Global mapping of the Chlamydia trachomatis conventional secreted effector - host interactome reveals CebN interacts with nucleoporins and Rae1 to impede STAT1 nuclear translocation.

Chlamydia trachomatis (C.t.), the leading cause of bacterial sexually transmitted infections, employs a type III secretion system (T3SS) to translocate two classes of effectors, inclusion membrane proteins and conventional T3SS (cT3SS) effectors, into the host cell to counter host defense mechanisms. Here we employed three assays to directly evaluate secretion during infection, validating secretion for 23 cT3SS effectors. As bioinformatic analyses have been largely unrevealing, we conducted affinity purification-mass spectrometry to identify host targets and gain insights into the functions of these effectors, identifying high confidence interacting partners for 21 cT3SS effectors. We demonstrate that CebN localizes to the nuclear envelope in infected and bystander cells where it interacts with multiple nucleoporins and Rae1, blocking STAT1 nuclear import following IFN-γ stimulation. By building a cT3SS effector-host interactome, we have identified novel pathways that are targeted during bacterial infection and have begun to address how C.t. effectors combat cell autonomous immunity.

Construct validity of the 12-item Short Form Health Survey (SF-12) version 2 and the impact of lifestyle modifications on the health-related quality of life among Indian adults with prediabetes: results from the D-CLIP trial.

PURPOSE: This study aimed to validate the factor structure of the 12-item Short-Form (SF-12) health-related quality of life (HRQOL) survey for Indian adults and assess the impact of lifestyle modification on the SF-12 of Indian adults with prediabetes. METHODS: To validate the context-specific construct of the SF-12, two-factor confirmatory factor analysis (CFA) was performed using data from 1285 adults residing in Chennai, India, who screened for the Diabetes Community Lifestyle Improvement Program (D-CLIP). D-CLIP was a randomized controlled trial of 578 participants with prediabetes (283 treatment, 293 control), focusing on the effect of lifestyle modifications on the prevention of diabetes. Physical and mental component scores (PCS and MCS) were computed by using CFA standardized factor loadings. Multiple linear regression was subsequently conducted to estimate the effect of lifestyle modification on post-study changes of PCS and MCS among D-CLIP participants. RESULTS: Cronbach's alpha and CFA fit indices demonstrated acceptable reliability and model fit of the SF-12 for Indian adults. The intervention group showed greater mean change in PCS after study participation compared to the controls (1.63 ± 0.82, p = 0.046); no significant difference was observed for MCS between two groups (1.00 ± 0.85, p = 0.242). CONCLUSION: The study confirmed that the SF-12 is suitable for assessing the physical and mental health dimensions of HRQOL for Indian adults. Our findings suggest that the benefits of diabetes prevention lifestyle modification strategies may primarily enhance the physical well-being of adults with prediabetes. Further studies validating the SF-12 in a broader Asian Indian population are needed. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01283308.

Changes in Diabetes Care and Management Practices during the COVID-19 Pandemic.

Background: Evidence suggests diabetes management was negatively impacted early in the pandemic. However, the impact of the pandemic on key healthcare services for diabetes control and diabetes self-management practices is less known. We examined changes in diabetes care and management practices before and during the COVID-19 pandemic. Methods: Population-based data regarding 4 diabetes-related healthcare engagement and 4 self-management indicators were obtained from adults with diabetes surveyed in 19 US States and Washington DC through the Behavioral Risk Factor Surveillance System. Using logistic regression, we estimated changes in the prevalence of each indicator, overall and by sociodemographic subgroups, before (2019; n = 15,307) and during (2021; n = 13,994) the COVID-19 pandemic. Results: Between 2019 and 2021, the prevalence of biannual HbA1c tests reduced by 2.6 percentage points (pp, 95% CI :-4.8, -0.4), from 75.4-73.1%, and prevalence of annual eye exams fell by 4.0 pp (-6.2, -2.8), from 72.2-68.7%. The composite indicator of engagement with healthcare for diabetes control fell by 3.5 pp (-5.9, -1.1), from 44.9-41.9%. Reductions in engagement with healthcare were largely seen across sex, age, education, employment status, marital status, insurance status, and urbanicity; and were more pronounced among those aged 18-34 and the uninsured. Reductions in engagement with healthcare were seen in several states, with Delaware and Washington DC reporting the largest decrease. Of self-management behaviors, we only observed change in avoidance of smoking, an increase of 2.0 pp (0.4, 3.6) from 84.7-87.1%. Conclusions: The pandemic had mixed impacts on diabetes care and self-management. The findings suggest a deterioration of the uptake of evidence-based, preventive health services requiring laboratory services and clinical examination for diabetes control during the pandemic. On the other hand, smoking rates decreased, suggesting potential positive impacts of the pandemic on health behaviors in people with diabetes.

