Cleavage of roquin and regnase-1 by the paracaspase MALT1 releases their cooperatively repressed targets to promote T(H)17 differentiation.

Humoral autoimmunity paralleled by the accumulation of follicular helper T cells (T(FH) cells) is linked to mutation of the gene encoding the RNA-binding protein roquin-1. Here we found that T cells lacking roquin caused pathology in the lung and accumulated as cells of the T(H)17 subset of helper T cells in the lungs. Roquin inhibited T(H)17 cell differentiation and acted together with the endoribonuclease regnase-1 to repress target mRNA encoding the T(H)17 cell-promoting factors IL-6, ICOS, c-Rel, IRF4, IκBNS and IκBζ. This cooperation required binding of RNA by roquin and the nuclease activity of regnase-1. Upon recognition of antigen by the T cell antigen receptor (TCR), roquin and regnase-1 proteins were cleaved by the paracaspase MALT1. Thus, this pathway acts as a 'rheostat' by translating TCR signal strength via graded inactivation of post-transcriptional repressors and differential derepression of targets to enhance T(H)17 differentiation.

Chatbot-Delivered COVID-19 Vaccine Communication Message Preferences of Young Adults and Public Health Workers in Urban American Communities: Qualitative Study.

BACKGROUND: Automated conversational agents, or chatbots, have a role in reinforcing evidence-based guidance delivered through other media and offer an accessible, individually tailored channel for public engagement. In early-to-mid 2021, young adults and minority populations disproportionately affected by COVID-19 in the United States were more likely to be hesitant toward COVID-19 vaccines, citing concerns regarding vaccine safety and effectiveness. Successful chatbot communication requires purposive understanding of user needs. OBJECTIVE: We aimed to review the acceptability of messages to be delivered by a chatbot named VIRA from Johns Hopkins University. The study investigated which message styles were preferred by young, urban-dwelling Americans as well as public health workers, since we anticipated that the chatbot would be used by the latter as a job aid. METHODS: We conducted 4 web-based focus groups with 20 racially and ethnically diverse young adults aged 18-28 years and public health workers aged 25-61 years living in or near eastern-US cities. We tested 6 message styles, asking participants to select a preferred response style for a chatbot answering common questions about COVID-19 vaccines. We transcribed, coded, and categorized emerging themes within the discussions of message content, style, and framing. RESULTS: Participants preferred messages that began with an empathetic reflection of a user concern and concluded with a straightforward, fact-supported response. Most participants disapproved of moralistic or reasoning-based appeals to get vaccinated, although public health workers felt that such strong statements appealing to communal responsibility were warranted. Responses tested with humor and testimonials did not appeal to the participants. CONCLUSIONS: To foster credibility, chatbots targeting young people with vaccine-related messaging should aim to build rapport with users by deploying empathic, reflective statements, followed by direct and comprehensive responses to user queries. Further studies are needed to inform the appropriate use of user-customized testimonials and humor in the context of chatbot communication.

Evaluating dose delivered of a behavioral intervention for childhood obesity prevention: a secondary analysis.

