Assessing Acceptability: The Role of Understanding Participant, Neighborhood, and Community Contextual Factors in Designing a Community-Tailored Cooking Intervention.

BACKGROUND: Cooking is an identified dietary strategy that is positively associated with optimal diet quality. Prior to initiating cooking interventions, evaluating the prospective acceptability of the intervention among community members living within low food access areas and understanding geospatial food shopping locations may aid in designing community-tailored interventions. METHODS: A sequential mixed methods study was conducted to determine the prospective acceptability of a planned community-located cooking intervention among African American adults living in a low food access area and with at least one cardiovascular disease risk factor. A semi-structured guide was used to conduct five virtual focus groups. Qualitative data were analyzed using thematic analysis and validated through participant check-in interviews. Survey responses were analyzed based on descriptive data. Geospatial analysis of participant locations that were reported for food shopping was conducted to show food environment utilization. RESULTS: Focus groups with study participants (n = 20, all female, mean age 60.3, SD 9.3, mean cooking frequency per week 4.0, food insecure n = 7) were conducted between March and April, 2021. Thematic analysis of the focus group transcripts identified five main themes as follows: (A) Barriers to Cooking (family and caregiving, transportation, COVID-19 pandemic, time availability, household composition); (B) Motivators for Cooking (family, caregiving, health, enjoyment, COVID-19 pandemic); (C) Strategies (food shopping, social support, social media, meal planning); (D) Neighborhood (gentrification, perceived safety, stigmatization, disparities in grocery stores); (E) and Acceptability of the Intervention (reasons to participate, barriers, recruitment, intervention delivery). Participant validation interviews confirmed the themes and subthemes as well as the illustrative quotes. Geospatial analysis showed a majority of locations were outside of the participants' residential areas. CONCLUSIONS: Prospective acceptability of a community-tailored cooking intervention found that the planned intervention could be modified to address individual level factors, such as caregiving and health, community contextual factors, such as perceived safety, and the general health needs of the community.

(Mg,Mn,Fe,Co,Ni)O: A rocksalt high-entropy oxide containing divalent Mn and Fe.

High-entropy oxides (HEOs) have aroused growing interest due to fundamental questions relating to their structure formation, phase stability, and the interplay between configurational disorder and physical and chemical properties. Introducing Fe(II) and Mn(II) into a rocksalt HEO is considered challenging, as theoretical analysis suggests that they are unstable in this structure under ambient conditions. Here, we develop a bottom-up method for synthesizing Mn- and Fe-containing rocksalt HEO (FeO-HEO). We present a comprehensive investigation of its crystal structure and the random cation-site occupancy. We show the improved structural robustness of this FeO-HEO and verify the viability of an oxygen sublattice as a buffer layer. Compositional analysis reveals the valence and spin state of the iron species. We further report the antiferromagnetic order of this FeO-HEO below the transition temperature ~218 K and predict the conditions of phase stability of Mn- and Fe-containing HEOs. Our results provide fresh insights into the design and property tailoring of emerging classes of HEOs.

Results and perinatal outcomes from 189 ICSI cycles of couples with asthenozoospermic men and flagellar defects assessed by transmission electron microscopy.

RESEARCH QUESTION: Do patients presenting with flagella ultrastructural defects as assessed by electron microscopy, and defined within three phenotypes (dysplasia of the fibrous sheath [DFS], primary flagellar dyskinesia [PFD] and non-specific flagellar abnormalities [NSFA]), have decreased chances of success in intracytoplasmic sperm injection (ICSI) or adverse obstetric and neonatal outcomes? DESIGN: Retrospective analysis of 189 ICSI cycles from 80 men with spermatozoa flagellum ultrastructural defects (DFS [n = 16]; PFD [n = 14]; NSFA [n = 50] compared with a control group (n = 97). Cycles were cumulatively analysed. All fresh and frozen embryo transfers resulting from each ICSI attempt were included. The effect of transmission electron microscopy (TEM) phenotype on the main ICSI outcomes was assessed by a multivariate logistic regression combined with a generalized linear mixed model to account for the non-independence of the observations. RESULTS: No predictive value of TEM phenotype was found on the main outcomes of ICSI, namely fertilization rates, pregnancy and delivery rates, and cumulative pregnancy and delivery rates. Cumulative pregnancy rates ranged from 29.0-43.3% in the different TEM phenotype subgroups compared with 36.8% in the control group. Cumulative live birth rates ranged from 24.6-36.7% compared with 31.4% in the control group. No increase was found in miscarriages, preterm births, low birth weights or birth abnormalities. CONCLUSIONS: Data on the cumulative chances of success in ICSI of patients with ultrastructural flagellar defects, a rare cause of male infertility often associated with an underlying genetic cause, are reassuring, as are obstetrical and neonatal outcomes in this population.

