A holistic approach to fragile X syndrome integrated guidance for person-centred care.

BACKGROUND: The Fragile X community has expressed a desire for centralised, national guidelines in the form of integrated guidance for Fragile X Syndrome (FXS). METHODS: This article draws on existing literature reviews, primary research and clinical trials on FXS, a Fragile X Society conference workshop and first-hand experience of clinicians who have worked with those living with FXS over many years. RESULTS: The article scopes proposed integrated guidance over the life course, including appendices of symptoms, comorbidities and referral options for FXS and Fragile X Premutation Associated Conditions. CONCLUSION: Integrated guidance would provide an authoritative source for doctors, health professionals, therapists, care workers, social workers, educators, employers, families and those living with FXS, so that a holistic, person-centred approach can be taken across the United Kingdom to garner the best outcomes for those with FXS.

eHealth literacy and web-based patient portal usage among kidney and liver transplant recipients.

Patient portals promote self-management, but require skills with electronic health information which can be measured by a patient's eHealth literacy. We aimed to describe eHealth literacy among a population of kidney transplant (KT) and liver transplant (LT) recipients and to investigate the relationship between eHealth literacy and Web-based patient portal utilization. We conducted phone surveys (August 2016-March 2017) among 178 KT and 110 LT recipients at two large transplant centers, including the eHealth Literacy Scale (eHEALS) and items assessing routine portal usage. Portal users were defined as routine if usage was every day, weekly, or monthly. The mean eHEALS score was 30.9 (SD: 5.4), and 45.4% routinely used the patient portal more than a few times per month. Routine users had higher eHealth literacy than non-routine users and non-users (31.97 vs. 29.97 vs. 28.20, p < .001). Routine users had higher eHealth literacy scores compared with non-users after adjusting for transplant organ type, age, educational level, employment status, mobile Internet access, and transplant center (OR: 1.10, 95% CI: 1.03-1.17). KT and LT recipients who routinely use patient portals have high eHealth literacy compared with other diseased populations, which should be leveraged by encouraging routine usage to improve post-transplant health and medication adherence.

Oxidation of Cytochrome 605 Is the Rate-Limiting Step when Ferrimicrobium acidiphilum Respires Aerobically on Soluble Iron.

Proteins that oxidize extracellular substrates in Gram-positive bacteria are poorly understood. Ferrimicrobium acidiphilum is an actinobacterium that respires aerobically on extracellular ferrous ions at pH 1.5. In situ absorbance measurements were conducted on turbid suspensions of intact Fm. acidiphilum using an integrating cavity absorption meter designed for that purpose. Initial velocity kinetic studies monitored the appearance of product ferric ions in the presence of catalytic quantities of cells. Cell-catalyzed iron oxidation obeyed the Michaelis-Menten equation with Km and Vmax values of 71 µM and 0.29 fmol/min/cell, respectively. Limited-turnover kinetic studies were conducted with higher concentrations of cells to detect and monitor changes in the absorbance properties of cellular redox proteins when the cells were exposed to limited quantities of soluble reduced iron. A single a-type cytochrome with reduced absorbance peaks at 448 and 605 nm was the only redox-active chromophore that was visible as the cells respired aerobically on iron. The reduced cytochrome 605 exhibited mathematical and correlational properties that were consistent with the hypothesis that oxidation of the cytochrome constituted the rate-limiting step in the aerobic respiratory process, with a turnover number of 35 ± 2 s-1 Genomic and proteomic analyses showed that Fm. acidiphilum could and did express only two a-type heme copper terminal oxidases. Cytochrome 605 was associated with the terminal oxidase gene that is located between nucleotides 31,090 and 33,039, inclusive, in the annotated circular genome of this bacterium.IMPORTANCE The identities and functions of proteins involved in aerobic respiration on extracellular ferrous ions at acidic pH are poorly understood in the four phyla of Gram-positive eukaryotes and archaea where such activities occur. In situ absorbance measurements were conducted on Fm. acidiphilum as it respired on extracellular iron using an integrating cavity absorption meter that permitted accurate optical measurements in turbid suspensions of the intact bacterium under physiological conditions. The significance of these measurements is that they permitted a direct spectrophotometric examination of the extents and rates of biological electron transfer events in situ under noninvasive physiological conditions without disrupting the complexity of the live cellular environment. One thing is certain: one way to understand how a protein functions in an intact organism is to actually observe that protein as it functions in the intact organism. This paper provides an example of just such an observation.

