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Hypertrophic burn scars (HTBSs) remain a significant source of morbidity. Contemporary treatment has evolved to use CO2 lasers and/or pulse-dye lasers (PDLs) to reduce scar thickness (ST) and erythema. This study seeks to compare treatment efficacy with CO2 or PDL individually and in combination.Patients undergoing laser treatments for HTBSs were enrolled. Three 3 × 3 cm squares of HTBSs were randomized to receive treatment with CO2 laser, PDL or CO2 + PDL. Patients underwent 3 treatments, 4 to 6 weeks apart and were followed up over 3 to 6 months. Scar assessments occurred at each visit before treatment and consisted of photographs, ultrasound, colorimetry, and the Patient and Observer Scar Assessment Score.Twenty-five patients were enrolled. Twenty completed 2 treatments (80%) and 11 completed all 3 treatments (44%). Median initial ST was 0.3 cm. Median time since injury was 8 months. Hypertrophic burn scars treated with CO2 or PDL showed a significant decrease in Patient and Observer Scar Assessment Scale score from visit 1 to 3 (P = 0.01 and 0.01, respectively). When separated by ST, thick scars (≥0.3 cm) showed a significant decrease in thickness between visit 1 and 2 using all laser modalities (CO2 + PDL, P = 0.01; CO2, P = 0.02; PDL, P = 0.03). Thin scars (0.3 cm) showed a reduction in thickness by visit 3 after CO2 + PDL or PDL alone (P = 0.01 and 0.04, respectively). Separating scars by age, younger scars (9 months) showed a significant reduction in thickness between visit 1 and 2 for CO2 treatment (P = 0.04), and between visit 2 and 3 for CO2 + PDL treatment (P = 0.04). Hypertrophic burn scars treated with PDL did not demonstrate a significant reduction in thickness until visit 3 (P = 0.002). Older scars (≥9 months) showed a significant reduction in thickness between visit 1 and 2 only after CO2 + PDL (P = 0.01).Hypertrophic burn scars of varying ages, etiologies, and thicknesses were examined in this study with greater degree of early reduction seen in thicker scars using all laser modalities of CO2, PDL or in combination. However, there was no clinically meaningful benefit found with combination as compared with individual treatment. These data support the use of laser to improve HTBS but does not support one modality or combination of modalities over another.

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure

Antimicrobial stewardship has been cited as a crucial component of orthopaedic surgical care; however, limited high-quality data exist to guide antibiotic use across the total joint arthroplasty continuum. Antimicrobial stewardship program (ASP) implementation and evaluation is needed in this space.We pursued a prospective, sequential cohort study of an interprofessional ASP for total joint arthroplasty (TJA) formed in late 2017 at the study institution. Twelve total evidence-based recommendations for protocol change were issued, with 11 accepted and implemented across three project phases spanning March 2018 to December 2019. The primary study outcome was the rate of optimal preoperative intravenous antibiotic selection as assessed for Baseline versus Postintervention time periods. Secondary outcomes included individual antibiotic utilization rates. Descriptive statistics were pursued for institutional surgical site infection (SSI) and postoperative acute kidney injury (AKI) rates across the affected time frame. A cost-benefit analysis of the ASP was estimated from the institutional perspective.The rate of optimal preoperative antibiotic selection increased from 64.9% in the Baseline Period (February 2018, n = 57) to 95.4% in the Postimplementation period (June 2018 to December 2019, n = 1,220) (P0.001). The rates of second-line preoperative antibiotics and total perioperative antibiotic exposures decreased. Total SSI and AKI rates in primary elective TJA seemed to decrease from calendar year 2018 to 2019 (deep SSI 1.00% to 0.22%, superficial SSI 0.66% to 0.00%, and AKI 1.97% to 1.03%). The institution realized an estimated $197,050 cost savings per 1000 TJA procedures.A comprehensive ASP for TJA was associated with an increased use of optimal preoperative antibiotic selection, decreased total antibiotic exposures, and cost savings, without apparent detriment to SSI or AKI rates.

To assess whether probiotic supplementation may reduce disease-linked systemic immune activation in people living with HIV with the immunologic nonresponder phenotype.Phase 2b, randomized, double-blind, placebo-controlled pilot trial.HIV-positive individuals with blood CD4+ T-cell counts350/mm3 despite viral suppression were randomized to 2:1 to receive De Simone Formulation Probiotic (DSFP; "Visbiome" commercially) or placebo for 48 weeks; target enrollment was 36 patients. The primary endpoint was the change in blood CD8+ T-cell coexpression of human leukocyte antigen-DR isotype and CD38 ("CD8 activation"). Secondary endpoints included biomarkers of inflammation, immune reconstitution, bacterial translocation, and gut permeability. Adjusted linear regression and linear mixed regression methods evaluated the differences between study arms from baseline to week 48. Study monitoring was performed by the CIHR Canadian HIV Trials Network Data Safety Monitoring Committee.Nineteen patients received DSFP, whereas 10 received placebo. One probiotic arm patient withdrew early. Blood CD8 activation increased 0.82 percentage points (pp) in the probiotic arm (95% confidence interval: -1.23 to 2.87;) and decreased by 2.06 pp in the placebo arm (-4.81 to 0.70; between arms P = 0.097). CD4+ T-cell activation (%HLA-DR+) decreased in the placebo arm [-3.79 pp (-7.32 to -0.26)] but increased in the probiotic arm [1.64 (-0.98 to 4.26); between arms P = 0.018]. No differences were observed in plasma or urine biomarkers of inflammation or microbial translocation.Blood immune activation markers in immunologic nonresponder individuals on effective antiretroviral treatment were not reduced by supplementation with DSFP; CD4+ T-cell activation may have been increased.

Background: Induction of labour is one of the most common obstetric interventions globally. Balloon catheters and vaginal prostaglandins are widely used to ripen the cervix in labour induction. We aimed to compare the effectiveness and safety profiles of these two induction methods. Methods: We did an individual participant data meta-analysis comparing balloon catheters and vaginal prostaglandins for cervical ripening before labour induction. We systematically identified published and unpublished randomised controlled trials that completed data collection between March 19, 2019, and May 1, 2021, by searching the Cochrane Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and PubMed. Further trials done before March 19, 2019, were identified through a recent Cochrane review. Data relating to the combined use of the two methods were not included, only data from women with a viable, singleton pregnancy were analysed, and no exclusion was made based on parity or membrane status. We contacted authors of individuals trials and participant-level data were harmonised and recoded according to predefined definitions of variables. Risk of bias was assessed with the ROB2 tool. The primary outcomes were caesarean delivery, indication for caesarean delivery, a composite adverse perinatal outcome, and a composite adverse maternal outcome. We followed the intention-to-treat principle for the main analysis. The primary meta-analysis used two-stage random-effects models and the sensitivity analysis used one-stage mixed models. All models were adjusted for maternal age and parity. This meta-analysis is registered with PROSPERO (CRD42020179924). Findings: Individual participant data were available from 12 studies with a total of 5460 participants. Balloon catheters, compared with vaginal prostaglandins, did not lead to a significantly different rate of caesarean delivery (12 trials, 5414 women; crude incidence 27·0%; adjusted OR [aOR] 1·09, 95% CI 0·95–1·24; I2=0%), caesarean delivery for failure to progress (11 trials, 4601 women; aOR 1·20, 95% CI 0·91–1·58; I2=39%), or caesarean delivery for fetal distress (10 trials, 4441 women; aOR 0·86, 95% CI 0·71–1·04; I2=0%). The composite adverse perinatal outcome was lower in women who were allocated to balloon catheters than in those allocated to vaginal prostaglandins (ten trials, 4452 neonates, crude incidence 13·6%; aOR 0·80, 95% CI 0·70–0·92; I2=0%). There was no significant difference in the composite adverse maternal outcome (ten trials, 4326 women, crude incidence 22·7%; aOR 1·02, 95% CI 0·89–1·18; I2=0%). Interpretation: In induction of labour, balloon catheters and vaginal prostaglandins have comparable caesarean delivery rates and maternal safety profiles, but balloon catheters lead to fewer adverse perinatal events. Funding: Australian National Health and Medical Research Council and Monash Health Emerging Researcher Fellowship.