Perceived stress and progression of cardiometabolic risk factors among South Asians with prediabetes in a lifestyle intervention trial.

AIMS: To examine associations between perceived stress and cardiometabolic risk factors in South Asians with prediabetes and assess whether a diabetes prevention program mitigates the impact of stress on cardiometabolic health. METHODS: We conducted a secondary analysis of the Diabetes Community Lifestyle Improvement Program, a lifestyle modification trial for diabetes prevention in India (n = 564). Indicators for cardiometabolic health (weight, waist circumference, blood pressure, glucose, HbA1c, and lipids) were measured at each visit while perceived stress was assessed via questionnaire at baseline. Multivariable linear regression assessed associations between stress and cardiometabolic parameters at baseline and 3-year follow up. RESULTS: At baseline, perceived stress was associated with higher weight (b=0.16; 95% CI: 0.04, 0.29) and waist circumference (b=0.11; 95% CI: 0.01, 0.21) but lower 30-minute postload glucose (b=-0.44; 95% CI: -0.76, -0.14) and LDL cholesterol (b=-0.40; 95% CI: -0.76, -0.03). Over the study period, perceived stress was associated with weight gain (b=0.20; 95% CI: 0.07, 0.33) and increased waist circumference (b=0.14; 95% CI: 0.04, 0.24). Additionally, higher perceived stress was associated with lower HDL cholesterol among the control arm (pinteraction = 0.02). CONCLUSIONS: Baseline stress was associated with negative cardiometabolic risk factor outcomes over time in those with prediabetes.

Adapting and scaling a proven diabetes prevention program across 11 worksites in India: the INDIA-WORKS trial.

BACKGROUND: Structured lifestyle change education reduces the burden of cardiometabolic diseases such as diabetes. Delivery of these programs at worksites could overcome barriers to program adoption and improve program sustainability and reach; however, tailoring to the worksite setting is essential. METHODS: The Integrating Diabetes Prevention in Workplaces (INDIA-WORKS) study tested the implementation and effectiveness of a multi-level program for reducing cardiometabolic disease risk factors at 11 large and diverse worksites across India. Herein, we describe and classify program adaptations reported during in-depth interviews and focus group discussions with worksite managers, program staff, and peer educators involved in program delivery, and program participants and drop-outs. We used thematic analysis to identify key themes in the data and classified reported program adaptations using the FRAME classification system. RESULTS: Adaptations were led by worksite managers, peer educators, and program staff members. They occurred both pre- and during program implementation and were both planned (proactive) and unplanned (proactive and reactive). The most frequently reported adaptations to the individual-level intervention were curriculum changes to tailor lessons to the local context, make the program more appealing to the workers at the site, or add a wider variety of exercise options. Other content adaptations included improvements to the screening protocol, intervention scheduling, and outreach plans to tailor participant recruitment and retention to the sites. Environment-level content adaptations included expanding or leveraging healthy food and exercise options at the worksites. Challenges to adaptation included scheduling and worksite-level challenges. Participants discussed the need to continue adapting the program in the future to continue making it relevant for worksite settings and engaging for employees. CONCLUSION: This study describes and classifies site-specific modifications to a structured lifestyle change education program with worksite-wide health improvements in India. This adds to the literature on implementation adaptation in general and worksite wellness in India, a country with a large and growing workforce with, or at risk of, serious cardiometabolic diseases. This information is key for program scale-up, dissemination, and implementation in other settings. TRIAL REGISTRATION: Clinicaltrials.gov NCT02813668. Registered June 27, 2016.

