Distinct Escherichia coli transcriptional profiles in the guts of recurrent UTI sufferers revealed by pangenome hybrid selection.

Low-abundance members of microbial communities are difficult to study in their native habitats. This includes Escherichia coli, a minor, but common inhabitant of the gastrointestinal tract and opportunistic pathogen, including of the urinary tract, where it is the primary pathogen. While multi-omic analyses have detailed critical interactions between uropathogenic Escherichia coli (UPEC) and the bladder that mediate UTI outcome, comparatively little is known about UPEC in its pre-infection reservoir, partly due to its low abundance there (<1% relative abundance). To accurately and sensitively explore the genomes and transcriptomes of diverse E. coli in gastrointestinal communities, we developed E. coli PanSelect which uses a set of probes designed to specifically recognize and capture E. coli's broad pangenome from sequencing libraries. We demonstrated the ability of E. coli PanSelect to enrich, by orders of magnitude, sequencing data from diverse E. coli using a mock community and a set of human stool samples collected as part of a cohort study investigating drivers of recurrent urinary tract infections (rUTI). Comparisons of genomes and transcriptomes between E. coli residing in the gastrointestinal tracts of women with and without a history of rUTI suggest that rUTI gut E. coli are responding to increased levels of oxygen and nitrate, suggestive of mucosal inflammation, which may have implications for recurrent disease. E. coli PanSelect is well suited for investigations of native in vivo biology of E. coli in other environments where it is at low relative abundance, and the framework described here has broad applicability to other highly diverse, low abundance organisms.

Early Life Stress Is Associated with Alterations in Lymphocyte Subsets Independent of Increased Inflammation in Adolescents.

Early life stress (ELS) is linked to an elevated risk of poor health and early mortality, with emerging evidence pointing to the pivotal role of the immune system in long-term health outcomes. While recent research has focused on the impact of ELS on inflammation, this study examined the impact of ELS on immune function, including CMV seropositivity, inflammatory cytokines, and lymphocyte cell subsets in an adolescent cohort. This study used data from the Early Life Stress and Cardiometabolic Health in Adolescence Study (N = 191, aged 12 to 21 years, N = 95 exposed to ELS). We employed multiple regression to investigate the association between ELS, characterized by early institutional care, cytomegalovirus (CMV) seropositivity (determined by chemiluminescent immunoassay), inflammation (CRP, IL-6, and TNF-a determined by ELISA), and twenty-one immune cell subsets characterized by flow cytometry (sixteen T cell subsets and five B cell subsets). Results reveal a significant association between ELS and lymphocytes that was independent of the association between ELS and inflammation: ELS was associated with increased effector memory helper T cells, effector memory cytotoxic T cells, senescent T cells, senescent B cells, and IgD- memory B cells compared to non-adopted youth. ELS was also associated with reduced percentages of helper T cells and naive cytotoxic T cells. Exploratory analyses found that the association between ELS and fewer helper T cells and increased cytotoxic T cells remained even in cytomegalovirus (CMV) seronegative youth. These findings suggest that ELS is associated with cell subsets that are linked to early mortality risk in older populations and markers of replicative senescence, separate from inflammation, in adolescents.

Evaluation of a novel eating disorder prevention program for young women with type 1 diabetes: A preliminary randomized trial.

OBJECTIVE: Evaluate whether the Body Project prevention program adapted for young women with type 1 diabetes (Diabetes Body Project) reduces eating disorder (ED) risk factors and symptoms. METHODS: Young women (aged 15-30) at high-risk for EDs due to having type 1 diabetes and body image concerns (N = 55) were randomized to virtually delivered Diabetes Body Project groups or an educational control condition, completing measures at pretest, posttest, and 3-month follow-up. RESULTS: Diabetes Body Project versus the control participants showed significantly greater reductions in thin-ideal internalization, body dissatisfaction, diabetes distress, diabetes eating pathology, and ED symptoms by posttest, and greater reductions in diabetes eating pathology and ED symptoms, and greater improvements in quality of life by 3-month follow-up, which were medium to large effects (d's ranged from -0.43 to -0.90). Although control participants showed a worsening of glycemic control (time in range) verses Diabetes Body Project participants, this difference was non-significant (d = 0.26). CONCLUSIONS: Virtually delivered Diabetes Body Project decreased ED risk factors and symptoms in young women with type 1 diabetes. A well powered randomized controlled trial is warranted to evaluate this intervention over longer follow-up.