Background Several cancer therapies have been associated with cardiovascular harm in early‐phase clinical trials. However, some cardiovascular harms do not manifest until later‐phase trials. To limit interdisease variability, we focused on breast cancer. Thus, we assessed the reporting of cardiovascular safety monitoring and outcomes in phase 2 and 3 contemporary breast cancer clinical trials. Methods and Results We searched Embase and Medline records for phase 2 and 3 breast cancer pharmacotherapy trials. We examined exclusion criterion as a result of cardiovascular conditions, adverse cardiovascular event reporting, and cardiovascular safety assessment through cardiovascular imaging, ECG, troponin, or natriuretic peptides. Fisher's exact test was utilized to compare reporting. Fifty clinical trials were included in our study. Patients were excluded because of cardiovascular conditions in 42 (84%) trials. Heart failure was a frequent exclusion criterion (n=31; 62% trials). Adverse cardiovascular events were reported in 43 (86%) trials. Cardiovascular safety assessments were not reported in 23 (46%) trials, whereas natriuretic peptide and troponin assessments were not reported in any trial. Cardiovascular safety assessments were more frequently reported in industry‐funded trials (69.2% versus 0.0%; P P Conclusions Our findings demonstrate significant under‐representation of patients with cardiovascular conditions or prevalent cardiovascular disease in contemporary later‐phase breast cancer trials. Additionally, cardiovascular safety is not routinely monitored in these trials. Therefore, contemporary breast cancer clinical trials may possibly underestimate the cardiovascular risks of cancer pharmacotherapy agents for use in clinical practice.

Phocaeicola vulgatus is one of the most abundant and ubiquitous bacterial species of the human gut microbiota, yet a comprehensive analysis of antibacterial toxin production by members of this species has not been reported. Here, we identify and characterize a previously undescribed antibacterial protein. This toxin, designated BcpT, is encoded on a small mobile plasmid that is largely confined to strains of the closely related species Phocaeicola vulgatus and Phocaeicola dorei. BcpT is unusual in that it requires cleavage at two distinct sites for activation, and we identify bacterial proteases that perform this activation. We further identify BcpT’s receptor as the Lipid A-core glycan, allowing BcpT to target species of other Bacteroidales families. Exposure of cells to BcpT induces a response involving an unusual sigma/anti-sigma factor pair that is likely triggered by cell envelope stress, resulting in the expression of genes that partially protect cells from multiple antimicrobial toxins.

Background: The ability to diagnose preeclampsia clinically is suboptimal. Our objective was to validate a novel multianalyte assay and characterize its performance, when intended for use as an aid to rule-out preeclampsia. Methods: Prospective, multicenter cohort study of pregnant individuals presenting between 28 0/7 and 36 6/7 weeks’ with preeclampsia-associated signs and symptoms. Individuals not diagnosed with preeclampsia after baseline evaluation were enrolled in the study cohort, with those who later developed preeclampsia, classified as cases and compared with a negative control group who did not develop preeclampsia. Individuals with assay values at time of enrollment ≥0.0325, determined using a previously developed algorithm, considered at risk. The primary analysis was the time to develop preeclampsia assessed using a multivariate Cox regression model. Results: One thousand thirty-six pregnant individuals were enrolled in the study cohort with an incidence of preeclampsia of 30.3% (27.6%–33.2%). The time to develop preeclampsia was shorter for those with an at-risk compared with negative assay result (log-rank P P Conclusions: We confirmed that a novel multianalyte assay was associated with the time to develop preeclampsia and has a moderate sensitivity and negative likelihood ratio but high negative predictive value when assessed as an aid to rule out preeclampsia within 7 days of enrollment. Registration: The study was registered on Clinicaltrials.gov (Identifier NCT02780414).

Vascularized composite allotransplantation (VCA) is the most advanced reconstructive technique available to patients who suffer devastating burns to the limbs or face. However, VCA requires donor–recipient matching. Burn patients have been reported to experience sensitization, or the development of anti-human leukocyte antigen antibodies, during resuscitation and wound coverage, potentially precluding them from future VCA. This study sought to investigate the contributions of both blood and allograft to sensitization in burn patients. Four groups were compared: burn patients who received blood products and allograft (group 1), burn patients who received blood products only (group 2), trauma patients who received blood products only (group 3), and healthy volunteer controls (group 4). The average calculated panel-reactive antibody (indicating sensitization) was higher in group 1 compared to group 4 (P = .035). Additionally, the incidence of severe sensitization was higher in group 1 relative to the other groups (P = .049). When comparing groups of patients who had no sensitization, mild sensitization, moderate sensitization, and severe sensitization, there were no significant differences in age, sex, blood products received, total body surface area burned, or allograft used between groups, though severely sensitized patients tended to have greater total body surface area involvement and received more units of packed red blood cells and allograft (P = .079, P = .196, and P = .072, respectively). We therefore conclude that while burn patients who received allograft and blood demonstrated a higher incidence of anti-human leukocyte antigen sensitization relative to healthy controls, this difference cannot solely be attributed to either allograft use or transfusion.

This study aimed to assess whether patient satisfaction differs between women beginning cervical ripening in the outpatient versus inpatient setting.We performed a planned secondary analysis evaluating patient satisfaction randomized to outpatient versus inpatient cervical ripening. In the original randomized controlled trial, low-risk parous women ≥39 weeks who required cervical ripening for induction and had reassuring fetal heart rate monitoring were included and randomized to inpatient versus outpatient ripening with a transcervical Foley's catheter. All women were then admitted to the labor ward on the following day. Patient satisfaction was evaluated using three separate surveys. The first two surveys, Six Simple Questions and Lady-X, were previously validated. The third survey used visual analog scales to assess overall pain experienced during Foley's placement, overall pain experienced during labor, how likely they would be to choose the same type of care for their next pregnancy, and how likely they would be to recommend their method of cervical ripening to friends/family.From May 2016 to October 2017, 129 women were randomized (outpatient, 65; inpatient, 64). Based on survey results, there was no difference in satisfaction between outpatient and inpatient cervical ripening with transcervical Foley's catheterization, with high satisfaction in both groups. Patients in both the outpatient and inpatient groups would choose the same type of care for their next pregnancy (on a scale of 1-7, median (25th-75th percentile): 7 [7-7] vs. 7 [6-7], respectively,Parous women's satisfaction does not differ between inpatient and outpatient cervical ripening with transcervical Foley's catheterization.· Outpatient cervical ripening may allow providers to incorporate the benefits of electively inducing women as well as decrease the time spent in the labor and delivery unit.. · Parous women's satisfaction does not differ between inpatient and outpatient cervical ripening with transcervical Foley.. · Additional prospective evaluation is warranted to further characterize patient preferences in relation to the location of cervical ripening..

Objective The aim of study is to compare, in a pilot study, combined dinoprostone vaginal insert and Foley catheter (DVI + Foley) with Foley alone (Foley) for cervical ripening and labor induction at term. Study Design In this open-label pilot randomized controlled trial, women not in labor, with intact membranes, no prior uterine incision, an unfavorable cervix, gestational age ≥37 weeks, and a live, nonanomalous singleton fetus in cephalic presentation were randomly assigned, stratified by parity, to DVI + Foley or Foley. Oxytocin was used in both groups after cervical ripening. Primary outcome was time to vaginal delivery. Results From April 2017 to January 2018, 100 women were randomized. Median (25–75th percentile) time to vaginal delivery for nulliparous women was 21.2 (16.6–38.0) hours with DVI + Foley (n = 26) compared with 31.3 (23.3–46.9) hours with Foley (n = 24) (Wilcoxon p = 0.05). Median time to vaginal delivery for parous women was 17.1 (13.6–21.9) hours with DVI + Foley (n = 25) compared with 14.8 (12.7–19.5) hours with Foley (n = 25) (Wilcoxon p = 0.21). Results were also analyzed to consider the competing risk of cesarean using cumulative incidence functions. Conclusion Compared with Foley alone, combined use of the dinoprostone vaginal insert and Foley for cervical ripening may shorten time to vaginal delivery for nulliparous but not parous women.

