The Relationship Between Trauma Exposure and Obsessive-Compulsive Disorder in Youth: A Systematic Review.

Extant literature suggests a possible relationship between childhood trauma exposure and the development and trajectory of obsessive-compulsive symptoms (OCS) and obsessive-compulsive disorder (OCD); however, this relationship is poorly understood. We conducted a systematic review that examined trauma exposure and OCS/OCD in youth. Primary inclusion criteria were English-language articles that addressed a sample with participants under 18 years of age. 46 articles met criteria for review, and were categorized into three groups of overlap: Post-traumatic Stress Disorder (PTSD) and OCS or OCD (n = 3), clearly defined Criterion A event trauma exposure and OCS or OCD (n = 30), and less well-defined potential trauma exposure and OCS or OCD (n = 13). There was mixed evidence linking trauma exposure and the development of OCS or OCD in youth. Major methodological limitations preclude formal conclusions. More research on co-occurring trauma exposure and OCD/OCS in youth is needed to advance research and improve treatment.

Self-report versus clinical interview: Discordance among measures of binge eating in a weight-loss seeking sample.

PURPOSE: Obese, behavioral weight-loss (BWL) seeking individuals may be prone to over-reporting binge-eating (BE). However, many studies rely on self-reported measures of BE in this population, which may be inaccurate. As such, this is the first-ever study to examine the concordance rates among one self-reported and one clinician- administered measure of BE in a BWL-seeking sample with overweight/obesity. METHODS: At baseline of a BWL trial, participants (N = 94) completed two measures of BE: The Eating Disorders Examination Questionnaire (EDE-Q) and the interview-based Eating Disorder Examination (EDE, Overeating section). RESULTS: Cohen's kappa detected poor agreement between measures (κ < 0). A paired samples t-test detected large, significant differences in OBE frequency across the EDE-Q and EDE, p < 0.001. The self-reported EDE-Q detected a significantly greater frequency of OBEs compared to the EDE (MEDE-Q = 0.73, SD = 1.29 vs. MEDE = 0.06, SD = 0.34). The EDE-Q detected that approximately 50% of participants have experienced OBEs, while the EDE detected that only 5% of participants have experienced OBEs. The frequency of OBEs detected by the EDE-Q was statistically greater than the frequency of OBEs detected by the EDE, p < 0.001. DISCUSSION: Results suggest poor agreement between one self-reported measure and the "gold-standard," clinician-administered measure of BE in a BWL-seeking sample with overweight/obesity. The EDE-Q exhibited high sensitivity but low-to-moderate specificity of OBEs, with the number of false positives (41) outweighing that of true positives (4). Studies measuring BE in this population should consider relying solely on assessor-administered measures, as this sample may require clinical guidance or clarification on the definition and features of BE. LEVEL OF EVIDENCE: Level V, cross-sectional, descriptive study.

Correction to: Use of an Integrated Pan-Cancer Oncology Enrichment Next-Generation Sequencing Assay to Measure Tumour Mutational Burden and Detect Clinically Actionable Variants.

This article was originally published under a [CC BY NC 4.0] license.

Use of an Integrated Pan-Cancer Oncology Enrichment Next-Generation Sequencing Assay to Measure Tumour Mutational Burden and Detect Clinically Actionable Variants.

INTRODUCTION: The identification of tumour mutational burden (TMB) as a biomarker of response to programmed cell death protein 1 (PD-1) immunotherapy has necessitated the development of genomic assays to measure this. We carried out comprehensive molecular profiling of cancers using the Illumina TruSight Oncology 500 (TSO500) panel and compared these to whole-genome sequencing (WGS). METHODS: Cancer samples derived from formalin-fixed material were profiled on the TSO500 panel, sequenced on an Illumina NextSeq 500 instrument and processed through the TSO500 Docker pipeline. Either FASTQ files (PierianDx) or vcf files (OncoKDM) were processed to understand clinical actionability. RESULTS: In total, 108 samples (a mixture of colorectal, lung, oesophageal and control samples) were processed via the DNA panel. There was good correlation between TMB, single-nucleotide variants (SNVs), indels and copy-number variations as predicted by TSO500 and WGS (R2 > 0.9) and good reproducibility, with less than 5% variability between repeated controls. For the RNA panel, 13 samples were processed, with all known fusions observed via orthogonal techniques. For clinical actionability, 72 tier 1 variants and 297 tier 2 variants were detected, with clinical trials identified for all patients. CONCLUSIONS: The TSO500 assay accurately measures TMB, microsatellite instability, SNVs, indels, copy-number/structural variation and gene fusions when compared to WGS and orthogonal technologies. Coupled with a clinical annotation pipeline, this provides a powerful methodology for identification of clinically actionable variants.

