Fit with Faith: An Exploratory Study Examining a Behavior Change Intervention for African-American Clergy and Their Spouses.

Fit with Faith is a 10-week, diet, physical activity, and stress reduction intervention for African-American clergy and spouses, which included: meetings, phone calls, a behavior tracking app. Survey, 24-h recall, accelerometer, anthropometric, and blood pressure data were collected. Wilcoxon signed ranked tests were used for analyses. In this one-arm study, clergy and spouses (n = 20) attended most meetings and calls, but only half posted daily goals or tracked behaviors using the app. Spouses' body mass index (BMI) decreased and physical activity self-regulation cognitive scores increased pre-post intervention. Statistically significant changes in BMI, systolic blood pressure, and self-regulations scores also were seen among younger (< 51 years) participants (n = 8). As positive changes were seen mostly among women and younger participants, more research is needed on how to engage all clergy in behavior change programs.

A Pragmatic Intervention Using Financial Incentives for Pregnancy Weight Management: Feasibility Randomized Controlled Trial.

BACKGROUND: Excessive gestational weight gain (GWG) is common and can result in maternal and child health complications. Pragmatic behavioral interventions that can be incorporated into standard obstetric care are needed, and financial incentives are a promising approach. OBJECTIVE: The aim of this study is to evaluate the feasibility of recruitment, randomization, and retention, as well as treatment engagement and intervention satisfaction, in a behavioral program. The program provided small incentives for meeting behavioral goals of self-weighing and physical activity as well as larger outcome incentives for meeting GWG goals. METHODS: We recruited 40 adult women in their first trimester of pregnancy from February 2019 to September 2019 at an obstetric clinic. Participants were randomized to 3 intervention components using a 2×2×2 factorial design: daily incentives for self-weighing (lottery vs certain loss), incentives for adhering to the Institute of Medicine's GWG guidelines based on BMI category (monthly vs overall), and incentives for reaching physical activity goals (yes vs no). Participants were asked to complete daily weigh-ins using the Withings Body wireless scale provided by the study, as well as wear a physical activity tracker (Fitbit Flex 2). Feasibility outcomes of recruitment, randomization, and retention, as well as treatment engagement and intervention satisfaction, were assessed. Weight assessments were conducted at baseline, 32-week gestation, and 36-week gestation. RESULTS: Participants were enrolled at, on average, 9.6 (SD 1.8) weeks' gestation. Of the 39 participants who were oriented to their condition and received the intervention, 24 (62%) were Black or African American, 30 (77%) were not married, and 29 (74%) had an annual household income of less than US $50,000. Of the 39 participants, 35 (90%) completed the follow-up data collection visit. Participants were generally quite positive about the intervention components, with a particular emphasis on the helpfulness of, and the enjoyment of using, the e-scale in both the quantitative and qualitative feedback. Participants who received the loss incentive, on average, had 2.86 times as many days of self-weighing as those who received the lottery incentive. Participants had a relatively low level of activity, with no difference between those who received a physical activity incentive and those who did not. CONCLUSIONS: A financial incentive-based pragmatic intervention was feasible and acceptable for pregnant women for promoting self-weighing, physical activity, and healthy GWG. Participants were successfully recruited early in their first trimester of pregnancy and retained for follow-up data collection in the third trimester. Participants demonstrated promising engagement in self-weighing, particularly with loss-based incentives, and reported finding the self-weighing especially helpful. This study supports further investigation of pragmatic, clinic-based financial incentive-based interventions for healthy GWG behaviors. TRIAL REGISTRATION: ClinicalTrials.gov NCT03834194; https://clinicaltrials.gov/ct2/show/NCT03834194.

Prevalence of Cardiovascular Disease Risk Factors by Key Demographic Variables Among Mid-South Church Leaders from 2012 to 2017.

Cardiovascular disease (CVD) risk factors were examined among church leaders (n = 2309) who attended Mid-South United Methodist Church annual meetings between 2012 and 2017 using repeated cross-sectional data. There was a significant increase in body mass index (BMI) (b = 0.24, p = 0.001) and significant decreases in blood pressure (systolic: b = - 1.08, p < 0.001; diastolic: b = - 0.41, p = 0.002), total cholesterol (b = - 1.76, p = 0.001), and blood sugar (b = - 1.78, p = 0.001) over time. Compared to Whites, a significant increase was seen in BMI (b = 1.14, p = 0.008) among participants who self-identified as "Other," and a significant increase was seen in blood pressure (systolic: b = 1.36, p = 0.010; diastolic: b = 1.01, p = 0.004) among African Americans over time. Results indicate BMI and blood pressure are important CVD risk factors to monitor and address among church leaders, especially among race/ethnic minority church leaders.

Premature T Cell Senescence in Pediatric CKD.