Objective The aim of this study was to evaluate the effect of a policy to deliver at 39 weeks for class III obesity. Methods This was a retrospective cohort study of women with class III obesity delivering at ≥ 37 weeks before (May 2012 to April 2014) and after the policy (September 2014 to August 2016). The primary outcome was the cesarean rate. Secondary outcomes included maternal morbidities and a neonatal morbidity composite. Modified Poisson regression was used to adjust for demographic differences between groups. Results The study included a total of 1,210 patients, 580 before the policy and 630 after the policy. Before and after the policy, cesarean rates were similar (41.6% vs. 47.1%; risk ratio [RR]: 1.13 [95% CI: 1.00-1.29]; adjusted RR [aRR]: 1.03 [95% CI: 0.92-1.14]). In adjusted comparisons of women undergoing labor induction, parous women had lower cesarean rates (aRR: 0.62; 95% CI: 0.41-0.94) but nulliparous women had higher cesarean rates (aRR: 1.32; 95% CI: 1.04-1.68) after the policy (P for interaction = 0.01). Rates of chorioamnionitis, endometritis, and cesarean wound infection were not different between groups. Composite neonatal morbidity was not different between pre- and postpolicy groups. Conclusions A policy of delivery at 39 weeks for class III obesity did not affect overall cesarean rate or rates of maternal or neonatal morbidity. Further investigation should evaluate subsets of women who may have a higher cesarean rate with this policy.

Background Screening for maternal anogenital Group B streptococci (GBS) colonization in pregnancy with initiation of intravenous intrapartum antibiotic prophylaxis as indicated has led to a significant reduction in the incidence of neonatal GBS infection. This study aims to evaluate the agreement between vaginal-perianal or vaginal-perineal culture and the more typically used vaginal-rectal culture for screening for maternal anogenital GBS colonization in the third trimester of pregnancy. Methods Eligible English-language studies published until January 2020 were retrieved from Scopus, Web of Science, PubMed, Embase, and ClinicalTrials.gov databases. Studies were compiled that assessed for GBS colonization utilizing vaginal-perianal or vaginal-perineal culture and vaginal-rectal culture during the third trimester of pregnancy. Nonoriginal research articles and studies that did not assess pregnant patients, did not use culture-based screening, or did not compare vaginal-perianal or vaginal-perineal culture with vaginal-rectal culture were excluded. The search identified 559 articles with three prospective cohort studies that met inclusion criteria, including 643 participants. Quality was assessed using the Newcastle–Ottawa Scale, and risk of bias was assessed using the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. Patient characteristics and associated pain with specimen collection were abstracted. Meta-analyses of both the raw agreement and the Cohen’s kappa statistic were performed. Results Within the three included studies, the range of GBS detection was 17.6–34.0%, consistent with the anticipated prevalence of GBS colonization reported in earlier publications. For both raw agreement and Cohen’s kappa coefficient, the test for heterogeneity was not significant, indicating low heterogeneity among studies. The pooled estimate of the raw agreement was 0.97 (95%CI 0.95–0.98) and of the Cohen's kappa coefficient was 0.91 (95% CI: 0.87–0.95), indicating (according to the Landis and Koch criteria) an “almost perfect” agreement between the compared clinical tests. In the two studies that assessed procedure-related patient discomfort, vaginal-rectal swabbing caused more discomfort. Conclusion Use of vaginal-perineal culture for assessment of maternal GBS colonization is comparable to the more typically utilized vaginal-rectal culture and is associated with less discomfort.

Women with obesity are at increased risk of complications during and after labor and delivery, including puerperal infection and cesarean delivery. As labor induction has become increasingly common, it is crucial to find ways to decrease complication rates in this high-risk population.This study aimed to explore the effect of prophylactic antibiotics during labor induction of nulliparous women with obesity on the rates of cesarean delivery and puerperal infection and to estimate the parameters needed to calculate the sample size for a larger, multicenter trial.In this randomized, placebo-controlled pilot trial, nulliparous patients with a body mass index of ≥30 kg/mFrom January 2019 to May 2021, 101 patients were randomized in the class III stratum (1 patient who was randomized ultimately did not undergo labor induction). From February 2020 to May 2021, 38 and 47 patients were randomized to class I and II strata, respectively (to assess the effect of obesity class on the outcomes expected to be influenced by antibiotic prophylaxis). In the antibiotics and placebo groups, the rates of cesarean delivery were 29.0% (95% confidence interval, 19.8-38.3) and 39.8% (95% confidence interval, 29.8-49.7), respectively, and puerperal infection occurred in 8.6% (95% confidence interval, 2.9-14.3) and 9.7% (95% confidence interval, 3.7-15.7), respectively. In the subgroup with class III obesity, in the antibiotics and placebo groups, the rates of cesarean delivery were 33.3% (95% confidence interval, 20.4-47.9) and 46.0% (95% confidence interval, 32.2-59.8), respectively, and puerperal infection occurred in 7.8% (95% confidence interval, 0.5-15.2) and 10.0% (95% confidence interval, 1.7-18.3), respectively. Note that this pilot study was not powered to detect differences of this magnitude but rather to estimate parameters.The administration of prophylactic antibiotics during labor induction of nulliparous patients with obesity resulted in a 27% lower cesarean delivery rate overall and a 28% lower rate in patients with class III obesity. A larger trial is warranted to evaluate these differences.

Adipose tissue homeostasis plays a central role in cardiovascular physiology, and the presence of thermogenically active brown adipose tissue (BAT) has recently been associated with cardiometabolic health. We have previously shown that adipose tissue-specific deletion of HuR (Adipo-HuR(−/−)) reduces BAT-mediated adaptive thermogenesis, and the goal of this work was to identify the cardiovascular impacts of Adipo-HuR(−/−). We found that Adipo-HuR(−/−) mice exhibit a hypercontractile phenotype that is accompanied by increased left ventricle wall thickness and hypertrophic gene expression. Furthermore, hearts from Adipo-HuR(−/−) mice display increased fibrosis via picrosirius red staining and periostin expression. To identify underlying mechanisms, we applied both RNA-seq and weighted gene coexpression network analysis (WGCNA) across both cardiac and adipose tissue to define HuR-dependent changes in gene expression as well as significant relationships between adipose tissue gene expression and cardiac fibrosis. RNA-seq results demonstrated a significant increase in proinflammatory gene expression in both cardiac and subcutaneous white adipose tissue (scWAT) from Adipo-HuR(−/−) mice that is accompanied by an increase in serum levels of both TNF-α and IL-6. In addition to inflammation-related genes, WGCNA identified a significant enrichment in extracellular vesicle-mediated transport and exosome-associated genes in scWAT, whose expression most significantly associated with the degree of cardiac fibrosis observed in Adipo-HuR(−/−) mice, implicating these processes as a likely adipose-to-cardiac paracrine mechanism. These results are significant in that they demonstrate the spontaneous onset of cardiovascular pathology in an adipose tissue-specific gene deletion model and contribute to our understanding of how disruptions in adipose tissue homeostasis may mediate cardiovascular disease. NEW & NOTEWORTHY The presence of functional brown adipose tissue in humans is known to be associated with cardiovascular health. Here, we show that adipocyte-specific deletion of the RNA binding protein HuR, which we have previously shown to reduce BAT-mediated thermogenesis, is sufficient to mediate a spontaneous development of cardiac hypertrophy and fibrosis. These results may have implications on the mechanisms by which BAT function and adipose tissue homeostasis directly mediate cardiovascular disease.