Impact of comorbidity on the short- and medium-term risk of revision in total hip and knee arthroplasty.

BACKGROUND: The impact of comorbidity on the risk of revision in patients undergoing Total Knee arthroplasty (TKA) and Total Hip Arthroplasty (THA) is not currently well known. The aim of this study was to analyze the impact of comorbidity on the risk of revision in TKA and THA. METHODS: Patients recorded in the Catalan Arthroplasty Register (RACat) between 01/01/2005 and 31/12/2016 undergoing TKA (n = 49,701) and THA (n = 17,923) caused by osteoarthritis were included. As main explanatory factors, comorbidity burden was assessed by the Elixhauser index, categorized, and specific comorbidities from the index were taken into account. Descriptive analyses for comorbidity burden and specific conditions were done. Additionally, incidence at 1 and 5 years' follow-up was calculated, and adjusted Competing Risks models were fitted. RESULTS: A higher incidence of revision was observed when the number of comorbidities was high, both at 1 and 5 years for THA, but only at 1 year for TKA. Of the specific conditions, only obesity was related to the incidence of revision at 1 year in both joints, and at 5 years in TKA. The risk of revision was related to deficiency anemia and liver diseases in TKA, while in THA, it was related to peripheral vascular disorders, metastatic cancer and psychoses. CONCLUSIONS: Different conditions, depending on the joint, might be related to higher revision rates. This information could be relevant for clinical decision-making, patient-specific information and improving the results of both TKA and THA.

Racial, Ethnic, and Socioeconomic Disparities in Web-Based Patient Portal Usage Among Kidney and Liver Transplant Recipients: Cross-Sectional Study.

BACKGROUND: Kidney and liver transplant recipients must manage a complex care regimen after kidney transplant. Although the use of Web-based patient portals is known to improve patient-provider communication and health outcomes in chronic disease populations by helping patients manage posttransplant care, disparities in access to and use of portals have been reported. Little is known about portal usage and disparities among kidney and liver transplant recipients. OBJECTIVE: The aim of this study was to examine patient racial/ethnic, socioeconomic, and clinical characteristics associated with portal usage among kidney and liver transplant recipients. METHODS: The study included all adult kidney and liver transplant recipients (n=710) at a large academic transplant center in the Southeastern United States between March 2014 and November 2016. Electronic medical record data were linked with Cerner portal usage data. Patient portal use was defined as any portal activity (vs no activity) recorded in the Cerner Web-based portal, including viewing of health records, lab results, medication lists, and the use of secure messaging. Multivariable log-binomial regression was used to determine the patient demographic, clinical, and socioeconomic characteristics associated with portal usage, stratified by organ. RESULTS: Among 710 transplant recipients (n=455 kidney, n=255 liver), 55.4% (252/455) of kidney recipients and 48.2% (123/255) of liver recipients used the patient portal. Black patients were less likely to use the portal versus white patients among both kidney (57% black vs 74% white) and liver (28% black vs 55% white) transplant recipients. In adjusted multivariable analyses, kidney transplant recipients were more likely to use the portal if they had higher education; among liver recipients, patients who were white versus black and had higher education were more likely to use the portal. CONCLUSIONS: Despite studies showing that patient portals have the potential to benefit transplant recipients as a tool for health management, racial and socioeconomic disparities should be considered before widespread implementation. Transplant centers should include portal training and support to all patients to encourage use, given its potential to improve outcomes.

Awareness of the New Kidney Allocation System among United States Dialysis Providers with Low Waitlisting.

It is unknown whether dialysis facility staff are aware of the new kidney allocation system implemented in December 2014, which changed how deceased donor kidneys are allocated and waiting time is calculated. U.S. dialysis facilities with low annual waitlisting (<15.2%) were surveyed as part of a large randomized study. Among 653 facilities, 57.9% of staff were aware of the policy change, with medical directors (84.4%) being more aware than social workers (73.3%), facility administrators (53.1%), nurse managers (46.4%), and other staff (43.8%). Targeted education among dialysis facilities with low waitlisting may help extend the reach of the new policy.

Ligand-mediated cytoplasmic retention of the Ah receptor inhibits macrophage-mediated acute inflammatory responses.