BACKGROUND: Current recommendations for intensive behavioral interventions for childhood obesity treatment do not account for variable participant attendance, optimal duration of the intervention, mode of delivery (phone vs. face-to-face), or address obesity prevention among young children. A secondary analysis of an active one-year behavioral intervention for childhood obesity prevention was conducted to test how "dose delivered" was associated with body mass index z-score (BMI-Z) across 3 years of follow-up. METHODS: Parent-child pairs were eligible if they qualified for government assistance and spoke English or Spanish. Children were between three and 5 years old and were at risk for but not yet obese (BMI percentiles ≥50th and < 95th). The intended intervention dose was 18 h over 3-months via 12 face-to-face "intensive sessions" (90 min each) and 6.75 h over the next 9 months via 9 "maintenance phone calls" (45 min each). Ordinary least-squares multivariable regression was utilized to test for associations between dose delivered and child BMI-Z immediately after the 1-year intervention, and at 2-, and 3-year follow-up, including participants who were initially randomized to the control group as having "zero" dose. RESULTS: Among 610 parent-child pairs (intervention n = 304, control n = 306), mean child age was 4.3 (SD = 0.9) years and 51.8% were female. Mean dose delivered was 10.9 (SD = 2.5) of 12 intensive sessions and 7.7 (SD = 2.4) of 9 maintenance calls. Multivariable linear regression models indicated statistically significant associations of intensive face-to-face contacts (B = -0.011; 95% CI [- 0.021, - 0.001]; p = 0.029) and maintenance calls (B = -0.015; 95% CI [- 0.026, - 0.004]; p = 0.006) with lower BMI-Z immediately following the 1-year intervention. Their interaction was also significant (p = 0.04), such that parent-child pairs who received higher numbers of both face-to-face intensive sessions (> 6) and maintenance calls (> 8) were predicted to have lower BMI-Z. Sustained impacts were not statistically significant at 2- or 3-year follow-up. CONCLUSIONS: In a behavioral intervention for childhood obesity prevention, the combination of a modest dose of face-to-face sessions (> 6 h over 3 months) with sustained maintenance calls (> 8 calls over 9 months) was associated with improved BMI-Z at 1-year for underserved preschool aged children, but sustained impacts were not statistically significant at 2 or 3 year follow-up. CLINICAL TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov (NCT01316653) on March 16, 2011, which was prior to participant enrollment.

Recipient and donor experiences of known egg donation: implications for fertility counselling.

OBJECTIVE: To explore the experiences of known egg donors and recipients in order to inform counselling practise. BACKGROUND: Relatively little is known about known egg donation as a form of family-building in the UK, and on the experiences of individuals who have sought this form of donation. As such, there is a lack of guidance for fertility counselling in this area. METHOD: This was a cross-sectional, qualitative study. A purposive sample of four recipient women were recruited via a national support group for women experiencing Premature Ovarian Insufficiency (POI). Known egg donors (n = 3) and recipient men (n = 3) were recruited via a snowball sample, as identified by recipient women. In-depth interviews were conducted with participants. Interviews were transcribed and analysed using thematic analysis. RESULTS: Four themes were generated from the data: 1) 'Doing anything': existing relationships as the motivation to donate; 2) 'It was my duty': feelings of obligation to donate and to receive; 3) 'Woman-to-woman': a woman-centred experience; and 4) 'Going through this together': changed versus unchanged relationships. CONCLUSIONS: The study highlights a number of implications in known egg donation, arising from the relationships involved. It is recommended that these implications are considered by infertility counsellors in the provision of counselling, and by those undergoing known egg donation when seeking information and support, before, during and after the donation.

Interleukin-10 Modulation of Virus Clearance and Disease in Mice with Alphaviral Encephalomyelitis.

