A US-based national surveillance study for the susceptibility and epidemiology of Clostridioides difficile isolates with special reference to ridinilazole: 2020-2021.

We have previously reported on the susceptibility and epidemiology of Clostridioides difficile isolates from six geographically dispersed medical centers in the United States. This current survey was conducted with isolates collected in 2020-2021 from six geographically dispersed medical centers in the United States, with specific attention to susceptibility to ridinilazole as well as nine comparators. C. difficile isolates or stools from patients with C. difficile antibiotic-associated diarrhea were collected and referred to a central laboratory. After species confirmation of 300 isolates at the central laboratory, antibiotic susceptibilities were determined by the agar dilution method [M11-A9, Clinical and Laboratory Standards Institute (CLSI)] against the 10 agents. Ribotyping was performed by PCR capillary gel electrophoresis on all isolates. Ridinilazole had a minimum inhibitory concentration (MIC) 90 of 0.25 mcg/mL, and no isolate had an MIC greater than 0.5 mcg/mL. In comparison, fidaxomicin had an MIC 90 of 0.5 mcg/mL. The vancomycin MIC 90 was 2 mcg/mL with a 0.7% resistance rate [both CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria]. The metronidazole MIC 90 was 1 mcg/mL, with none resistant by CLSI criteria, and a 0.3% resistance rate by EUCAST criteria. Among the 50 different ribotypes isolated in the survey, the most common ribotype was 014-020 (14.0%) followed by 106 (10.3%), 027 (10%), 002 (8%), and 078-126 (4.3%). Ridinilazole maintained activity against all ribotypes and all strains resistant to any other agent tested. Ridinilazole showed excellent in vitro activity against C. difficile isolates collected between 2020 and 2021 in the United States, independent of ribotype.

Investigating two mobile just-in-time adaptive interventions to foster psychological resilience: research protocol of the DynaM-INT study.

BACKGROUND: Stress-related disorders such as anxiety and depression are highly prevalent and cause a tremendous burden for affected individuals and society. In order to improve prevention strategies, knowledge regarding resilience mechanisms and ways to boost them is highly needed. In the Dynamic Modelling of Resilience - interventional multicenter study (DynaM-INT), we will conduct a large-scale feasibility and preliminary efficacy test for two mobile- and wearable-based just-in-time adaptive interventions (JITAIs), designed to target putative resilience mechanisms. Deep participant phenotyping at baseline serves to identify individual predictors for intervention success in terms of target engagement and stress resilience. METHODS: DynaM-INT aims to recruit N = 250 healthy but vulnerable young adults in the transition phase between adolescence and adulthood (18-27 years) across five research sites (Berlin, Mainz, Nijmegen, Tel Aviv, and Warsaw). Participants are included if they report at least three negative burdensome past life events and show increased levels of internalizing symptoms while not being affected by any major mental disorder. Participants are characterized in a multimodal baseline phase, which includes neuropsychological tests, neuroimaging, bio-samples, sociodemographic and psychological questionnaires, a video-recorded interview, as well as ecological momentary assessments (EMA) and ecological physiological assessments (EPA). Subsequently, participants are randomly assigned to one of two ecological momentary interventions (EMIs), targeting either positive cognitive reappraisal or reward sensitivity. During the following intervention phase, participants' stress responses are tracked using EMA and EPA, and JITAIs are triggered if an individually calibrated stress threshold is crossed. In a three-month-long follow-up phase, parts of the baseline characterization phase are repeated. Throughout the entire study, stressor exposure and mental health are regularly monitored to calculate stressor reactivity as a proxy for outcome resilience. The online monitoring questionnaires and the repetition of the baseline questionnaires also serve to assess target engagement. DISCUSSION: The DynaM-INT study intends to advance the field of resilience research by feasibility-testing two new mechanistically targeted JITAIs that aim at increasing individual stress resilience and identifying predictors for successful intervention response. Determining these predictors is an important step toward future randomized controlled trials to establish the efficacy of these interventions.

