Maternal diet modulates the infant microbiome and intestinal Flt3L necessary for dendritic cell development and immunity to respiratory infection.

Poor maternal diet during pregnancy is a risk factor for severe lower respiratory infections (sLRIs) in the offspring, but the underlying mechanisms remain elusive. Here, we demonstrate that in mice a maternal low-fiber diet (LFD) led to enhanced LRI severity in infants because of delayed plasmacytoid dendritic cell (pDC) recruitment and perturbation of regulatory T cell expansion in the lungs. LFD altered the composition of the maternal milk microbiome and assembling infant gut microbiome. These microbial changes reduced the secretion of the DC growth factor Flt3L by neonatal intestinal epithelial cells and impaired downstream pDC hematopoiesis. Therapy with a propionate-producing bacteria isolated from the milk of high-fiber diet-fed mothers, or supplementation with propionate, conferred protection against sLRI by restoring gut Flt3L expression and pDC hematopoiesis. Our findings identify a microbiome-dependent Flt3L axis in the gut that promotes pDC hematopoiesis in early life and confers disease resistance against sLRIs.

CXCR3+ effector regulatory T cells associate with disease tolerance during lower respiratory pneumovirus infection.

Lifestyle factors like poor maternal diet or antibiotic exposure disrupt early life microbiome assembly in infants, increasing the risk of severe lower respiratory infections (sLRI). Our prior studies in mice indicated that a maternal low-fibre diet (LFD) exacerbates LRI severity in infants by impairing recruitment of plasmacytoid dendritic cells (pDC) and consequently attenuating expansion of lung regulatory T (Treg) cells during pneumonia virus of mice (PVM) infection. Here, we investigated whether maternal dietary fibre intake influences Treg cell phenotypes in the mediastinal lymph nodes (mLN) and lungs of PVM-infected neonatal mice. Using high dimensional flow cytometry, we identified distinct clusters of regulatory T cells (Treg cells), which differed between lungs and mLN during infection, with notably greater effector Treg cell accumulation in the lungs. Compared to high-fibre diet (HFD)-reared pups, frequencies of various effector Treg cell subsets were decreased in the lungs of LFD-reared pups. Particularly, recruitment of chemokine receptor 3 (CXCR3+) expressing Treg cells was attenuated in LFD-reared pups, correlating with lower lung expression of CXCL9 and CXCL10 chemokines. The recruitment of this subset in response to PVM infection was similarly impaired in pDC depleted mice or following anti-CXCR3 treatment, increasing immunopathology in the lungs. In summary, PVM infection leads to the sequential recruitment and expansion of distinct Treg cell subsets to the lungs and mLN. The attenuated recruitment of the CXCR3+ subset in LFD-reared pups increases LRI severity, suggesting that strategies to enhance pDCs or CXCL9/CXCL10 expression will lower immune-mediated pathogenesis.

Religious Coping and Quality of Life Among Black and White Men With Prostate Cancer.

Prostate cancer is a significant impediment in men's lives as this condition often exacerbates stress and reduces quality of life. Faith can be a resource through which men cope with health crises; however, few studies examine how religion or spirituality can have implications for racial disparities in health outcomes among men. The purpose of this study is to assess the associations between religious coping and quality of life among black and white men with prostate cancer. Data for this investigation were drawn from the Diagnosis and Decisions in Prostate Cancer Treatment Outcomes Study that consisted of 624 black and white men with complete information on the primary outcome and predictor variables. The primary outcome for this study was overall quality of life as measured by the Functional Assessment of Cancer Therapy-Prostate questionnaire. The main independent variable was religious coping measured by 2 subscales capturing positive and negative forms of coping. Black men in the study had lower overall quality of life scores (134.6 ± 19.6) than their white peers (139.8 ± 14.1). Black men in the sample also had higher average positive religious coping scores (12.9 ± 3.3) than white men (10.3 ± 4.5). Fully adjusted linear regression models of the total sample produced results indicating that positive religious coping was correlated with an increase in quality of life (ß = .38, standard error [SE] = 0.18, P < .05). Negative religious coping was associated with a reduction in quality of life (ß = -1.48, SE = 0.40, P < .001). Faith-oriented beliefs or perceptions can have implications for quality of life among men with prostate cancer. Sensitivity to the role of religion, spirituality, and faith should be seen by providers of health care as potential opportunities for improved outcomes in patients with prostate cancer and survivors.

