded trial (i.e. trained interviewers; blinded to group allocation). The target population included adolescent girls in the Kumbo West Health District (KWHD) of Cameroon. This trial tested the efficacy of weekly educational one-way text messages to improve perception of adolescent girls on sexo-reproductive health.

Allocation concealment (11) was determined by sequentially numbered sealed opaque envelopes. A total of 398 participants either received the mobile phone sexo-reproductive health text messages (199) or not (199). A blinded program secretary send out text messages and recorded delivery. Data was collected and managed at baseline and at 6month intervals using an interviewer-administered questionnaire before and after intervention, then analysed using the independent T-test (mean differences) and ANOVA on SPSS version 21.

The mean knowledge, attitude and practice scores respectively increased significantly from 6.03, 4.01 and 3.45 at baseline to 7.99, 5.83 and 4.99 at the end of the study. After performing ANOVA for the overall correct knowledge, positive attitudes and good practices respectively for between and within the intervention groups, we obtained (F = 15.12, P = 0.023), (F = 60.21, P = 0.001) and (F = 57., P = 0.013) which showed statistical significance thus indicating the overall improvement in adolescents girls perception as a result of the intervention and not by chance. Majority (65.3%) of the participants were satisfied with the Short Message Service (SMS).

This trial has contributed to the body of knowledge and evidence on the use of mobile phone technology using educative SMS to improve adolescent girl's perception on sexo-reproductive health in Cameroon.

Pan African Clinical Trials Registry, PACTR201805003259293 . Registered 28 March 2018.

Pan African Clinical Trials Registry, PACTR201805003259293 . Registered 28 March 2018.

Androgen deprivation therapy (ADT) is still the first-line treatment of prostate cancer (PCa). However, after a certain period of therapy, primary PCa inevitably progresses into castration-resistant PCa (CRPC). Enzalutamide (Enz) is an androgen receptor (AR) signal inhibitor which can delay the progression of CRPC and increase survival of patients with metastatic CRPC. However, the mechanisms involved in enzalutamide-resistant (EnzR) CRPC are still controversial. In the study, we used bioinformatic methods to find potential genes that correlated with the occurrence of EnzR CRPC.

We collected RNA sequencing data of the EnzR CRPC cell line LNCaP (EnzR LNCaP) from GSE44905, GSE78201, and GSE150807. We found the hub genes from the three datasets. Then we tested the expression of the hub genes in different databases and the potential drugs that can affect the hub genes. Finally, we verified the hub gene expression and drug function.

From GSE44905, GSE78201 and GSE150807, we found 45 differentially expressed genes (DEGs) between LNCaP and EnzR LNCaP. Ten hub genes were found in the protein-protein interaction (PPI) network. The expression of hub gene and survival analysis were analyzed by different databases. We found that cyclin-dependent kinase 6 (CDK6) was highly expressed in both the EnzR LNCaP cell and PCa patients. Ten potential small molecules could suppress CDK6 expression as per "CLUE COMMAND" findings. Finally, we found the expression of CDK6 increased in both PCa patients' samples, CRPC and EnzR PCa cell lines. Three potential CDK6 inhibitors, namely apigenin, chrysin and fisetin, can decrease cell proliferation.

The study proved that the abnormal overexpression of CDK6 may be a reason behind EnzR CRPC occurrence and suppression CDK6 expression may help treat EnzR CRPC.

The study proved that the abnormal overexpression of CDK6 may be a reason behind EnzR CRPC occurrence and suppression CDK6 expression may help treat EnzR CRPC.As the most well-known electrocatalyst for cathodic hydrogen evolution in water splitting electrolyzers, platinum is unfortunately inefficient for anodic oxygen evolution due to its over-binding with oxygen species and excessive dissolution in oxidative environment. Herein we show that single Pt atoms dispersed in cobalt hydrogen phosphate with an unique Pt(OH)(O3)/Co(P) coordination can achieve remarkable catalytic activity and stability for oxygen evolution. The catalyst yields a high turnover frequency (35.1 ± 5.2 s-1) and mass activity (69.5 ± 10.3 A mg-1) at an overpotential of 300 mV and excellent stability. Mechanistic studies elucidate that the superior catalytic performance of isolated Pt atoms herein stems from optimal binding energies of oxygen intermediate and also their strong electronic coupling with neighboring Co atoms that suppresses the formation of soluble Ptx>4 species. Alkaline water electrolyzers assembled with an ultralow Pt loading realizes an industrial-level current density of 1 A cm-2 at 1.8 volts with a high durability.Oxidative carbene organocatalysis, inspired from Vitamin B1 catalyzed oxidative activation from pyruvate to acetyl coenzyme A, have been developed as a versatile synthetic method. To date, the α-, β-, γ-, δ- and carbonyl carbons of (unsaturated)aldehydes have been successfully activated via oxidative N-heterocyclic carbene (NHC) organocatalysis. In comparison with chemical redox or photoredox methods, electroredox methods, although widely used in mechanistic study, were much less developed in NHC catalyzed organic synthesis. Herein, an iodide promoted electroredox NHC organocatalysis system was developed. This system provided general solutions for electrochemical single-electron-transfer (SET) oxidation of Breslow intermediate towards versatile transformations. Radical clock experiment and cyclic voltammetry results suggested an anodic radical coupling pathway.

Τo assess the outcome of direct pulp capping in asymptomatic carious primary molars using three pulp capping materials.

In this prospective clinical trial, carious primary molars free of irreversible pulp inflammation signs and symptoms, with negative pain history and pulp exposure following caries removal were included. Teeth were divided into groups A Ca(OH)

, B Pure Portland cement

, C Biodentine™. Following anaesthesia, isolation, caries removal, pulp exposure, hemorrhage control, pulp capping, additional lining in groups A, B, teeth were restored with composite resin. Descriptive statistics, Chi-squared and Fisher's exact tests, Kaplan-Meier survival curves, multivariable random effects Cox regression model were performed.

Sixty-six patients (25 girls, 41 boys) with mean age 7.2 (± 1.7) years participated. The mean follow-up time was 13months. Seventy-nine primary molars were assigned to groups A (n = 27), B (29), C (n = 23). The overall failure was 16% and the distribution by group was A 5 teeth, B 5 teeth, C 3 teeth.