Sequencing of symptom emergence in anorexia nervosa, bulimia nervosa, binge eating disorder, and purging disorder in adolescent girls and relations of prodromal symptoms to future onset of these eating disorders.

BACKGROUND: To advance knowledge regarding the etiology of eating disorders, we characterized the sequencing of eating disorder symptom emergence for adolescent girls who subsequently developed anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and purging disorder (PD) for community-recruited adolescents and tested whether prodromal symptoms increased risk for future onset of each eating disorder. METHODS: Data collected from adolescent girls (N = 496; M age = 13.02, s.d.= 0.73) who completed a diagnostic interview annually over an 8-year period were used to address these aims. RESULTS: For all four eating disorders, compensatory weight-control behaviors were the first behavioral symptom to emerge and weight/shape overvaluation was the first cognitive symptom to emerge. Moreover, lower-than-expected BMI predicted future AN onset, binge eating and all cognitive symptoms predicted future BN onset, weight/shape overvaluation predicted future BED onset, and compensatory behavior and all cognitive symptoms predicted future PD onset. These predictive effects were small-to-large in magnitude. Collectively, prodromal symptoms predicted an eating disorder onset with 83-87% accuracy. CONCLUSIONS: Results suggest that compensatory weight-control behaviors and weight/shape overvaluation typically emerge before other prodromal symptoms in all eating disorders during adolescence. Moreover, different prodromal symptoms seem to predict future onset of different eating disorders. Screening adolescent girls for these prodromal symptoms and implementing indicated prevention programs designed to reduce these symptoms may prove effective in preventing future onset of eating disorders.

Enhancing Efficacy of a Brief Obesity and Eating Disorder Prevention Program: Long-Term Results from an Experimental Therapeutics Trial.

Objective: Test whether the efficacy of Project Health, an obesity/eating disorder prevention program, is improved by delivering it in single-sex groups and adding food response inhibition and attention training. Method: High-risk young adults (N = 261; M age = 19.3, 74% female) were randomized to (1) single-sex or (2) mixed-sex groups that completed food response inhibition and attention training or (3) single-sex or (4) mixed-sex groups that completed sham training with nonfood images in a 2 × 2 factorial design. Results: There was a significant sex-composition by training-type by time interaction; participants who completed single- or mixed-sex Project Health groups plus food response and attention training showed significant reductions in body fat over a 2-year follow-up, though this effect was more rapid and persistent in single-sex groups, whereas those who completed single- or mixed-sex Project Health groups plus sham training did not show body fat change. However, there were no differences in overweight/obesity onset over the follow-up. The manipulated factors did not affect eating disorder symptoms or eating disorder onset, but there was a significant reduction in symptoms across the conditions (within-condition d = -0.58), converging with prior evidence that Project Health produced larger reductions in symptoms (within-condition d = -0.48) than educational control participants. Average eating disorder onset over the 2-year follow-up (6.4%) was similar to that observed in Project Health in a past trial (4.5%). Conclusions: Given that Project Health significantly reduced future onset of overweight/obesity in a prior trial and the present trial found that body fat loss effects were significantly greater when implemented in single-sex groups and paired with food response and attention training, there might be value in broadly implementing this combined intervention.

Efficacy of virtual delivery of a dissonance-based eating disorder prevention program and evaluation of a donation model to support sustained implementation.