Social Determinants modulate NK cell activity via obesity, LDL, and DUSP1 signaling.

Adverse social determinants of health (aSDoH) are associated with obesity and related comorbidities like diabetes, cardiovascular disease, and cancer. Obesity is also associated with natural killer cell (NK) dysregulation, suggesting a potential mechanistic link. Therefore, we measured NK phenotypes and function in a cohort of African-American (AA) women from resource-limited neighborhoods. Obesity was associated with reduced NK cytotoxicity and a shift towards a regulatory phenotype. In vitro, LDL promoted NK dysfunction, implicating hyperlipidemia as a mediator of obesity-related immune dysregulation. Dual specific phosphatase 1 (DUSP1) was induced by LDL and was upregulated in NK cells from subjects with obesity, implicating DUSP1 in obesity-mediated NK dysfunction. In vitro, DUSP1 repressed LAMP1/CD107a, depleting NK cells of functional lysosomes to prevent degranulation and cytokine secretion. Together, these data provide novel mechanistic links between aSDoH, obesity, and immune dysregulation that could be leveraged to improve outcomes in marginalized populations.

Specific Ion Effects at the Vapor-Formamide Interface: A Reverse Hofmeister Series in Ion Concentration Depth Profiles.

Employing neutral impact collision ion scattering spectroscopy (NICISS), we have directly measured the concentration depth profiles (CDPs) of various monovalent ions at the vapor-formamide interface. NICISS provides CDPs of individual ions by measuring the energy loss of neutral helium atoms backscattered from the solution interface. CDPs at the vapor-formamide interface of Cl-, Br-, I-, Na+, K+, and Cs+ are measured and compared to elucidate the interfacial specific ion trends. We report a reverse Hofmeister series in the presence of inorganic ions (anion and cation) at the vapor-formamide interface relative to the water-vapor interface, and the CDPs are found to be independent of the counterion for most ions studied. Thus, ions at the surface of formamide follow a "Hofmeister paradigm" where the counterion does not impact the ion series. These specific ion trends are complemented with surface tension and X-ray absorption near-edge structure (XANES) measurements on formamide electrolyte solutions.

Associations between neighborhood socioeconomic deprivation, IFNγ, and high-density lipoprotein particle size: Data from the Washington, D.C. cardiovascular health and needs assessment.

INTRODUCTION: Neighborhood socioeconomic deprivation is associated with increased cardiovascular risk factors, including inflammation. Inflammation plays an important role in modifying the cardioprotective function of high-density lipoprotein (HDL). Moreover, recent studies suggest that very high HDL is associated with adverse cardiovascular disease (CVD) outcomes. Thus, we sought to explore the relationships between neighborhood socioeconomic deprivation as a marker of chronic stress, inflammation, proprotein convertase subtilisin/kexin type 9 (PCSK9) (a core component of the HDL proteome), HDL characterisitcs, and biological aging as a predictor of CVD and all-cause mortality. METHODS: Sixty African American subjects were recruited to the NIH Clinical Center as part of a community-based participatory research-designed observational study. Neighborhood deprivation index (NDI), a marker of neighborhood socioeconomic deprivation, was measured using US Census data. HDL characteristics (cholesterol, particle number, size, subspecies) were determined from NMR lipoprotein profiling, and plasma cytokines (IL-1ß, IL-6, IL-8, TNFα, IFNγ) were measured using an ELISA-based multiplex technique. Epigenetic clock biomarkers of aging were measured using DNA methylation data obtained from participants' buffy coat samples. We used linear regression modeling adjusted for atherosclerotic cardiovascular disease (ASCVD) risk score, body mass index (BMI), and lipid-lowering medication use to investigate relationships of interest. RESULTS: NDI directly associated with large HDL particle count (H7P) and IFNγ and trended toward significance with HDL-C and PCSK9. IFNγ and PCSK9 then directly associated with H7P. H7P also directly associated with higher DNA methylation phenotypic age (PhenoAge). CONCLUSION: We highlight associations between neighborhood socioeconomic deprivation, IFNγ, PCSK9, HDL subspecies, and epigenetic biomarkers of aging. Taken together, our findings suggest indirect pathways linking neighborhood deprivation-related stress and inflammation to HDL and immune epigenetic changes. Moreover, these results add to recent work showing the pathogenicity of high HDL levels and underscore the need to understand how chronic stress-related inflammation and lipoprotein subspecies relate to CVD risk across diverse populations.