Many people in the world lack safe basic drinking water sources and rely on untreated water source. Packaged water can be considered as an alternative to other water sources if measures are put in place to ensure its safety for consumption. This study aimed to assess the bacteriological and chemical quality of packaged water produced in Lusaka, Zambia and associated quality control measures. A cross-sectional study was conducted in May 2019 where 18 brands of packaged water were analyzed for total and feacal coliforms as well as concentrations of Lead, Chromium and Cadmium. The study found that 33.5% of the packaged water produced in Lusaka did not comply with the standard for drinking water on bacteriological quality. We also found that the concentrations for Lead were less than 0.01mg/l in all the 17 samples, thus compliant to WHO/ZABS standards. Concentrations of Chromium were between 0.002mg/l and 0.62mg/l and compliance to the standard was 11.8%. Concentrations for Cadmium were as low as 0.009mg/l and as high as 0.2mg/l as such, non-compliant. Most brands of the packaged water did not conform to the bacteriological standards for drinking water and none of the brands conformed to the chemical quality.

Background A recent large clinical trial demonstrated an approximately 50% decrease in the rate of postoperative infection in women who were laboring and/or had rupture of membranes for >4 hours and who received azithromycin in addition to standard preoperative antibiotic prophylaxis at the time of cesarean delivery. Given these results, our institution made a policy change in May 2017 to add azithromycin to standard preoperative prophylaxis for all cesarean deliveries. Objective This study aimed to evaluate the clinical effectiveness of adding azithromycin to preoperative antibiotic prophylaxis for cesarean delivery. Study Design We conducted a before-and-after cohort study of women delivered via cesarean delivery at our institution. The preimplementation group included women who delivered from March 1, 2016, to February 28, 2017, (before an institutional practice change of adding azithromycin to standard preoperative prophylaxis), and the postimplementation group included women who delivered from September 1, 2017, to August 31, 2018 (allowing a 6-month period for uptake of the practice change). The primary outcome was a composite of postoperative infections (endometritis, wound infection, other maternal infections). Unadjusted and adjusted risk ratios and 95% confidence intervals were estimated using a modified Poisson regression model. Results In the preimplementation (n=1171) and postimplementation (n=1168) groups, the incidence rates of the composite outcomes were 4.7% and 5.3%, respectively (P=.49). Both unadjusted (relative risk, 1.13; 95% confidence interval, 0.78–1.62) and adjusted (adjusted relative risk, 1.06; 95% confidence interval, 0.74–1.52) comparisons were not significantly different. In addition, results were statistically nonsignificant, but in the direction of lower rates of infection, in the after cohort for women in labor and/or with rupture of membranes for ≥4 hours (relative risk, 0.88 [95% confidence interval, 0.56–1.39]; adjusted relative risk, 0.82 [95% confidence interval, 0.52–1.30]) and for women with clinical chorioamnionitis (relative risk, 0.37 [95% confidence interval, 0.08–1.67]; data too sparse for adjusted analysis). In the subgroup of women who were not in labor, the after cohort had a statistically nonsignificant increased risk of the composite outcome in both unadjusted (relative risk, 1.53; 95% confidence interval, 0.86–2.72) and adjusted (adjusted relative risk, 1.48; 95% confidence interval, 0.83–2.65]) comparisons. Conclusion In clinical practice, the addition of azithromycin to standard preoperative antibiotic prophylaxis for cesarean delivery may have an effect size smaller than seen in the large clinical trial prompting this practice change. Extrapolation of this regimen to women not in labor may be ineffective.

Background Although Black adults are more likely to die from coronary heart disease (CHD) compared with White adults, few studies have examined the relationship between cigarette smoking and CHD risk among Black adults. We evaluated the relationship between cigarette smoking, incident CHD, and coronary artery calcification in the JHS (Jackson Heart Study). Methods and Results We classified JHS participants without a history of CHD (n=4432) by self‐reported baseline smoking status into current, former (smoked at least 400 cigarettes/life) or never smokers at baseline (2000–2004). We further classified current smokers by smoking intensity (number of cigarettes smoked per day [1–19 or ≥20]) and followed for incident CHD (through 2016). Hazard ratios (HR) for incident CHD for each smoking group compared with never smokers were estimated with adjusted Cox proportional hazard regression models. At baseline, there were 548 (12.4%) current, 782 (17.6%) former, and 3102 (70%) never smokers. During follow‐up (median, 13.8 years), 254 participants developed CHD. After risk factor adjustment, CHD risk was significantly higher in current smokers compared with never smokers (HR, 2.11; 95% CI, 1.39–3.18); the difference between former smokers and never smokers (HR, 1.37; 95% CI, 1.0–1.90) did not achieve statistical significance. Among current smokers, we did not observe a dose‐response effect for CHD risk. Additionally, in multivariable logistic regression models with a subset of our analytic cohort, current smokers had greater odds of coronary artery calcification score >0 compared with never smokers (odds ratio, 2.63; 95% CI, 1.88–3.68). Conclusions In a large prospective cohort of Black adults, current smoking was associated with a >2‐fold increased risk of CHD over a median follow‐up of greater than a decade.

ObjectiveTo explore whether physical activity is inversely associated with the onset of depression, we quantified the cumulative association of customary physical activity with incident depression and with an increase in subclinical depressive symptoms over time as reported from prospective observational studies.DesignSystematic review and meta-analysis.Data sourcesMEDLINE, PsycINFO, PsycARTICLES and CINAHL Complete databases, supplemented by Google Scholar.Eligibility criteriaProspective cohort studies in adults, published prior to January 2020, reporting associations between physical activity and depression.Study appraisal and synthesisMultilevel random-effects meta-analysis was performed adjusting for study and cohort or region. Mixed-model meta-regression of putative modifiers.ResultsSearches yielded 111 reports including over 3 million adults sampled from 11 nations in five continents. Odds of incident cases of depression or an increase in subclinical depressive symptoms were reduced after exposure to physical activity (OR, 95% CI) in crude (0.69, 0.63 to 0.75; I2=93.7) and adjusted (0.79, 0.75 to 0.82; I2=87.6) analyses. Results were materially the same for incident depression and subclinical symptoms. Odds were lower after moderate or vigorous physical activity that met public health guidelines than after light physical activity. These odds were also lower when exposure to physical activity increased over time during a study period compared with the odds when physical activity was captured as a single baseline measure of exposure.ConclusionCustomary and increasing levels of moderate-to-vigorous physical activity in observational studies are inversely associated with incident depression and the onset of subclinical depressive symptoms among adults regardless of global region, gender, age or follow-up period.

Carbon dioxide (CO2) laser treatment is routinely used to treat hypertrophic burn scars (HBS). Although prior research has documented subjective improvement in HBS after treatment, there is little data evaluating objective changes in scar characteristics after therapy. The aim of our process improvement project was to evaluate changes to scar thickness (ST) using high-frequency ultrasound in patients with HBS undergoing CO2 laser therapy.Ultrasound measurements of ST were obtained from patients with HBS before initial and at each subsequent treatment. ST, reduction in ST per treatment, and percentage reduction in ST from baseline were tabulated. Post hoc analyses examining the effect of initial ST and scar maturity on outcome were performed. First, patients were grouped by baseline ST into thicker (group 1, initial ST ≥ median value) and thinner (group 2, initial STmedian value) scar groups. Second, patients were divided into quartiles based on time from injury to treatment. Outcomes at each time point were compared with either Mann-Whitney U or Kruskal-Wallis tests, with Bonferonni corrections performed for post hoc subgroup analyses. Significance was set at P0.05.Twenty-one consecutive patients with HBS treated with CO2 laser were included. All patients completed 1 or more treatment, 48% completed 2 or more treatments, and 28% completed 3 treatments. Median initial ST was 0.71 cm (0.44-0.98 cm), and median scar maturity was 7.5 months (4.9-9.8 months). Overall, ST decreased over the treatment course (P0.001), with post hoc analysis demonstrating that 2 treatments were required to achieve a significant ST reduction (P0.01). On subgroup analysis comparing initial ST, ST decreased significantly in group 1 (thicker scars) overall (P0.001) but not in group 2 (P = 0.109). ST reduction was greatest after 1 treatment in group 1 (P = 0.022) and group 2 (P = 0.061). Percent reduction was greater in group 1 relative to group 2 after 1 treatment (P = 0.016). On subgroup analysis of scar maturity, there were no significant differences in either baseline ST or ST at any subsequent visit.Fractionated ablative CO2 laser treatment improved ST after 1 to 2 treatments. Patients with thicker scars demonstrated greater ST reduction than those with thinner scars. Ultrasound adequately assessed treatment response.