The Ah receptor (AHR) has been shown to exhibit both inflammatory and anti-inflammatory activity in a context-specific manner. In vivo macrophage-driven acute inflammation models were utilized here to test whether the selective Ah receptor modulator 1-allyl-7-trifluoromethyl-1H-indazol-3-yl]-4-methoxyphenol (SGA360) would reduce inflammation. Exposure to SGA360 was capable of significantly inhibiting lipopolysaccharide (LPS)-mediated endotoxic shock in a mouse model, both in terms of lethality and attenuating inflammatory signaling in tissues. Topical exposure to SGA360 was also able to mitigate joint edema in a monosodium urate (MSU) crystal gout mouse model. Inhibition was dependent on the expression of the high-affinity allelic AHR variant in both acute inflammation models. Upon peritoneal MSU crystal exposure SGA360 pretreatment inhibited neutrophil and macrophage migration into the peritoneum. RNA-seq analysis revealed that SGA360 attenuated the expression of numerous inflammatory genes and genes known to be directly regulated by AHR in thioglycolate-elicited primary peritoneal macrophages treated with LPS. In addition, expression of the high-affinity allelic AHR variant in cultured macrophages was necessary for SGA360-mediated repression of inflammatory gene expression. Mechanistic studies revealed that SGA360 failed to induce nuclear translocation of the AHR and actually enhanced cytoplasmic localization. LPS treatment of macrophages enhanced the occupancy of the AHR and p65 to the Ptgs2 promoter, whereas SGA360 attenuated occupancy. AHR ligand activity was detected in peritoneal exudates isolated from MSU-treated mice, thus suggesting that the anti-inflammatory activity of SGA360 is mediated at least in part through AHR antagonism of endogenous agonist activity. These results underscore an important role of the AHR in participating in acute inflammatory signaling and warrants further investigations into possible clinical applications.

Benefits of a Culturally Tailored Health Promotion Program for Latino Youth With Disabilities and Their Families.

Little research is available about youth with disabilities, who experience numerous inequalities in health outcomes compared with youth without disabilities. Youth with disabilities experience many environmental and attitudinal barriers in maintaining healthy lifestyles, which put them at risk for obesity. Strong evidence has suggested that obesity rates are higher among youth with disabilities than among their nondisabled peers. The purpose of this study was to implement and examine the benefits of a culturally tailored healthy lifestyles program for Latino youth with disabilities and their families. Several cultural adaptations were made to align with the target population's cultural norms. Seventeen Latino families identified 67 behaviors they wanted to change or new habits they wanted to establish. The postassessment data showed that several family routines improved, and families reported engaging in many of the healthy habits they had identified for themselves. Implications of culturally appropriate and accessible programming are discussed.

Alternative translation initiation codons for the plastid maturase MatK: unraveling the pseudogene misconception in the Orchidaceae.

BACKGROUND: The plastid maturase MatK has been implicated as a possible model for the evolutionary "missing link" between prokaryotic and eukaryotic splicing machinery. This evolutionary implication has sparked investigations concerning the function of this unusual maturase. Intron targets of MatK activity suggest that this is an essential enzyme for plastid function. The matK gene, however, is described as a pseudogene in many photosynthetic orchid species due to presence of premature stop codons in translations, and its high rate of nucleotide and amino acid substitution. RESULTS: Sequence analysis of the matK gene from orchids identified an out-of-frame alternative AUG initiation codon upstream from the consensus initiation codon used for translation in other angiosperms. We demonstrate translation from the alternative initiation codon generates a conserved MatK reading frame. We confirm that MatK protein is expressed and functions in sample orchids currently described as having a matK pseudogene using immunodetection and reverse-transcription methods. We demonstrate using phylogenetic analysis that this alternative initiation codon emerged de novo within the Orchidaceae, with several reversal events at the basal lineage and deep in orchid history. CONCLUSION: These findings suggest a novel evolutionary shift for expression of matK in the Orchidaceae and support the function of MatK as a group II intron maturase in the plastid genome of land plants including the orchids.

PSYCHOSOCIAL PREDICTORS OF FEMALE COLLEGE STUDENTS' MOTIVATIONAL RESPONSES: A PROSPECTIVE ANALYSIS.