Alphaviruses are an important cause of mosquito-borne outbreaks of arthritis, rash, and encephalomyelitis. Previous studies in mice with a virulent strain (neuroadapted SINV [NSV]) of the alphavirus Sindbis virus (SINV) identified a role for Th17 cells and regulation by interleukin-10 (IL-10) in the pathogenesis of fatal encephalomyelitis (K. A. Kulcsar, V. K. Baxter, I. P. Greene, and D. E. Griffin, Proc Natl Acad Sci U S A 111:16053-16058, 2014, https://doi.org/10.1073/pnas.1418966111). To determine the role of virus virulence in generation of immune responses, we analyzed the modulatory effects of IL-10 on disease severity, virus clearance, and the CD4+ T cell response to infection with a recombinant strain of SINV of intermediate virulence (TE12). The absence of IL-10 during TE12 infection led to longer morbidity, more weight loss, higher mortality, and slower viral clearance than in wild-type mice. More severe disease and impaired virus clearance in IL-10-/- mice were associated with more Th1 cells, fewer Th2 cells, innate lymphoid type 2 cells, regulatory cells, and B cells, and delayed production of antiviral antibody in the central nervous system (CNS) without an effect on Th17 cells. Therefore, IL-10 deficiency led to more severe disease in TE12-infected mice by increasing Th1 cells and by hampering development of the local B cell responses necessary for rapid production of antiviral antibody and virus clearance from the CNS. In addition, the shift from Th17 to Th1 responses with decreased virus virulence indicates that the effects of IL-10 deficiency on immunopathologic responses in the CNS during alphavirus infection are influenced by virus strain.IMPORTANCE Alphaviruses cause mosquito-borne outbreaks of encephalomyelitis, but determinants of outcome are incompletely understood. We analyzed the effects of the anti-inflammatory cytokine IL-10 on disease severity and virus clearance after infection with an alphavirus strain of intermediate virulence. The absence of IL-10 led to longer illness, more weight loss, more death, and slower viral clearance than in mice that produced IL-10. IL-10 influenced development of disease-causing T cells and entry into the brain of B cells producing antiviral antibody. The Th1 pathogenic cell subtype that developed in IL-10-deficient mice infected with a less virulent virus was distinct from the Th17 subtype that developed in response to a more virulent virus, indicating a role for virus strain in determining the immune response. Slow production of antibody in the nervous system led to delayed virus clearance. Therefore, both the virus strain and the host response to infection are important determinants of outcome.

Predicting Early Emergence of Childhood Obesity in Underserved Preschoolers.

OBJECTIVE: To determine the magnitude of risk of factors that contribute to the emergence of childhood obesity among low-income minority children. STUDY DESIGN: We conducted a prospective cohort analysis of parent-child pairs with children aged 3-5 years who were nonobese (n = 605 pairs) who participated in a 3-year randomized controlled trial of a healthy lifestyle behavioral intervention. After baseline, height and weight were measured 5 times over 3 years to calculate body mass index (BMI) percentiles and classify children as normal, overweight, or obese. Multivariable logistic regression was used to estimate the odds of obesity after 36 months. Predictors included age, sex, birth weight, gestational age, months of breastfeeding, ethnicity, baseline child BMI, energy intake, physical activity, food security, parent baseline BMI, and parental depression. RESULTS: Among this predominantly low-income minority population, 66% (398/605) of children were normal weight at baseline and 34% (n = 207/605) were overweight. Among normal weight children at baseline, 24% (85/359) were obese after 36 months; among overweight children at baseline, 55% (n = 103/186) were obese after 36 months. Age at enrollment (OR 2.11, 95% CI 1.64-2.72), child baseline BMI (OR 3.37, 95% CI 2.51-4.54), and parent baseline BMI (OR for a 6-unit change 1.36, 95% CI 1.09-1.70) were significantly associated with the odds of becoming obese for children. CONCLUSIONS: The combination of child age, parent BMI, and child overweight as predictors of child obesity suggest a paradigm of family-centered obesity prevention beginning in early childhood, emphasizing the relevance of child overweight as a phenotype highly predictive of child obesity. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01316653.

Research Capacity Strengthening in Sub-Saharan Africa: Recognizing the Importance of Local Partnerships in Designing and Disseminating HIV Implementation Science to Reach the 90-90-90 Goals.

Capacity building in implementation science is integral to PEPFAR's mission and to meeting the 90-90-90 goals. The USAID funded Project SOAR sponsored a 4 day workshop for investigators and governmental and non-governmental partners from 12 African countries. The workshop was designed to address both findings from a pre-workshop online needs assessment as well as capacity challenges across the capacity building pyramid, from individual skills to institutional systems and resources. Activities were output-oriented and skill based. An online survey evaluated sessions and changes in perceptions of needs; a majority of respondents strongly agreed that after the workshop, they better understood their personal and institutional capacity strengthening needs. Participants 'strongly agreed' that workshop content was relevant to their jobs (90%) and that they left the workshop with a specific plan for conducting future research (65%). Workshop results suggest that skill-building should be done in conjunction with systems capacity building within the cultural context.