To determine the risk of wound complications by skin incision type in obese women undergoing cesarean delivery. Data sources: Electronic databases (MEDLINE, Scopus, and Ovid) were searched from their inception through August 2018. Methods of study selection: We included all randomized controlled trials and cohort studies reporting the placement of skin incision during cesarean section in obese women, defined as those with BMI ≥30 kg/m2. Studies were included if they compared one placement of skin incision with a different one as comparison group. The primary outcome was incidence of wound complications, while secondary outcomes included wound infection, hematoma, seroma, postpartum hemorrhage, and endometritis. Demographics and outcomes for each individual study identified were reported as part of the review. Meta-analysis was performed using the random effects model of DerSimonian and Laird, to produce summary treatment effects in terms of mean difference (MD) or relative risk (RR) with 95% confidence interval (CI). Sub-group analyses (vertical versus Pfannenstiel) were also reported. Tabulation, integration and results: Seventeen studies (including 3 RCTs; 8960 participants among the 15 non-overlapping studies) were included in the systematic review. Vertical incisions were associated with a relative risk of 2.07 (95% CI1.61–2.67) for wound complications compared to transverse incisions, however significant possible confounders were present. Studies were mildly-moderately heterogeneous (I2 44.81%, 95% CI 0.00–71.85%) with varying definitions of obesity and wound complications. High transverse incisions (3 studies, 218 participants) trend toward a lower risk of wound complications compared to low transverse incisions (RR 0.338, 95% CI 0.114–1.004). Vertical incisions may be associated with an increased risk for wound complications compared to transverse incisions for cesarean delivery in obese women. Randomized controlled trials are needed to evaluate optimal cesarean skin incisions for these women.

OBJECTIVES: To evaluate if midtrimester maternal serum contains microbial DNA and whether it differs between women with spontaneous preterm birth (SPTB) and those delivering at term. STUDY DESIGN: In this retrospective case-control study, we identified 20 healthy nulliparas with SPTB at 24–33 weeks of a non-anomalous singleton in 2014. Each case was matched by race/ethnicity to a control delivering at 39–40 weeks. Serum samples, collected at 15–20 weeks and stored at −80C, were thawed and DNA extracted. PCR with primers targeting the 16S rDNA V4 region were used to prepare an amplicon library, sequenced using Illumina MiSeq, and analyzed using QIIME. Taxonomy was assigned using RDP Classifier (threshold 0.8) against a modified Greengenes database. Differences in number of observed species, microbial alpha-diversity and beta-diversity, and taxa level analyses were undertaken. RESULTS: All 40 samples were included. Women with SPTB had more unique observed species (p=0.046) and higher mean alpha-diversity by Shannon index (but not Chao1 or Simpson) (p=0.024). Microbial composition was different between groups by Bray-Curtis clustering (p=0.03) but not by weighted (p=0.13) or unweighted Unifrac (p=0.11). Numerous taxa in the Firmicutes, Proteobacteria, and Actinobacteria phyla differed between groups (p

To assess whether outpatient cervical ripening with a transcervical Foley catheter in parous women undergoing elective induction of labor shortens the total duration of time from admission to the labor ward until delivery.We performed an open-label randomized controlled trial at a single academic center in parous women at 39 weeks of gestation or greater with a cervix 3 cm or less dilated, or, if 2-3 cm dilated, less than 80% effaced and reassuring fetal heart rate monitoring (defined as moderate variability with a normal baseline and absence of decelerations). Exclusions were obstetric and neonatal conditions deemed unsuitable for outpatient cervical ripening, contraindications to vaginal delivery, or conditions that required immediate hospitalization. Women were randomized in the ambulatory setting to either an outpatient transcervical catheter (with immediate placement) or inpatient transcervical catheter placement and concomitant oxytocin infusion on the labor ward. Women in the outpatient group were instructed to return to the hospital the next day or sooner if labor occurred. Induction of labor was managed per institutional protocol, and once participants were admitted, oxytocin was initiated. The primary outcome was the duration of time from labor ward admission until delivery. Based on a prior study in our institution, a total of 128 women were needed for 80% power to detect a 12-hour difference in total duration spent from labor ward admission until delivery with a two-sided α of 0.05.Of 743 women screened, 129 provided consent and were randomized from May 2016 to October 2017. Baseline characteristics were balanced between groups. Outpatient cervical ripening did not significantly shorten the time from labor ward admission until delivery (12.4±7.4 vs 13.5±7.0 hours, P=.38).Outpatient cervical ripening in parous women does not shorten the time from labor ward admission until delivery if oxytocin is initiated simultaneously with inpatient transcervical catheter placement.ClinicalTrials.gov, NCT02756689.

Background The proximal tibia is geometrically complex, asymmetrical, and variable, is heavily implicated in arthrokinematics of the knee joint, and thus a contributor to knee pathologies such as non-contact anterior cruciate ligament injury. Medial, lateral, and coronal tibial slopes are anatomic parameters that may increase predisposition to knee injuries, but the extent to which each contributes has yet to be fully realized. Previously, two-dimensional methods have quantified tibial slopes, but more reliable 3D methods may prove advantageous. Aims (1) to explore the reliability of two-dimensional methods, (2) to introduce a novel three-dimensional measurement approach, and (3) to compare data derived from traditional and novel methods. Methods Medial, lateral, and coronal tibial slope geometry from both knees (left and right) of one subject were obtained via magnetic resonance images and measured by four trained observers from two-dimensional views. The process was repeated via three-dimensional approaches and data evaluated for intra- and inter-rater reliability. Results The conventional method presented a weaker Intraclass Correlation Coefficient (ICC) for the measured slopes (ranging from 0.43 to 0.81) while the resultant ICC for the proposed method indicated greater reliability (ranging from 0.84 to 0.97). Statistical analysis supported the novel approach for production of more reliable and repeatable results for tibial slopes. Conclusions The novel three-dimensional method for calculating tibial plateau slope may be more reliable than previously established methods and may be applicable in assessment of susceptibility to osteoarthritis, as part of anterior cruciate ligament injury risk assessment, and in total knee implant design.

Approximately 25% of women are colonized with group B streptococcus (GBS). We assessed whether body mass index (BMI) is an independent risk factor for GBS colonization.We performed a retrospective cohort study using a previously collected database of women who delivered singleton gestations at term. Individual patient medical record review was undertaken to add GBS-related information to the database. Univariable logistic regression was used to assess the relationship between GBS colonization and BMI. Multivariable logistic regression was used to adjust for confounders.A total of 2045 patients met enrollment criteria. The prevalence of GBS colonization was 29%. In the unadjusted analysis, there was a statistically significant increase in GBS colonization per unit increase in BMI (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.04). This relationship remained significant after adjusting for confounders (race, marital status, payer, chronic hypertension, concomitant genital infections) (OR 1.01, 95% CI 1.00-1.03; p = 0.04). By BMI category, there were no differences in antibiotic susceptibilities or mode of ascertainment of GBS colonization.Obesity is an independent risk factor for GBS colonization; however, this association is weak.

Group B Streptococcus (GBS) infection remains a significant cause of neonatal morbidity and mortality. Adoption of screening for maternal genital tract colonization and intrapartum antibiotic prophylaxis has significantly reduced early-onset neonatal GBS infections. For women with an allergy to penicillin, recommended agents for prophylaxis have been well-outlined, but compliance with guideline recommendations is poor. There have been ongoing efforts in vaccine development, but no vaccination currently is available for either preconception or antenatal administration. This article will review established screening techniques, intrapartum antibiotic prophylactic regimens, and management specifically of the penicillin-allergic pregnant woman who is colonized with GBS.