OBJECTIVE: Evaluate whether the Body Project prevention program reduces eating disorder risk factors and symptoms when implemented via synchronous video telepsychiatry, which could markedly increase the reach of this intervention and test whether a pay-it-forward donation model could support sustained implementation of this intervention. METHOD: Young women at high risk for eating disorders because of body image concerns (N = 75; age range 16-27) were randomized to Body Project groups delivered virtually by peer educators or a waitlist control condition; participants who completed the Body Project for free because of past donations were encouraged to donate money so that this intervention could be provided for free to others. RESULTS: Participants randomized to virtually delivered Body Project groups showed significantly or marginally greater pretest-to-posttest reductions in pursuit of the thin ideal, body dissatisfaction, dieting, negative affect, and eating disorder symptoms than controls. The average effect was large (d = .79), which was 49% larger than the average effect observed previously for in-person peer-educator-delivered Body Project groups (d = .53; [.76-.53 = .23/.53 = 49%]). However, only 3.6% of participants donated money to support future implementation of this intervention. CONCLUSIONS: The evidence that the Body Project produced large reductions in eating disorder risk factors and symptoms when implemented virtually and that the effects were larger than for in-person Body Project groups suggests it would be useful to implement this prevention program virtually, which could expand the reach of this intervention. Future studies should evaluate alternative methods for supporting sustained implementation of this prevention program. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Young women who develop anorexia nervosa exhibit a persistently low premorbid body weight on average: A longitudinal investigation of an important etiologic clue.

OBJECTIVE: test whether (1) young women who subsequently show onset of anorexia nervosa (AN) exhibit persistently lower average premorbid BMI than those who subsequently show onset of bulimia nervosa (BN), binge eating disorder (BED), purging disorder (PD), or no eating disorder; (2) a proximal spike in other risk factors occurs immediately before AN emergence; and (3) psychological and behavioral factors differentiate youth who show persistently low BMI from those who do not. METHOD: Data from a sample (N = 1952) of young women at high-risk for eating disorders followed for 3 years and a socioethno-racially representative sample (N = 496) of adolescent girls followed for 8 years were used to address these aims. RESULTS: Participants who developed AN exhibited significantly lower average measured premorbid BMI over repeated assessments than those who showed onset of other or no eating disorders. Dietary restraint, negative affect, and eating affect regulation expectancies significantly increased immediately before AN onset. Youth who showed persistently low BMI reported lower pressure for thinness, body dissatisfaction, and dieting at baseline, implying that elevations in these factors did not drive the low BMI. CONCLUSIONS: The evidence that young women who subsequently show AN onset exhibit a low premorbid BMI on average is novel and suggests that etiologic models should incorporate this finding and selective prevention programs should target low-BMI adolescent girls. The finding that dieting, negative affect, affect-regulation eating expectances spiked immediately before emergence of AN is also novel and suggests that it might be useful for selective prevention programs to target these factors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Longitudinal multi-omics analyses link gut microbiome dysbiosis with recurrent urinary tract infections in women.

Recurrent urinary tract infections (rUTIs) are a major health burden worldwide, with history of infection being a significant risk factor. While the gut is a known reservoir for uropathogenic bacteria, the role of the microbiota in rUTI remains unclear. We conducted a year-long study of women with (n = 15) and without (n = 16) history of rUTI, from whom we collected urine, blood and monthly faecal samples for metagenomic and transcriptomic interrogation. During the study 24 UTIs were reported, with additional samples collected during and after infection. The gut microbiome of individuals with a history of rUTI was significantly depleted in microbial richness and butyrate-producing bacteria compared with controls, reminiscent of other inflammatory conditions. However, Escherichia coli gut and bladder populations were comparable between cohorts in both relative abundance and phylogroup. Transcriptional analysis of peripheral blood mononuclear cells revealed expression profiles indicative of differential systemic immunity between cohorts. Altogether, these results suggest that rUTI susceptibility is in part mediated through the gut-bladder axis, comprising gut dysbiosis and differential immune response to bacterial bladder colonization, manifesting in symptoms.

Sequencing of symptom emergence in anorexia nervosa, bulimia nervosa, binge eating disorder, and purging disorder and relations of prodromal symptoms to future onset of these disorders.