Spatiotemporal niche partitioning in a specious silphid community (Coleoptera: Silphidae Nicrophorus).

Resource niche partitioning mediates the coexistence of similar species by reducing the chance of competitive encounters. For co-occurring species that share an ephemeral resource, contrasting activity in space and time may facilitate their persistence. Burying beetles (Silphidae: Nicrophorus) depend entirely on small vertebrate carcasses to reproduce. Given the unpredictability of this resource, and its value to congeners and other scavenger species, burying beetles likely endure intense competition to secure a carcass. Here, contrasting spatial and temporal niche patterns are explored as resource allocation strategies among five sympatric species of burying beetles (N. americanus, N. marginatus, N. pustulatus, N. orbicollis, and N. tomentosus). Specifically, the space-use and daily activity patterns are measured, at a fine scale, across species pairs to extrapolate contrasting niche-use patterns within a nicrophorine-rich grassland community in North-Central Oklahoma, USA. The results of this study reveal an important interplay between space-use and daily temporal activity in mediating the scramble competition associated with carrion resources. Where spatial or temporal overlap between burying beetle species is high, direct competition is mediated along an alternative niche dimension. For instance, N. americanus and N. orbicollis, a species dyad thought to be in direct competition, do overlap temporally but were found to have segregated space-use patterns. Our findings provide key insights into the competitive interactions within a necrophilous community and further inform our broader understanding of the spatial and temporal resource dimensions that drive the ecological niche.

Black Pastors' Views on preaching about sex: barriers, facilitators, and opportunities for HIV prevention messaging.

OBJECTIVES: Despite the disproportionately high rates of heterosexually transmitted HIV infection among US Blacks and ongoing need for effective inexpensive behavioral interventions, the use of sermons as an HIV prevention tool in Black churches has received little research attention. The Black church plays an important role in Black communities and is a potential ally in development and delivery of sexual risk prevention messages. The objective of this study was to examine Black pastors' thoughts about whether sermons should address issues related to heterosexual relationships - and the barriers and facilitators to discussing these topics in a sermon setting. DESIGN: We conducted in-depth semi-structured, individual interviews among 39 pastors of Black churches in North Carolina and analyzed the interview data using thematic analysis strategies based on grounded theory. RESULTS: Pastors expressed widely ranging opinions, especially about discussion of condom use, but generally agreed that sermons should discuss marriage, abstinence, monogamy, dating, and infidelity - behaviors that impact sexual networks and HIV transmission. The major barriers to incorporation of these subjects into sermons include the extent to which a concept undermines their religious beliefs and uncertainty about how to incorporate it. However, scriptural support for a prevention message and the pastor's perception that the message is relevant to the congregation facilitate incorporation of related topics into sermons. CONCLUSIONS: These findings have implications for the potential utility of sermons as an HIV prevention tool and suggest that it is possible for public health professionals and pastors of Black churches to form partnerships to develop messages that are consonant with pastors' religious convictions as well as public health recommendations.

Cost-effectiveness of perampanel for the treatment of primary generalized tonic-clonic seizures (PGTCS) in epilepsy: A Spanish perspective.

BACKGROUND: Persistent seizures are associated with physical injury, reduced quality of life, and psychosocial impairment. Perampanel is approved for the adjunctive treatment of primary generalized tonic-clonic seizures (PGTCS). OBJECTIVE: This study aimed to determine the cost-effectiveness of perampanel as adjunctive therapy to other antiepileptic drugs (AED) compared with AED maintenance therapy alone for the treatment of PGTCS. METHODS: We developed a Markov model for PGTCS where transitions were based on treatment response rates. The analysis was conducted over a 33-year time horizon from the Spanish National Health Service (NHS) and societal perspectives. Efficacy data were derived from clinical studies. Resource use, market shares, costs, and utilities were obtained from Kantar Health's National Health and Wellness Survey. Drug costs were obtained from the Consejo General de Colegios Oficiales de Farmacéuticos. One-way and probabilistic sensitivity analyses were performed. RESULTS: In the base case analysis from the NHS perspective, perampanel was associated with an incremental cost-effectiveness ratio (ICER) of €16,557/quality-adjusted life year (QALY) relative to AED maintenance therapy for the treatment of PGTCS. Incremental costs were €5475 and incremental QALYs were 0.33. In one-way sensitivity analyses, the ICERs were strongly influenced by discounting rate for costs and health effects, with little influence of other parameters, including perampanel cost and utilities. In probabilistic sensitivity analyses, the probability of perampanel being cost-effective at a willingness-to-pay threshold of €30,000/QALY was 89.3%. From the societal perspective, perampanel provided a cost-savings of €5288 per patient compared with AED maintenance therapy alone. CONCLUSION: Our study demonstrates that perampanel is likely to be a cost-effective option.