A Prospective, Cohort Study of SITOIGANAP to Treat Glioblastoma When Given in Combination With Granulocyte-Macrophage Colony-Stimulating Factor/Cyclophosphamide/Bevacizumab/Nivolumab or Granulocyte-Macrophage Colony-Stimulating Factor/Cyclophosphamide/Bevacizumab/Pembrolizumab in Patients Who Failed Prior Treatment With Surgical Resection, Radiation, and Temozolomide.

Background: Glioblastoma (GBM) is the most common primary, malignant brain tumor in adults and has a poor prognosis. The median progression-free survival (mPFS) of newly diagnosed GBM is approximately 6 months. The recurrence rate approaches 100%, and the case-fatality ratio approaches one. Half the patients die within 8 months of recurrence, and 5-year survival is less than 10%. Advances in treatment options are urgently needed. We report on the efficacy and safety of a therapeutic vaccine (SITOIGANAP: Epitopoietic Research Corporation) administered to 21 patients with recurrent GBM (rGBM) under a Right-to-Try/Expanded Access program. SITOIGANAP is composed of both autologous and allogeneic tumor cells and lysates. Methods: Twenty-one patients with rGBM received SITOIGANAP on 28-day cycles in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), cyclophosphamide, bevacizumab, and an anti-programmed cell death protein-1 (anti-PD-1) monoclonal antibody (either nivolumab or pembrolizumab). Results: The mPFS was 9.14 months, and the median overall survival (mOS) was 19.63 months from protocol entry. Currently, 14 patients (67%) are at least 6 months past their first SITOIGANAP cycle; 10 patients (48%) have received at least six cycles and have a mOS of 30.64 months and 1-year survival of 90%. The enrollment and end-of-study CD3+/CD4+ T-lymphocyte counts strongly correlate with OS. Conclusions: The addition of SITOIGANAP/GM-CSF/cyclophosphamide to bevacizumab and an anti-PD-1 monoclonal antibody resulted in a significant survival benefit compared to historic control values in rGBM with minimal toxicity compared to current therapy.

Lactational performance of dairy cows in response to supplementing N-acetyl-l-methionine as source of rumen-protected methionine.

The objective of this experiment was to evaluate the effects of supplementing a rumen-protected source of Met, N-acetyl-l-methionine (NALM), on lactational performance and nitrogen metabolism in early- to mid-lactation dairy cows. Sixty multiparous Holstein dairy cows in early lactation (27 ± 4.3 d in milk, SD) were assigned to 4 treatments in a randomized complete block design. Cows were blocked by actual milk yield. Treatments were as follows: (1) no NALM (control); (2) 15 g/d of NALM (NALM15); (3) 30 g/d of NALM (NALM30); and (4) 45 g/d of NALM (NALM45). Diets were formulated using a Cornell Net Carbohydrate and Protein System (CNCPS) v.6.5 model software to meet or exceed nutritional requirements of lactating dairy cows producing 42 kg/d of milk and to undersupply metabolizable Met (control) or supply incremental amounts of NALM. The digestible Met (dMet) supply for control, NALM15, NALM30, and NALM45 were 54.7, 59.8, 64.7, and 72.2 g/d, respectively. The supply of dMet was 88, 94, 104, and 115% of dMet requirement for control, NALM15, NALM30, and NALM45, respectively. Milk yield data were collected, dry matter intake (DMI) was measured daily, and milk samples were collected twice per week for 22 wk. Blood, ruminal fluid, urine, and fecal samples were collected during the covariate period and during wk 4, 8, and 16. Data were analyzed using the GLIMMIX procedure of SAS (SAS Institute) using covariates in the model for all variables except body weight. Linear, quadratic, and cubic contrasts were also tested. Treatments did not affect DMI, milk yield, and milk component concentration and yield; however, feed efficiency expressed as milk yield per DMI and 3.5% fat-corrected milk per DMI were quadratically affected, with greater response observed for NALM15 and NALM30 compared with control. Acetate proportion linearly increased, whereas propionate proportion linearly decreased with NALM supplementation. Blood urea nitrogen linearly decreased with NALM supplementation. Total plasma essential AA concentrations were quadratically affected, as greater values were observed for control and NALM45 than other treatments. Plasma Met concentration was quadratically affected as lower levels were observed with NALM15, whereas Met concentrations increased with NALM45 compared with control. Nitrogen utilization efficiency and apparent total-tract nutrient digestibility were not affected by treatment. Supplementation of NALM at 15 or 30 g/head per day resulted in the greatest improvements in feed efficiency without affecting N metabolism of early- to mid-lactation dairy cows.

