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Relative bioavailability of the optimized SD compared to plain drug was 229.52% and 262.02% in healthy adults and geriatrics, respectively. Our study reports the utility of PBPK modeling for formulation development of BCS II APIs, via predicting their oral bio-performance.Pecan bacterial leaf scorch caused by Xylella fastidiosa is an emerging disease for the U.S. and international pecan industries and can be transmitted from scion to rootstock via grafting. With the expanse of global transportation and trade networks, phytosanitation is critical for reducing the spread of economically significant pathogens, such as X. fastidiosa. We developed and evaluated thermal treatments using microwave irradiation and microwave absorbers [sterile deionized water (dH2O) and carbon nanotubes (CNTs)] as novel disinfectant methods for remediating X. fastidiosa in pecan scions. Partial submergence of scions in dH2O or CNT dispersions resulted in the transport of microwave absorbers in the xylem tissue via transpiration but did not compromise plant health. The microwave absorbers effectively transferred heat to the scion wood to reach an average temperature range of 55-65°C. Microwave radiation exposure for 6 sec (3 sec for two iterations) of CNT- or dH2O-treated scions reduced the frequency of X. BIX 02189 clinical trial fastidiosa-positive in pecan scions without negatively affecting plant viability when compared to the control group (dH2O-treated with no microwave). The efficacy of the new thermal treatments based on microwave irradiation was comparable to the conventional hot-water treatment (HWT) method, in which scions were submerged in 46°C water for 30 min. Microwave irradiation can be employed to treat X. fastidiosa-infected scions where the conventional HWT treatment is not feasible. This study is the first report to demonstrate novel thermal treatment methods based on the microwave irradiation and microwave absorbers of dH2O and CNT as an application for the phytosanitation of xylem-inhabiting bacteria in graftwood.Antioxidant uptake and regular exercise are two well-acknowledged measures used for rejuvenation and oxidative stress elimination. Previous studies have revealed that moderate exercise mildly increases intracellular signaling oxidant levels and strengthens the ability of an organism to deal with escalating oxidative stress by upregulating antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase. Antioxidant supplementation directly scavenges intracellular reactive oxygen species (ROS) to reduce oxidative stress. However, research to understand the impacts of these enzymes on mitigating oxidative stress from the perspective of simple animals is limited. Herein, we show that exercise combined with antioxidant supplementation ameliorates the physiological phenotypes and markers of aging in wild-type and SOD/CAT-deficient Caenorhabditis elegans. We discovered that treated wild-type and gene-deficient worms show better survivorship, reproduction, and motility compared with their control counterparts. Assays of biochemical indices revealed that variations in sod-3 expression under different stress levels imply an inducible enzyme response resulting from exercise training and antioxidant supplementation. In addition, induced ROS resistance obtained from any type of treatment could persist for several days even after treatment cessation, thus suggesting a potential long-term antioxidative stress effect. Our findings confirm that exercise, antioxidant supplementation, and their combination could significantly improve the ability of C. elegans to withstand adverse stress. Our observations provide promising insights into future therapies of anti-oxidative stress in higher animals.Monolignol glucosides are storage forms of monolignols, which are polymerized to lignin to strengthen plant cell walls. The conversion of monolignol glucosides to monolignols is catalyzed by monolignol β-glucosidases. Rice Os4BGlu18 β-glucosidase catalyzes hydrolysis of the monolignol glucosides, coniferin, syringin, and p-coumaryl alcohol glucoside more efficiently than other natural substrates. To understand more clearly the basis for substrate specificity of a monolignol β-glucosidase, the structure of Os4BGlu18 was determined by X-ray crystallography. Crystals of Os4BGlu18 and its complex with δ-gluconolactone diffracted to 1.7 and 2.1 Å resolution, respectively. Two protein molecules were found in the asymmetric unit of the P212121 space group of their isomorphous crystals. The Os4BGlu18 structure exhibited the typical (β/α)8 TIM barrel of glycoside hydrolase family 1 (GH1), but the four variable loops and two disulfide bonds appeared significantly different from other known structures of GH1 β-glucosidases. Molecular docking studies of the Os4BGlu18 structure with monolignol substrate ligands placed the glycone in a similar position to the δ-gluconolactone in the complex structure and revealed the interactions between protein and ligands. Molecular docking, multiple sequence alignment, and homology modeling identified amino acid residues at the aglycone-binding site involved in substrate specificity for monolignol β-glucosides. Thus, the structural basis of substrate recognition and hydrolysis by monolignol β-glucosidases was elucidated.The emergence of a new tech elite in Silicon Valley and beyond raises questions about the economic reach, political influence, and social importance of this group. How do these inordinately influential people think about the world and about our common future? In this paper, we test a) whether members of the tech elite share a common, meritocratic view of the world, b) whether they have a "mission" for the future, and c) how they view democracy as a political system. Our data set consists of information about the 100 richest people in the tech world, according to Forbes, and rests on their published pronouncements on Twitter, as well as on their statements on the websites of their philanthropic endeavors. Automated "bag-of-words" text and sentiment analyses reveal that the tech elite has a more meritocratic view of the world than the general US Twitter-using population. The tech elite also frequently promise to "make the world a better place," but they do not differ from other extremely wealthy people in this respect. However, their relationship to democracy is contradictory. Based on these results, we conclude that the tech elite may be thought of as a "class for itself" in Marx's sense-a social group that shares particular views of the world, which in this case means meritocratic, missionary, and inconsistent democratic ideology.

