Expanding opportunities for chronic disease prevention for Hispanics: the Better Together REACH program in Pennsylvania.

Background: Hispanics in Lebanon and Reading, Pennsylvania, experience high levels of socioeconomic and health disparities in risk factors for chronic disease. In 2018, our community-academic coalition "Better Together" received a Racial and Ethnic Approaches to Community Health (REACH) award to improve healthy lifestyles. This report describes our work-in-progress and lessons learned to date from our REACH-supported initiatives in Lebanon and Reading. Methods: For the past 4 years, our coalition has leveraged strong community collaborations to implement and evaluate culturally-tailored practice- and evidence-based activities aimed at increasing physical activity, healthy nutrition, and community-clinical linkages. This community case report summarizes the context where our overall program was implemented, including the priority population, target geographical area, socioeconomic and health disparities data, community-academic coalition, conceptual model, and details the progress of the Better Together initiative in the two communities impacted. Results: To improve physical activity, we are: (1) creating new and enhancing existing trails connecting everyday destinations through city redesigning and master planning, (2) promoting outdoor physical activity, (3) increasing awareness of community resources for chronic disease prevention, and (4) supporting access to bikes for youth and families. To improve nutrition, we are: (1) expanding access to locally-grown fresh fruit and vegetables in community and clinical settings, through the Farmers Market Nutrition Program to beneficiaries of the Women, Infants, and Children (WIC) program and the Veggie Rx to patients who are at risk for or have diabetes, and (2) providing bilingual breastfeeding education. To enhance community-clinical linkages, we are training bilingual community health workers to connect at-risk individuals with diabetes prevention programs. Conclusions: Intervening in areas facing high chronic disease health disparities leads us to develop a community-collaborative blueprint that can be replicated across Hispanic communities in Pennsylvania and the United States.

Impact of a Prescription Produce Program on Diabetes and Cardiovascular Risk Outcomes.

OBJECTIVE: To evaluate the impact of a fruit and vegetable prescription program on diabetes and cardiovascular risk outcomes. DESIGN: Single-arm pre-post study. SETTING: Primary care clinic in a community-based hospital. PARTICIPANTS: Adults with type 2 diabetes (n = 97), aged > 18 years, with hemoglobin A1c (HbA1c) ≥ 7.0%, and a body mass index (BMI) of ≥ 25 kg/m2. INTERVENTION: Over 7 months, participants received monthly group-based diabetes self-management education (DSME) and monthly vouchers ($28-$140/month) redeemable for fruits and vegetables at local markets. ANALYSIS: Biomarker changes (HbA1c, BMI, and blood pressure) were assessed with paired t tests. Voucher distribution and redemption were tracked, and voucher redemption rates were calculated. Linear mixed-effect regression models tested associations between biomarkers, voucher redemption rates, and participant characteristics. RESULTS: There was a -1.3% (P < 0.001) postprogram change in HbA1c. Reduced HbA1c was associated with higher voucher redemption rates (P = 0.032) and a change in diabetes medications (P = 0.003). There were no associations with BMI, but blood pressure was positively associated with voucher redemption. CONCLUSIONS AND IMPLICATIONS: Fruit and vegetable prescription programs may improve diabetes outcomes by incentivizing DSME uptake and retention. Future randomized trials are warranted to identify strategies to improve DSME engagement and voucher redemption rates and assess mechanisms through which these programs influence health outcomes.

NaV1.2 EFL domain allosterically enhances Ca2+ binding to sites I and II of WT and pathogenic calmodulin mutants bound to the channel CTD.

Neuronal voltage-gated sodium channel NaV1.2 C-terminal domain (CTD) binds calmodulin (CaM) constitutively at its IQ motif. A solution structure (6BUT) and other NMR evidence showed that the CaM N domain (CaMN) is structurally independent of the C-domain (CaMC) whether CaM is bound to the NaV1.2IQp (1,901-1,927) or NaV1.2CTD (1,777-1,937) with or without calcium. However, in the CaM + NaV1.2CTD complex, the Ca2+ affinity of CaMN was more favorable than in free CaM, while Ca2+ affinity for CaMC was weaker than in the CaM + NaV1.2IQp complex. The CTD EF-like (EFL) domain allosterically widened the energetic gap between CaM domains. Cardiomyopathy-associated CaM mutants (N53I(N54I), D95V(D96V), A102V(A103V), E104A(E105A), D129G(D130G), and F141L(F142L)) all bound the NaV1.2 IQ motif favorably under resting (apo) conditions and bound calcium normally at CaMN sites. However, only N53I and A102V bound calcium at CaMC sites at [Ca2+] < 100 µM. Thus, they are expected to respond like wild-type CaM to Ca2+ spikes in excitable cells.

SARS-CoV-2 innate effector associations and viral load in early nasopharyngeal infection.