Refining an algorithm-powered just-in-time adaptive weight control intervention: A randomized controlled trial evaluating model performance and behavioral outcomes.

Suboptimal weight losses are partially attributable to lapses from a prescribed diet. We developed an app (OnTrack) that uses ecological momentary assessment to measure dietary lapses and relevant lapse triggers and provides personalized intervention using machine learning. Initially, tension between user burden and complete data was resolved by presenting a subset of lapse trigger questions per ecological momentary assessment survey. However, this produced substantial missing data, which could reduce algorithm performance. We examined the effect of more questions per ecological momentary assessment survey on algorithm performance, app utilization, and behavioral outcomes. Participants with overweight/obesity (n = 121) used a 10-week mobile weight loss program and were randomized to OnTrack-short (i.e. 8 questions/survey) or OnTrack-long (i.e. 17 questions/survey). Additional questions reduced ecological momentary assessment adherence; however, increased data completeness improved algorithm performance. There were no differences in perceived effectiveness, app utilization, or behavioral outcomes. Minimal differences in utilization and perceived effectiveness likely contributed to similar behavioral outcomes across various conditions.

OnTrack: development and feasibility of a smartphone app designed to predict and prevent dietary lapses.

Given that the overarching goal of weight loss programs is to remain adherent to a dietary prescription, specific moments of nonadherence known as "dietary lapses" can threaten weight control via the excess energy intake they represent and by provoking future lapses. Just-in-time adaptive interventions could be particularly useful in preventing dietary lapses because they use real-time data to generate interventions that are tailored and delivered at a moment computed to be of high risk for a lapse. To this end, we developed a smartphone application (app) called OnTrack that utilizes machine learning to predict dietary lapses and deliver a targeted intervention designed to prevent the lapse from occurring. This study evaluated the feasibility, acceptability, and preliminary effectiveness of OnTrack among weight loss program participants. An open trial was conducted to investigate subjective satisfaction, objective usage, algorithm performance, and changes in lapse frequency and weight loss among individuals (N = 43; 86% female; body mass index = 35.6 kg/m2) attempting to follow a structured online weight management plan for 8 weeks. Participants were adherent with app prompts to submit data, engaged with interventions, and reported high levels of satisfaction. Over the course of the study, participants averaged a 3.13% weight loss and experienced a reduction in unplanned lapses. OnTrack, the first Just-in-time adaptive intervention for dietary lapses was shown to be feasible and acceptable, and OnTrack users experienced weight loss and lapse reduction over the study period. These data provide the basis for further development and evaluation.

Are individuals with loss-of-control eating more prone to dietary lapse in behavioural weight loss treatment? An ecological momentary assessment study.

OBJECTIVE: Individuals with overweight/obesity and loss-of-control eating (LOC) may experience poorer outcomes from behavioural weight loss due to reactivity to internal (e.g., affective and physical) states that impact treatment adherence (e.g., dietary lapses). This study examined (a) whether the presence of LOC increased risk for dietary lapses and (b) the moderating role of LOC on the relation between internal states and dietary lapses. METHOD: Individuals (n = 189) with overweight and obesity completed ecological momentary assessment early in behavioural weight loss. RESULTS: LOC was positively associated with dietary lapse. LOC did not moderate the relation between momentary changes in internal states and dietary lapses. However, the effect of average levels of internal states on lapses was attenuated for those with LOC. DISCUSSION: Results suggest that those with LOC are at higher risk of dietary lapse, whereas elevated average levels of internal states may contribute to early inadherence for those without LOC.

Ecological momentary assessment of self-attitudes in response to dietary lapses.

