Neuromuscular Adaptions Following a Daily Strengthening Exercise in Individuals with Rotator Cuff Related Shoulder Pain: A Pilot Case-Control Study

Background: The goal of therapeutic exercise is to facilitate a neuromuscular response by increasing or decreasing muscular activity in order to reduce pain and improve function. It is not clear what dosage of exercise will create a neuromuscular response. Purpose: The purpose of this study was to assess the effects following a three-week home program of a daily single exercise, the prone horizontal abduction exercise (PHA), on neuromuscular impairments of motor control as measured by scapular muscle EMG amplitudes, strength, and secondarily outcomes of self-reported pain and function between individuals with and without subacromial pain syndrome. Study Design: Prospective Case-Control, Pilot Study. Methods: Twenty-five individuals participated; eleven with shoulder pain during active and resistive motions (Penn Shoulder Score: 77 ± 11) and 14 matched healthy controls (Penn Shoulder Score: 99 ± 27) (p \u3c 0.001). Participants underwent baseline and follow up testing at three weeks including surface electromyography (EMG) of the serratus anterior, upper, and lower trapezius of the involved (painful group) or matched shoulder (control group) during an elevation task and maximal isometric shoulder strength testing. All participants were instructed in a PHA exercise to be performed daily (3 sets; 10 reps). Subjects logged daily exercise adherence. Neuromuscular adaptations were defined by changes in EMG amplitudes (normalized to MVIC) of serratus anterior, upper trapezius, and lower trapezius and strength. Secondary outcomes of self-reported pain and function were also compared between groups following the three-week intervention. Results: After three weeks of a daily PHA exercise, the painful group demonstrated a greater decrease in baseline-elevated EMG amplitudes in the lower trapezius by 7% (95%CI 2.6-11%) during the concentric phase of the overhead lifting task (p 0.006). EMG amplitudes of the healthy control group did not change at three-week follow-up. Additionally, the change in serratus anterior mean EMG amplitude in the painful group -1.6% (IQR -22.9 to 0.8%) was significantly greater (p 0.033) than the healthy group change score, 2.5% (IQR -2.3 to 5.7%) during the eccentric phase (p 0.034). While the painful group was weaker in abduction and flexion at baseline and at follow up, both groups had a significant increase in all strength measures (p≤0.014). Concurrent with increased strength and normalizing EMG amplitudes, the painful group significantly improved on the Penn Shoulder Score with a mean change 9.8 points (95%CI 7.0, 12.6) (p \u3c 0.001). Conclusion: In this pilot case-control study, a single home exercise performed daily for three weeks demonstrated neuromuscular adaptations with improvements in muscle activity and strength. These were concurrent with modest, yet significant improvements pain and function in individuals with mild rotator cuff related shoulder pain. Level of Evidence: 3

A novel murine infection model for Shiga toxin-producing Escherichia coli

Enterohemorrhagic E. coli (EHEC) is an important subset of Shiga toxin-producing (Stx-producing) E. coli (STEC), pathogens that have been implicated in outbreaks of food-borne illness and can cause intestinal and systemic disease, including severe renal damage. Upon attachment to intestinal epithelium, EHEC generates attaching and effacing (AE) lesions characterized by intimate attachment and actin rearrangement upon host cell binding. Stx produced in the gut transverses the intestinal epithelium, causing vascular damage that leads to systemic disease. Models of EHEC infection in conventional mice do not manifest key features of disease, such as AE lesions, intestinal damage, and systemic illness. In order to develop an infection model that better reflects the pathogenesis of this subset of STEC, we constructed an Stx-producing strain of Citrobacter rodentium, a murine AE pathogen that otherwise lacks Stx. Mice infected with Stx-producing C. rodentium developed AE lesions on the intestinal epithelium and Stx-dependent intestinal inflammatory damage. Further, the mice experienced lethal infection characterized by histopathological and functional kidney damage. The development of a murine model that encompasses AE lesion formation and Stx-mediated tissue damage will provide a new platform upon which to identify EHEC alterations of host epithelium that contribute to systemic disease

Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children

This article is made available for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing.BACKGROUND: Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. Therefore, we aimed to develop a highly sensitive metagenomic next-generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children. METHODS: We collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children's hospitals from 2014-2016. Samples underwent mechanical homogenization, parallel RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the National Center for Biotechnology Information nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort. RESULTS: We identified a rich cross-domain pulmonary microbiome that contained bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median, 0.61; interquartile range [IQR], 0.33-0.72 vs median, 0.96; IQR, 0.94-0.96; P < .001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (P < .001). CONCLUSIONS: An optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease

Investigation of relative risk estimates from studies of the same population with contrasting response rates and designs

Background: There is little empirical evidence regarding the generalisability of relative risk estimates from studies which have relatively low response rates or are of limited representativeness. The aim of this study was to investigate variation in exposure-outcome relationships in studies of the same population with different response rates and designs by comparing estimates from the 45 and Up Study, a population-based cohort study (self-administered postal questionnaire, response rate 18%), and the New South Wales Population Health Survey (PHS) (computer-assisted telephone interview, response rate ~60%). Methods: Logistic regression analysis of questionnaire data from 45 and Up Study participants (n = 101,812) and 2006/ 2007 PHS participants (n = 14,796) was used to calculate prevalence estimates and odds ratios (ORs) for comparable variables, adjusting for age, sex and remoteness. ORs were compared using Wald tests modelling each study separately, with and without sampling weights. Results: Prevalence of some outcomes (smoking, private health insurance, diabetes, hypertension, asthma) varied between the two studies. For highly comparable questionnaire items, exposure-outcome relationship patterns were almost identical between the studies and ORs for eight of the ten relationships examined did not differ significantly. For questionnaire items that were only moderately comparable, the nature of the observed relationships did not differ materially between the two studies, although many ORs differed significantly. Conclusions: These findings show that for a broad range of risk factors, two studies of the same population with varying response rate, sampling frame and mode of questionnaire administration yielded consistent estimates of exposure-outcome relationships. However, ORs varied between the studies where they did not use identical questionnaire items

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from -183 to 178 grams per 10% increase in methylation (P-Bonferroni <1.06 x 10(-7)). In additional analyses in 7,278 participants,Peer reviewe

CpG-creating mutations are costly in many human viruses.