Prostate Lesions in a Tertiary Institution in North Central Nigeria: A Histopathology Review.

BACKGROUND: Prostatic lesions are a significant cause of morbidity and mortality among middle aged and elderly men of African ancestry. Reviews on cancer distribution displayed prostate cancer as the most prevalent site specific cancer among adult Nigerian men. OBJECTIVE: This study provided baseline data of the frequency, histologic spectrum, and pathological characteristics of prostate lesions in a Tertiary institution in North Central Nigeria. MATERIALS AND METHOD: This was a descriptive review of all histologically diagnosed prostate lesions at the pathology department of the University of Abuja Teaching Hospital over a 5-year period from January 1, 2015 to December 31, 2019. RESULTS: Prostatic lesions represented 4.1% of all surgical specimens in the period under review. The age range of the patients' was 32 to 95 years with a mean age of 66.5 years at diagnosis and peak age incidence seen in the 7th decade. There were 259 (52.9%) cases of nodular hyperplasia and 231 (47.1%) cases of cancer of the prostate, giving a nodular hyperplasia to prostate cancer ratio of 1.12:1. Fifty two (52, 20.1%) cases of the nodular hyperplasia were associated with chronic inflammation while 7 (2.7%) were associated with prostatic intraepithelial neoplasm. Prostate adenocarcinoma was the predominant subtype, accounting for 99.1% of cases while ductal carcinoma constituted the remaining 0.9% cases. Gleason scores were adapted to the Grade Group system of the International Society of Urological Pathology and showed that high grade cancers; Grade Groups 4 and 5 were the predominant grades (n=130, 60.5%) followed by Grade Group 1 (n=64, 29.8%) cancers. CONCLUSION: Prostate lesions are common lesions encountered in our setting in keeping with reports from other regions in Nigeria. A significant proportion of these lesions are prostate cancers that are poorly differentiated with higher risk of mortality.

CONTEXTE: Les lésions prostatiques sont une cause importante de morbidité et de mortalité chez les hommes d'âge moyen et âgés d'ascendance africaine. Les revues sur la distribution du cancer ont montré que le cancer de la prostate est le cancer spécifique le plus répandu chez les hommes adultes du Nigeria. OBJECTIF: Cette étude a fourni des données de base sur la fréquence, le spectre histologique et les caractéristiques pathologiques des lésions de la prostate dans une institution tertiaire du centre-nord du Nigeria. MATÉRIEL ET MÉTHODE: Il s'agissait d'une revue descriptive de toutes les lésions prostatiques diagnostiquées histologiquement au département de pathologie de l'hôpital universitaire d'Abuja sur une période de 5 ans, du 1er janvier 2015 au 31 décembre 2019. RÉSULTATS: Les lésions prostatiques représentaient 4,1 % de toutes les pièces chirurgicales au cours de la période étudiée. La tranche d'âge des patients' était de 32 à 95 ans avec un âge moyen de 66,5 ans au moment du diagnostic et un pic d'incidence d'âge observé dans la 7e décennie. Il y a eu 259 (52,9 %) cas d'hyperplasie nodulaire et 231 (47,1 %) cas de cancer de la prostate, soit un rapport hyperplasie nodulaire/cancer de la prostate de 1,12:1. Cinquante-deux (52, 20,1 %) cas d'hyperplasie nodulaire étaient associés à une inflammation chronique, tandis que 7 (2,7 %) étaient associés à un néoplasme intraépithélial prostatique. L'adénocarcinome prostatique était le sous-type prédominant, représentant 99,1 % des cas, tandis que le carcinome canalaire constituait les 0,9 % de cas restants. Les scores de Gleason ont été adaptés au système de groupes de grades de la Société internationale de pathologie urologique et ont montré que les cancers de haut grade ; les groupes de grades 4 et 5 étaient les grades prédominants (n=130, 60,5%) suivis par les cancers de grade 1 (n=64, 29,8%). CONCLUSION: Les lésions de la prostate sont des lésions courantes rencontrées dans notre contexte, conformément aux rapports d'autres régions du Nigeria. Une proportion significative de ces lésions sont des cancers de la prostate qui sont peu différenciés avec un risque de mortalité plus élevé. MOTS CLÉS: Prostate, Hyperplasie nodulaire, Adénocarcinome.