Primary Care Physicians Beliefs about Prostate-Specific Antigen Evidence Uncertainty, Screening Efficacy, and Test Use.

BACKGROUND/PURPOSE: Little is known about primary care physicians' (PCPs) beliefs about prostate cancer screening efficacy, evidence uncertainty, and their actual screening behaviors. We examined factors associated with PCP beliefs about screening efficacy and uncertainty and whether beliefs were associated with prostate specific-antigen (PSA) test use. METHODS: The 2008 National Survey of Primary Care Physicians' Practices Regarding Prostate Cancer Screening collected information on physicians' attitudes, beliefs, and practices related to prostate cancer and screening (n=1,256). Two factors were constructed that measured belief in certainty of evidence for PSA testing and belief in screening efficacy. These factors, along with PCP sociodemographic and practice-related factors, were used to examine associations with offering the PSA test. RESULTS: Most PCPs were male (70%), Caucasian (76%), under age 50 (56%), and practiced in communities with more than 50,000 residents (54%). In bivariate analysis, variables associated with PCP belief in evidence uncertainty included female gender, younger age, and lower patient volume. Variables associated with belief in screening efficacy included older age and general and family practice specialty. After adjustment, PCPs with high belief in evidence uncertainty were less likely (OR=0.19, 95% CI=0.06, 0.62) to offer PSA and more likely to practice shared decision making (OR=1.80, 95% CI=1.22-2.67). PCPs with high belief in screening efficacy were more likely (OR=2.99, 95% CI=1.15, 7.77) to offer PSA and less likely to practice shared decision making (OR=0.47, 95% CI=0.32-0.70). CONCLUSION: Our data indicate that belief patterns about evidence uncertainty and the efficacy of using PSA may play a role in whether PCPs offer PSA.

High Levels of Medical Mistrust Are Associated With Low Quality of Life Among Black and White Men With Prostate Cancer.

BACKGROUND: Medical mistrust is thought to affect health care-based decisions and has been linked to poor health outcomes. The effects of medical mistrust among men with prostate cancer are unknown. Thus, the goal of the current study is to examine the association between medical mistrust and quality of life (QOL) among black and white men with prostate cancer. METHODS: A total of 877 men (415 black, 462 white) with prostate cancer between the ages of 40 to 81 years who entered the North Carolina Central Cancer Registry during the years 2007 and 2008 were retrospectively recruited. The dependent variable was overall QOL measured by the Functional Assessment of Cancer Therapy-Prostate questionnaire. The primary independent variable was medical mistrust. Multivariate regression analysis was used to assess the association between medical mistrust and overall QOL. RESULTS: Compared with white men, black men reported a higher level of medical mistrust (black = 2.7, white = 2.4; P < .001) and lower QOL (black = 134.4, white = 139.5; P < 0.001). After controlling for demographical and clinical variables, higher levels of medical mistrust were associated with a reduction in overall QOL among men with prostate cancer (beta = -7.73; standard error = 1.54) CONCLUSIONS: Higher levels of medical mistrust are associated with reduced overall QOL among black and white men with prostate cancer. Interventions targeted to reduce medical mistrust may be effective in increasing the overall QOL of men with prostate cancer.

Prevalence and Correlates of Major Depressive Symptoms among Black Men with Prostate Cancer.