A structural equation model of CFIR inner and outer setting constructs, organization characteristics, and national DPP enrollment.

BACKGROUND: The National Diabetes Prevention Program (DPP) has made great strides in increasing accessibility to its year-long, evidence-based lifestyle change program, with around 3000 organizations having delivered the program. This large dissemination effort offers a unique opportunity to identify organization-level factors associated with program implementation and reach (enrollment) across diverse settings. The purpose of this study was to quantitatively examine the relationships among Consolidated Framework for Implementation Research (CFIR) Inner Setting and Outer Setting constructs and the implementation outcome of reach. METHODS: This study analyzed data from a 2021 cross-sectional online survey with 586 National DPP Staff (lifestyle coaches, master trainers, program coordinators) with information about their organization, implementation outcomes, and responses to quantitative CFIR Inner Setting and Outer Setting construct items. Structural equation modeling was used to test a hypothesized path model with Inner and Outer Setting variables to explore direct and indirect pathways to enrollment. RESULTS: The CFIR items had good internal consistency and indicated areas of implementation strength and weakness. Eight variables included as part of the CFIR structural characteristics and one organization characteristic variable had significant direct relationships with enrollment. The length of delivery, number of lifestyle coaches, number of full-time staff, large organization size, and organizations delivering in rural, suburban, and/or urban settings all had positive significant direct relationships with enrollment, while academic organizations and organizations with only non-White participants enrolled in their National DPP lifestyle change programs had a negative association with enrollment. CONCLUSIONS: Participant reach is an important implementation outcome for the National DPP and vital to making population-level decreases in diabetes incidence in the USA. Our findings suggest that to facilitate enrollment, program implementers should focus on organizational structural characteristics such as staffing. Strengths of this study include the use of adapted and newly developed quantitative CFIR measures and structural equation modeling. Health prevention programs can use the methods and findings from this study to further understand and inform the impact of organization factors on implementation outcomes.

Patterns of Sustainability Capacity Among Organizations That Deliver the National Diabetes Prevention Program: A Latent Profile Analysis.

INTRODUCTION: Since the launch of the National Diabetes Prevention Program (DPP) in 2010, more than 3,000 organizations have registered with the Centers for Disease and Control and Prevention to deliver the program; today, however, only approximately 2,000 organizations are registered, indicating challenges with sustainability. We used the Program Sustainability Assessment Tool (PSAT) to explore patterns of sustainability capacity among National DPP delivery organizations. METHODS: We used data from a cross-sectional online survey conducted in August and September 2021 of staff members (N = 440) at National DPP delivery organizations. We conducted a latent profile analysis to identify latent subpopulations on the basis of respondent PSAT domain scores. Regression analyses were used to estimate associations between derived latent classes, PSAT scores, and respondent characteristics. RESULTS: The 4-class model included 4 groups of capacity for program sustainability, ranging from low to high: low (class 1) with 8.0% of the sample, medium-low (class 2) with 22.0%, medium-high (class 3) with 41.6%, and high (class 4) with 28.4%. Program evaluation (mean score = 5.1 [SD = 1.4]) and adaptation (mean score = 5.3 [SD = 1.3]) were the domains with the highest scores, while funding stability (mean score = 4.0 [SD = 1.6]) and Partnerships (mean score = 4.0 [SD = 1.7]) had the lowest scores. In our sample of National DPP delivery organizations, most reported relatively high capacity for program sustainability, and key indicators associated with sustainability capacity were virtual delivery, location of delivery, funding sources, and organization type. DISCUSSION: Similar to sustainability capacity findings from other PSAT studies, our study found that funding stability and partnerships are areas to strengthen. This insight is useful in sustainability planning at organizational and national levels across multiple programs.

Global implementation research capacity building to address cardiovascular disease: An assessment of efforts in eight countries.