OBJECTIVE: To examine whether self-attitudes and self-efficacy after dietary lapses relate to lapse frequency or predict risk for lapsing again on the same day. METHOD: Adults with overweight/obesity (n = 91) completed ecological momentary assessment for 14 days at the start of a lifestyle modification program. At each survey, participants reported whether they had experienced a dietary lapse, and, if so, reported their self-attitudes (i.e., self-criticism, self-forgiveness, self-regard) and self-efficacy. The relationships between participants' typical (i.e., average level for each participant across lapses) self-attitudes/self-efficacy after lapsing and lapse frequency were examined using correlations. Generalized estimating equations examined whether participants' typical (average across lapses; between-person effect) self-attitudes/self-efficacy or momentary (i.e., level of each variable at a particular lapse relative to one's typical level; within-person effect) self-attitudes/self-efficacy predicted same-day lapse occurrence. RESULTS: Lower typical self-efficacy and more negative typical self-regard related to greater lapse frequency. Additionally, lower momentary self-criticism predicted greater likelihood of same-day lapse occurrence. There also was a quadratic relationship between typical self-regard and risk of same-day lapse occurrence, such that individuals with either more negative or more positive typical self-regard were more likely to lapse on the same day. CONCLUSION: Findings provide preliminary support for the relevance of self-attitudes and self-efficacy to lapses during early lifestyle modification. While greater typical self-efficacy and more positive typical self-regard are associated with fewer lapses, lower momentary self-criticism and very positive or negative typical self-regard may confer risk for same-day lapses. (PsycINFO Database Record

Using fluorescence correlation spectroscopy (FCS) for IFN-g detection: a preliminary study.

Nowadays, enzyme-linked immunosorbent assay (ELISA) based detection of Mycobacterium tuberculosis (M. tuberculosis) antigen triggered interferon-gamma (IFN-g) secretion by blood T cells displays an improved diagnostic value for M. tuberculosis infection. Applications of fluorescence correlation spectroscopy (FCS) have been explored in various subfields of medicine and molecular biology, including detection of a certain biomarker in liquid instead of ELISA. Here, we present a preliminary study of detecting IFN-g using FCS-based technique.

In vitro detection of adrenocorticotropic hormone levels by fluorescence correlation spectroscopy immunoassay for mathematical modeling of glucocorticoid-mediated feedback mechanisms.

Performing quantitative, highly sensitive measurements at a single molecule level is often necessary to address specific issues related to complex molecular and biochemical systems. For that purpose, we present a technique exploiting both the flexibility of immunoassays as well as the low operating costs and high throughput rates of the fluorescence correlation spectroscopy (FCS) method. That way we have established a quantitative measurement technique providing accurate and flexibly time resolved data of single molecules. Nanomolar changes in adrenocorticotropic hormone (ACTH) levels have been detected in a short time-frame that are caused by fast feedback actions in AtT-20 anterior pituitary glands in vitro. Especially with respect to clinical diagnostic or mathematical modeling this improved FCS setup may be of high relevance in order to accurately quantify the amounts of peptide hormones-such as ACTH-as well as signaling molecules, transcription factors, etc., being involved in intra- and extracellular reaction networks.

In vitro propagation of two tuberous medicinal plants: Holostemma ada-kodien and Ipomoea mauritiana.

Medicinal plants are sources of important therapeutic aid for healing human diseases. The depletion of the wild resources has prompted conservation, propagation, and enhancement of resources for medicinal plants. Micropropagation offers an alternate method to propagate and improve medicinal plants through selection of high-yield lines and their efficient cloning. This chapter describes cost effective and efficient protocols that have been successfully applied for the micropropagation and large-scale production of quality planting material in two important tuberous medicinal plants viz., Holostemma ada-kodien Schult. and Ipomoea mauritiana Jacq.

Evaluation of five ELISA test kits for the measurement of antibodies against Mycobacterium avium subspecies paratuberculosis in bovine serum.

Five commercially available ELISA tests for the detection of antibodies against Mycobacterium avium subsp. paratuberculosis in bovine serum were evaluated at the individual animal level using sera from 286 paratuberculosis-free and 110 paratuberculosis-infected dairy cattle. Sensitivity (Se) and specificity (Sp) of the tests were estimated after determination of the cut-off dtheta by TG-ROC analysis or using the cut-off values recommended by the manufacturers, respectively. When the dtheta cut-off values were applied, the five ELISA tests showed sub-optimal Se and Sp. Adopting the cut-offs recommended by the manufacturers, the Sp of four of the five ELISA increased, two tests reaching Sp > or = 99.0%. Test sensitivity clearly depended on the disease state of the animals examined. Se was significantly higher in clinically diseased than in latently infected dairy cattle. Calculation of the positive and negative predictive values indicated that, depending on the test, a considerable proportion of false positive and false negative results have to be expected. Therefore, the suitability of antibody detection for the diagnosis of paratuberculosis in individual animals is questioned.