Objectives: The objectives of our study were to determine the prevalence of major depressive symptoms and identify factors that are associated with major depressive symptoms among Black men with prostate cancer (PCa). Design: This study consisted of 415 Black men aged 40-81 years that entered the North Carolina Central Cancer Registry during the years 2007-2008. The primary outcome variable was depressive symptoms (CES-D). Factors included age, income, education, insurance status, treatment received, time between diagnosis and treatment, Gleason score, medical mistrust and experience with racism/discrimination. Logistic regression models were used to assess factors associated with the odds of having major depressive symptoms. Results: The prevalence of major depressive symptoms (≥16 on CES-D) among our sample of Black men with PCa was approximately 33%. Approximately 15% of the study participants underwent radiation beam treatment. Age was significantly associated with the odds of reporting major depressive symptoms (OR= .95, CI .91-.99) among Black men. In addition, compared with all other forms of treatment, Black men who underwent radiation beam treatment had higher odds (OR=2.38, CI 1.02- 5.51) of reporting major depressive symptoms. Conclusion: Nearly one-third of Black men with PCa in this study reported major depressive symptoms. Clinicians should pay closer attention to the mental health status of Black men with PCa, especially those who are younger and those who have undergone radiation beam treatment. Cancer survivorship, particularly quality of life, may be enhanced by opportunities for assessment, evaluation and intervention of depressive symptoms among these men disproportionately affected by PCa.

Cost-benefit analysis of routine pathology examination in primary shoulder arthroplasty.

BACKGROUND: The annual number of shoulder arthroplasty procedures is continuing to increase. Specimens from shoulder arthroplasty cases are routinely sent for pathologic examination. This study sought to evaluate the clinical utility and associated costs of routine pathologic examination of tissue removed during primary shoulder arthroplasty cases and to determine cost-effectiveness of this practice. METHODS: This is a retrospective review of primary shoulder arthroplasty cases. Patients whose humeral head was sent for routine pathologic examination were included. Cases were determined to have concordant, discrepant, or discordant diagnoses based on preoperative/postoperative diagnosis and pathology diagnosis. Costs were estimated in 2015 U.S. dollars, and cost-effectiveness was determined by the cost per discrepant diagnosis and cost per discordant diagnosis. RESULTS: We identified 714 cases of primary shoulder arthroplasty in 646 patients who met inclusion criteria. The prevalence of concordant diagnoses was 94.1%, the prevalence of discrepant diagnoses was 5.9%, and no cases had discordant diagnoses. There were 172 cases that had biceps tendon specimens sent for pathology examination, and none led to a change in patient care. Total estimated costs were $77,309.34 in 2015 U.S. dollars. Cost per discrepant diagnosis for humeral head specimens was $1424.09, and cost per discordant diagnosis is at least $59,811.78. DISCUSSION/CONCLUSION: Primary shoulder arthroplasty has a high rate of concordant diagnosis. Discrepant diagnoses were 5.9% in our study, and there were no discordant diagnoses. This study showed limited clinical utility in routinely sending specimens from primary shoulder arthroplasty cases for pathology examination, and calculation using a traditional life-year value of $50,000 showed that the standard for cost-effectiveness is not met.

In memoriam: Richard G. Harrison - his life and legacy.

Richard G. Harrison passed away unexpectedly on April 12th, 2016. In this memoriam we pay tribute to the life and legacy of an extraordinary scientist, mentor, friend, husband, and father.

Racial Disparity in Time Between First Diagnosis and Initial Treatment of Prostate Cancer.

BACKGROUND: Disparities among patients with prostate cancer exist across the continuum of care. The interval of time that lapses between first diagnosis and treatment is another disparity that may exist but has not been fully explored. METHODS: Our study looked at the data of 749 men (353 black and 396 white) who were 40 to 81 years of age when they entered the North Carolina Central Cancer Registry during the years 2007 and 2008. Our dependent variable was the amount of months that had passed between first diagnosis and treatment. Our main independent variable was self-reported race. Covariates included age, income, level of education, insurance status, treatment received, Gleason score, and level of medical mistrust. We used negative binomial regression analysis to determine the association between the amount of time that lapsed between a diagnosis of prostate cancer and treatment by race. RESULTS: Compared with white men, black men were more likely to experience a longer wait time between diagnosis and treatment of prostate cancer (incidence rate ratio [IRR] 1.19; 95% confidence interval [CI], 1.04-1.36). Controls for demographical, clinical, and psychosocial variables (IRR 1.24; 95% CI, 1.04-1.43) did not explain this difference between the races. CONCLUSIONS: These results suggest that the amount of time that lapses between first diagnosis and treatment of prostate cancer is longer for black men compared with white men. Our findings have identified an underreported racial disparity in the disease continuum of prostate cancer.

