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Acute liver failure, commonly caused by acetaminophen overdose, is associated with numerous systemic complications including cerebral edema, hypotension, acute kidney injury, and infection. Management is primarily supportive, with an emphasis on excellent neurocritical care. Although some antidotes and targeted treatments exist, the only definitive treatment remains orthotopic liver transplant. [ABSTRACT FROM AUTHOR]

Within a response to intervention framework, Tier 2 is commonly conceptualized as a supplemental, 30-minute intervention that is provided in addition to the core instructional program. Given the resource constraints that many schools face, this type of model might not be feasible. However, in the light of data that suggest a need for a well-designed, targeted intervention system, schools need to do something. This article describes one school's approach to data evaluation and Tier 2 implementation for struggling first grade readers. Working within resource constraints, the school was able to realize positive outcomes for its struggling readers by adhering to effective instructional principles, responding to data, and challenging the conventional wisdom of core plus supplement. (Contains 1 note and 1 figure.)

Immune recognition by T lymphocytes and natural killer (NK) cells is in large part dependent on the identification of cell surface MHC molecules bearing peptides generated from either endogenous (MHC I) or exogenous (MHC II) dependent pathways. This review focuses on MHC I molecules that coordinately fold to bind self or foreign peptides for such surface display. Peptide loading occurs in an antigen presentation pathway that includes either the multimolecular peptide loading complex (PLC) or a single chain chaperone/catalyst, TAP binding protein, related, TAPBPR, that mimics a key component of the PLC, tapasin. Recent structural and dynamic studies of TAPBPR reveal details of its function and reflect on mechanisms common to tapasin. Regions of structural conservation among species suggest that TAPBPR and tapasin have evolved to satisfy functional complexities demanded by the enormous polymorphism of MHC I molecules. Recent studies suggest that these two chaperone/catalysts exploit structural flexibility and dynamics to stabilize MHC molecules and facilitate peptide loading. [ABSTRACT FROM AUTHOR]

Neoantigen formation due to the interaction of drug molecules with human leukocyte antigen (HLA)-peptide complexes can lead to severe hypersensitivity reactions. Flucloxacillin (FLX), a β-lactam antibiotic for narrow-spectrum gram-positive bacterial infections, has been associated with severe immune-mediated drug-induced liver injury caused by an influx of T-lymphocytes targeting liver cells potentially recognizing drug-haptenated peptides in the context of HLA-B*57:01. To identify immunopeptidome changes that could lead to drug-driven immunogenicity, we used mass spectrometry to characterize the proteome and immunopeptidome of B-lymphoblastoid cells solely expressing HLA-B*57:01 as MHC-I molecules. Selected drug-conjugated peptides identified in these cells were synthesized and tested for their immunogenicity in HLA-B*57:01-transgenic mice. T cell responses were evaluated in vitro by immune assays. The immunopeptidome of FLX-treated cells was more diverse than that of untreated cells, enriched with peptides containing carboxy-terminal tryptophan and FLX-haptenated lysine residues on peptides. Selected FLX-modified peptides with drug on P4 and P6 induced drug-specific CD8+ T cells in vivo. FLX was also found directly linked to the HLA K146 that could interfere with KIR-3DL or peptide interactions. These studies identify a novel effect of antibiotics to alter anchor residue frequencies in HLA-presented peptides which may impact drug-induced inflammation. Covalent FLX-modified lysines on peptides mapped drug-specific immunogenicity primarily at P4 and P6 suggesting these peptide sites as drivers of off-target adverse reactions mediated by FLX. FLX modifications on HLA-B*57:01-exposed lysines may also impact interactions with KIR or TCR and subsequent NK and T cell function. [ABSTRACT FROM AUTHOR]