Neighborhood socioeconomic deprivation and individual-level socioeconomic status are associated with dopamine-mediated changes to monocyte subset CCR2 expression via a cAMP-dependent pathway.

Social determinants of health (SDoH) include socioeconomic, environmental, and psychological factors that impact health. Neighborhood socioeconomic deprivation (NSD) and low individual-level socioeconomic status (SES) are SDoH that associate with incident heart failure, stroke, and cardiovascular mortality, but the underlying biological mechanisms are not well understood. Previous research has demonstrated an association between NSD, in particular, and key components of the neural-hematopoietic-axis including amygdala activity as a marker of chronic stress, bone marrow activity, and arterial inflammation. Our study further characterizes the role of NSD and SES as potential sources of chronic stress related to downstream immunological factors in this stress-associated biologic pathway. We investigated how NSD, SES, and catecholamine levels (as proxy for sympathetic nervous system activation) may influence monocytes which are known to play a significant role in atherogenesis. First, in an ex vivo approach, we treated healthy donor monocytes with biobanked serum from a community cohort of African Americans at risk for CVD. Subsequently, the treated monocytes were subjected to flow cytometry for characterization of monocyte subsets and receptor expression. We determined that NSD and serum catecholamines (namely dopamine [DA] and norepinephrine [NE]) associated with monocyte C-C chemokine receptor type 2 (CCR2) expression (p < 0.05), a receptor known to facilitate recruitment of monocytes towards arterial plaques. Additionally, NSD associated with catecholamine levels, especially DA in individuals of low SES. To further explore the potential role of NSD and the effects of catecholamines on monocytes, monocytes were treated in vitro with epinephrine [EPI], NE, or DA. Only DA increased CCR2 expression in a dose-dependent manner (p < 0.01), especially on non-classical monocytes (NCM). Furthermore, linear regression analysis between D2-like receptor surface expression and surface CCR2 expression suggested D2-like receptor signaling in NCM. Indicative of D2-signaling, cAMP levels were found to be lower in DA-treated monocytes compared to untreated controls (control 29.78 pmol/ml vs DA 22.97 pmol/ml; p = 0.038) and the impact of DA on NCM CCR2 expression was abrogated by co-treatment with 8-CPT, a cAMP analog. Furthermore, Filamin A (FLNA), a prominent actin-crosslinking protein, that is known to regulate CCR2 recycling, significantly decreased in DA-treated NCM (p < 0.05), indicating a reduction of CCR2 recycling. Overall, we provide a novel immunological mechanism, driven by DA signaling and CCR2, for how NSD may contribute to atherogenesis. Future studies should investigate the importance of DA in CVD development and progression in populations disproportionately experiencing chronic stress due to SDoH.

Total scattering measurements at the Australian Synchrotron Powder Diffraction beamline: capabilities and limitations.

This study describes the capabilities and limitations of carrying out total scattering experiments on the Powder Diffraction (PD) beamline at the Australian Synchrotron, ANSTO. A maximum instrument momentum transfer of 19 Å-1 can be achieved if the data are collected at 21 keV. The results detail how the pair distribution function (PDF) is affected by Qmax, absorption and counting time duration at the PD beamline, and refined structural parameters exemplify how the PDF is affected by these parameters. There are considerations when performing total scattering experiments at the PD beamline, including (1) samples need to be stable during data collection, (2) highly absorbing samples with a µR > 1 always require dilution and (3) only correlation length differences >0.35 Šmay be resolved. A case study comparing the PDF atom-atom correlation lengths with EXAFS-derived radial distances of Ni and Pt nanocrystals is also presented, which shows good agreement between the two techniques. The results here can be used as a guide for researchers considering total scattering experiments at the PD beamline or similarly setup beamlines.

Use of a focus group-based cognitive interview methodology to validate a cooking behavior survey among African-American adults.