According to social cognitive theory, group cohesion and self-efficacy have been identified as important environmental and individual elements in students' physical activity. This study examined the correlations among group cohesion, exercise self-efficacy, perceived interest, and physical activity among 143 female college students (M age = 21.2 yr., SD = 4.2) enrolled in aerobics dance classes. Participants were recruited by researchers at the beginning of the semester. In the 6th wk., students completed a questionnaire measuring group cohesion construct. At the end of the 13th wk., a survey on self-efficacy, perceived interest, and physical activity measures was completed by the students. Multiple regression analyses indicated both exercise self-efficacy and task cohesion explained significant variance in students' physical activity; also, Individual Attraction to the Group-Task (ATG-T) accounted for 9.6% of the variance in exercise self-efficacy. The results suggest that enhancing group cohesiveness may promote competence beliefs, which could motivate students' participation in group activity programs.

An Integrated Approach to Address Perinatal Mental Health Within an Obstetrics Practice.

Outpatient perinatal care providers (one certified nurse-midwife, one nurse practitioner, and one physician assistant) at a high-volume, suburban health system in southeastern Pennsylvania developed and implemented a care model to identify and care for patients at risk for perinatal and postpartum mental health conditions. The program, Women Adjusting to Various Emotional States (WAVES), was created to bring the most up-to-date, evidence-based treatment recommendations to patients while addressing the increased demand placed on the health care system by pregnant and postpartum patients in need of psychiatric services. WAVES is a specialized program offered for anyone who is pregnant or up to one year postpartum who is struggling with mental health symptoms or concerns. Perinatal mood and anxiety disorders have become one of the most prevalent pregnancy ailments, yet mental health is not always addressed during routine prenatal care visits. Common obstacles to patients obtaining mental health care during pregnancy include lack of access, clinician gaps in knowledge, and stigma surrounding diagnoses. WAVES offers a method to empower perinatal providers with the education and tools to address this need. The model outlines how to appropriately assess, diagnose, manage, or refer patients for mental health services. Patient feedback has been overwhelmingly positive, and this novel care model shows great promise for the future of perinatal care. The development of integrated programs like WAVES may be a valuable resource to help combat the perinatal mental health epidemic.

Association between goal nutrition and intubation in patients with bronchiolitis on noninvasive ventilation: A retrospective cohort study.

BACKGROUND: Acute bronchiolitis causes many hospitalizations in children younger than 2 years. Early enteral nutrition is associated with improved outcomes in these patients. However, often nutrition is withheld when patients require noninvasive respiratory support because of the risk of aspiration worsening respiratory failure, possibly requiring intubation. We hypothesize that achieving goal energy intake is associated with a lower intubation rate in hospitalized children with bronchiolitis who require noninvasive ventilation. METHODS: This retrospective cohort study examined the association between goal enteral nutrition (60% of dietary reference energy intake) and intubation rates. We grouped patients by severity of illness and compared intubation rates in those who met goal energy to those who did not. We use stratified analysis methods (for both level of respiratory support and feeding route) to evaluate progression to intubation. RESULTS: Of the 272 patients, 215 met goal feeds. These groups had similar demographics, but the goal-feeds group started on higher respiratory support in the pediatric intensive care unit. We found that 4.65% of the patients who met goal feeds required intubation compared with 24.6% of patients who did not meet goal feeds (P < 0.0001), even after controlling for respiratory status at admission and time of feed initiation and feeding route. CONCLUSION: We observed when adjusting for severity, feeding route, and respiratory support, achieving goal energy intake remained associated with a lower rate of intubation, without higher rates of aspiration. Confounding factors include practice variation and difference in severity of illness that objective scoring may have missed.

Developmental associations between motor and communication outcomes in Fragile X syndrome: Variation in the context of co-occurring autism.

LAY ABSTRACT: Fragile X syndrome (FXS), the leading heritable cause of intellectual disability, has a co-occurrence rate of autism spectrum disorder (ASD) estimated at ~60%. Children with FXS experience delayed achievement and slower development of key motor abilities, which happens to an even greater extent for children with both FXS and ASD. A multitude of studies have demonstrated that motor abilities are foundational skills related to later communication outcomes in neurotypical development, as well as in the context of ASD. However, these associations remain unexamined in FXS, or FXS + ASD. In this study, we aimed to determine the associations between early motor skills and their rate of development on communication outcomes in FXS. Furthermore, we investigated whether these associations varied in the context of co-occurring FXS + ASD. Results revealed within-FXS variation in the context of co-occurring ASD between some aspects of motor development and communication outcomes, yet within-FXS consistency between others. Findings provide evidence for variability in developmental processes and outcomes in FXS in the context of co-occurring ASD and offer implications for intervention.

The UCSC Cancer Genomics Browser: update 2011.