An individual's immune function, susceptibility to infection, and response to immunosuppressive therapy are influenced in part by his/her T cell maturation state. Although childhood is the most dynamic period of immune maturation, scant information regarding the variability of T cell maturation in children with renal disease is available. In this study, we compared the T cell phenotype in children with renal failure (n=80) with that in healthy children (n=20) using multiparameter flow cytometry to detect markers of T cell maturation, exhaustion, and senescence known to influence immune function. We correlated data with the degree of renal failure (dialysis or nondialysis), prior immunosuppression use, and markers of inflammation (C-reactive protein and inflammatory cytokines) to assess the influence of these factors on T cell phenotype. Children with renal disease had highly variable and often markedly skewed maturation phenotypes, including CD4/CD8 ratio reversal, increased terminal effector differentiation in CD8+ T cells, reduction in the proportion of naïve T cells, evidence of T cell exhaustion and senescence, and variable loss of T cell CD28 expression. These findings were most significant in patients who had experienced major immune insults, particularly prior immunosuppressive drug exposure. In conclusion, children with renal disease have exceptional heterogeneity in the T cell repertoire. Cognizance of this heterogeneity might inform risk stratification with regard to the balance between infectious risk and response to immunosuppressive therapy, such as that required for autoimmune disease and transplantation.

In vivo T cell costimulation blockade with abatacept for acute graft-versus-host disease prevention: a first-in-disease trial.

We performed a first-in-disease trial of in vivo CD28:CD80/86 costimulation blockade with abatacept for acute graft-versus-host disease (aGVHD) prevention during unrelated-donor hematopoietic cell transplantation (HCT). All patients received cyclosporine/methotrexate plus 4 doses of abatacept (10 mg/kg/dose) on days -1, +5, +14, +28 post-HCT. The feasibility of adding abatacept, its pharmacokinetics, pharmacodynamics, and its impact on aGVHD, infection, relapse, and transplantation-related mortality (TRM) were assessed. All patients received the planned abatacept doses, and no infusion reactions were noted. Compared with a cohort of patients not receiving abatacept (the StdRx cohort), patients enrolled in the study (the ABA cohort) demonstrated significant inhibition of early CD4(+) T cell proliferation and activation, affecting predominantly the effector memory (Tem) subpopulation, with 7- and 10-fold fewer proliferating and activated CD4(+) Tem cells, respectively, at day+28 in the ABA cohort compared with the StdRx cohort (P < .01). The ABA patients demonstrated a low rate of aGVHD, despite robust immune reconstitution, with 2 of 10 patients diagnosed with grade II-IV aGVHD before day +100, no deaths from infection, no day +100 TRM, and with 7 of 10 evaluable patients surviving (median follow-up, 16 months). These results suggest that costimulation blockade with abatacept can significantly affect CD4(+) T cell proliferation and activation post-transplantation, and may be an important adjunct to standard immunoprophylaxis for aGVHD in patients undergoing unrelated-donor HCT.

A comparison of non-toxin vaccine adjuvants for their ability to enhance the immunogenicity of nasally-administered anthrax recombinant protective antigen.

Development of nasal immunization for human use is hindered by the lack of acceptable adjuvants. Although CT is an effective adjuvant, its toxicity will likely prevent its use in nasal vaccines. This study compared non-toxin adjuvants to CT for their ability to induce protective antibody responses with nasal immunization. C3H/HeN and C57BL/6 mice were immunized with rPA formulated with the following adjuvants: CT, IL-1α, LPS, CpG, Pam3CSK4, 3M-019, resiquimod/R848 or c48/80. Serum and nasal wash cytokine concentrations were monitored 6h post-vaccination as biomarkers for acute activation of the innate immune system. Not all of the adjuvants induced significant changes in innate serum or nasal wash cytokines, but when changes were observed, the cytokine signatures were unique for each adjuvant. All adjuvants except Pam3CSK4 induced significantly increased anti-rPA serum IgG titers in both strains of mice, while only IL-1α, c48/80 and CpG enhanced mucosal anti-rPA IgA. Pam3CSK4 was the only adjuvant unable to enhance the induction of serum LeTx-neutralizing antibodies in C3H/HeN mice while c48/80 was the only adjuvant to induce increased serum LeTx-neutralizing antibodies in C57BL/6 mice. Only CT enhanced total serum IgE in C3H/HeN mice while IL-1α enhanced total serum IgE in C57BL/6 mice. The adjuvant influenced antigen-specific serum IgG subclass and T cell cytokine profiles, but these responses did not correlate with the induction of LeTx-neutralizing activity. Our results demonstrate the induction of diverse innate and adaptive immune responses by non-toxin nasal vaccine adjuvants that lead to protective humoral immunity comparable to CT and that these responses may be influenced by the host strain.

Maximal adjuvant activity of nasally delivered IL-1α requires adjuvant-responsive CD11c(+) cells and does not correlate with adjuvant-induced in vivo cytokine production.