Are you ready? A systematic review of pre-departure resources for global health electives.

BACKGROUND: There has been an exponential increase in the offering of short-term international field experiences in recent years in response to student demands for global health opportunities. Pre-departure preparation is an essential component to equip trainees with the adequate safety, wellness, and cultural competence needed to engage in a meaningful and mutually beneficial elective. This review seeks to quantify the plethora of pre-departure preparation training available to public health, clinical, and undergraduate trainees across the continuum of education for short-term experiences in low-and middle-income countries (LMICs). METHODS: We performed a systematic review of Pubmed, Embase, Web of Science, Scopus, and Ovid Global Health in February, 2018. A three-concept search was employed and included "global or international health"; "education or preparation of personnel/students"; and "field programs or travel." The study teamed used PRISMA reporting guidelines to conduct title and full-text reviews and conduct data extraction and analysis. RESULTS: The search returned 2506 unique articles. Of these, 55 met inclusion criteria and were included in the final review. Ninety one percent (91%) of articles focused on pre-departure trainings for medical students and residents. Nine thematic domains for short-term international field experiences emerged; culture, safety, and project-specific knowledge were the most frequently covered domains while mentorship, professionalism, and emotional wellness and culture shock were least common. Approximately half (53.3%) of studies specifically evaluated the pre-departure component of the international experience using a survey or evaluation form. Recommendations emerged from these evaluations including early engagement with international partners, inclusion of self-reflection exercises and site-specific content, and utilization of interactive approaches in learning. Some institutions face barriers to conducting pre-departure preparation such as lack of dedicated faculty, finances, and institutional support. CONCLUSIONS: Interest in pre-departure training for international experiences is growing but few programs conduct and publish evaluations of these trainings. Pre-departure trainings should be developed in partnership with receiving institutions and faculty and incorporate critical self- reflection throughout the experience. In addition to the experience itself, institutions need to evaluate these curricula to better understand how they influence trainees' capacity to effectively engage in LMIC settings.

Sustained adoption of water, sanitation and hygiene interventions: systematic review.

OBJECTIVE: To understand factors that influence sustained adoption of water, sanitation and hygiene (WASH) technologies or behaviours. METHODS: Systematic review of the current literature. Articles were gathered from databases of peer-reviewed articles and grey literature, and screened for relevance. After exclusion, we created a descriptive map of 148 articles and analysed in-depth 44 articles that had an explicit focus on promoting or evaluating sustained adoption or programme sustainability. Twenty-two of these articles met our definition of measuring sustained adoption. RESULTS: Definitions of sustained adoption varied widely and were often inadequate, making comparison of sustained adoption across studies difficult. The time frame for measurements of sustained adoption is frequently inadequate for examination of longer-term behaviour change. CONCLUSIONS: Ideally, an evaluation should specify the project period and describe the context surrounding adoption, make measurements at multiple time points, diversify measurement methods and describe and measure a range of factors affecting sustained adoption. Additional consideration needs to be given to developing behaviour change models that emphasise factors related to sustained adoption, and how they differ from those related to initial adoption.

"The era of single disease cowboys is out": evaluating the experiences of students, faculty, and collaborators in an interdisciplinary global health training program.