Disparities in diet-related diseases persist among African-Americans despite advances in risk factor identification and evidence-based management strategies. Cooking is a dietary behavior linked to improved dietary quality and cardiometabolic health outcomes. However, epidemiologic studies suggest that African-American adults report a lower frequency of cooking at home when compared to other racial groups, despite reporting on average cooking time. To better understand cooking behavior among African-Americans and reported disparities in behavior, we sought to develop a survey instrument using focus group-based cognitive interviews, a pretesting method that provides insights into a survey respondent's interpretation and mental processing of survey questions. A comprised survey instrument was developed based on input from a community advisory board, a literature review, and a content review by cooking behavior experts. The cognitive interview pretesting of the instrument involved African-American adults (n = 11) at risk for cardiovascular disease who were recruited from a community-based participatory research study in Washington, D.C., to participate in a focus group-based cognitive interview. Cognitive interview methodologies included the verbal think-aloud protocol and the use of retrospective probes. Thematic analysis and evaluation of verbalized cognitive processes were conducted using verbatim transcripts. Five thematic themes related to the survey were generated: (1) Clarity and relevancy of question items; (2) influence of participants' perspectives and gender roles; (3) participant social desirability response to questions; (4) concern regarding question intent. Eleven survey items were determined as difficult by participants. Cooking topics for these items were: cooking practices, cooking skills, cooking perception (how one defines cooking), food shopping skills, and socialization around cooking. Question comprehension and interpreting response selections were the most common problems identified. Cognitive interviews are useful for cooking research as they can evaluate survey questions to determine if the meaning of the question as intended by the researcher is communicated to the respondents-specific implications from the results that apply to cooking research include revising questions on cooking practice and skills. Focus-group-based cognitive interviews may provide a feasible method to develop culturally grounded survey instruments to help understand disparities in behavior for culturally relevant diet behaviors such as cooking.

Going virtual during the COVID-19 pandemic: adaptation of a mixed-methods dietary behavior study within a community-based participatory research study of African-American adults at risk for cardiovascular disease.

BACKGROUND: Identifying mechanisms to maintain CBPR studies during an infectious disease pandemic is vital. The current paper describes the changes in methods and processes conducted within a CBPR mixed-methods study to a virtual setting during the novel coronavirus (COVID-19) pandemic. METHOD: The DC Community Organizing for Optimal Culinary Knowledge study with Heart (DC COOKS with Heart) was designed to assess the feasibility of a dietary behavior intervention among African-American adults that are at risk for cardiovascular disease (CVD). The study is under the umbrella of an ongoing CBPR study and community advisory board that facilitates community involvement in study design and promotes ongoing engagement with community members and leaders. The study population for D.C. COOKS with Heart consists of adult African-American individuals who live in two low-resource neighborhoods in Washington, D.C., which were impacted disproportionately by COVID. Eligible study participants who previously participated in the DC CHOC community-based studies were contacted to participate in Phase 1. The quantitative part of the mixed-methods included survey data collection. RESULTS: Due to the pandemic, the mode of data collection for surveys changed from self-administered face-to-face to internet-based. All virtual study procedures were conducted between March and April, 2021. Anticipated benefits of the virtual setting included participant safety during the pandemic, ease of logistics for participants. Anticipated challenges included administration of electronic devices to participants, research team training, and potential threats to established trust related to the privacy and confidentiality of participants. CONCLUSION: The transition to a virtual setting for study procedures in a mixed-methods study was conducted successfully in terms of recruitment, retention of participants, and training of research team members. The virtual transition required established and ongoing engagement through the community advisory board and CBPR practices, institutional support through virtual research policies, collaborations with information technology-based teams, and equipment administration for the study. TRIALS REGISTRATION: NCT04305431 . Registered on March 12, 2020.

LDL associates with pro-inflammatory monocyte subset differentiation and increases in chemokine receptor profile expression in African Americans.