Cardiovascular diseases are the leading causes of morbidity and mortality worldwide, but implementation of evidence-based interventions for risk factors such as hypertension is lacking, particularly in low and middle income countries (LMICs). Building implementation research capacity in LMICs is required to overcome this gap. Members of the Global Research on Implementation and Translation Science (GRIT) Consortium have been collaborating in recent years to establish a research and training infrastructure in dissemination and implementation to improve hypertension care. GRIT includes projects in Ghana, Guatemala, India, Kenya, Malawi, Nepal, Rwanda, and Vietnam. We collected data from each site on capacity building activities using the Potter and Brough (2004) model, mapping formal and informal activities to develop (a) structures, systems and roles, (b) staff and infrastructure, (c) skills, and (d) tools. We captured information about sites' needs assessments and metrics plus program adaptations due to the COVID-19 pandemic. All sites reported capacity building activities in each layer of the Capacity Pyramid, with the largest number of activities in the Skills and Tools categories, the more technical and easier to implement categories. All sites included formal and informal training to build Skills. All sites included a baseline needs assessment to guide capacity building activities or assess context and inform intervention design. Sites implementing evidence-based hypertension interventions used common implementation science frameworks to evaluate implementation outcomes. Although the COVID-19 pandemic affected timelines and in-person events, all projects were able to pivot and carry out planned activities. Although variability in the activities and methods used existed, GRIT programs used needs assessments to guide locally appropriate design and implementation of capacity building activities. COVID-19 related changes were necessary, but strong collaborations and relationships with health ministries were maintained. The GRIT Consortium is a model for planning capacity building in LMICs.

National Changes in Diabetes Care Practices during the COVID-19 Pandemic: Prospective Study of US Adults.

Background: There is a lack of nationally representative prospective data on the impact of the COVID-19 pandemic on diabetes care and management in adults with type 2 diabetes. We examined changes in diabetes care and management practices before and after the onset of the COVID-19 pandemic. Methods: Using the National Health Interview Survey, we analyzed data from 870 adults living with type 2 diabetes who were interviewed in 2019 and re-interviewed between August and December 2020. Exposure to the COVID-19 pandemic was defined by year of survey (2019, pre-pandemic; 2020, pandemic). We estimated percent change in past year blood sugar check by a health professional and current use of blood sugar lowering medication overall and by sociodemographic subgroups. Results: Receiving an annual blood sugar test fell by -3.3 percentage points (pp) (95% CI -5.7, -1.0), from 98.3% in 2019 to 95.0% in late 2020. The reduction in annual blood glucose testing was largely consistent across socio-demographic groups and was particularly pronounced among adults not working and adults aged 65 years and older. In the same time period, current use of diabetes medications increased by +3.8 pp (0.7, 6.9), from 85.9% to 89.7%. The increase in medication use was most pronounced among individuals aged 40-64-year old, employed, and those living in large central metropolitan areas. Conclusions: Nationally, adults with Type 2 diabetes reported a reduction in annual blood glucose testing by a health professional and an increase in diabetes medication usage during the COVID-19 pandemic. If sustained after the end of the COVID-19 public health emergency, these changes have implications for national diabetes management and care.

Effect of Conventional Lifestyle Interventions on Type 2 Diabetes Incidence by Glucose-Defined Prediabetes Phenotype: An Individual Participant Data Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To examine whether the effect of conventional lifestyle interventions on type 2 diabetes incidence differs by glucose-defined prediabetes phenotype. RESEARCH DESIGN AND METHODS: We searched multiple databases until 1 April 2023 for randomized controlled trials that recruited people with isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), and impaired fasting glucose plus impaired glucose tolerance (IFG+IGT). Individual participant data were pooled from relevant trials and analyzed through random-effects models with use of the within-trial interactions approach. RESULTS: Four trials with 2,794 participants (mean age 53.0 years, 60.7% men) were included: 1,240 (44.4%), 796 (28.5%), and 758 (27.1%) had i-IFG, i-IGT, and IFG+IGT, respectively. After a median of 2.5 years, the pooled hazard ratio for diabetes incidence in i-IFG was 0.97 (95% CI 0.66, 1.44), i-IGT 0.65 (0.44, 0.96), and IFG+IGT 0.51 (0.38, 0.68; Pinteraction = 0.01). CONCLUSIONS: Conventional lifestyle interventions reduced diabetes incidence in people with IGT (with or without IFG) but not in those with i-IFG.