The objective of this study was to characterize the temporal sequencing of symptom emergence for anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and purging disorder (PD), as well as to test whether prodromal symptoms increase risk for future onset of each type of eating disorder and compare the predictive effects to those of established risk factors. Data from four prevention trials that targeted high-risk young women with body image concerns (N = 1,952; Mage = 19.7, SD = 5.7) and collected annual diagnostic interview data over 3-year follow-up were combined to address these aims. Regarding behavioral symptoms, compensatory weight control behaviors typically emerged first for AN, BN, and PD, whereas binge eating typically emerged first for BED. Regarding cognitive symptoms, for AN, weight/shape overvaluation typically emerged first, whereas for BN, BED, and PD, overvaluation typically emerged simultaneously with feeling fat and fear of weight gain. Binge eating, compensatory behaviors, weight/shape overvaluation, fear of weight gain, and feeling fat predicted BN, BED, and PD onset, whereas weight/shape overvaluation, fear of weight gain, and lower than expected body mass index predicted AN onset. Predictive effects of prodromal symptoms were similar in magnitude to those of established risk factors: Collectively, prodromal symptoms and risk factors predicted onset of specific eating disorders with 67-83% accuracy. Results suggest that compensatory weight control behaviors and cognitive symptoms are likely to emerge before binge eating in the various eating disorders and that offering indicated prevention programs to youth with prodromal symptoms may be an effective way to prevent eating disorders. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Limited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections.

BACKGROUND: Urinary tract infections (UTIs) affect 15 million women each year in the United States, with > 20% experiencing frequent recurrent UTIs. A recent placebo-controlled clinical trial found a 39% reduction in UTI symptoms among recurrent UTI sufferers who consumed a daily cranberry beverage for 24 weeks. Using metagenomic sequencing of stool from a subset of these trial participants, we assessed the impact of cranberry consumption on the gut microbiota, a reservoir for UTI-causing pathogens such as Escherichia coli, which causes > 80% of UTIs. RESULTS: The overall taxonomic composition, community diversity, carriage of functional pathways and gene families, and relative abundances of the vast majority of observed bacterial taxa, including E. coli, were not changed significantly by cranberry consumption. However, one unnamed Flavonifractor species (OTU41), which represented ≤1% of the overall metagenome, was significantly less abundant in cranberry consumers compared to placebo at trial completion. Given Flavonifractor's association with negative human health effects, we sought to determine OTU41 characteristic genes that may explain its differential abundance and/or relationship to key host functions. Using comparative genomic and metagenomic techniques, we identified genes in OTU41 related to transport and metabolism of various compounds, including tryptophan and cobalamin, which have been shown to play roles in host-microbe interactions. CONCLUSION: While our results indicated that cranberry juice consumption had little impact on global measures of the microbiome, we found one unnamed Flavonifractor species differed significantly between study arms. This suggests further studies are needed to assess the role of cranberry consumption and Flavonifractor in health and wellbeing in the context of recurrent UTI. TRIAL REGISTRATION: Clinical trial registration number: ClinicalTrials.gov NCT01776021 .

SER-109, an Investigational Microbiome Drug to Reduce Recurrence After Clostridioides difficile Infection: Lessons Learned From a Phase 2 Trial.

BACKGROUND: Recurrent Clostridioides difficile infection (rCDI) is associated with loss of microbial diversity and microbe-derived secondary bile acids, which inhibit C. difficile germination and growth. SER-109, an investigational microbiome drug of donor-derived, purified spores, reduced recurrence in a dose-ranging, phase (P) 1 study in subjects with multiple rCDIs. METHODS: In a P2 double-blind trial, subjects with clinical resolution on standard-of-care antibiotics were stratified by age (< or ≥65 years) and randomized 2:1 to single-dose SER-109 or placebo. Subjects were diagnosed at study entry by PCR or toxin testing. Safety, C. difficile-positive diarrhea through week 8, SER-109 engraftment, and bile acid changes were assessed. RESULTS: 89 subjects enrolled (67% female; 80.9% diagnosed by PCR). rCDI rates were lower in the SER-109 arm than placebo (44.1% vs 53.3%) but did not meet statistical significance. In a preplanned analysis, rates were reduced among subjects ≥65 years (45.2% vs 80%, respectively; RR, 1.77; 95% CI, 1.11-2.81), while the <65 group showed no benefit. Early engraftment of SER-109 was associated with nonrecurrence (P < .05) and increased secondary bile acid concentrations (P < .0001). Whole-metagenomic sequencing from this study and the P1 study revealed previously unappreciated dose-dependent engraftment kinetics and confirmed an association between early engraftment and nonrecurrence. Engraftment kinetics suggest that P2 dosing was suboptimal. Adverse events were generally mild to moderate in severity. CONCLUSIONS: Early SER-109 engraftment was associated with reduced CDI recurrence and favorable safety was observed. A higher dose of SER-109 and requirements for toxin testing were implemented in the current P3 trial. CLINICAL TRIALS REGISTRATION: NCT02437487, https://clinicaltrials.gov/ct2/show/NCT02437487?term=SER-109&draw= 2&rank=4.