BACKGROUND: In the United States, African Americans (AAs) have greater risk for Class III obesity and cardiovascular disease (CVD). Previous reports suggest that AAs have a different immune cell profile when compared to Caucasians. METHODS: The immune cell profile of AAs was characterized by flow cytometry using two experimental setups: ex vivo (N = 40) and in vitro (N = 10). For ex vivo experiments, PBMC were treated with participant serum to understand how lipid contents may contribute to monocyte phenotypic differences. For in vitro experiments, monocytes were low-density lipoprotein (LDL)- or vehicle-treated for four hours and subsequently analyzed by flow cytometry and RT-qPCR. RESULTS: When PBMCs were treated with participant sera, subsequent multivariable regression analysis revealed that serum triglycerides and LDL levels were associated with monocyte subset differences. In vitro LDL treatment of monocytes induced a phenotypic switch in monocytes away from classical monocytes accompanied by subset-specific chemokine receptor CCR2 and CCR5 expression changes. These observed changes are partially translation-dependent as determined by co-incubation with cycloheximide. CONCLUSIONS: LDL treatment of monocytes induces a change in monocyte subsets and increases CCR2/CCR5 expression in a subset-specific manner. Understanding the molecular mechanisms could prove to have CVD-related therapeutic benefits, especially in high-risk populations with hyperlipidemia and increased risk for CVD.

Defining Reference Ranges for Serum Anti-Müllerian Hormone on a Large Cohort of Normozoospermic Adult Men Highlights New Potential Physiological Functions of AMH on FSH Secretion and Sperm Motility.

BACKGROUND: Few studies to date have attempted to measure serum anti-Müllerian hormone (AMH) levels in adult men, and solid references ranges have not yet been defined in a large cohort. OBJECTIVE: In this study, we aimed, first, to establish the reference ranges for serum AMH and AMH-to-total testosterone ratio (AMH/tT) in adult males. Second, we investigated the relationship between serum AMH and both reproductive hormones and semen parameters. METHODS: This single-center retrospective study included 578 normozoospermic adult men. Serum AMH concentrations were determined with an automated sandwich chemiluminescent immunoassay. RESULTS: The median serum AMH was 43.5 pmol/L. The 2.5th and 97.5th percentile values for serum AMH and AMH/tT were 16.4 and 90.3 pmol/L and 0.45 and 3.43, respectively. AMH was positively correlated with inhibin B and sperm concentration and negatively correlated with age, follicle-stimulating hormone (FSH), and progressive sperm motility. Interestingly, using immunofluorescence, we documented for the first time that AMH type II receptor (AMH-R2) is expressed in ejaculated human spermatozoa and gonadotrophic cells in the postmortem pituitary gland. CONCLUSIONS: We establish a new age-specific reference range for serum AMH and AMH/tT. Moreover, AMH-R2 expression in human spermatozoa and gonadotrophic cells, together with the relationship between serum AMH levels and sperm motility or mean FSH levels, highlight new potential functions of AMH in regulating sperm motility or FSH secretion in adult men.

Use of a community advisory board to build equitable algorithms for participation in clinical trials: a protocol paper for HoPeNET.

INTRODUCTION: Participation from racial and ethnic minorities in clinical trials has been burdened by issues surrounding mistrust and access to healthcare. There is emerging use of machine learning (ML) in clinical trial recruitment and evaluation. However, for individuals from groups who are recipients of societal biases, utilisation of ML can lead to the creation and use of biased algorithms. To minimise bias, the design of equitable ML tools that advance health equity could be guided by community engagement processes. The Howard University Partnership with the National Institutes of Health for Equitable Clinical Trial Participation for Racial/Ethnic Communities Underrepresented in Research (HoPeNET) seeks to create an ML-based infrastructure from community advisory board (CAB) experiences to enhance participation of African-Americans/Blacks in clinical trials. METHODS AND ANALYSIS: This triphased cross-sectional study (24 months, n=56) will create a CAB of community members and research investigators. The three phases of the study include: (1) identification of perceived barriers/facilitators to clinical trial engagement through qualitative/quantitative methods and systems-based model building participation; (2) operation of CAB meetings and (3) development of a predictive ML tool and outcome evaluation. Identified predictors from the participant-derived systems-based map will be used for the ML tool development. ETHICS AND DISSEMINATION: We anticipate minimum risk for participants. Institutional review board approval and informed consent has been obtained and patient confidentiality ensured.

Liquid-Metal-Enabled Mechanical-Energy-Induced CO2 Conversion.

A green carbon capture and conversion technology offering scalability and economic viability for mitigating CO2 emissions is reported. The technology uses suspensions of gallium liquid metal to reduce CO2 into carbonaceous solid products and O2 at near room temperature. The nonpolar nature of the liquid gallium interface allows the solid products to instantaneously exfoliate, hence keeping active sites accessible. The solid co-contributor of silver-gallium rods ensures a cyclic sustainable process. The overall process relies on mechanical energy as the input, which drives nano-dimensional triboelectrochemical reactions. When a gallium/silver fluoride mix at 7:1 mass ratio is employed to create the reaction material, 92% efficiency is obtained at a remarkably low input energy of 230 kWh (excluding the energy used for dissolving CO2 ) for the capture and conversion of a tonne of CO2 . This green technology presents an economical solution for CO2 emissions.