Context Anxiety symptoms and disorders are highly prevalent and costly. Prospective studies suggest that physical activity may prevent anxiety development; however, this body of literature has not been reviewed comprehensively. Evidence acquisition Studies measuring physical activity at baseline and anxiety at a designated follow-up at least 1 year later were located using MEDLINE, PsycINFO, and CINAHL Complete through June 2018. Evidence synthesis Data were analyzed July–December 2018. Study quality was assessed using Q-Coh. Among studies of adults, a random-effects meta-analysis was conducted for crude and the most fully adjusted models for three outcomes: self-reported anxiety symptoms, a diagnosis of any anxiety disorder, and a diagnosis of generalized anxiety disorder. As there were few studies with diverse samples and outcome measures, findings were elaborated with a critical narrative review of all studies. Twenty-four studies (median follow-up, 4.75 years) of >80,000 unique individuals were included in the systematic review; thirteen were included in the meta-analyses. Six studies were assessed as low quality, nine as acceptable, and nine as good. From adjusted models, odds of elevated anxiety symptoms (OR=0.8742, 95% CI=0.7731, 0.9886, n=9), any anxiety disorder (OR=0.6626, 95% CI=0.5337, 0.8227, n=3), and generalized anxiety disorder specifically (OR=0.5438, 95% CI=0.3231, 0.9153, n=3) were significantly lower after physical activity exposure. Conclusions Available evidence suggests that engaging in physical activity protects against anxiety symptoms and disorders. However, notable challenges in the current evidence base include issues regarding exposure and outcome measures, consistent adjustment for putative confounders, representativeness of samples, and attrition bias, which warrant further research.

Background Excessive hindfoot pronation, talotarsal joint (TTJ) instability, has been attributed to an increase in medial knee compartment pathology. Advocacy for hindfoot realignment has been the subject of research. An internal solution for TTJ instability, extra-osseous talotarsal stabilization (EOTTS), exists but its effect on knee forces is unknown. This is the first study to measure the in vivo forces acting within the medial knee compartment before and after EOTTS. We hypothesized that following EOTTS there should be a reduction of force acting on the medial knee compartment. Methods 10 fresh frozen cadaver lower extremities exhibiting clinical and radiographic evidence of TTJ instability were evaluated. The proximal femur segment was mounted to a mechanical testing unit. Pressure sensors were placed within the medial knee compartment. A force of 1000 newtons was then applied, and the femur was internally rotated 10 degrees. Measurements were recorded before and after the insertion of a type II EOTTS stent. Results Pre-EOTTS resulted in an average of 842 ± 247N acting within the medial knee joint compartment. These forces then decreased to an average of 565 ± 260N (

Objective This study aims to assess class III obese women's preferences and concerns regarding cesarean delivery (CD) skin incisions. Study Design Through the National Perinatal Research Consortium (NPRC), women with body mass index ≥ 40 kg/m2 at the time of enrollment completed an anonymous survey in English or Spanish. We evaluated seven domains of preferences and concerns about the cesarean skin incision. Results We surveyed 546 women at five NPRC sites. Median age (interquartile range) was 29 (25, 35) years; 364 (66%) were parous and 161 (30%) had a prior CD. Women self-identified race/ethnicity as White (31%), non-Hispanic Black (31%), Hispanic (31%), other (6%), and not reported (1%). A total of 542 women (99%) rated both delivering the baby in the best possible condition and decreasing incision opening/infection risk as important. Women were less likely to rate other domains as important (all p Conclusion Women with class III obesity prioritize immediate maternal and fetal safety regarding CD skin incision over other concerns including cosmetic outcome.

OBJECTIVE: This study aims to evaluate differences in the midtrimester cervicovaginal microbiota between women who developed puerperal infections at term and those who did not, and whether obesity modulates this relationship. METHODS: Previously, cervicovaginal swabs were collected at 21 to 25 weeks gestation (stored at −80°C). Samples were identified from Black women with normal vaginal flora (Nugent score: 0–2) delivering term singletons. Patients were in one of four equally sized groups (total n = 120) characterized by absence or presence of puerperal infection and maternal obesity. Samples were thawed, DNA extracted, and polymerase chain reaction with primers targeting the 16S rDNA V4 region was used to prepare an amplicon library sequenced and analyzed using Quantitative Insights into Microbial Ecology (QIIME) suite. Microbiota differences were assessed using permutation-based anodis over three β-diversity measures; Kruskal-Wallis test was used for taxa level analysis. RESULTS: After quality control measures, 113 samples were analyzed. Overall, there was significant clustering by puerperal infection (p = 0.03), but not by obesity (p > 0.05). Detailed taxa level analysis revealed approximately 66% less Proteobacteria phylum and 400% more BVAB1 genera in the second-trimester microbiota of women who had puerperal infections at term (p < 0.05). CONCLUSION: Women who develop puerperal infections at term have a significantly altered midtrimester cervicovaginal microbiome with less Proteobacteria and greater BVAB1. This finding may represent a potential method to identify women at an increased risk of puerperal infection.

Objectives We identified classes of physical activity (PA) and sedentary behaviors (SB) in 5th grade children, associated factors, and trajectories of change into 7th grade. Methods This study included N = 495 children (221 boys, 274 girls) who participated in the Transitions and Activity Changes in Kids (TRACK) Study. PA was assessed objectively as well as by self-report. Children, parents, and school administrators completed surveys to assess related factors. Latent class analysis, growth modeling, and adjusted multinomial logistic regression procedures were used to classify children based on self-reported PA and SB and examine associated factors. Results Three classes of behavior were identified: Class 1: Low PA/Low SB; Class 2: Moderate PA/ High SB; and Class 3: High PA/High SB (boys) or Class 3: High PA (girls). Class 3 children had higher levels of self-efficacy (boys), and enjoyment, parental support, and physical activity equipment at home (girls). Class 2 boys and Class 3 girls did not experience decline in PA (accelerometer) over time. Conclusions Self-efficacy (boys) and home environment (girls) may play a role in shaping patterns of PA in children. Findings may help to inform future interventions to encourage children to meet national PA guidelines.

Burns and subsequent contractures are common in developing nations. Contracture release is performed to treat such patients with functional limitations. The aim of this study is to evaluate post-operative functional and psychosocial outcomes following contracture release in a mission setting.During a surgical mission in Mumbai, India, 39 patients burn contractures underwent surgical release. A total of 31 patients (64% female, mean age 27 years) chose to participate in the study. Patients were scored preoperatively and postoperatively using a SF-36 validated survey and AMA impairment guideline assessment.Thirty-one patients completed questionnaires pre-operative and 6-weeks post operatively. Twenty-four patients completed a survey 3-months post operatively (77.4%). Among those enrolled, 67% were women with the majority sustaining20% total body surface area burns (70.7%) but had multiple contractures (80.6%). SF-36 physical component score increased from a mean score of 49.8 preoperatively to 55.6 by 3 months following contracture release (P0.001). The SF-36 mental component score similarly increased from 38.8 to 51.1 by 3 months (P0.001). AMA Whole Person Impairment (WPI) scores improved from 40.3% impairment pre-operative to 26.6% at 6-weeks post-operative (P0.001).Patients SF-36 and WPI scores improved following burn contracture release, confirming both functional and psychologic improvement following surgery. During the acute post-operative period, this study suggests that contracture release in a mission setting is of benefit to patients.