The National Early Care and Education Learning Collaboratives Project (ECELC) was a multistate intervention that was highly effective in implementing best practices for healthy eating physical activity (HEPA) in early care and education (ECE) programs across the USA. The ECELC included didactic in-person learning sessions, technical assistance, and self-assessment-guided action planning. This study aimed to describe the effectiveness of adaptions to the self-assessments, learning sessions, and overall support, and also aimed to compare the effectiveness of each to the Original ECELC Model, when applicable. This study utilized a pre-poststudy design using data collected via the Nutrition and Physical Activity Self-Assessment for Child Care (NAP SACC) instrument for ECE programs that adapted the Original ECELC Model. Adaptations to the Original ECELC Model were found to promote best practices and policies with regard to Breastfeeding & Infant Feeding, Child Nutrition, Infant & Child Physical Activity, Outdoor Play & Learning, and/or Screen Time as demonstrated by the NAP SACC (p <.05), with some exceptions of nonstatistically significant increases. Improvements were found to be statistically similar to improvements made among participants of the Original ECELC Model. Partner-driven, scalable, and customizable policy- and practice-based interventions to promote HEPA among children in ECE settings may serve as a key strategy to work toward reducing risk for childhood obesity. [ABSTRACT FROM AUTHOR]

Despite efforts to develop effective treatments and vaccines, Mycobacterium tuberculosis (Mtb), particularly pulmonary Mtb, continues to provide major health challenges worldwide. To improve immunization against the persistent health challenge of Mtb infection, we have studied the CD8+ T cell response to Bacillus Calmette‐Guérin (BCG) and recombinant BCG (rBCG) in mice. Here, we generated CD8+ T cells with an rBCG‐based vaccine encoding the Ag85B protein of M. kansasii, termed rBCG‐Mkan85B, followed by boosting with plasmid DNA expressing the Ag85B gene (DNA‐Mkan85B). We identified two MHC‐I (H2‐Kd)‐restricted epitopes that induce cross‐reactive responses to Mtb and other related mycobacteria in both BALB/c (H2d) and CB6F1 (H2b/d) mice. The H2‐Kd‐restricted peptide epitopes elicited polyfunctional CD8+ T cell responses that were also highly cross‐reactive with those of other proteins of the Ag85 complex. Tetramer staining indicated that the two H2‐Kd‐restricted epitopes elicit distinct CD8+ T cell populations, a result explained by the X‐ray structure of the two peptide/H2‐Kd complexes. These results suggest that rBCG‐Mkan85B vector‐based immunization and DNA‐Mkan85B boost may enhance CD8+ T cell response to Mtb, and might help to overcome the limited effectiveness of the current BCG in eliciting tuberculosis immunity. [ABSTRACT FROM AUTHOR]

Objective: To describe low-income parents' and caregivers' perceptions of the Cooking Matters Mobile Application (CM App) meal planning and preparation features.Design: Explanatory mixed-methods design where data were gathered via online surveys based on the Theory of Planned Behaviour and the Theory of Reasoned Action, followed by telephone interviews.Setting: CM App, a mobile phone-based resource geared towards low-income parents and caregivers of young children (pregnancy/infant to age 5 years) for meal planning and preparation, with features based on skills taught in the Cooking Matters course: recipes, shopping list and meal planning.Participants: Low-income parents and caregivers (survey participants, n 461; interview participants, n 20) who had downloaded the CM App to their smartphone and agreed to participate in the current evaluation.Results: Attitudes and self-efficacy related to CM App's subject matter and functions (meal planning; recipe use; creating and using a shopping list) were measured via surveys and interviews. Mean (sd) responses were positive towards 'meal planning' and 'shopping and cooking' (4·17 (0·63) and 3·49 (0·86) on a 5-point Likert scale, respectively). Interviewees described meal planning and preparation behaviours as intrinsic, based on habit, and influenced by family preference and food costs. Early adopters of the CM App may already be engaged in and/or are motivated to engage in the targeted health behaviours.Conclusions: Users may benefit most from incorporating into their routines new ways to prepare easy, cost-efficient, healthy meals at home that their families will enjoy. [ABSTRACT FROM AUTHOR]