BACKGROUND: Global Health is an inherently interdisciplinary field but overseas training in global health, particularly among health science institutions, has been an 'individual' or 'individual discipline' experience. Team-based training is an approach to global health education which is increasing in popularity; research on team-training demonstrates that teams are more productive than individuals. In 2015, the Johns Hopkins Center for Global Health (CGH) developed the Global Established Multidisciplinary Sites (GEMS) program, an interdisciplinary training program which was designed to establish a new norm in global health training by bringing interdisciplinary teams of faculty and students together to identify and solve complex global health challenges. This research aims to evaluate the program's first year and contribute to the literature on interdisciplinary team training. We conducted 22 in-depth interviews with students, faculty, and local collaborators from 3 GEMS project sites. Findings were analyzed for themes through a framework approach. RESULTS: The program exposed students, faculty, and collaborators to a wide range of disciplines in global health. Students' desire to learn how other disciplines contribute to global health solutions was an important motivator for joining GEMS; many participants including faculty and collaborators valued exposure to multiple disciplines. Mentorship and communication were a challenge across all teams in part due to members having distinct "disciplinary languages". Balancing disciplinary representation on teams and establishing work plans were also key challenges. CONCLUSIONS: Based on the data the CGH provides four recommendations for institutions developing global health interdisciplinary teams to optimize team functioning and address challenges in mentorship, language, and roles: 1) address interdisciplinary communication early, 2) develop work plans during group formation, 3) meet as a team prior to travel, and 4) establish regular check ins. This article provides first-hand reflections on interdisciplinary team experiences in a global context and provides a pathway for the development of innovative strategies in global health training.

Effect of a Behavioral Intervention for Underserved Preschool-Age Children on Change in Body Mass Index: A Randomized Clinical Trial.

Importance: Prevention of obesity during childhood is critical for children in underserved populations, for whom obesity prevalence and risk of chronic disease are highest. Objective: To test the effect of a multicomponent behavioral intervention on child body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) growth trajectories over 36 months among preschool-age children at risk for obesity. Design, Setting, and Participants: A randomized clinical trial assigned 610 parent-child pairs from underserved communities in Nashville, Tennessee, to a 36-month intervention targeting health behaviors or a school-readiness control. Eligible children were between ages 3 and 5 years and at risk for obesity but not yet obese. Enrollment occurred from August 2012 to May 2014; 36-month follow-up occurred from October 2015 to June 2017. Interventions: The intervention (n = 304 pairs) was a 36-month family-based, community-centered program, consisting of 12 weekly skills-building sessions, followed by monthly coaching telephone calls for 9 months, and a 24-month sustainability phase providing cues to action. The control (n = 306 pairs) consisted of 6 school-readiness sessions delivered over the 36-month study, conducted by the Nashville Public Library. Main Outcomes and Measures: The primary outcome was child BMI trajectory over 36 months. Seven prespecified secondary outcomes included parent-reported child dietary intake and community center use. The Benjamini-Hochberg procedure corrected for multiple comparisons. Results: Participants were predominantly Latino (91.4%). At baseline, the mean (SD) child age was 4.3 (0.9) years; 51.9% were female. Household income was below $25 000 for 56.7% of families. Retention was 90.2%. At 36 months, the mean (SD) child BMI was 17.8 (2.2) in the intervention group and 17.8 (2.1) in the control group. No significant difference existed in the primary outcome of BMI trajectory over 36 months (P = .39). The intervention group children had a lower mean caloric intake (1227 kcal/d) compared with control group children (1323 kcal/d) (adjusted difference, -99.4 kcal [95% CI, -160.7 to -38.0]; corrected P = .003). Intervention group parents used community centers with their children more than control group parents (56.8% in intervention; 44.4% in control) (risk ratio, 1.29 [95% CI, 1.08 to 1.53]; corrected P = .006). Conclusions and Relevance: A 36-month multicomponent behavioral intervention did not change BMI trajectory among underserved preschool-age children in Nashville, Tennessee, compared with a control program. Whether there would be effectiveness for other types of behavioral interventions or implementation in other cities would require further research. Trial Registration: ClinicalTrials.gov Identifier: NCT01316653.

Multiple entries and exits and other complex human patterns of insecticide-treated net use: a possible contributor to residual malaria transmission?