Background:A positive association between physical activity and mental health is well established, particularly for lower symptoms of depression and anxiety among active adults. However, it is unclear whether the association is influenced by personality, which might moderate or otherwise explain the association. In addition, past studies have not confirmed the association using an objective measure of physical activity.Objective:Our objective was to examine whether Extraversion and Neuroticism influence the association between mental health and physical activity measured by convergent self-reports and an accelerometer.Methods:Structural equation modeling was used to test competing models of the relationships between personality, physical activity, and mental health in a sample of female undergraduates.Results:In bivariate analysis, mental health was negatively related to Neuroticism and positively related to Extraversion, self-reported physical activity (which was related only to Extraversion, positively), and objective physical activity (which was related only to Neuroticism, negatively). In structural equation modeling, a 3-way interaction indicated that objective physical activity and mental health were unrelated in extraverts, but related positively in neurotic-introverts and negatively in stable-introverts.Conclusions:Higher levels of physical activity were associated with better mental health only in neurotic-introverts, who are at higher risk for mental health problems.

We sought to compare the skin microbiota above and below the panniculus of third-trimester pregnant women with class III obesity.We collected swabs from the anterior panniculus and from the intertriginous area under the panniculus of women with class III obesity (body mass index ≥40 kg/m(2)) carrying a live singleton at ≥28 weeks. DNA was extracted. PCR with primers targeting the 16S rDNA V4 region were used to prepare an amplicon library. PCR products were sequenced (Illumina MiSeq platform). The 16S rDNA sequences were processed, integrated, analyzed and reported using QIIME and in-house developed scripts. Taxonomy was assigned using RDP Classifier (threshold 0.8) against the Greengenes 16S rDNA database.Twenty women were enrolled. One sample pair was excluded for low sequence depth. Using permutation testing, there was significantly less bacterial diversity in the samples above compared to below the panniculus (beta diversity using weighted UniFrac metrics; p 0.001).In pregnant women with class III obesity, the skin microbiota in the subpannicular fold differs from and is more diverse than that on the anterior panniculus.

Resistance training (RT) has been investigated as a potential intervention strategy for improving muscle function, but the effects on lower-extremity muscle power in middle-aged and older adults have not been systematically reviewed. The aim of this meta-analysis is to provide a quantitative estimate of the effect of RT on lower-extremity muscle power in middle-aged and older adults and to examine independent moderators of this relationship. Randomized controlled trials that examined the effects of RT on either leg press (LP) or knee extension (KE) muscle power in adults aged ≥50 years were included. Data were aggregated with meta-analytic techniques, and multi-level modeling was used to adjust for nesting effects. A total of 52 effects from 12 randomized controlled trials were analyzed with a random-effects model to estimate the effect of RT on lower-extremity muscle power. A multiple-regression analysis was conducted to examine independent moderators of the mean effect. The adjusted aggregated results from all studies indicate that RT has a small-to-moderate effect on lower-extremity muscle power (Hedges’ d = 0.34, 95 % confidence interval [CI] 0.25–0.43), which translated to 54.90 watts (95 % CI 40.37–69.43). Meta-regression analyses indicated that high-velocity RT was superior to traditional RT (Δ = 0.62 vs. 0.20, respectively) for increasing lower-extremity muscle power. In addition, training volume significantly moderated the effect of RT on muscle power. The findings from this meta-analysis indicate that RT is an efficacious intervention strategy for improving LP and KE muscle power in adults aged ≥50 years. Training mode and volume independently moderate the effect of RT on lower-extremity muscle power, and should be considered when prescribing RT exercise for middle-aged and older adults.

The aim of this study was to examine whether people differed in change in performance across the first five blocks of an online flanker task and whether those trajectories of change were associated with self-reported aerobic or resistance exercise frequency according to age. A total of 8752 men and women aged 13–89 completed a lifestyle survey and five 45-s games (each game was a block of ~46 trials) of an online flanker task. Accuracy of the congruent and incongruent flanker stimuli was analyzed using latent class and growth curve modeling adjusting for time between blocks, whether the blocks occurred on the same or different days, education, smoking, sleep, caffeinated coffee and tea use, and Lumosity training status (“free play” or part of a “daily brain workout”). Aerobic and resistance exercise were unrelated to first block accuracies. For the more cognitively demanding incongruent flanker stimuli, aerobic activity was positively related to the linear increase in accuracy [B=0.577%, 95% confidence interval (CI), 0.112 to 1.25 per day above the weekly mean of 2.8 days] and inversely related to the quadratic deceleration of accuracy gains (B=−0.619% CI, −1.117 to −0.121 per day). An interaction of aerobic activity with age indicated that active participants younger than age 45 had a larger linear increase and a smaller quadratic deceleration compared to other participants. Age moderates the association between self-reported aerobic, but not self-reported resistance, exercise and changes in cognitive control that occur with practice during incongruent presentations across five blocks of a 45-s online, flanker task. (JINS, 2015, 21, 802–815)

Viral infections complicated by a bacterial infection are typically referred to as coinfections or superinfections. Streptococcus pyogenes, the group A streptococcus (GAS), is not the most common bacteria associated with influenza A virus (IAV) superinfections but did cause significant mortality during the 2009 influenza pandemic even though all isolates are susceptible to penicillin. One approach to improve the outcome of these infections is to use passive immunization targeting GAS. To test this idea, we assessed the efficacy of passive immunotherapy using antisera against either the streptococcal M protein or streptolysin O (SLO) in a murine model of IAV-GAS superinfection. Prophylactic treatment of mice with antiserum to either SLO or the M protein decreased morbidity compared to mice treated with non-immune sera; however, neither significantly decreased mortality. Therapeutic use of antisera to SLO decreased morbidity compared to mice treated with non-immune sera but neither antisera significantly reduced mortality. Overall, the results suggest that further development of antibodies targeting the M protein or SLO may be a useful adjunct in the treatment of invasive GAS diseases, including IAV-GAS superinfections, which may be particularly important during influenza pandemics.

Maintaining body temperature is a unique challenge with burn care. We sought to describe core temperature goals in the operating room (OR) and the methods used to achieve and maintain these goals, along with current methods of warming in the intensive care unit (ICU), the perception of effect of increased ambient temperature on work performance, and concerns with contamination of sterile fields due to increased ambient temperature. A 24 question survey was disseminated to burn centers in the United States and Canada. The questions included demographics, target core and ambient temperatures, warming methods, and beliefs on ambient temperature's effects. Of 121 burn centers, 52 questionnaires were completed (43% response rate). The majority of centers targeted a core temperature between 36 and 38°C in the OR and an ambient temperature between 75 and 95°F in the ICU. The most common methods for maintaining core temperature included warmed ambient temperature, forced air devices, and intravenous fluids. Although the majority of centers reported the belief that increased ambient temperature benefits patients, many also reported that there is a negative impact on staff performance and risk of staff perspiration contaminating sterile fields. Burn centers reported a range of target core temperatures and methods to reach target temperatures. More than a third of respondents perceived a negative impact work performance while more than half acknowledged the potential for contamination of sterile fields. A prospective observational study is needed to determine actual temperature regulation practice patterns and its impact on outcomes.

BACKGROUND: Generalized anxiety disorder (GAD) is prevalent and costly. Physical activity (PA) may protect against other mental health disorders, including depression, but its protective effect on GAD remains under-studied in the general population and unstudied among older adults. Therefore, the present study examines associations between meeting World Health Organization PA guidelines (i.e. ≥150 min of moderate PA, ≥75 min of vigorous PA or ≥600MET min of moderate and vigorous PA weekly) and the prevalence of probable GAD and incidence of GAD. METHODS: Participants (n = 3950; 56.2% female) aged ≥50 years completed the short-form International Physical Activity Questionnaire and the abbreviated Penn State Worry Questionnaire at baseline and the Composite International Diagnostic Interview - Short Form to clinically assess GAD 2 years later. Prospective analyses included participants without probable GAD at baseline (n = 3236). RESULTS: Prevalence and incidence of GAD were 18.1% (n = 714) and 0.9% (n = 29), respectively. More respondents with GAD were female (72.2% vs 52.7%), aged 50-59 years (51.7% vs 38.7%), had normal waist circumference (52.7% vs 47.8) and smoked (20.4% vs 13.3%; all P