Validity of electrodermal activity-based measures of sympathetic nervous system activity from a wrist-worn device.

Measuring electrodermal activity (EDA) on the wrist with the use of dry electrodes is a promising method to help identify person-specific stressors during prolonged recordings in daily life. While the feasibility of this method has been demonstrated, detailed testing of validity of such ambulatory EDA is scarce. In a controlled laboratory study, we examine SCL and ns.SCR derived from wrist-based dry electrodes (Philips DTI) and palm-based wet electrodes (VU-AMS) in 112 healthy adults (57% females, mean age = 22.3, SD = 3.4) across 26 different conditions involving mental stressors or physical activities. Changes in these EDA measures were compared to changes in the Pre-ejection period (PEP) and stressor-induced changes in affect. Absolute SCL and ns.SCR frequency were lower at the wrist compared to the palm. Wrist-based ns.SCR and palm-based ns.SCR and SCL responded directionally consistent with our experimental manipulation of sympathetic nervous system (SNS) activity. Average within-subject correlations between palm-based and wrist-based EDA were significant but modest (r SCL = 0.31; r ns.SCR = 0.42). Changes in ns.SCR frequency at the palm (r = -0.44) and the wrist (r = -0.36) were correlated with changes in PEP. Both palm-based and wrist based EDA predicted changes in affect (6.5%-14.5%). Our data suggest that wrist-based ns.SCR frequency is a useful addition to the psychophysiologist's toolkit, at least for epidemiology-sized ambulatory studies of changes in sympathetic activity during daily life.

Primary Fibrosarcoma of the Breast: Case Report of a Rare Breast Neoplasm.

Breast fibrosarcoma is an uncommon primary breast neoplasm. We report a case of a 57-year old woman who presented at our facility with a right breast mass having histomorphological and immunohistochemical features consistent with fibrosarcoma. She had simple mastectomy and an uneventful hospital stay. The mass recurred 4-weeks later for which she had supportive care and started on cyclical chemotherapy (Adriamycin, Cyclophosphamide and Dacarbazine). She was referred for haemostatic radiotherapy and her clinic follow-up scheduled.

Le fibrosarcome du sein est une tumeur primitive du sein rare. Nous rapportons le cas d'une femme de 57 ans qui s'est présentée dans notre établissement avec une masse mammaire droite présentant des caractéristiques histomorphologiques et immunohistochimiques compatibles avec un fibrosarcome. Elle a eu une mastectomie simple et un séjour à l'hôpital sans incident. La masse est réapparue 4 semaines plus tard pour laquelle elle a reçu des soins de soutien et a commencé une chimiothérapie cyclique (Adriamycine, Cyclophosphamide et Dacarbazine). Elle a été référée pour une radiothérapie hémostatique et son suivi clinique a été programmé.

Predictors of functional capacity as measured by the Glittre activities of daily living test in women with rheumatoid arthritis.

Although pulmonary involvement is the most common extra-articular manifestation of rheumatoid arthritis (RA), traditional pulmonary function tests (PFTs) do not show a good correlation with the field tests usually performed in these patients. In recent decades, measurement of ventilation distribution heterogeneity through the nitrogen single-breath washout (N2SBW) test and evaluation of functional capacity during exercise using the Glittre activities of daily living test (GA-T) have been increasingly used. Therefore, the objective of this study was to evaluate predictors of GA-T outcomes in women with RA considering demographic, anthropometric, clinical, functional variables, and chest computed tomography (CT) findings. Forty-three women with RA underwent the GA-T, the N2SBW test, spirometry, measurement of the diffusing capacity for carbon monoxide (DLco), measurement of respiratory muscle strength, and evaluation of physical function of the lower and upper limbs through the Health Assessment Questionnaire Disability Index (HAQ-DI). Chest CT scans were analyzed retrospectively. The GA-T time showed significant correlations with the DLco (rs=-0.397, P=0.008), forced vital capacity/DLco (rs=0.307, P=0.044), phase III slope of the N2SBW test (SIIIN2, rs=0.644, P<0.0001), and the HAQ-DI (rs=0.482, P=0.001). Disease extent as assessed by chest CT was associated with the GA-T time. On multiple regression analysis, the SIIIN2 and HAQ-DI were the only predictors of the GA-T time, explaining 40% of its variability. Thus, ventilation distribution heterogeneity and worse physical function substantially explain the variability in GA-T time in women with RA and varying extents of disease on chest CT.