BACKGROUND: Increased insecticide-treated net (ITN) use over the last decade has contributed to dramatic declines in malaria transmission and mortality, yet residual transmission persists even where ITN coverage exceeds 80%. This article presents observational data suggesting that complex human net use patterns, including multiple entries to and exits from ITNs by multiple occupants throughout the night, might be a contributing factor. METHODS: The study included dusk-to-dawn observations of bed net use in 60 households in the Peruvian Amazon. Observers recorded number of net occupants and the time and number of times each occupant entered and exited each net. The study team then tabulated time of first entry, total times each net was lifted, and, where possible, minutes spent outside by each occupant. RESULTS: The sample included 446 individuals and 171 observed sleeping spaces with nets. Household size ranged from 2 to 24 occupants; occupants per net ranged from 1 to 5. Nets were lifted a mean 6.1 times per night (SD 4.35, range 1-22). Observers captured substantial detail about time of and reasons for net entry and exit as well as length of time and activities undertaken outside. CONCLUSIONS: These findings suggest that the ITN use patterns observed in this study may contribute to residual transmission. As a result, respondents to net use surveys may truthfully report that they slept under a net the previous night but may not have received the anticipated protection. More research is warranted to explore the impact of this phenomenon. Concurrent entomological data would help assess the magnitude of the effect.

Quality issues with malaria rapid diagnostic test accessories and buffer packaging: findings from a 5-country private sector project in Africa.

BACKGROUND: Use of antigen-detecting malaria rapid diagnostic tests (RDTs) has increased exponentially over the last decade. WHO's Global Malaria Programme, FIND, and other collaborators have established a quality assurance scheme to guide product selection, lot verification, transport, storage, and training procedures. Recent concerns over the quality of buffer packaging and test accessories suggest a need to include these items in product assessments. This paper describes quality problems with buffer and accessories encountered in a project promoting private sector RDT use in five African countries and suggests steps to avoid or more rapidly identify and resolve such problems. METHODS: Private provider complaints about RDT buffer vials and kit accessories were collected during supervisory visits, and a standard assessment process was developed. Using 100 tests drawn from six different lots produced by two manufacturers, lab technicians visually assessed alcohol swab packaging, blood transfer device (BTD) usability, and buffer appearance, then calculated mean blood volume from 10 BTD transfers and mean buffer volume from 10 individual buffer vials. WHO guided complaint reporting and follow-up with manufacturers. RESULTS: Supervisory visits confirmed user reports of dry alcohol swabs, poorly functioning BTDs, and non-uniform volumes of buffer. Lot testing revealed further evidence of quality problems, leading one manufacturer to replace buffer vials and accessories for 40,000 RDTs. In December 2014, WHO issued an Information Notice for Users regarding variable buffer volumes in single-use vials and recommended against procurement of these products until defects were addressed. DISCUSSION: Though not necessarily comprehensive or generalizable, the findings presented here highlight the need for extending quality assessment to all malaria RDT test kit contents. Defects such as those described in this paper could reduce test accuracy and increase probability of invalid, false positive, or false negative results. Such deficiencies could undermine provider confidence in RDTs, prompting a return to presumptive treatment or reliance on poor quality microscopy. In partial response to this experience, WHO, FIND, and other project partners have developed guidance on documenting, troubleshooting, reporting, and resolving such problems when they occur.

Parental perception of built environment characteristics and built environment use among Latino families: a cross-sectional study.

BACKGROUND: Perception of undesirable features may inhibit built environment use for physical activity among underserved families with children at risk for obesity. METHODS: To examine the association of perceived availability, condition, and safety of the built environment with its self-reported use for physical activity, we conducted a cross-sectional analysis on baseline data from a randomized controlled trial. Adjusted Poisson regression was used to test the association between the primary independent variables (perceived availability, physical condition, and safety) with the primary outcome of self-reported use of built environment structures. RESULTS: Among 610 parents (90% Latino) of preschool-age children, 158 (26%) reported that there were no available built environment structures for physical activity in the neighborhood. The use of built environment structures was associated with the perceived number of available structures (B = 0.34, 95% CI 0.31, 0.37, p < 0.001) and their perceived condition (B = 0.19, 95% CI 0.12, 0.27, p = 0.001), but not with perceived safety (B = 0.00, 95% CI -0.01, 0.01, p = 0.7). CONCLUSIONS: In this sample of underserved families, perceived availability and condition of built environment structures were associated with use rather than perceived safety. To encourage physical activity among underserved families, communities need to invest in the condition and availability of built environment structures. TRIAL REGISTRATION: Registered at ClinicalTrials.gov ( NCT01316653 ) on March 11, 2011.