The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu) comprises a suite of web-based tools to integrate, visualize and analyze cancer genomics and clinical data. The browser displays whole-genome views of genome-wide experimental measurements for multiple samples alongside their associated clinical information. Multiple data sets can be viewed simultaneously as coordinated 'heatmap tracks' to compare across studies or different data modalities. Users can order, filter, aggregate, classify and display data interactively based on any given feature set including clinical features, annotated biological pathways and user-contributed collections of genes. Integrated standard statistical tools provide dynamic quantitative analysis within all available data sets. The browser hosts a growing body of publicly available cancer genomics data from a variety of cancer types, including data generated from the Cancer Genome Atlas project. Multiple consortiums use the browser on confidential prepublication data enabled by private installations. Many new features have been added, including the hgMicroscope tumor image viewer, hgSignature for real-time genomic signature evaluation on any browser track, and 'PARADIGM' pathway tracks to display integrative pathway activities. The browser is integrated with the UCSC Genome Browser; thus inheriting and integrating the Genome Browser's rich set of human biology and genetics data that enhances the interpretability of the cancer genomics data.

ENCODE whole-genome data in the UCSC genome browser (2011 update).

The ENCODE project is an international consortium with a goal of cataloguing all the functional elements in the human genome. The ENCODE Data Coordination Center (DCC) at the University of California, Santa Cruz serves as the central repository for ENCODE data. In this role, the DCC offers a collection of high-throughput, genome-wide data generated with technologies such as ChIP-Seq, RNA-Seq, DNA digestion and others. This data helps illuminate transcription factor-binding sites, histone marks, chromatin accessibility, DNA methylation, RNA expression, RNA binding and other cell-state indicators. It includes sequences with quality scores, alignments, signals calculated from the alignments, and in most cases, element or peak calls calculated from the signal data. Each data set is available for visualization and download via the UCSC Genome Browser (http://genome.ucsc.edu/). ENCODE data can also be retrieved using a metadata system that captures the experimental parameters of each assay. The ENCODE web portal at UCSC (http://encodeproject.org/) provides information about the ENCODE data and links for access.

The UCSC Genome Browser database: update 2011.

The University of California, Santa Cruz Genome Browser (http://genome.ucsc.edu) offers online access to a database of genomic sequence and annotation data for a wide variety of organisms. The Browser also has many tools for visualizing, comparing and analyzing both publicly available and user-generated genomic data sets, aligning sequences and uploading user data. Among the features released this year are a gene search tool and annotation track drag-reorder functionality as well as support for BAM and BigWig/BigBed file formats. New display enhancements include overlay of multiple wiggle tracks through use of transparent coloring, options for displaying transformed wiggle data, a 'mean+whiskers' windowing function for display of wiggle data at high zoom levels, and more color schemes for microarray data. New data highlights include seven new genome assemblies, a Neandertal genome data portal, phenotype and disease association data, a human RNA editing track, and a zebrafish Conservation track. We also describe updates to existing tracks.

General practice experiences for parents of children with intellectual disability: a systematic review.

BACKGROUND: Parents of children diagnosed with intellectual disability are at increased risk of mental and physical health difficulties compared with other parents. They are likely to regularly seek medical treatment for their health concerns from general practice as well as on behalf of their child with intellectual disability, yet there is limited evaluation of the role general practice plays for this patient group. AIM: To explore parents' experiences of general practice support when caring for a child with intellectual disability. DESIGN & SETTING: Systematic review of studies reporting experiences of general practice as described by parents who care for children with intellectual disability. METHOD: Databases were searched using a pre-defined search strategy. Studies were included based on detailed inclusion criteria, title, abstract, and full-text screening. Quality assessment was conducted using the Mixed Methods Appraisal Tool (MMAT). A narrative synthesis was conducted. RESULTS: A total of nine studies were identified. There was a clear absence of data on parents' own health experience and consultation in general practice. Findings related to navigating general practice on behalf of their child's health including accessibility of general practice and positive and negative experiences of GPs. CONCLUSION: Findings from this review highlight priority areas for research, including further exploration of parents' perspectives on seeking support specifically for their own health concerns, while caring for a child with intellectual disability, to bring more awareness and understanding of the role general practice plays in supporting the health of this carer group. This review also considers implications for clinical services, including tailoring appointments for this patient group as a priority for continuity of care, which may result in improved experiences of general practice and encourage better communication.