Phenoscreening: a developmental approach to research domain criteria-motivated sampling.

BACKGROUND: To advance early identification efforts, we must detect and characterize neurodevelopmental sequelae of risk among population-based samples early in development. However, variability across the typical-to-atypical continuum and heterogeneity within and across early emerging psychiatric/neurodevelopmental disorders represent fundamental challenges to overcome. Identifying multidimensionally determined profiles of risk, agnostic to DSM categories, via data-driven computational approaches represents an avenue to improve early identification of risk. METHODS: Factor mixture modeling (FMM) was used to identify subgroups and characterize phenotypic risk profiles, derived from multiple parent-report measures of typical and atypical behaviors common to autism spectrum disorder, in a community-based sample of 17- to 25-month-old toddlers (n = 1,570). To examine the utility of risk profile classification, a subsample of toddlers (n = 107) was assessed on a distal, independent outcome examining internalizing, externalizing, and dysregulation at approximately 30 months. RESULTS: FMM results identified five asymmetrically sized subgroups. The putative high- and moderate-risk groups comprised 6% of the sample. Follow-up analyses corroborated the utility of the risk profile classification; the high-, moderate-, and low-risk groups were differentially stratified (i.e., HR > moderate-risk > LR) on outcome measures and comparison of high- and low-risk groups revealed large effect sizes for internalizing (d = 0.83), externalizing (d = 1.39), and dysregulation (d = 1.19). CONCLUSIONS: This data-driven approach yielded five subgroups of toddlers, the utility of which was corroborated by later outcomes. Data-driven approaches, leveraging multiple developmentally appropriate dimensional RDoC constructs, hold promise for future efforts aimed toward early identification of at-risk-phenotypes for a variety of early emerging neurodevelopmental disorders.

Weight for length measures may not accurately reflect adiposity in preterm infants born appropriate for gestational age during hospitalisation or after discharge from the neonatal intensive care unit.

BACKGROUND: Weight/length (W/L) indices are poor surrogates for adiposity in preterm infants born appropriate for gestational age (AGA) at birth, but whether the association subsequently improves is unknown. OBJECTIVE: To determine if W/L indices accurately reflect adiposity in premature infants born AGA in later infancy. METHODS: Associations between W/L indices and fat mass, fat mass index and percent body fat (%BF) obtained via air displacement plethysmography (ADP) were examined in 260 preterm infants (majority born AGA) at 28 to 63 weeks' postmenstrual age (PMA). Accuracy of W/L indices as indicators of adiposity was assessed by proportion of variance explained (R2 ) and root mean square error from linear regression of adiposity on W/L indices and proportion of infants misclassified by W/L indices. Accuracy was further compared in term vs preterm infants at term-equivalent age. The impact of early vs late preterm status on associations between W/L indices and %BF was also examined. RESULTS: BMI and W/L were most strongly associated with %BF but yielded poorly fitting models (maximum R2 = 0.35; 53% misclassification). A significant interaction of W/L indices and early vs late preterm status on %BF revealed that estimation of %BF differs by status. Accuracy of W/L indices was worse in preterm infants at term-equivalent age. CONCLUSIONS: W/L indices were not good indicators of adiposity in preterm infants from 28 to 63 weeks' PMA (born AGA) with all categories of W/L indices combined. Future research should examine whether results are similar in preterm infants born with disproportionate W/L or who experience disproportionate growth postnatally.

The Child Life Challenges Scale (CLCS): Associations of a Single-Item Rating of Global Child Adversity with Children's Total Life Stressors and Parent's Childhood Adversity.