Adapting and scaling a proven diabetes prevention program across 11 worksites in India: the INDIA-WORKS trial.

Background: Delivery of proven structured lifestyle change education for reducing the burden of cardiometabolic diseases such as diabetes at worksites could overcome barriers to program adoption and improve sustainability and reach of these programs; however, tailoring to the worksite setting is essential. Methods: The Integrating Diabetes Prevention in Workplaces (INDIA-WORKS) study tested the implementation and effectiveness of a multi-level program for reducing cardiometabolic disease risk factors at eleven large and diverse worksites across India. Herein, we describe and classify program adaptations reported during in-depth interviews and focus group discussions with worksite managers, program staff, peer educators involved in program delivery, and program participants and drop-outs. We used thematic analysis to identify key themes in the data and classified reported program adaptations using the FRAME classification system. Results: Adaptations were led by worksite managers, peer educators, and program staff members. They occurred both pre- and during program implementation and were both planned (proactive) and unplanned (proactive and reactive). The most frequently reported adaptations to the individual-level intervention were curriculum changes to tailor lessons to the local context, make the program more appealing to the workers at the site, or add exercise options. Other content adaptations included improvements to the screening protocol, intervention scheduling, and outreach plans to tailor participant recruitment and retention to the sites. Environment-level content adaptations included expanding or leveraging healthy food and exercise options at the worksites. Challenges to adaptation included scheduling and worksite-level challenges. Participants discussed the need to continue adapting the program in the future to continue making it relevant for worksite settings and engaging for employees. Conclusion: This study describes and classifies site-specific modifications to a structured lifestyle change education program with worksite-wide health improvements in India. This adds to the literature on implementation adaptation in general and worksite wellness in India, a country with a large and growing workforce with, or at risk of, serious cardiometabolic diseases. This information is key for program scale-up, dissemination, and implementation in other settings. Trial Registration: Clinicaltrial.gov NCT02813668, registered June 27, 2016.

Identification and Preliminary Characterization of Novel Type III Secreted Effector Proteins in Chlamydia trachomatis.

Chlamydia trachomatis is an obligate intracellular pathogen that replicates in a host-derived vacuole termed the inclusion. Central to pathogenesis is a type III secretion system that translocates effector proteins into the host cell, which are predicted to play major roles in host cell invasion, nutrient acquisition, and immune evasion. However, until recently, the genetic intractability of C. trachomatis hindered identification and characterization of these important virulence factors. Here, we sought to expand the repertoire of identified effector proteins and confirm they are secreted during C. trachomatis infection. Utilizing bioinformatics, we identified 18 candidate substrates that had not been previously assessed for secretion, of which we show four to be secreted, using Yersinia pseudotuberculosis as a surrogate host. Using adenylate cyclase (CyaA), BlaM, and glycogen synthase kinase (GSK) secretion assays, we identified nine novel substrates that were secreted in at least one assay. Interestingly, only three of the substrates, shown to be translocated by C. trachomatis, were similarly secreted by Y. pseudotuberculosis. Using large-scale screens to determine subcellular localization and identify effectors that perturb crucial host cell processes, we identified one novel substrate, CT392, that is toxic when heterologously expressed in Saccharomyces cerevisiae. Toxicity required both the N- and C-terminal regions of the protein. Additionally, we show that these newly described substrates traffic to distinct host cell compartments, including vesicles and the cytoplasm. Collectively, our study expands the known repertoire of C. trachomatis secreted factors and highlights the importance of testing for secretion in the native host using multiple secretion assays when possible.

Disparities in diabetes prevalence and management by race and ethnicity in the USA: defining a path forward.