Predictors of functional capacity as measured by the Glittre activities of daily living test in women with rheumatoid arthritis

Although pulmonary involvement is the most common extra-articular manifestation of rheumatoid arthritis (RA), traditional pulmonary function tests (PFTs) do not show a good correlation with the field tests usually performed in these patients. In recent decades, measurement of ventilation distribution heterogeneity through the nitrogen single-breath washout (N2SBW) test and evaluation of functional capacity during exercise using the Glittre activities of daily living test (GA-T) have been increasingly used. Therefore, the objective of this study was to evaluate predictors of GA-T outcomes in women with RA considering demographic, anthropometric, clinical, functional variables, and chest computed tomography (CT) findings. Forty-three women with RA underwent the GA-T, the N2SBW test, spirometry, measurement of the diffusing capacity for carbon monoxide (DLco), measurement of respiratory muscle strength, and evaluation of physical function of the lower and upper limbs through the Health Assessment Questionnaire Disability Index (HAQ-DI). Chest CT scans were analyzed retrospectively. The GA-T time showed significant correlations with the DLco (rs=-0.397, P=0.008), forced vital capacity/DLco (rs=0.307, P=0.044), phase III slope of the N2SBW test (SIIIN2, rs=0.644, P<0.0001), and the HAQ-DI (rs=0.482, P=0.001). Disease extent as assessed by chest CT was associated with the GA-T time. On multiple regression analysis, the SIIIN2 and HAQ-DI were the only predictors of the GA-T time, explaining 40% of its variability. Thus, ventilation distribution heterogeneity and worse physical function substantially explain the variability in GA-T time in women with RA and varying extents of disease on chest CT.

Full strain tensor measurements with X-ray diffraction and strain field mapping: a simulation study.

Strain tensor measurements are important for understanding elastic and plastic deformation, but full bulk strain tensor measurement techniques are still lacking, in particular for dynamic loading. Here, such a methodology is reported, combining imaging-based strain field mapping and simultaneous X-ray diffraction for four typical loading modes: one-dimensional strain/stress compression/tension. Strain field mapping resolves two in-plane principal strains, and X-ray diffraction analysis yields volumetric strain, and thus the out-of-plane principal strain. This methodology is validated against direct molecular dynamics simulations on nanocrystalline tantalum. This methodology can be implemented with simultaneous X-ray diffraction and digital image correlation in synchrotron radiation or free-electron laser experiments.

Epidemiologic trends in Clostridioides difficile isolate ribotypes in United States from 2011 to 2016.

BACKGROUND: Geographic and temporal trends in the distribution of PCR ribotypes for Clostridioides difficile associated diarrheal isolates obtained in the United States (US) are changing. As part of a US national surveillance program of C. difficile susceptibility to fidaxomicin, we quantified the distribution of PCR ribotypes of stool isolates collected from 2011 to 2016. METHODS: C. difficile isolates or C. difficile toxin + stools from patients with C. difficile infection (CDI) were submitted for testing to Tufts Medical Center from 6 geographically distinct medical centers. Following isolation and confirmation as C. difficile, approximately 35% of the isolates were randomly sampled, stratified by center, for PCR ribotyping by capillary gel electrophoresis. Toxin gene profiling was performed on all isolates. RESULTS: 939 isolates from a total of 2814 (33.4%) isolated over the 6 years were analyzed. Seventy unique ribotypes were observed, including 19 ribotypes observed 10 or more times. Sixteen ribotypes were not previously observed in our data base. Ribotype 027 declined by more than 60% over the 6 years of the survey from 35.3% to 13.1% (p < 0.001). Ribotype 106 was the most common in 2016, followed by 027 and 014-020. There were strong correlations between 027 and binary toxin with the 18 base pair deletion of tcdC and ribotype 078-126 had 100% concordance with the previously described tcdC 39 base pair deletion. CONCLUSIONS: The frequency of ribotypes in the US has changed with a marked decline in 027. Each of the geographical areas had variations which differed from each other, but collectively, these results suggest that the changing epidemiology of C. difficile in the US is consistent with what is being seen in Europe. Continued surveillance and monitoring of changes in ribotype distributions of C. difficile are warranted.