Predictors of Youths' Posttraumatic Stress Symptoms Following a Natural Disaster: The 2010 Nashville, Tennessee, Flood.

Framed by a previously established conceptual model of youths' posttraumatic stress (PTS) responses following a disaster, the current longitudinal study examined the relation of predisaster child characteristics (age, gender, depressive symptoms, ruminative coping), predisaster environmental characteristics (negative life events and supportive and negative friendship interactions), and level of disaster exposure to youths' PTS symptoms in the wake of a natural disaster. Prior to the 2010 Nashville, Tennessee, flood, 239 predominantly Caucasian youth from four elementary and middle schools (ages = 10-15, 56% girls) completed measures of depressive symptoms, rumination, negative life events, and social support in the form of both supportive and negative friendship interactions. Approximately 10 days after returning to school, 125 completed measures of disaster exposure and postflood PTS symptoms. Bivariate correlations revealed that disaster-related PTS symptoms were unrelated to age, gender, or predisaster supportive friendship interactions and significantly positively related to level of disaster exposure and predisaster levels of negative life events, depressive symptoms, rumination, and negative friendship interactions. After controlling for level of disaster exposure and other predisaster child and environmental characteristics, depressive symptoms and negative friendship interactions predicted postdisaster PTS symptoms. The effect of child's flood-related experiences on PTS symptoms was not moderated by any of the preexisting child characteristics or environmental indicators. Faced with limited resources after a natural disaster, school counselors and other health professionals should focus special attention on youths who experienced high levels of disaster-related losses and whose predisaster emotional and interpersonal lives were problematic.

Cyclophilin D extramitochondrial signaling controls cell cycle progression and chemokine-directed cell motility.

Mitochondria control bioenergetics and cell fate decisions, but how they influence nuclear gene expression is understood poorly. Here, we show that deletion or reduction in the levels of cyclophilin D (CypD, also called Ppif), a mitochondrial matrix peptidyl prolyl isomerase and apoptosis regulator, results in increased cell proliferation and enhanced cell migration and invasion. These responses are associated with extensive transcriptional changes, modulation of a chemokine/chemokine receptor gene signature, and activation of the pleiotropic inflammatory mediator, STAT3. In the absence of CypD, active STAT3 enhances cell proliferation via accelerated entry into S-phase and stimulates autocrine/paracrine cell motility through Cxcl12-Cxcr4-directed chemotaxis. Therefore, CypD directs mitochondria-to-nuclei inflammatory gene expression in normal and tumor cells. This pathway may contribute to malignant traits under conditions of CypD modulation.

Design of an innovative digital application to facilitate access to healthy foods in low-income urban settings.

Background: Under-resourced urban minority communities in the United States are characterized by food environments with low access to healthy foods, high food insecurity, and high rates of diet-related chronic disease. In Baltimore, Maryland, low access to healthy food largely results from a distribution gap between small food sources (retailers) and their suppliers. Digital interventions have the potential to address this gap, while keeping costs low. Methods: In this paper, we describe the technical (I) front-end design and (II) back-end development process of the Baltimore Urban food Distribution (BUD) application (app). We identify and detail four main phases of the process: (I) information architecture; (II) low and high-fidelity wireframes; (III) prototype; and (IV) back-end components, while considering formative research and a pre-pilot test of a preliminary version of the BUD app. Results: Our lessons learned provide valuable insight into developing a stable app with a user-friendly experience and interface, and accessible cloud computing services for advanced technical features. Conclusions: Next steps will involve a pilot trial of the app in Baltimore, and eventually, other urban and rural settings nationwide. Once iterative feedback is incorporated into the app, all code will be made publicly available via an open source repository to encourage adaptation for desired communities. Trial Registration: ClinicalTrials.gov NCT05010018.