Self-reported levels of disability in individuals with low back pain (LBP) have not improved in the last decade. A broader perspective and a more comprehensive management framework may improve disability outcomes. We recently developed and validated the Low Back Pain and Disability Drivers Management (PDDM) model, which aims to identify the domains driving pain and disability to guide clinical decisions. The objectives of this study were to determine the applicability of the PDDM model to a LBP population and the feasibility of conducting a pragmatic trial, as well as to explore clinicians' perceived acceptability of the PDDM model's use in clinical settings.

This study was an one-arm prospective feasibility trial. Participants included physiotherapists working with a population suffering from LBP and their patients aged 18 years or older presenting with a primary complaint of LBP that sought a new referral and deemed fit for rehabilitation from private and public clinical settings. Clinicians participate49179.Recent findings on Antibiotic Resistance (AR) have brought renewed attention to the comparison of data on AR from human and animal sectors. This is however a major challenge since the data is not harmonized. This study performs a comparative analysis of data on resistance combinations in Escherichia coli (E. coli) from different routine surveillance and monitoring systems for human and different animal populations in Germany. Data on E. coli isolates were collected between 2014 and 2017 from human clinical isolates, non-clinical animal isolates from food-producing animals and food, and clinical animal isolates from food-producing and companion animals from national routine surveillance and monitoring for AR in Germany. Sixteen possible resistance combinations to four antibiotics-ampicillin, cefotaxime, ciprofloxacin and gentamicin-for these populations were used for hierarchical clustering (Euclidian and average distance). All analyses were performed with the software R 3.5.1 (Rstudio 1.1.442). Data of 333,49esistance combinations. Further analyses based on these findings might support a better one-health approach for AR in Germany.

Addressing the burden of HPV-associated diseases among men is increasingly becoming a public health issue. The main objective of this study was to determine HPV prevalence among a healthy community-based Malaysian men.

This was a cross-sectional study that recruited 503 healthy males from 3 community-based clinics in Selangor, Malaysia. Genital and anal samples were collected from each participant for 14 high risk and 2 low risk HPV DNA detection and genotyping. All participants responded to a set of detailed sociodemographic and sexual behaviour questionnaire.

The median age at enrolment was 40 years old (IQR 31-50). The anogenital HPV6/11 prevalence was 3.2% whereas high risk HPV prevalence was 27.1%. The genital HPV prevalence for HPV6/11 was 2.9% while high risk HPV was 18.8%. HPV6/11 prevalence in the anal canal was 1.6% and high risk HPV was 12.7%. HPV 18 was the most prevalent genotype detected in the anogenital area. There was a significant independent association between genital and anal HPV infections.

Anogenital HPV infection is common among Malaysian men. These findings emphasize the ubiquity of HPV infection and thus the value of population-wide access to HPV prevention.

Anogenital HPV infection is common among Malaysian men. These findings emphasize the ubiquity of HPV infection and thus the value of population-wide access to HPV prevention.

Patients with pulmonary hypertension (PH) frequently suffer from supraventricular tachycardias (SVT). The main purpose of our study was to identify the cumulative incidence of SVT in patients with different etiologies of PH. The secondary objective was to analyse the clinical impact of SVT.

We retrospectively studied the prevalence of SVT and the clinical outcome in 755 patients (41% males; 60 ± 15 years; mean follow-up 3.8 ± 2.8 years) with PH of different etiologies. The prevalence of SVT was analysed separately in isolated pre-capillary PH (Ipc-PH) and in patients with combined post- and pre-capillary PH (Cpc-PH).

The prevalence of SVT in the Ipc-PH group (n = 641) was 25% (n = 162). The most prevalent arrhythmias were atrial fibrillation followed by a typical atrial flutter (17% and 4.4% of all Icp-PH patients). An excessive prevalence of SVT was found in patients with pulmonary arterial hypertension associated with congenital heart disease (35%, p = 0.01). Out of the overall study population, Cpc-PH was present in 114 (15%) patients.