Streptococcus pneumoniae is a major cause of pneumonia wherein infection of respiratory mucosa drives a robust influx of neutrophils. We have previously shown that S. pneumoniae infection of the respiratory epithelium induces the production of the 12-lipoxygenase- (12-LOX-) dependent lipid inflammatory mediator hepoxilin A3 (HXA(3)), which promotes recruitment of neutrophils into the airways, tissue damage and lethal septicemia. Pneumolysin (PLY), a member of the cholesterol-dependent cytolysin (CDC) family, is a major S. pneumoniae virulence factor that generates ~25 nm diameter pores in eukaryotic membranes and promotes acute inflammation, tissue damage, and bacteremia. We show that a PLY-deficient S. pneumoniae mutant was impaired in triggering human neutrophil transepithelial migration in vitro. Ectopic production of PLY endowed the nonpathogenic Bacillus subtilis with the ability to trigger neutrophil recruitment across human cultured monolayers. Purified PLY, several other CDC family members, and the α-toxin of Clostridium septicum, which generates pores with cross-sectional areas nearly 300-times smaller than CDCs, reproduced this robust neutrophil transmigration. PLY non-pore forming point mutants that are trapped at various stages of pore assembly did not recruit neutrophils. PLY triggered neutrophil recruitment in a 12-LOX-dependent manner in vitro. Instillation of wild type PLY, but not inactive derivatives, into the lungs of mice induced robust 12-LOX-dependent neutrophil migration into the airways, although residual inflammation induced by PLY in 12-LOX deficient mice indicates that 12-LOX-independent pathways also contribute to PLY-triggered pulmonary inflammation. These data indicate that PLY is an important factor in promoting HXA(3)-dependent neutrophil recruitment across pulmonary epithelium in a pore-dependent fashion.

Objectives: To evaluate the sensitivity of prenatal ultrasound (US) for trisomy (T18) diagnosis and describe US findings in a large tertiary care institution in the USA. Materials and methods: This was a retrospective cohort of all T18 cases diagnosed at our institution from October 2004 to October 2014 based on prenatal or postnatal genetic diagnostic testing. We included all women with a fetus affected by T18 who had a comprehensive US by a maternal–fetal medicine specialist performed at our institution. US findings were reviewed, classified by organ system, and categorized as an anomaly or soft marker. Chi-square or t-test was used for statistical analysis. Results: We included 128 cases of T18 with confirmed cytogenetic analysis −110 (86%) of which were diagnosed prenatally or suspected by cell-free DNA and confirmed postnatally, and 18 of which underwent neonatal blood sampling alone. One hundred and twenty-one (95%) had at least one abnormal US finding. Anomalies were more frequently identified on US at ≥20 weeks as compared with p = .004). The mean number of findings detected per fetus was 5.1 ± 3.0. Fetuses diagnosed by postnatal sampling alone had a similar number of US exams performed and number of abnormal findings compared to those diagnosed prenatally. Conclusion: Ninety-five percent of fetuses with T18 had at least one abnormal US finding. This sensitivity of is higher than reported in most prior studies, but is not 100%, and should be considered when counseling women regarding prenatal diagnosis of T18. Rationale: Historical detection rates for abnormal sonographic findings in trisomy 18 fetuses range from 70% to 100%. These studies are limited by small sample sizes. This is a contemporary study of ultrasound findings in a large group of women with confirmed trisomy 18 by prenatal or postnatal genetic diagnosis. We provide expansive detail on soft markers and anomalies broken down by organ-system and gestational age.

Adipose-derived stem cells are capable of self-renewal and differentiation along multiple cell lineages, and have potential applications in a wide range of therapies. ASCs are commonly cultured as monolayers on tissue culture plastic, but there are indications that they may lose their cell-specific properties with time in vitro. There has been a growing interest in culturing adherent cells using three-dimensional techniques based on the understanding that growing cells on plastic surfaces cannot truly recapitulate 3D in vivo conditions. Here we describe a novel method for generating and culturing rabbit ASCs as scaffold-free 3D cell aggregates using micropatterned wells via a forced aggregation technique.

Hypotension that occurs after a single bout of aerobic exercise also attenuates the vascular response to discrete stressors, an effect that can last for hours. It is unknown whether the hypotensive benefits of traditional exercise extend to alternative forms of mindful exercise, such as yoga, to confer transient protection against neurovascular challenges that increase blood pressure (BP).The study intended to examine the effects of acute exercise on neurovascular responses to exposure of the forehead of female yoga practitioners to vasoconstrictive cold (ie, to cold pressor stress).The research team designed a study with 3 conditions (ie, with participants' participation in 3 activities on separate days in a repeated-measures design). Participants were randomly assigned to perform the activities in 1 of 3 orders across successive visits.Participants were 9 females, 20 to 33 y old, who had regularly practiced Hatha yoga from 6 mo to 12 y before the start of the study. All participants were normotensive at entry to the study and had normal body weights for their heights.All participants performed 3 activities: (1) self-directed yoga practice, the intervention; (2) cycling exercise at a self-selected intensity, a positive control; and (3) quiet rest, a negative control.Postintervention, participants' foreheads were exposed to cold. Their systolic blood pressures (SBPs), diastolic blood pressures (DBPs), pulse rates, and forearm oxygenation were assessed using near-infrared spectroscopy.Participants' SBPs and DBPs increased during cold pressor stress under all conditions, concurrent with decreased forearm oxygenation. During recovery from the cold, participants' BPs declined to near precold pressor baseline levels after yoga and cycling but remained elevated after quiet rest.The enhanced recovery of BP from cold applied to the forehead after yoga practice or cycling exercise suggests that both types of exercise promote a hypotensive response, which could indicate lowered cardiovascular risk.

Burn injuries are a pervasive clinical problem. Extensive thermal trauma can be life-threatening or result in long-lasting complications, generating a significant impact on quality of life for patients as well as a cost burden to the healthcare system. The importance of addressing global or systemic issues such as resuscitation and management of inhalation injuries is not disputed but is beyond the scope of this review, which focuses on cutaneous pathophysiologic mechanisms for current treatments, both in the acute and long-term settings. Pathophysiological mechanisms of burn progression and wound healing are mediated by highly complex cascades of cellular and biochemical events, which become dysregulated in slow-healing wounds such as burns. Burns can result in fibroproliferative scarring, skin contractures, or chronic wounds that take weeks or months to heal. Burn injuries are highly individualized owing to wound-specific differences such as burn depth and surface area, in addition to patient-specific factors including genetics, immune competency, and age. Other extrinsic complications such as microbial infection can complicate wound healing, resulting in prolonged inflammation and delayed re-epithelialization. Although mortality is decreasing with advancements in burn care, morbidity from postburn deformities continues to be a challenge. Optimizing specialized acute care and late burn outcome intervention on a patient-by-patient basis is critical for successful management of burn wounds and the associated pathological scar outcome. Understanding the fundamentals of integument physiology and the cellular processes involved in wound healing is essential for designing effective treatment strategies for burn wound care as well as development of future therapies. Published 2018. Compr Physiol 8:371-405, 2018.

MicroRNAs (miRNAs) have emerged as critical regulators of cellular metabolism. To characterise miRNAs crucial to the maintenance of hepatic lipid homeostasis, we examined the overlap between the miRNA signature associated with inhibition of peroxisome proliferator activated receptor-α (PPAR-α) signaling, a pathway regulating fatty acid metabolism, and the miRNA profile associated with 25-hydroxycholesterol treatment, an oxysterol regulator of sterol regulatory element binding protein (SREBP) and liver X receptor (LXR) signaling. Using this strategy, we identified microRNA-7 (miR-7) as a PPAR-α regulated miRNA, which activates SREBP signaling and promotes hepatocellular lipid accumulation. This is mediated, in part, by suppression of the negative regulator of SREBP signaling: ERLIN2. miR-7 also regulates genes associated with PPAR signaling and sterol metabolism, including liver X receptor β (LXR-β), a transcriptional regulator of sterol synthesis, efflux, and excretion. Collectively, our findings highlight miR-7 as a novel mediator of cross-talk between PPAR, SREBP, and LXR signaling pathways in the liver.