Type 2 diabetes disparities in the USA persist in both the prevalence of disease and diabetes-related complications. We conducted a literature review related to diabetes prevention, management, and complications across racial and ethnic groups in the USA. The objective of this review is to summarise the current understanding of diabetes disparities by examining differences between and within racial and ethnic groups and among young people (aged <18 years). We also examine the pathophysiology of diabetes as it relates to race and ethnic differences. We use a conceptual framework built on the socioecological model to categorise the causes of diabetes disparities across the lifespan looking at factors in five domains of health behaviours and social norms, public awareness, structural racism, economic development, and access to high-quality care. The range of disparities in diabetes prevalence and management in the USA calls for a community-engaged and multidisciplinary approach that must involve community partners, researchers, practitioners, health system administrators, and policy makers. We offer recommendations for each of these groups to help to promote equity in diabetes prevention and care in the USA.

The Chlamydia trachomatis type III-secreted effector protein CteG induces centrosome amplification through interactions with centrin-2.

The centrosome is the main microtubule organizing center of the cell and is crucial for mitotic spindle assembly, chromosome segregation, and cell division. Centrosome duplication is tightly controlled, yet several pathogens, most notably oncogenic viruses, perturb this process leading to increased centrosome numbers. Infection by the obligate intracellular bacterium Chlamydia trachomatis (C.t.) correlates with blocked cytokinesis, supernumerary centrosomes, and multipolar spindles; however, the mechanisms behind how C.t. induces these cellular abnormalities remain largely unknown. Here we show that the secreted effector protein, CteG, binds to centrin-2 (CETN2), a key structural component of centrosomes and regulator of centriole duplication. Our data indicate that both CteG and CETN2 are necessary for infection-induced centrosome amplification, in a manner that requires the C-terminus of CteG. Strikingly, CteG is important for in vivo infection and growth in primary cervical cells but is dispensable for growth in immortalized cells, highlighting the importance of this effector protein to chlamydial infection. These findings begin to provide mechanistic insight into how C.t. induces cellular abnormalities during infection, but also indicate that obligate intracellular bacteria may contribute to cellular transformation events. Centrosome amplification mediated by CteG-CETN2 interactions may explain why chlamydial infection leads to an increased risk of cervical or ovarian cancer.

Screening and Brief Interventions for Alcohol Use During Pregnancy: Practices Among US Primary Care Clinicians, DocStyles 2019.

INTRODUCTION: Alcohol use during pregnancy can cause birth defects and developmental disabilities. From 2018 through 2020, 13.5% of pregnant women reported current drinking. The US Preventive Services Task Force recommends evidence-based tools (eg, AUDIT-C and SASQ) for implementing screening and brief interventions to reduce excessive alcohol use among adults, including pregnant people, for whom any alcohol use is considered excessive. METHODS: We used DocStyles 2019 data to conduct a cross-sectional analysis to examine current screening and brief intervention practices that primary care clinicians conduct among pregnant patients; clinicians' confidence levels in conducting screening, brief interventions, and referral to treatment; and the documentation of brief interventions in the medical record. RESULTS: A total of 1,500 US adult medicine clinicians completed the entire survey. Among the respondents who conduct screening (N = 1,373) and brief interventions (N = 1,357) in their practice, nearly all reported implementing screening (94.6%) and brief interventions (94.9%) with their pregnant patients for alcohol use, but fewer than half felt confident about conducting their screening practices (46.5%). Two-thirds (64%) reported using a tool that met the criteria recommended by the US Preventive Services Task Force (USPSTF). Over half documented brief interventions in electronic health record notes (51.7%) or designated space (50.7%). CONCLUSION: Pregnancy presents a unique opportunity for clinicians to incorporate screening into routine obstetric care and encourage behavior change among patients. Most providers reported always screening their pregnant patients for alcohol use, but fewer used evidence-based USPSTF-recommended screening tools. Increased clinician confidence in screening and brief intervention, the use of standardized screening tools tailored to pregnant people, and maximal use of electronic health record technology may enhance the benefits of their application to alcohol use, which ultimately can reduce adverse outcomes associated with alcohol use during pregnancy.