BACKGROUND: Although many existing measures tabulate specific risk factors to yield cumulative risk indices, there is a need for low-burden strategies to estimate general adversity exposure. AIMS AND METHODS: This study introduces a brief, new measure of lifetime adversity, the Child Life Challenges Scale (CLCS), and examines its validity in a sample of parents and children residing in emergency housing. The CLCS comprises a single global item for rating cumulative life challenges utilizing either a paper-pencil scale or a sliding scale on a tablet. Parents are provided with anchor examples of mild and extreme challenges and asked to mark a location along the scale reflecting number and severity of challenges in their children's lives to date. Study participants included 99 parents and their 3- to 6-year-old children. RESULTS: CLCS scores were moderately associated with children's parent-reported total life stressors, and these associations were robust to controls for parental history of adversity, parental distress, and family demographics. Control variables also did not moderate associations between CLCS scores and total life stressors, suggesting that the CLCS functions similarly across a range of sociodemographic risk. Paper-pencil and tablet versions showed similar convergent validity. CONCLUSION: The CLCS shows promise as an efficient measure for estimating children's lifetime adversity with minimal parent or administrator burden.

Sexual orientation correlates with baseline characteristics but shows no moderating effects of dissonance-based eating disorder prevention programs for women.

This study provided the first test of whether sexual orientation (categorized as heterosexual vs. sexual minority) is associated with baseline eating disorder risk factors and symptoms, moderated the intervention effects of variants of the dissonance-based Body Project, or moderated the relation of baseline risk factors to future change in eating disorder symptoms. A total of 680 women with body image concerns were randomized to clinician-or peer-led Body Project groups, the eBody Project, or educational video control and completed assessment of eating disorder risk factors and symptoms at pretest, posttest, and at six-, 12-, 24-, and 36-month follow-up. Results indicated that sexual minority women had significantly higher negative affect and impaired psychosocial functioning at baseline, but did not differ on other eating disorder risk factors or symptoms. We found no evidence that sexual orientation moderates the effects of the Body Project on risk factor or symptom change over follow-up or the relation of baseline risk factors to future change in eating disorder symptoms. Overall, sexual minority and heterosexual women differ on two, less specific eating disorder-related risk factors at baseline, but did not differ in response to different versions of the Body Project or the relations of risk factors to future symptom change.

Landscape of gene expression variation of natural isolates of Cryptococcus neoformans in response to biologically relevant stresses.

Cryptococcus neoformans is an opportunistic fungal pathogen that at its peak epidemic levels caused an estimated million cases of cryptococcal meningitis per year worldwide. This species can grow in diverse environmental (trees, soil and bird excreta) and host niches (intracellular microenvironments of phagocytes and free-living in host tissues). The genetic basic for adaptation to these different conditions is not well characterized, as most experimental work has relied on a single reference strain of C. neoformans. To identify genes important for yeast infection and disease progression, we profiled the gene expression of seven C. neoformans isolates grown in five representative in vitro environmental and in vivo conditions. We characterized gene expression differences using RNA-Seq (RNA sequencing), comparing clinical and environmental isolates from two of the major lineages of this species, VNI and VNBI. These comparisons highlighted genes showing lineage-specific expression that are enriched in subtelomeric regions and in lineage-specific gene clusters. By contrast, we find few expression differences between clinical and environmental isolates from the same lineage. Gene expression specific to in vivo stages reflects available nutrients and stresses, with an increase in fungal metabolism within macrophages, and an induction of ribosomal and heat-shock gene expression within the subarachnoid space. This study provides the widest view to date of the transcriptome variation of C. neoformans across natural isolates, and provides insights into genes important for in vitro and in vivo growth stages.

Deciphering drug resistance in Mycobacterium tuberculosis using whole-genome sequencing: progress, promise, and challenges.

Tuberculosis (TB) is a global infectious threat that is intensified by an increasing incidence of highly drug-resistant disease. Whole-genome sequencing (WGS) studies of Mycobacterium tuberculosis, the causative agent of TB, have greatly increased our understanding of this pathogen. Since the first M. tuberculosis genome was published in 1998, WGS has provided a more complete account of the genomic features that cause resistance in populations of M. tuberculosis, has helped to fill gaps in our knowledge of how both classical and new antitubercular drugs work, and has identified specific mutations that allow M. tuberculosis to escape the effects of these drugs. WGS studies have also revealed how resistance evolves both within an individual patient and within patient populations, including the important roles of de novo acquisition of resistance and clonal spread. These findings have informed decisions about which drug-resistance mutations should be included on extended diagnostic panels. From its origins as a basic science technique, WGS of M. tuberculosis is becoming part of the modern clinical microbiology laboratory, promising rapid and improved detection of drug resistance, and detailed and real-time epidemiology of TB outbreaks. We review the successes and highlight the challenges that remain in applying WGS to improve the control of drug-resistant TB through monitoring its evolution and spread, and to inform more rapid and effective diagnostic and therapeutic strategies.