Objective: To use cognitive interviewing and pilot testing to develop a survey instrument feasible for administering in the food pantry setting to assess daily intake frequency from several major food groups and dietary correlates (e.g. fruit and vegetable barriers) - the FRESH Foods Survey.Design: New and existing survey items were adapted and refined following cognitive interviews. After piloting the survey with food pantry users in the USA, preliminary psychometric and construct validity analyses were performed.Setting: Three US food banks and accompanying food pantries in Atlanta, GA, San Diego, CA, and Buffalo, NY.Participants: Food pantry clients (n 246), mostly female (68 %), mean age 54·5 (sd 14·7) years.Results: Measures of dietary correlates performed well psychometrically: Cronbach's α range 0·71-0·90, slope (α) parameter range 1·26-6·36, and threshold parameters (β) indicated variability in the 'difficulty' of the items. Additionally, all scales had only one eigenvalue above 1·0 (range 2·07-4·71), indicating unidimensionality. Average (median, Q1-Q3) daily intakes (times/d) across six dietary groups were: fruits and vegetables (2·87, 1·87-4·58); junk foods (1·16, 0·58-2·16); fast foods and similar entrées (1·45, 0·58-2·03); whole-grain foods (0·87, 0·58-1·71); sugar-sweetened beverages (0·58, 0·29-1·29); milk and milk alternatives (0·71, 0·29-1·29). Significant correlations between dietary groups and dietary correlates were largely in the directions expected based on the literature, giving initial indication of convergent and discriminant validity.Conclusions: The FRESH Foods Survey is efficient, tailored to food pantry populations, can be used to monitor dietary behaviours and may be useful to measure intervention impact. [ABSTRACT FROM AUTHOR]

England’s national Improving Access to Psychological Therapies (IAPT) programme advocates stepped care as its organizational delivery of psychological therapies to common mental health problems. There is limited evidence regarding the efficacy of stepped care as a service delivery model, heterogeneity of definition and differences in model implementation in both research and routine practice, hence outcome comparison in terms of effectiveness of model is difficult. Despite sound evidence of the efficacy of low intensity interventions there appears to be a perpetuation of the notion that severity and complexity should only be treated by a high intensity intervention through the continuation of a stratified care model. Yet no psychotherapy treatment is found to be more superior to another, and not enough is known about what works for whom to aid the matching of treatment decision. In the absence of understanding precise treatment factors optimal for recovery, it may be useful to better understand the impact of a service delivery model, and whether different models achieve different outcomes. This study aims to contribute to the discussion regarding the stepped care definition and delivery, and explores the impact on clinical outcomes where different types of stepped care have been implemented within the same service. An observational cohort study analysed retrospective data (n = 16,723) over a 4 year period, in a single IAPT service, where delivery changed from one type of stepped care model to another. We compared the outcomes of treatment completers with a stratified care model and a progression care model. We also explored the assumption that patients who score severe on psychological measures, and therefore are potentially complex, would achieve better outcomes in a stratified model. Outcomes in each model type were compared, alongside baseline factor variables. A significant association was observed between a recovery outcome and model type, with patients 1.5 times more likely to recover in the progression delivery model. The potential implications are that with a progression stepped care model of service delivery, more patients can be treated with a lower intensity intervention, even with initial severe presentations, ensuring that only those that need high intensity CBT or equivalent are stepped up. This could provide services with an effective clinical model that is efficient and potentially more cost effective. [ABSTRACT FROM AUTHOR]