Centering Equity and Fostering Stakeholder Collaboration and Trust-Pillars of the Maternal Health Innovation Program in Maryland.

Objective: To describe two main pillars of the Maryland Maternal Health Innovation Program (MDMOM): (1) centering equity and (2) fostering broad stakeholder collaboration and trust. Methods: We summarized MDMOM's key activities and used severe maternal morbidity (SMM) surveillance and program monitoring data to quantify MDMOM's work on the two pillars. We developed measures of hospital engagement with MDMOM (participation in quality improvement [QI] activities, participation in check-in meetings, staff involvement) and with other partners (participation in QI activities, representation in state-level groups). We examined Bonferroni-adjusted correlations between these hospital engagement measures and with key hospital characteristics: level of maternity care, annual delivery volume, and SMM rate. Results: Over 100 national and state organizations and individual stakeholders contributed to our building the MDMOM program and implementing key activities centering equity: hospital-based SMM surveillance in 20 of Maryland's 32 hospitals; almost 5,000 trainings offered to perinatal health care providers; two telemedicine/telehealth interventions; training of home visitors and community-based organization staff. Birthing hospitals represent MDMOM's main implementation partners. The strength of their participation in MDMOM QI activities is positively correlated to their participation in check-in meetings and with the degree of involvement by physicians in such activities. Higher engagement in MDMOM QI activities is also positively correlated to hospitals' participation in other state-level maternal health initiatives or groups. Conclusion: Our experience with the MDMOM program demonstrates that an equity focus and broad stakeholder collaboration building strong relationships and providing implementation support can lead to high levels of engagement in innovative maternal health interventions.

A randomized controlled trial of a cognitive-behavioral program for the prevention of depression in adolescents compared with nonspecific and no-intervention control conditions.

Adolescent depression is a common and recurrent disorder associated with significant impairment and other forms of psychopathology. Finding an effective intervention that prevents depression in adolescents is an important public health priority. Participants were 518 high school students (mean age = 15.09; SD = 0.76) from the mid-south of the United States. Participants were randomly assigned to 1 of 3 conditions: a cognitive-behavioral program (CB; n = 166), nonspecific control (NSp; n = 175), or a no-intervention control condition (NIC; n = 177). Both the CB and NSp conditions consisted of 90-min sessions administered once a week over a 10-week period during regular school hours. Depressive symptoms were assessed with the Children's Depression Inventory (CDI) at baseline; postintervention; and at 4-, 8-, and 12-month follow-ups. The Time × Condition interaction was significant, F(8, 478.57) = 3.32, p = .001, indicating that at the 4-month follow-up, youth in the CB condition had significantly lower CDI scores compared with those in the NSp (p = .047, g = 0.29; CI [0.06, 0.52]) and the NIC conditions (p = .003, g = 0.30; CI [0.07, 0.53]). Future studies need to examine the importance of theory-driven change mechanisms, interpersonal relationships, and structural circumstances in schools as factors impacting the long-term effects of CB prevention programs.

"Treat Me Like a Dumb American": a Qualitative Exploration of the American Immigrant Counselor Experience.

This qualitative study addresses the gap in the limited literature on the experiences of American immigrant counselors practicing overseas. Seven American immigrant counselors were interviewed regarding their experience. Interviews were transcribed verbatim and analyzed using inductive Thematic Analysis. Three themes were identified: lack of cultural knowledge as counseling technique, American stereotypes/politics within the counseling session, and issues surrounding lack of counseling regulation and transfer of professional credentials. Implications for American counselor education are discussed.