COVID-19 causes severe disease with poor outcomes. We tested the hypothesis that early SARS-CoV-2 viral infection disrupts innate immune responses. These changes may be important for understanding subsequent clinical outcomes. We obtained residual nasopharyngeal swab samples from individuals who requested COVID-19 testing for symptoms at drive-through COVID-19 clinical testing sites operated by the University of Utah. We applied multiplex immunoassays, real-time polymerase chain reaction assays and quantitative proteomics to 20 virus-positive and 20 virus-negative samples. ACE-2 transcripts increased with infection (OR =17.4, 95% CI [CI] =4.78-63.8) and increasing viral N1 protein transcript load (OR =1.16, CI =1.10-1.23). Transcripts for two interferons (IFN) were elevated, IFN-λ1 (OR =71, CI =7.07-713) and IFN-λ2 (OR =40.2, CI =3.86-419), and closely associated with viral N1 transcripts (OR =1.35, CI =1.23-1.49 and OR =1.33 CI =1.20-1.47, respectively). Only transcripts for IP-10 were increased among systemic inflammatory cytokines that we examined (OR =131, CI =1.01-2620). We found widespread discrepancies between transcription and translation. IFN proteins were unchanged or decreased in infected samples (IFN-γ OR =0.90 CI =0.33-0.79, IFN-λ2,3 OR =0.60 CI =0.48-0.74) suggesting viral-induced shut-off of host antiviral protein responses. However, proteins for IP-10 (OR =3.74 CI =2.07-6.77) and several interferon-stimulated genes (ISG) increased with viral load (BST-1 OR =25.1, CI =3.33-188; IFIT1 OR =19.5, CI =4.25-89.2; IFIT3 OR =245, CI =15-4020; MX-1 OR =3.33, CI =1.44-7.70). Older age was associated with substantial modifications of some effects. Ambulatory symptomatic patients had an innate immune response with SARS-CoV-2 infection characterized by elevated IFN, proinflammatory cytokine and ISG transcripts, but there is evidence of a viral-induced host shut-off of antiviral responses. Our findings may characterize the disrupted immune landscape common in patients with early disease.

SARS-CoV-2 Innate Effector Associations and Viral Load in Early Nasopharyngeal Infection.

To examine innate immune responses in early SARS-CoV-2 infection that may change clinical outcomes, we compared nasopharyngeal swab data from 20 virus-positive and 20 virus-negative individuals. Multiple innate immune-related and ACE-2 transcripts increased with infection and were strongly associated with increasing viral load. We found widespread discrepancies between transcription and translation. Interferon proteins were unchanged or decreased in infected samples suggesting virally-induced shut-off of host anti-viral protein responses. However, IP-10 and several interferon-stimulated gene proteins increased with viral load. Older age was associated with modifications of some effects. Our findings may characterize the disrupted immune landscape of early disease.

Juvenile Justice Risk Factors and Functional Family Therapy Fidelity on Felony Recidivism.

Families (n = 5,884) received Functional Family Therapy (FFT) provided as part of court-ordered probation services by 11 community sites throughout Florida. Sites provided home-based FFT to families with male (72%) or female (28%) delinquent youth. Juvenile justice courts referred clients to these services in an effort to redirect them away from incarceration. Clients were Hispanic (18%), Black (41%), and White Non-Hispanic (36%), while therapists (female, 79%) were of Hispanic (28%), Black (20%), and White Non-Hispanic (50%) ethnic/racial origins. Analyses of clients' pretreatment recidivism risk and therapist's caseload of risky clients demonstrated that both individual and treatment site case-mix of client criminal risk levels were associated with higher adjudicated felony recidivism. Furthermore, clinical process indicators suggest that therapists with larger rather than smaller caseloads of high-risk clients provided treatment with greater fidelity. Results suggest that experience in working with challenging clients is critical for achieving fidelity with these cases.

Summary of comparison between FFT-CW® and Usual Care sample from Administration for Children's Services.

This evaluation compared the efficiency and effectiveness of Functional Family Therapy-Child Welfare (FFT-CW®, n=1625) to Usual Care (UC: n=2250) in reducing child maltreatment. FFT-CW® is a continuum of care model based on the family's risk status. In a child welfare setting, families received either UC or FFT-CW® in a quasi-experimental, stepped wedge design across all five boroughs of New York City. The families were matched using stratified propensity scoring on their pre-service risk status and followed for 16 months. The ethnically diverse sample included African American (36%), Asian (4%); Hispanic (49%), and Non-Hispanic White (6%) or Other (6%) participants. Referral reasons included abuse or neglect (57.4%), child service needs (56.9%) or child health and safety concerns (42.8%). Clinical process variables included staff fidelity, service duration, and number of contacts. Positive outcomes included whether all clinical goals were met and negative outcomes included transfers, outplacement, recurring allegations and service participation within 16 months of the case open date. Families receiving FFT-CW® completed treatment more quickly than UC and they were significantly more likely to meet all of the planned service goals. Higher treatment fidelity was associated with more favorable outcomes. Fewer FFT-CW® families were transferred to another program at closing, and they had fewer recurring allegations. FFT-CW® had fewer out-of-home placements in families with higher levels of risk factors. The FFT-CW® program was more efficient in completing service, and more effective than UC in meeting treatment goals while also avoiding adverse outcomes.