Factors Associated with Men's Assessment of Prostate Cancer Treatment Choice.

The objective of this study is to examine factors among a group of African American and White men in North Carolina and their assessment of prostate cancer treatment choice or belief that treatment chosen was best. A sample of men (N = 877) with a history of prostate cancer diagnosis was recruited from the North Carolina Cancer Registry during 2007-2008 and asked to participate in a telephone interview covering several measures about their initial prostate cancer treatment. Logistic regression was used to assess demographic, psychosocial, and clinical factors on whether they felt that they had chosen the best treatment for the disease. Respondents were majority White (52.7 %), married (75.9 %), and had surgery (67.9 %) as their initial treatment. At the bivariate level, factors associated with the belief that the treatment chosen was best were as follows: White race/ethnicity, higher levels of education, a more recent treatment date, having health insurance coverage, type of treatment received, higher levels of bother from side effects, greater contentment with their quality of life, and doctor discussions of the various treatment options. Similarly, the multivariate analysis showed increased odds of belief that the treatment chosen was the best among demographic (i.e., race/ethnicity, level of education, and health insurance coverage) as well as psychosocial and clinical variables (i.e., greater bother from side effects, greater contentment with their quality of life, and initial treatment received). Results suggest that demographic, psychosocial, and clinical factors play an important role for men in assessing their treatment choices for prostate cancer.

Examining characteristics of congregation members willing to attend health promotion in African American churches.

BACKGROUND: Although churches are an important partner for improving health within the African American community, it is not known how congregants are best reached by health promotion activities and thus how best to target members in recruitment. This study examined how characteristics of churches and congregants' beliefs and interests in faith-based health promotion related to their willingness to attend church-based health promotion activities. METHOD: We surveyed adult congregants (n = 1,204) of 11 predominately African American churches in North Carolina. Surveys collected data within four domains: demographics (age, sex, education), behavioral (church attendance, respondent food choices, and physical activity), cognitive (church-based health promotion belief, Bible-based healthy living interest, healthy living resource interest), or environmental (family health, church travel distance, church health ministry activity, church members' food choices). Analyses used a dichotomous outcome, interest in attending programs offered by the health ministry. Domain-specific models were constructed. Logistic generalized estimating equations adjusted for clustering. RESULTS: Of the 1,204 congregants, 72% were female, 57% were 50 years or older, 84% had a high school education or more, and 77% had a chronic health condition. In bivariate analyses and in models adjusting for all four domains, cognitive factors had the highest odds of willingness to attend. CONCLUSION: Congregants' belief in the church's role in health promotion and their desire to learn about healthy behaviors highlight the role of the African American church as a partner in addressing health disparities and the need to capitalize on this expectation through stronger partnerships between medical and faith communities.

Participating in research: attitudes within the African American church.

We assessed associations between pastor and congregant characteristics and congregant attitudes about research participation among African American churches. Respondents shared their attitudes regarding how willing, ready, and confident they were about research participation. The outcome measure, the index of research preparedness, summed responses across the domains of willingness, readiness, and confidence. Pastor age and pastor educational attainment were independently associated with a congregants' higher index of research preparedness. Young and educated pastors were significantly associated with congregant attitudes about participation preparedness, a finding that highlights the importance of the pastor regarding congregant research participation decisions.

Identifying the Heterogeneity in the Association between Workforce Diversity and Retention in Opioid Treatment among Black clients.