Molecular fingerprinting of Mycobacterium bovis subsp. caprae isolates from central Europe.

To study the dissemination of Mycobacterium bovis subsp. caprae, 79 European isolates from cattle, humans, and other hosts were examined by spoligotyping and IS6110 restriction fragment length polymorphism (RFLP) analysis. Among a total of 11 different spoligotypes identified, type C1 proved to be predominant (n = 62). Five of the spoligotypes are described for the first time. A total of 43 different RFLP types were identified, thus allowing further differentiation for epidemiological tracking. Isolates from a series of outbreaks in one village proved to be of the same spoligotype and of identical or closely related RFLP types.

Snapshot of moving and expanding clones of Mycobacterium tuberculosis and their global distribution assessed by spoligotyping in an international study.

The present update on the global distribution of Mycobacterium tuberculosis complex spoligotypes provides both the octal and binary descriptions of the spoligotypes for M. tuberculosis complex, including Mycobacterium bovis, from >90 countries (13,008 patterns grouped into 813 shared types containing 11,708 isolates and 1,300 orphan patterns). A number of potential indices were developed to summarize the information on the biogeographical specificity of a given shared type, as well as its geographical spreading (matching code and spreading index, respectively). To facilitate the analysis of hundreds of spoligotypes each made up of a binary succession of 43 bits of information, a number of major and minor visual rules were also defined. A total of six major rules (A to F) with the precise description of the extra missing spacers (minor rules) were used to define 36 major clades (or families) of M. tuberculosis. Some major clades identified were the East African-Indian (EAI) clade, the Beijing clade, the Haarlem clade, the Latin American and Mediterranean (LAM) clade, the Central Asian (CAS) clade, a European clade of IS6110 low banders (X; highly prevalent in the United States and United Kingdom), and a widespread yet poorly defined clade (T). When the visual rules defined above were used for an automated labeling of the 813 shared types to define nine superfamilies of strains (Mycobacterium africanum, Beijing, M. bovis, EAI, CAS, T, Haarlem, X, and LAM), 96.9% of the shared types received a label, showing the potential for automated labeling of M. tuberculosis families in well-defined phylogeographical families. Intercontinental matches of shared types among eight continents and subcontinents (Africa, North America, Central America, South America, Europe, the Middle East and Central Asia, and the Far East) are analyzed and discussed.

Identification of Salmonella enterica serovar Typhimurium genes associated with growth suppression in stationary-phase nutrient broth cultures and in the chicken intestine.

Over 2,800 Tn 5 insertion mutants of Salmonella enterica sv. Typhimurium were screened for the loss of ability to suppress the multiplication of a spectinomycin-resistant (Spc(r)) but otherwise isogenic S. enterica sv. Typhimurium strain, when the Spc(r) mutant was added to 24-h LB broth cultures of the mutants. Selected "growth non-suppressive" (GNS) mutants were defective in respiration (insertions in arcA and fnr), amino acid biosynthesis (aroA and aroD), nutrient uptake and its regulation (tdcC and crp), and chemotaxis (fliD). In the last GNS mutant, the transposon inactivated yhjH, an ORF with unknown function which shows sequence similarity to di-guanylate cyclase and to novel two-component signal transduction proteins. In newly hatched chickens, all of the mutants, with the exception of the fliDmutant, were also unable to suppress colonization of the alimentary tract by the parent strain inoculated 1 day later. Defined mutations in luxS or sdiA,genes which contribute to quorum sensing in S. enterica sv. Typhimurium, had no effect on the stationary-phase growth suppression. Analysis of a transcriptional fusion construct indicated that yhjH was moderately expressed in the exponential phase of growth and up-regulated upon entry into stationary phase. Expression of yhjH was also considerably suppressed by the addition of supernatant from a 24-h stationary-phase S. enterica sv. Typhimurium culture, suggesting that the gene belongs to a new sensing and signaling regulatory pathway in S. enterica sv. Typhimurium.

Global distribution of Mycobacterium tuberculosis spoligotypes.

We present a short summary of recent observations on the global distribution of the major clades of the Mycobacterium tuberculosis complex, the causative agent of tuberculosis. This global distribution was defined by data-mining of an international spoligotyping database, SpolDB3. This database contains 11708 patterns from as many clinical isolates originating from more than 90 countries. The 11708 spoligotypes were clustered into 813 shared types. A total of 1300 orphan patterns (clinical isolates showing a unique spoligotype) were also detected.