IL-1 has been shown to have strong mucosal adjuvant activities, but little is known about its mechanism of action. We vaccinated IL-1R1 bone marrow (BM) chimeric mice to determine whether IL-1R1 expression on stromal cells or hematopoietic cells was sufficient for the maximal adjuvant activity of nasally delivered IL-1α as determined by the acute induction of cytokine responses and induction of Bacillus anthracis lethal factor (LF)-specific adaptive immunity. Cytokine and chemokine responses induced by vaccination with IL-1α were predominantly derived from the stromal cell compartment and included G-CSF, IL-6, IL-13, MCP-1, and keratinocyte chemoattractant. Nasal vaccination of Il1r1(-/-) (knock-out [KO]) mice given wild-type (WT) BM (WT→KO) and WT→WT mice with LF + IL-1α induced maximal adaptive immune responses, whereas vaccination of WT mice given Il1r1(-/-) BM (KO→WT) resulted in significantly decreased production of LF-specific serum IgG, IgG subclasses, lethal toxin-neutralizing Abs, and mucosal IgA compared with WT→KO and WT→WT mice (p < 0.05). IL-1α adjuvant activity was not dependent on mast cells. However, the ability of IL-1α to induce serum LF-specific IgG2c and lethal toxin-neutralizing Abs was significantly impaired in CD11c-Myd88(-/-) mice when compared with WT mice (p < 0.05). Our results suggest that CD11c(+) cells must be directly activated by nasally administered IL-1α for maximal adjuvant activity and that, although stromal cells are required for maximal adjuvant-induced cytokine production, the adjuvant-induced stromal cell cytokine responses are not required for effective induction of adaptive immunity.

LFA-1-specific therapy prolongs allograft survival in rhesus macaques.

Outcomes in transplantation have been limited by suboptimal long-term graft survival and toxicities associated with current immunosuppressive approaches. T cell costimulation blockade has shown promise as an alternative strategy to avoid the side effects of conventional immunosuppressive therapies, but targeting CD28-mediated costimulation alone has proven insufficient to prevent graft rejection in primates. Donor-specific memory T (TM) cells have been implicated in costimulation blockade-resistant transplant rejection, due to their enhanced effector function and decreased reliance on costimulatory signaling. Thus, we have tested a potential strategy to overcome TM cell-driven rejection by targeting molecules preferentially expressed on these cells, such as the adhesion molecule lymphocyte function-associated antigen 1 (LFA-1). Here, we show that short-term treatment (i.e., induction therapy) with the LFA-1-specific antibody TS-1/22 in combination with either basiliximab (an IL-2Rα-specific mAb) and sirolimus (a mammalian target of rapamycin inhibitor) or belatacept (a high-affinity variant of the CD28 costimulation-blocker CTLA4Ig) prolonged islet allograft survival in nonhuman primates relative to control treatments. Moreover, TS-1/22 masked LFA-1 on TM cells in vivo and inhibited the generation of alloproliferative and cytokine-producing effector T cells that expressed high levels of LFA-1 in vitro. These results support the use of LFA-1-specific induction therapy to neutralize costimulation blockade-resistant populations of T cells and further evaluation of LFA-1-specific therapeutics for use in transplantation.

Cavus foot reconstruction in 3 patients with Charcot-Marie-Tooth disease.

UNLABELLED: Charcot-Marie-Tooth (CMT) is a progressive genetic disorder that produces motor and sensory neuropathy that affects the legs, feet, and hands. A dorsally based closing wedge midfoot osteotomy at the apex of the cavus foot deformity combined with soft tissue and other osseous procedures are procedures performed for CMT patients at The Western Pennsylvania Hospital. The focus of this article is to present a prospective evaluation of 3 patients using radiographic assessment, static biomechanical and the malleolar valgus index (MVI), dynamic alignment, and function results using the F-scan. These results demonstrate that patients have improved function with a plantigrade foot and decreased pain. The Short Form McGill Pain Questionnaire (SF-MPQ) showed that there was a decrease in pain. There was a decrease in the MVI and improved function comparing the preoperative and postoperative F-scan in all patients. The midfoot osteotomy addresses the apex of the progressive cavus foot deformity and provides a plantigrade foot in 3 CMT patients. LEVEL OF CLINICAL EVIDENCE: 4.

Tibiotalocalcaneal arthrodesis with retrograde intramedullary nailing.

Nineteen patients (20 feet) with severe hindfoot and ankle deformity underwent tibiotalocalcaneal fusion with a retrograde locked intramedullary nail as a limb-salvage procedure. The purpose of this study was to compare the complication rates of this procedure in diabetic versus nondiabetic patients. There were 8 men and 11 women with preoperative diagnoses including Charcot neuroarthropathy, primary osteoarthritis, rheumatoid arthritis, equinocavovarus, posttraumatic osteoarthritis, gouty arthritis, and ankle malunion. Ten of 20 procedures were performed in patients with diabetes. The average patient age was 56 years, and the average postoperative follow-up was 19.8 months. Nineteen of 20 ankles (95%) achieved successful fusion with an average time of 4.1 months. Four patients (21%) required either a fracture brace or an ankle foot orthosis at final follow-up. Five patients (25%) had major complications and 11 patients had minor complications. Major complications included osteomyelitis (n = 2), Charcot arthropathy (n = 2), failure of fixation (n =1), soft-tissue necrosis (n = 1), cardiac arrest (n = 1), cerebral vascular accident (n = 1), and fatal pulmonary embolus (n = 1). All patients with major complications were diabetic, and 14 of 20 combined major and minor complications occurred in patients with diabetes. The complication rate was found to be high in diabetic patients with end-stage deformity undergoing a limb salvage