An Extended Twin-Pedigree Study of Different Classes of Voluntary Exercise Behavior.

We investigated the familial clustering of different classes of voluntary regular exercise behavior in extended twin-family pedigrees. In contrast to the earlier work based on twin data only, this allowed us to estimate the contributions of shared household effects (C), additive (A), and non-additive (D) genetic effects on voluntary exercise behavior. To test whether shared household effects were inflated by assortative mating we examined the causes of spousal resemblance. For adolescent and adult participants (aged 16 to 65) in the Netherlands Twin Register we constructed 19,543 pedigrees which specified all relations among nuclear family members and larger families in the register (N = 50,690 individuals). Data were available on total weekly MET minutes spent on leisure time exercise, and on total weekly MET minutes spent on exercise activities in team-based, solitary, competitive, non-competitive, externally paced and internally paced exercise. We analyzed the data in the Mendel software package (Lange et al. in Bioinformatics 29(12):1568-1570, 2013) under multiple definitions of household sharing and used data from spouses of twins to test phenotypic assortment, social homogamy, and marital interaction as potential sources of spousal resemblance. Results confirmed the influence of genetic factors on the total volume of weekly exercise behavior throughout the life span. Broad sense heritability ranged from 34 to 41% (19-26% A, 12-21% D), and did not depend on the definition for household sharing. Engaging in team-based, competitive, externally paced activities (e.g., soccer) was ~ 13% more heritable than engaging in non-competitive, solitary activities (e.g., jogging). Having shared a household as siblings explained 4-8% of the variance in adult exercise behavior, whereas sharing a household by spouses yielded higher C estimates (20-24%), as it incorporates spousal resemblance. Spousal resemblance was explained by both social homogamy and marital interaction, with little evidence for phenotypic assortment. We conclude that both the amount of voluntary exercise behavior and the preference for specific classes of exercise activities in adults is explained by additive and non-additive genetic factors and unique environmental influences that include correlated exercise behavior of spouses.

The short Sing-a-Song Stress Test: A practical and valid test of autonomic responses induced by social-evaluative stress.

The Sing-a-Song Stress Test (SSST) was recently developed as an alternative to the Trier Social Stress Test (TSST) to investigate autonomic nervous system responses to social-evaluative stress. In the SSST, participants are suddenly cued to sing a song in the presence of confederates. However, the SSST is still quite long (~15 min) and the requirement for confederates makes it labor-intensive. The current study tested whether a shorter (~6.5 min), single-experimenter, version of the SSST can still reliably elicit subjective and physiological stress reactivity. Our sample consisted of 87 healthy young adult participants (age range: 18-35 years). During the short SSST and a speeded reaction time task, in which aversive loud tones were to be avoided (TA), we measured heart period (HP), sympathetic nervous system (SNS) activity using pre-ejection-period (PEP), skin conductance level (SCL), and non-specific skin conductance responses (ns.SCR), and parasympathetic nervous system (PNS) activity using respiratory-sinus-arrhythmia (RSA) and the root-mean-square of successive differences (RMSSD). The short SSST induced significant decreases in positive affect and increases in negative affect. MANOVAs on the clusters of SNS and PNS variables showed that the short SSST elicited significant HP (-118.46 ms), PEP (-7.76 ms), SCL (+4.85 µS), ns.SCR (+8.42 peaks/min) and RMSSD (-14.67) reactivity. Affective, SNS, and PNS reactivity to the new SSST social-evaluative stress task were of comparable magnitude to that evoked by the TA mental stressor. We conclude that the short SSST is a valid and cost-effective task for large scaled studies to induce social-evaluative stress to a sufficient degree to evoke measurable changes in PNS and SNS activity and affective state.