Background: This study investigates the impact of workforce diversity, specifically staff identified as Black/African American, on retention in opioid use disorder (OUD) treatment, aiming to enhance patient outcomes. Employing a novel machine learning technique known as 'causal forest,' we explore heterogeneous treatment effects on retention. Methods: We relied on four waves of the National Drug Abuse Treatment System Survey (NDATSS), a nationally representative longitudinal dataset of treatment programs. We analyzed OUD program data from the years 2000, 2005, 2014 and 2017 (n = 627). Employing the 'causal forest' method, we analyzed the heterogeneity in the relationship between workforce diversity and retention in OUD treatment. Interviews with program directors and clinical supervisors provided the data for this study. Results: The results reveal diversity-related variations in the association with retention across 61 out of 627 OUD treatment programs (less than 10%). These programs, associated with positive impacts of workforce diversity, were more likely private-for-profit, newer, had lower percentages of Black and Latino clients, lower staff-to-client ratios, higher proportions of staff with graduate degrees, and lower percentages of unemployed clients. Conclusions: While workforce diversity is crucial, our findings underscore that it alone is insufficient for improving retention in addiction health services research. Programs with characteristics typically linked to positive outcomes are better positioned to maximize the benefits of a diverse workforce in client retention. This research has implications for policy and program design, guiding decisions on resource allocation and workforce diversity to enhance retention rates among Black clients with OUDs.

Utilization of lasso peptides for biodegradation of polycyclic aromatic hydrocarbons.

Many microbial genes involved in degrading recalcitrant environmental contaminants such as polycyclic aromatic hydrocarbons (PAHs) have been identified and characterized. However, all molecular mechanisms required for PAH utilization have not yet been elucidated. In this work, we demonstrate the proposed involvement of lasso peptides in the utilization of the PAH phenanthrene in Sphingomonas BPH. Transpositional mutagenesis of Sphingomonas BPH with the miniTn5 transposon yielded 3 phenanthrene utilization deficient mutants, #257, #1778, and #1782. In mutant #1782, Tn5 had inserted into the large subunit of the naph/bph dioxygenase gene. In mutant #1778, Tn5 had inserted into the B2 protease gene of a lasso peptide cluster. This finding is the first report on the role of lasso peptides in PAH utilization. Our studies also demonstrate that interruption of the lasso peptide cluster resulted in a significant increase in the amount of biosurfactant produced in the presence of glucose when compared to the wild-type strain. Collectively, these results suggest that the mechanisms Sphingomonas BPH utilizes to degrade phenanthrene are far more complex than previously understood and that the #1778 mutant may be a good candidate for bioremediation when glucose is applied as an amendment due to its higher biosurfactant production.

The impact of post-operative enteral nutrition on duodenal injury outcomes: A post hoc analysis of an EAST multicenter trial.

BACKGROUND: Leak following surgical repair of traumatic duodenal injuries results in prolonged hospitalization and oftentimes nil per os(NPO) treatment. Parenteral nutrition(PN) has known morbidity; however, duodenal leak(DL) patients often have complex injuries and hospital courses resulting in barriers to enteral nutrition(EN). We hypothesized EN alone would be associated with 1)shorter duration until leak closure and 2)less infectious complications and shorter hospital length of stay(HLOS) compared to PN. METHODS: This was a post-hoc analysis of a retrospective, multicenter study from 35 Level-1 trauma centers, including patients >14 years-old who underwent surgery for duodenal injuries(1/2010-12/2020) and endured post-operative DL. The study compared nutrition strategies: EN vs PN vs EN + PN using Chi-Square and Kruskal-Wallis tests; if significance was found pairwise comparison or Dunn's test were performed. RESULTS: There were 113 patients with DL: 43 EN, 22 PN, and 48 EN + PN. Patients were young(median age 28 years-old) males(83.2%) with penetrating injuries(81.4%). There was no difference in injury severity or critical illness among the groups, however there were more pancreatic injuries among PN groups. EN patients had less days NPO compared to both PN groups(12 days[IQR23] vs 40[54] vs 33[32],p = <0.001). Time until leak closure was less in EN patients when comparing the three groups(7 days[IQR14.5] vs 15[20.5] vs 25.5[55.8],p = 0.008). EN patients had less intra-abdominal abscesses, bacteremia, and days with drains than the PN groups(all p < 0.05). HLOS was shorter among EN patients vs both PN groups(27 days[24] vs 44[62] vs 45[31],p = 0.001). When controlling for predictors of leak, regression analysis demonstrated EN was associated with shorter HLOS(ß -24.9, 95%CI -39.0 to -10.7,p < 0.001). CONCLUSION: EN was associated with a shorter duration until leak closure, less infectious complications, and shorter length of stay. Contrary to some conventional thought, PN was not associated with decreased time until leak closure. We therefore suggest EN should be the preferred choice of nutrition in patients with duodenal leaks whenever feasible. LEVEL OF EVIDENCE: IV.