Spatial Clustering of County-Level COVID-19 Rates in the U.S.

Despite the widespread prevalence of cases associated with the coronavirus disease 2019 (COVID-19) pandemic, little is known about the spatial clustering of COVID-19 in the United States. Data on COVID-19 cases were used to identify U.S. counties that have both high and low COVID-19 incident proportions and clusters. Our results suggest that there are a variety of sociodemographic variables that are associated with the severity of COVID-19 county-level incident proportions. As the pandemic evolved, communities of color were disproportionately impacted. Subsequently, it shifted from communities of color and metropolitan areas to rural areas in the U.S. Our final period showed limited differences in county characteristics, suggesting that COVID-19 infections were more widespread. The findings might address the systemic barriers and health disparities that may result in high incident proportions of COVID-19 clusters.

Geospatial Analysis of Neighborhood Environmental Stress in Relation to Biological Markers of Cardiovascular Health and Health Behaviors in Women: Protocol for a Pilot Study.

BACKGROUND: Innovative analyses of cardiovascular (CV) risk markers and health behaviors linked to neighborhood stressors are essential to further elucidate the mechanisms by which adverse neighborhood social conditions lead to poor CV outcomes. We propose to objectively measure physical activity (PA), sedentary behavior, and neighborhood stress using accelerometers, GPS, and real-time perceived ecological momentary assessment via smartphone apps and to link these to biological measures in a sample of White and African American women in Washington, DC, neighborhoods. OBJECTIVE: The primary aim of this study is to test the hypothesis that living in adverse neighborhood social conditions is associated with higher stress-related neural activity among 60 healthy women living in high or low socioeconomic status neighborhoods in Washington, DC. Sub-aim 1 of this study is to test the hypothesis that the association is moderated by objectively measured PA using an accelerometer. A secondary objective is to test the hypothesis that residing in adverse neighborhood social environment conditions is related to differences in vascular function. Sub-aim 2 of this study is to test the hypothesis that the association is moderated by objectively measured PA. The third aim of this study is to test the hypothesis that adverse neighborhood social environment conditions are related to differences in immune system activation. METHODS: The proposed study will be cross-sectional, with a sample of at least 60 women (30 healthy White women and 30 healthy Black women) from Wards 3 and 5 in Washington, DC. A sample of the women (n=30) will be recruited from high-income areas in Ward 3 from census tracts within a 15% of Ward 3's range for median household income. The other participants (n=30) will be recruited from low-income areas in Wards 5 from census tracts within a 15% of Ward 5's range for median household income. Finally, participants from Wards 3 and 5 will be matched based on age, race, and BMI. Participants will wear a GPS unit and accelerometer and report their stress and mood in real time using a smartphone. We will then examine the associations between GPS-derived neighborhood variables, stress-related neural activity measures, and adverse biological markers. RESULTS: The National Institutes of Health Institutional Review Board has approved this study. Recruitment will begin in the summer of 2021. CONCLUSIONS: Findings from this research could inform the development of multilevel behavioral interventions and policies to better manage environmental factors that promote immune system activation or psychosocial stress while concurrently working to increase PA, thereby influencing CV health. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/29191.

Contribution of serum anti-Müllerian hormone in the management of azoospermia and the prediction of testicular sperm retrieval outcomes: a study of 155 adult men.