Implementing pelvic floor muscle training in women's childbearing years: A critical interpretive synthesis of individual, professional, and service issues.

AIMS: Antenatal pelvic floor muscle training (PFMT) may be effective for the prevention and treatment of urinary and fecal incontinence both in pregnancy and postnatally, but it is not routinely implemented in practice despite guideline recommendations. This review synthesizes evidence that exposes challenges, opportunities, and concerns regarding the implementation of PFMT during the childbearing years, from the perspective of individuals, healthcare professionals (HCPs), and organizations. METHODS: Critical interpretive synthesis of systematically identified primary quantitative or qualitative studies or research syntheses of women's and HCPs attitudes, beliefs, or experiences of implementing PFMT. RESULTS: Fifty sources were included. These focused on experiences of postnatal urinary incontinence (UI) and perspectives of individual postnatal women, with limited evidence exploring the views of antenatal women and HCP or wider organizational and environmental issues. The concept of agency (people's ability to effect change through their interaction with other people, processes, and systems) provides an over-arching explanation of how PFMT can be implemented during childbearing years. This requires both individual and collective action of women, HCPs, maternity services and organizations, funders and policymakers. CONCLUSION: Numerous factors constrain women's and HCPs capacity to implement PFMT. It is unrealistic to expect women and HCPs to implement PFMT without reforming policy and service delivery. The implementation of PFMT during pregnancy, as recommended by antenatal care and UI management guidelines, requires policymakers, organizations, HCPs, and women to value the prevention of incontinence throughout women's lives by using low-risk, low-cost, and proven strategies as part of women's reproductive health.

Combined Single-Cell Manipulation and Chemomechanical Modeling to Probe Cell Migration Mechanism During Cell-to-Cell Interaction.

Spatial presentations of chemical and mechanical information are key parameters for cell migration. However, previous theoretical and experimental studies focus on probing the mechanisms caused by a single type of stimulus, while ignoring the synergetic effects, especially for single cell migration during cell-to-cell interaction. Here we develop a chemomechanical model to assess the biochemical and biophysical modulators of single cell migration during cell-to-cell interaction. This model considers the stimulation of chemoattractant concentration gradient, influence of dynamic adhesion strength and relative motion between cells. The model is validated with single cell manipulation of leukemia cancer cell on stromal cell layer using optical tweezers. Both the modeling and experimental results demonstrate that cell migration velocity caused by chemotaxis can be biased by dynamic adhesion force, which is related to the retrograde flow of stromal cell layer. Besides, the biophysical modulators can influence the effect of drug treatment for specific signaling pathway. Our work provides a quantitative description of single cell migration in a complex environment that is close to realistic in vivo situation and is useful for further exploration of cell signaling pathway during cell-to-cell interactions for investigation of potential therapeutic strategy.

Probability learning and feedback processing in dyslexia: A performance and heart rate analysis.

Recent studies suggest that individuals with dyslexia may be impaired in probability learning and performance monitoring. These observations are consistent with findings indicating atypical neural activations in frontostriatal circuits in the brain, which are important for associative learning. The current study further examined probability learning and performance monitoring in adult individuals with dyslexia (n = 23) and typical readers (n = 31) using two varieties of a typical probabilistic learning task. In addition to performance measures, we measured heart rate, focusing on cardiac slowing with negative feedback as a manifestation of the automatic performance monitoring system. One task required participants to learn associations between artificial script and speech sounds and the other task required them to learn associations between geometric forms and bird sounds. Corrective feedback (informative or random) was provided in both tasks. Performance results indicated that individuals with dyslexia and typical readers learned the associations equally well in contrast to expectations. We found the typical cardiac response associated with feedback processing consisting of a heart rate slowing with the presentation of the feedback and a return to baseline thereafter. Interestingly, the heart rate slowing associated with feedback was less pronounced and the return to baseline was delayed in individuals with dyslexia relative to typical readers. These findings were interpreted in relation to current theorizing of performance monitoring linking the salience network in the brain to autonomic functioning.