Mutations can occur throughout the virus genome and may be beneficial, neutral or deleterious. We are interested in mutations that yield a C next to a G, producing CpG sites. CpG sites are rare in eukaryotic and viral genomes. For the eukaryotes, it is thought that CpG sites are rare because they are prone to mutation when methylated. In viruses, we know less about why CpG sites are rare. A previous study in HIV suggested that CpG-creating transition mutations are more costly than similar non-CpG-creating mutations. To determine if this is the case in other viruses, we analyzed the allele frequencies of CpG-creating and non-CpG-creating mutations across various strains, subtypes, and genes of viruses using existing data obtained from Genbank, HIV Databases, and Virus Pathogen Resource. Our results suggest that CpG sites are indeed costly for most viruses. By understanding the cost of CpG sites, we can obtain further insights into the evolution and adaptation of viruses

Microbial diversity and biogeochemical cycling in soda lakes

Soda lakes contain high concentrations of sodium carbonates resulting in a stable elevated pH, which provide a unique habitat to a rich diversity of haloalkaliphilic bacteria and archaea. Both cultivation-dependent and -independent methods have aided the identification of key processes and genes in the microbially mediated carbon, nitrogen, and sulfur biogeochemical cycles in soda lakes. In order to survive in this extreme environment, haloalkaliphiles have developed various bioenergetic and structural adaptations to maintain pH homeostasis and intracellular osmotic pressure. The cultivation of a handful of strains has led to the isolation of a number of extremozymes, which allow the cell to perform enzymatic reactions at these extreme conditions. These enzymes potentially contribute to biotechnological applications. In addition, microbial species active in the sulfur cycle can be used for sulfur remediation purposes. Future research should combine both innovative culture methods and state-of-the-art ‘meta-omic’ techniques to gain a comprehensive understanding of the microbes that flourish in these extreme environments and the processes they mediate. Coupling the biogeochemical C, N, and S cycles and identifying where each process takes place on a spatial and temporal scale could unravel the interspecies relationships and thereby reveal more about the ecosystem dynamics of these enigmatic extreme environments

Development and Testing of the First-Episode Psychosis Services Fidelity Scale

Objective: The purpose of this study was to test the reliability and validity of the First-Episode Psychosis Services Fidelity Scale (FEPS-FS) and compare it with similar scales. Methods: A fidelity scale was developed from previously identified essential components of first-episode psychosis services. The scale was tested in six programs in two countries and compared with three existing scales. Results: Program data collection from multiple sources indicated the feasibility and reliability of the FEPS-FS (intraclass correlation coefficient for interrater reliability=.842; 95% confidence interval=.795–.882). Satisfactory programs scored an average of 86% of the maximum total score; the single unsatisfactory program scored 70%. Compared with the other scales, the FEPS-FS has fewer items, but it has the highest proportion of items common to all scales. Conclusions: The FEPS-FS is a feasible, compact, reliable, and valid measure of adherence to evidence-based practices for first-episode psychosis services that can be applied to any first-episode psychosis service

Challenges in improving the quality of osteoporosis care for long-term glucocorticoid users: a prospective randomized trial

BACKGROUND: In light of widespread undertreatment for glucocorticoid-induced osteoporosis (GIOP), we designed a group randomized controlled trial to increase bone mineral density (BMD) testing and osteoporosis medication prescribing among patients receiving long-term glucocorticoid therapy. METHODS: Using administrative databases of a large US health plan, we identified physicians who prescribed long-term glucocorticoid therapy to at least 3 patients. One hundred fifty-three participating physicians were randomized to receive a 3-module Web-based GIOP intervention or control course. Intervention modules focused on GIOP management and incorporated case-based continuing medical education and personalized audit and feedback of GIOP management compared with that of the top 10% of study physicians. In the year following the intervention, we compared rates of BMD testing and osteoporosis medication prescribing between intervention and control physicians. RESULTS: Following the intervention, intent-to-treat analyses showed that 78 intervention physicians (472 patients) vs 75 control physicians (477 patients) had similar rates of BMD testing (19% vs 21%, P = .48; rate difference, -2%; 95% confidence interval [CI], -8% to 4%) and osteoporosis medication prescribing (32% vs 29%, P = .34; rate difference, 3%; 95% CI, -3% to 9%). Among 45 physicians completing all modules (343 patients), intervention physicians had numerically but not significantly higher rates of BMD testing (26% vs 16%, P =.04; rate difference, 10%; 95% CI, 1%-20%) and bisphosphonate prescribing (24% vs 17%, P =.09; rate difference, 7%; 95% CI, -1% to 16%) or met a combined end point of BMD testing or osteoporosis medication prescribing (54% vs 44%, P =.07; rate difference, 10%; 95% CI, -1% to 21%) compared with control physicians. CONCLUSIONS: In the main analysis, a Web-based intervention incorporating performance audit and feedback and case-based continuing medical education had no significant effect on the quality of osteoporosis care. However, dose-response trends showed that physicians with greater exposure to the intervention had higher rates of GIOP management. New cost-effective modalities are needed to improve the quality of osteoporosis care