Background: Group prenatal care is a promising strategy to improve perinatal outcomes. Research in larger more diverse populations with attention to adherence is needed to inform clinical practice recommendations. We examined the impact of group prenatal care on preterm birth and low birth weight in a large metropolitan hospital, accounting for patient adherence, over an 8.5-year period. Materials and Methods: We analyzed data from 9,348 pregnant women with a live, singleton birth who received group (CenteringPregnancy or Expect With Me) or individual prenatal care at Vanderbilt University Medical Center from January 2009 through June 2016. Propensity scores were used for matching based on year of delivery, age, race, pregnancy risk, and adequacy of care. The propensity score matched sample included 1,384 group and 5,055 individual prenatal care patients (total = 6,439 women). Preterm birth (<37 weeks gestation) and low birth weight (<2,500 g) were obtained from systematic medical review. Risks were estimated using Poisson regression. Results: Controlling for individual visits, receiving group prenatal care resulted in significantly lower risk of having a preterm birth (Rate ratio [RR] 0.63, 95% confidence interval [CI] 0.49–0.81) and low birth weight baby (RR 0.62, 95% CI 0.47–0.81), compared to receiving individual care only. Women with ≥5 group prenatal care visits experienced even greater benefits: 68% (RR = 0.32; 95% CI 0.22–0.45) and 66% (RR = 0.34; 95% CI 0.23–0.50) risk reduction in preterm birth and low birth weight, respectively. Conclusions: Participation in group prenatal care may improve birth outcomes. Efforts to promote adoption and sustainability of group prenatal care by health systems may be warranted. [ABSTRACT FROM AUTHOR]

Antigen presentation is a cellular process that involves a number of steps, beginning with the production of peptides by proteolysis or aberrant synthesis and the delivery of peptides to cellular compartments where they are loaded on MHC class I (MHC-I) or MHC class II (MHC-II) molecules. The selective loading and editing of high-affinity immunodominant antigens is orchestrated by molecular chaperones: tapasin/TAP-binding protein, related for MHC-I and HLA-DM for MHC-II. Once peptide/MHC (pMHC) complexes are assembled, following various steps of quality control, they are delivered to the cell surface, where they are available for identification by αβ receptors on CD8+ or CD4+ T lymphocytes. In addition, recognition of cell surface peptide/MHC-I complexes by natural killer cell receptors plays a regulatory role in some aspects of the innate immune response. Many of the components of the pathways of antigen processing and presentation and of T cell receptor (TCR)-mediated signaling have been studied extensively by biochemical, genetic, immunological, and structural approaches over the past several decades. Until recently, however, dynamic aspects of the interactions of peptide with MHC, MHC with molecular chaperones, or of pMHC with TCR have been difficult to address experimentally, although computational approaches such as molecular dynamics (MD) simulations have been illuminating. Studies exploiting X-ray crystallography, cryo-electron microscopy, and multidimensional nuclear magnetic resonance (NMR) spectroscopy are beginning to reveal the importance of molecular flexibility as it pertains to peptide loading onto MHC molecules, the interactions between pMHC and TCR, and subsequent TCR-mediated signals. In addition, recent structural and dynamic insights into how molecular chaperones define peptide selection and fine-tune the MHC displayed antigen repertoire are discussed. Here, we offer a review of current knowledge that highlights experimental data obtained by X-ray crystallography and multidimensional NMR methodologies. Collectively, these findings strongly support a multifaceted role for protein plasticity and conformational dynamics throughout the antigen processing and presentation pathway in dictating antigen selection and recognition. [ABSTRACT FROM AUTHOR]

Adolescents in stepfamilies and single-parent families tend to report lower levels of well-being than adolescents who live with two biological parents. Using data from Add Health (n = 16,684), the present study builds on this literature by examining family-level predictors of adolescent depressive symptoms, delinquency, failing a class, heavy alcohol use, tobacco use, and marijuana use. We focus on feelings of family belonging as a predictor of adolescent well-being and find that this measure is significantly associated with well-being in all family types, and particularly in two-biological-parent families. In addition, results indicate that family belonging mediates associations between parent-adolescent closeness and well-being for most outcomes. [ABSTRACT FROM AUTHOR]

Examines the mechanism of assembly/dissociation of a recombinant water-soluble class I major histocompatibility complex H-2Kb molecule. Allosteric mechanism control of interactions among the heavy chains and antigenic peptides; Effects of peptide interactions; Comparison of peptide dissociation rate.