U.S.-Based National Surveillance for Fidaxomicin Susceptibility of Clostridioides difficile-Associated Diarrheal Isolates from 2013 to 2016.

In 2011, we initiated a sentinel surveillance network to assess changes in Clostridioides (formerly Clostridium) difficile antimicrobial susceptibility to fidaxomicin from 6 geographically dispersed medical centers in the United States. This report summarizes data from 2013 to 2016. C. difficile isolates or toxin-positive stools from patients were referred to a central laboratory. Antimicrobial susceptibility was determined by agar dilution. CLSI, EUCAST, or FDA breakpoints were used, where applicable. Toxin gene profiles were characterized by multiplex PCR on each isolate. A random sample of approximately 40% of isolates, stratified by institution and year, was typed by restriction endonuclease analysis (REA). Among 1,889 isolates from 2013 to 2016, the fidaxomicin MIC90 was 0.5 µg/ml; all isolates were inhibited at ≤1 µg/ml. There were decreases in metronidazole and vancomycin MICs over time. Clindamycin resistance remained unchanged (27.3%). An increase in imipenem resistance was observed. By 2015 to 2016, moxifloxacin resistance decreased in all centers. The proportion of BI isolates decreased from 25.5% in 2011 to 2012 to 12.8% in 2015 to 2016 (P < 0.001). The BI REA group correlated with moxifloxacin resistance (BI 84% resistant versus non-BI 12.5% resistant). Fidaxomicin MICs have not changed among C. difficile isolates of U.S. origin over 5 years post licensure. There has been an overall decrease in MICs for vancomycin, metronidazole, moxifloxacin, and rifampin and an increase in isolates resistant to imipenem. Moxifloxacin resistance remained high among the BI REA group, but the proportion of BI isolates has decreased. Continued geographic variations in REA groups and antimicrobial resistance persist.

Deducing density and strength of nanocrystalline Ta and diamond under extreme conditions from X-ray diffraction.

In situ X-ray diffraction with advanced X-ray sources offers unique opportunities for investigating materials properties under extreme conditions such as shock-wave loading. Here, Singh's theory for deducing high-pressure density and strength from two-dimensional (2D) diffraction patterns is rigorously examined with large-scale molecular dynamics simulations of isothermal compression and shock-wave compression. Two representative solids are explored: nanocrystalline Ta and diamond. Analysis of simulated 2D X-ray diffraction patterns is compared against direct molecular dynamics simulation results. Singh's method is highly accurate for density measurement (within 1%) and reasonable for strength measurement (within 10%), and can be used for such measurements on nanocrystalline and polycrystalline solids under extreme conditions (e.g. in the megabar regime).

Correction to: A Genetic Investigation of the Well-Being Spectrum.

In the original version of this article, unfortunately, in the acknowledgement section "National Institutes of Health (NIH, R37 AG033590-08) to J Cacioppo" was omitted. This has been corrected by publishing this erratum.

A Genetic Investigation of the Well-Being Spectrum.

The interrelations among well-being, neuroticism, and depression can be captured in a so-called well-being spectrum (3-phenotype well-being spectrum, 3-WBS). Several other human traits are likely linked to the 3-WBS. In the present study, we investigate how the 3-WBS can be expanded. First, we constructed polygenic risk scores for the 3-WBS and used this score to predict a series of traits that have been associated with well-being in the literature. We included information on loneliness, big five personality traits, self-rated health, and flourishing. The 3-WBS polygenic score predicted all the original 3-WBS traits and additionally loneliness, self-rated health, and extraversion (R2 between 0.62% and 1.58%). Next, using LD score regression, we calculated genetic correlations between the 3-WBS and the traits of interest. From all candidate traits, loneliness and self-rated health were found to have the strongest genetic correlations (rg = - 0.79, and rg= 0.64, respectively) with the 3-WBS. Lastly, we use Genomic SEM to investigate the factor structure of the proposed spectrum. The best model fit was obtained for a two-factor model including the 5-WBS traits, with two highly correlated factors representing the negative- and positive end of the spectrum. Based on these analyses we propose to include loneliness and self-rated health in the WBS and use a 5-phenotype well-being spectrum in future studies to gain more insight into the determinants of human well-being.