The role of biotin in regulating 3-methylcrotonyl-coenzyme a carboxylase expression in Arabidopsis.

As a catalytic cofactor, biotin has a critical role in the enzymological mechanism of a number of enzymes that are essential in both catabolic and anabolic metabolic processes. In this study we demonstrate that biotin has additional non-catalytic functions in regulating gene expression in plants, which are biotin autotrophic organisms. Biotin controls expression of the biotin-containing enzyme, methylcrotonyl-coenzyme A (CoA) carboxylase by modulating the transcriptional, translational and/or posttranslational regulation of the expression of this enzyme. The bio1 mutant of Arabidopsis, which is blocked in the de novo biosynthesis of biotin, was used to experimentally alter the biotin status of this organism. In response to the bio1-associated depletion of biotin, the normally biotinylated A-subunit of methylcrotonyl-CoA carboxylase (MCCase) accumulates in its inactive apo-form, and both MCCase subunits hyperaccumulate. This hyperaccumulation occurs because the translation of each subunit mRNA is enhanced and/or because the each protein subunit becomes more stable. In addition, biotin affects the accumulation of distinct charge isoforms of MCCase. In contrast, in response to metabolic signals arising from the alteration in the carbon status of the organism, biotin modulates the transcription of the MCCase genes. These experiments reveal that in addition to its catalytic role as an enzyme cofactor, biotin has multiple roles in regulating gene expression.

Translocation of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase precursor into isolated chloroplasts.

A cDNA encoding 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) synthase (EC 4.1.2.15) from potato (Solanum tuberosum L.) presumably specifies a chloroplast transit sequence near its 5'-end. In order to show the function of this transit sequence, we constructed a plasmid that contains the entire coding region of the cDNA downstream from a T7 promoter. Using this plasmid as template, DAHP synthase mRNA was synthesized in vitro with T7 RNA polymerase. The resulting mRNA served as template for the in vitro synthesis of a 59-kDa polypeptide. This translation product was identified as the DAHP synthase precursor by immunoprecipitation with a monospecific polyclonal antibody raised against pure tuber DAHP synthase and by radiosequencing of the [(3)H]leucine-labeled translation product. Incubation of the 59-kDa polypeptide with isolated spinach (Spinacia oleracea L.) chloroplasts resulted in a 53-kDa polypeptide that was resistant to protease treatment. Fractionation of chloroplasts, reisolated after import, showed the mature DAHP synthase in the stroma fraction. Incubation of the 59-kDa polypeptide with a chloroplast precursor-processing enzyme cleaved the precursor between Ser49 and Ala50, generating a mature DAHP synthase of 489 residues. The uptake of the DAHP synthase precursor into isolated chloroplasts was inhibited by anti-DAHP synthase, and the precursor was not processed cotranslationally by canine microsomal membranes. We conclude that the transit sequence is able to direct DAHP synthase into chloroplasts.

THE SHIKIMATE PATHWAY.

The shikimate pathway links metabolism of carbohydrates to biosynthesis of aromatic compounds. In a sequence of seven metabolic steps, phosphoenolpyruvate and erythrose 4-phosphate are converted to chorismate, the precursor of the aromatic amino acids and many aromatic secondary metabolites. All pathway intermediates can also be considered branch point compounds that may serve as substrates for other metabolic pathways. The shikimate pathway is found only in microorganisms and plants, never in animals. All enzymes of this pathway have been obtained in pure form from prokaryotic and eukaryotic sources and their respective DNAs have been characterized from several organisms. The cDNAs of higher plants encode proteins with amino terminal signal sequences for plastid import, suggesting that plastids are the exclusive locale for chorismate biosynthesis. In microorganisms, the shikimate pathway is regulated by feedback inhibition and by repression of the first enzyme. In higher plants, no physiological feedback inhibitor has been identified, suggesting that pathway regulation may occur exclusively at the genetic level. This difference between microorganisms and plants is reflected in the unusually large variation in the primary structures of the respective first enzymes. Several of the pathway enzymes occur in isoenzymic forms whose expression varies with changing environmental conditions and, within the plant, from organ to organ. The penultimate enzyme of the pathway is the sole target for the herbicide glyphosate. Glyphosate-tolerant transgenic plants are at the core of novel weed control systems for several crop plants.