Infant and young child feeding practices and the factors that influence them: a qualitative study.

BACKGROUND: Early child feeding is important for healthy growth and forming positive eating behaviors. METHODS: This qualitative study sought to describe early childhood feeding behaviors, challenges, and opportunities through four focus group discussions with a diverse group of mothers of at least one child under two years or pregnant with their first child. RESULTS: Although providing healthy foods was a priority, feeding behaviors reflected the mothers' partial understanding of infant and child nutrition. Mothers sought guidance on early child feeding from several sources, including in-person and virtual relationships but made decisions based largely on their own instincts. Participants consulted clinicians the least often, and mothers often felt frustrated by strict guidelines and negative messaging. Mothers were most receptive to suggestions when they felt supported and valued in the decision-making process. CONCLUSIONS: In order to help mothers provide the best nutrition for their young children, clinicians should use positive tones, provide flexibility when possible, and work to create open lines of communication with parents.

In Search of a Mechanistic Link between Chlamydia trachomatis-Induced Cellular Pathophysiology and Oncogenesis.

Centrosome duplication and cell cycle progression are essential cellular processes that must be tightly controlled to ensure cellular integrity. Despite their complex regulatory mechanisms, microbial pathogens have evolved sophisticated strategies to co-opt these processes to promote infection. While misregulation of these processes can greatly benefit the pathogen, the consequences to the host cell can be devastating. During infection, the obligate intracellular pathogen Chlamydia trachomatis induces gross cellular abnormalities, including supernumerary centrosomes, multipolar spindles, and defects in cytokinesis. While these observations were made over 15 years ago, identification of the bacterial factors responsible has been elusive due to the genetic intractability of Chlamydia. Recent advances in techniques of genetic manipulation now allows for the direct linking of bacterial virulence factors to manipulation of centrosome duplication and cell cycle progression. In this review, we discuss the impact, both immediate and downstream, of C. trachomatis infection on the host cell cycle regulatory apparatus and centrosome replication. We highlight links between C. trachomatis infection and cervical and ovarian cancers and speculate whether perturbations of the cell cycle and centrosome are sufficient to initiate cellular transformation. We also explore the biological mechanisms employed by Inc proteins and other secreted effector proteins implicated in the perturbation of these host cell pathways. Future work is needed to better understand the nuances of each effector's mechanism and their collective impact on Chlamydia's ability to induce host cellular abnormalities.

Improving Access to Integrated Behavioral Health in a Nurse-Led Federally Qualified Health Center.

INTRODUCTION: All patients of a nurse-led federally qualified health center and faculty practice interested in medication management were automatically referred to the psychiatric mental health nurse practitioner in the clinic. This approach was not sustainable to provide access to patients who needed both simple and complex medication management. Thus, a search for a new care model that also focused on the full-scope practice of a psychiatric RN was initiated. AIMS: The specific aims of this project were to create a fully integrated, nurse-led model of a psychiatric nurse practitioner and behavioral health care team within primary care to facilitate (1) patients receiving an appropriate level of care and (2) care team members performing at the top of their scope of practice. METHODS: The guiding model for process implementation was Rapid Cycle Quality Improvement. Three task forces were established to develop interventions in the areas of Roles and Responsibilities, Training and Implementation, and the electronic health record. RESULTS: The process measures of referrals to the psychiatric care team and psychiatric assessment intakes performed as expected. Both measures were higher at the onset of the project and lower 1 year later. The outcome indicator, number of case reviews, increased dramatically over time. CONCLUSIONS: For psychiatric nurse practitioners, this quality improvement effort provides evidence that a consultative role can be effective in supporting primary care providers. Through providing education, establishing patient tiers, and establishing an effective workflow, more patients may have access to psychiatric services.

Training in eight low-and middle-income countries: lessons learned from a pilot study using the WHO-TDR dissemination and implementation massive open online course.