Extensive global movement of multidrug-resistantM. tuberculosis strains revealed by whole-genome analysis.

BACKGROUND: While the international spread of multidrug-resistant (MDR) Mycobacterium tuberculosis strains is an acknowledged public health threat, a broad and more comprehensive examination of the global spread of MDR-tuberculosis (TB) using whole-genome sequencing has not yet been performed. METHODS: In a global dataset of 5310 M. tuberculosis whole-genome sequences isolated from five continents, we performed a phylogenetic analysis to identify and characterise clades of MDR-TB with respect to geographic dispersion. RESULTS: Extensive international dissemination of MDR-TB was observed, with identification of 32 migrant MDR-TB clades with descendants isolated in 17 unique countries. Relatively recent movement of strains from both Beijing and non-Beijing lineages indicated successful global spread of varied genetic backgrounds. Migrant MDR-TB clade members shared relatively recent common ancestry, with a median estimate of divergence of 13-27 years. Migrant extensively drug-resistant (XDR)-TB clades were not observed, although development of XDR-TB within migratory MDR-TB clades was common. CONCLUSIONS: Application of genomic techniques to investigate global MDR migration patterns revealed extensive global spread of MDR clades between countries of varying TB burden. Further expansion of genomic studies to incorporate isolates from diverse global settings into a single analysis, as well as data sharing platforms that facilitate genomic data sharing across country lines, may allow for future epidemiological analyses to monitor for international transmission of MDR-TB. In addition, efforts to perform routine whole-genome sequencing on all newly identified M. tuberculosis, like in England, will serve to better our understanding of the transmission dynamics of MDR-TB globally.

Moderators of two dual eating disorder and obesity prevention programs.

Few trials have investigated factors that moderate the effects of eating disorder and obesity prevention programs, which may inform inclusion criteria and intervention refinements. We examined factors hypothesized to moderate the effects of the Healthy Weight eating disorder/obesity prevention program that promotes gradual healthy changes, and Project Health that adds cognitive dissonance activities. College students at risk for both outcomes because of weight concerns (N = 364, 72% female) were randomized to these interventions or an educational video condition, completing pretest, posttest, and 6, 12, and 24-month follow-up assessments. Healthy Weight and Project Health produced significantly larger reductions in eating disorder symptoms versus video controls for individuals with higher negative affect, emotional eating, dietary fat/sugar intake, and perceived pressure to be thin. Project Health also produced significantly less increases in BMI versus video controls for individuals with lower negative affect. Results suggest that these interventions produce larger eating disorder symptom reductions for individuals at elevated risk for eating pathology but hint that weight gain prevention effects may be attenuated by elevated negative affect. Results imply that larger eating disorder symptom reductions will result when implemented with individuals with both weight concerns and one of the additionally identified risk factors.

Emotion regulation and cortisol reactivity during a social evaluative stressor: A study of post-institutionalized youth.

In the current study, we compared emotion regulation abilities between post-institutionalized (PI; N = 124) and never-institutionalized non-adopted (NA; N = 172) children and adolescents (7-15 years). We assessed cortisol reactivity and coded emotion regulation during the speech portion of Trier Social Stress Test (TSST-M). Parents reported on their children's social, academic, and behavioral adjustment. Results suggest that emotion regulation abilities increased with age, but this increase was greater for NA than PI youth. With regard to cortisol, piecewise growth modeling revealed that at higher levels of emotion regulation PI youth had greater baseline values (after a period of time allowing for acclimation to the laboratory) and had steeper recovery slopes than NA youth. There was also a main effect of emotion regulation on the reactivity slope suggesting that for both groups, as emotion regulation increased, the cortisol reactivity slope decreased. Finally, greater emotion regulation predicted fewer internalizing behavior problems for PI youth but not for NA youth.