Behavioural and physiological indicators of anxiety reflect shared and distinct profiles across individuals with neurogenetic syndromes.

Anxiety is heightened in individuals with intellectual disability, particularly in those with specific neurogenetic syndromes. Assessment of anxiety for these individuals is hampered by a lack of appropriate measures that cater for communication impairment, differences in presentation, and overlapping features with co-occurring conditions. Here, we adopt a multi-method approach to identify fine-grained behavioural and physiological (via salivary cortisol) responses to anxiety presses in people with fragile X (FXS; n = 27; Mage = 20.11 years; range 6.32 - 47.04 years) and Cornelia de Lange syndromes (CdLS; n = 27; Mage = 18.42 years; range 4.28 - 41.08 years), two neurogenetic groups at high risk for anxiety, compared to neurotypical children (NT; n = 21; Mage = 5.97 years; range 4.34 - 7.30 years). Results indicate that physical avoidance of feared stimuli and proximity seeking to a familiar adult are prominent behavioural indicators of anxiety/stress in FXS and CdLS. Heightened pervasive physiological arousal was identified in these groups via salivary cortisol. An association between autistic characteristics and anxiety was evident in the FXS group but not in the CdLS group pointing to syndrome-specific nuances in the association between anxiety and autism. This study furthers understanding of the behavioural and physiological presentation of anxiety in individuals with intellectual disability and progresses theoretical developments regarding the development and maintenance of anxiety at the intersection of autism.

Lead optimization of aryl hydrocarbon receptor ligands for treatment of inflammatory skin disorders.

Therapeutic aryl hydrocarbon receptor (AHR) modulating agents gained attention in dermatology as non-steroidal anti-inflammatory drugs that improve skin barrier properties. By exploiting AHR's known ligand promiscuity, we generated novel AHR modulating agents by lead optimization of a selective AHR modulator (SAhRM; SGA360). Twenty-two newly synthesized compounds were screened yielding two novel derivatives, SGA360f and SGA388, in which agonist activity led to enhanced keratinocyte terminal differentiation. SGA388 showed the highest agonist activity with potent normalization of keratinocyte hyperproliferation, restored expression of skin barrier proteins and dampening of chemokine expression by keratinocytes upon Th2-mediated inflammation in vitro. The topical application of SGA360f and SGA388 reduced acute skin inflammation in vivo by reducing cyclooxygenase levels, resulting in less neutrophilic dermal infiltrates. The minimal induction of cytochrome P450 enzyme activity, lack of cellular toxicity and mutagenicity classifies SGA360f and SGA388 as novel potential therapeutic AHR ligands and illustrates the potential of medicinal chemistry to fine-tune AHR signaling for the development of targeted therapies in dermatology and beyond.

Testing adaptive interventions to improve PTSD treatment outcomes in Federally Qualified Health Centers: Protocol for a randomized clinical trial.

BACKGROUND: Posttraumatic stress disorder (PTSD) disproportionately affects low-income individuals and is untreated in 70% of those affected. One third of low-income Americans are treated in Federally Qualified Health Centers (FQHCs), which do not have the capacity to provide all patients with first-line treatments such as Prolonged Exposure (PE). To address this problem, FQHCs could use low-intensity interventions (e.g., Clinician-Supported PTSD Coach: CS PTSD Coach) and medium-intensity interventions (e.g., PE for Primary Care: PE-PC) to treat PTSD with fewer resources. However, some patients will still require high-intensity treatments (e.g., full-length PE) for sustained clinical benefit. Thus, there is a critical need to develop stepped-care models for PTSD in FQHCs. METHOD: We are conducting a Sequential, Multiple Assignment, Randomized Trial (SMART) with 430 adults with PTSD in FQHCs. Participants are initially randomized to CS PTSD Coach or PE-PC. After four sessions, early responders step down to lower frequency interaction within their assigned initial treatment strategy. Slow responders are re-randomized to either continue their initial treatment strategy or step up to Full PE for an additional eight weeks. The specific aims are to test the effectiveness of initiating treatment with PE-PC versus CS PTSD Coach in reducing PTSD symptoms and to test the effectiveness of second-stage strategies (continue versus step-up to Full PE) for slow responders. CONCLUSIONS: This project will provide critical evidence to inform the development of an effective stepped-care model for PTSD. Testing scalable, sustainable sequences of PTSD treatments delivered in low-resource community health centers will improve clinical practice for PTSD.