Introduction: Non-communicable diseases (NCDs) are a leading cause of morbidity and mortality in low-and middle- income countries (LMICs). Despite this, a lack of funding, training and mentorship for NCD investigators in LMICs exists. In an effort to gain knowledge and skills to address these gaps, participants from the Global Research on Implementation and Translation Science (GRIT), a consortium of studies in eight LMICs and their networks, attended the dissemination and implementation (D&I) massive open online course (MOOC) developed by the Special Programme for Research and Training in Tropical Diseases at the World Health Organization to strengthen D&I capacity building. Here, we report on the pilot of this MOOC, which was implemented during the SARS COVID-19 pandemic from April- November 2020. Methods: Participants completed pre-and post-training questionnaires to assess self-reported D&I competencies, general research skills, and research mentor access and quality. D&I competencies were measured by use of a scale developed for a US-based training program, with change in competency scores assessed by paired t test. We used univariate statistics to analyze the data for all other outcomes. Results: Of the 247 participants enrolled, 32 (13%) completed all course requirements, 21 (9%) completed the pre-and post-surveys and are included in the analysis. D&I competency scores suggest improvement for those who had complete pre- and post-assessments. Trainee's average score on the full competency scale improved 1.45 points (0-5 scale) from pre- to post-test; all four subscales also showed evidence of improvements. There were small but not significant increases in competencies for grant writing, proposal/ manuscript writing and presentations from pre- to post-test assessment. 40% of trainees reported access to a research mentor and 12% reported access to a D&I specific mentor. Participants reported barriers (e.g., unstable internet access and challenges due to COVID-19) and facilitators (e.g., topical interests, collaboration with colleagues) to completing the MOOC. Conclusions: Although COVID-19 affected program usage and completion, the MOOC was feasible. We also had signals of effectiveness, meaning among LMIC participants completing the course, there was improvement in self-report D&I competency scores. Recommendations for future D&I trainings in LMICs include (1) adding more topic specific modules (i.e., NCD research, general research skills) for scalability; (2) fostering more collaboration with participants across LMICs; and (3) establishing partnerships with D&I mentors for course participants.

Inner and outer setting factors that influence the implementation of the National Diabetes Prevention Program (National DPP) using the Consolidated Framework for Implementation Research (CFIR): a qualitative study.

BACKGROUND: Scaling evidence-based interventions are key to impacting population health. The National DPP lifestyle change program is one such intervention that has been scaled across the USA over the past 20 years; however, enrollment is an ongoing challenge. Furthermore, little is known about which organizations are most successful with program delivery, enrollment, and scaling. This study aims to understand more about the internal and external organization factors that impact program implementation and reach. METHODS: Between August 2020 and January 2021, data were collected through semi-structured key informant interviews with 30 National DPP delivery organization implementers. This study uses a qualitative cross-case construct rating methodology to assess which Consolidated Framework for Implementation Research (CFIR) inner and outer setting constructs contributed (both in valence and magnitude) to the organization's current level of implementation reach (measured by average participant enrollment per year). A construct by case matrix was created with ratings for each CFIR construct by interviewee and grouped by implementation reach level. RESULTS: Across the 16 inner and outer setting constructs and subconstructs, the interviewees with greater enrollment per year provided stronger and more positive examples related to implementation and enrollment of the program, while the lower reach groups reported stronger and more negative examples across rated constructs. Four inner setting constructs/subconstructs (structural characteristics, compatibility, goals and feedback, and leadership engagement) were identified as "distinguishing" between enrollment reach levels based on the difference between groups by average rating, the examination of the number of extreme ratings within levels, and the thematic analysis of the content discussed. Within these constructs, factors such as organization size and administrative processes; program fit with existing organization services and programs; the presence of enrollment goals; and active leadership involvement in implementation were identified as influencing program reach. CONCLUSIONS: Our study identified a number of influential CFIR constructs and their impact on National DPP implementation reach. These findings can be leveraged to improve efforts in recruiting and assisting delivery organizations to increase the reach and scale of the National DPP as well as other evidence-based interventions.