BACKGROUND: Testicular sperm extraction (TESE) is the method of choice for recovering spermatozoa in patients with azoospermia. However, the lack of reliable biomarkers makes it impossible to predict sperm retrieval outcomes at TESE. To date, little attention has been given to anti-Müllerian hormone (AMH) serum levels in adult men with altered spermatogenesis. In this study we aimed to investigate whether serum concentrations of AMH and the AMH to total testosterone ratio (AMH/T) might be predictive factors for sperm retrieval outcomes during TESE in a cohort of 155 adult Caucasian men with azoospermia. RESULTS: AMH serum levels were significantly lower in nonobstructive azoospermia (NOA) that was unexplained, cryptorchidism-related, cytotoxic and genetic (medians [pmol/l] = 30.1; 21.8; 26.7; 7.3; and p = 0.02; 0.001; 0.04; <0.0001, respectively]) compared with obstructive azoospermia (OA) (median = 44.8 pmol/l). Lowest values were observed in cases of genetic NOA (p < 0.0001, compared with unexplained NOA) and especially in individuals with non-mosaic Klinefelter syndrome (median = 2.3 pmol/l, p <0.0001). Medians of AMH/T values were significantly lower in genetic NOA compared to unexplained, cryptorchidism-related NOA as well as OA. Only serum concentrations of AMH differed significantly between positive and negative groups in men with non-mosaic Klinefelter syndrome. The optimal cut-off of serum AMH was set at 2.5 pmol/l. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of this cut-off to predict negative outcomes of SR were 100 %, 76.9 %, 66.6 %, 100 and 84.2 %, respectively. CONCLUSIONS: Serum AMH levels, but not AMH/T values, are a good marker for Sertoli and germ cell population dysfunction in adult Caucasian men with non-mosaic Klinefelter syndrome and could help us to predict negative outcomes of SR at TESE with 100 % sensitivity when serum levels of AMH are below 2.5 pmol/l.

RéSUMé: INTRODUCTION: L'extraction chirurgicale de spermatozoïdes testiculaires (ECST) est la méthode qui permet d'offrir aux hommes ayant une azoospermie des chances de paternité via l'assistance médicale à la procréation. Cependant, le manque de biomarqueurs fiables rend impossible de prédire les résultats de l'ECST. À ce jour, peu d'attention a été accordée aux valeurs sériques d'hormone anti-müllérienne (AMH) chez les hommes adultes ayant une spermatogenèse altérée. Dans cette étude, nous avons cherché à déterminer si les concentrations sériques d'AMH et le rapport AMH sur testostérone totale (AMH/T) pouvaient être des facteurs prédictifs des résultats de l'ECST dans une cohorte de 155 hommes adultes caucasiens ayant une azoospermie. RéSULTATS: Les concentrations sériques d'AMH étaient significativement plus faibles dans l'azoospermie non-obstructive (ANO) non inexpliquée, ANO associée à un antécédent de cryptorchidie, ANO d'origine cytotoxique et génétique (médianes [pmol/l] = 30,1; 21,8; 26,7; 7,3; et p = 0,02; 0,001; 0,04; <0,0001, respectivement) comparativement au groupe contrôle d'azoospermie obstructive (AO) (médiane = 44,8 pmol/l). Les plus faibles valeurs ont été observées dans le groupe d'ANO d'origine génétique (p = 0,0001, par rapport à l'ANO non inexpliquée) et particulièrement chez les individus avec un syndrome de Klinefelter (médiane = 2,3 pmol/l, p <0,0001). Seules les concentrations sériques d'AMH différaient significativement entre les individus avec résultats positifs et négatifs d'extraction de spermatozoïdes chez les hommes atteints d'un syndrome de Klinefelter non mosaïque. Un seuil optimal du taux sérique d'AMH a été fixé à 2,5 pmol/l. La sensibilité, la spécificité, la valeur prédictive positive, la valeur prédictive négative et l'exactitude de ce seuil pour prédire un résultat négatif étaient de 100 %, 76,9 %, 66,6 %, 100 % et 84,2 %, respectivement. CONCLUSIONS: Seules les concentrations sérique d'AMH, et non pas le rapport AMH/T, sont un bon marqueur du dysfonctionnement des cellules de Sertoli ainsi que des cellules germinales chez les hommes adultes caucasiens atteints du syndrome de Klinefelter non mosaïque. Elles peuvent prédire un résultat négatif du prélèvement de spermatozoïdes lors de l'ECST avec une sensibilité de 100 % lorsque les niveaux sériques sont inférieurs à 2,5 pmol/l.

Neighborhood Environment Associates with Trimethylamine-N-Oxide (TMAO) as a Cardiovascular Risk Marker.

BACKGROUND: Neighborhoods and the microbiome are linked to cardiovascular disease (CVD), yet investigations to identify microbiome-related factors at neighborhood levels have not been widely investigated. We sought to explore relationships between neighborhood deprivation index (NDI) and the microbial metabolite, trimethylamine-N-oxide. We hypothesized that inflammatory markers and dietary intake would be mediators of the relationship. METHODS: African-American adults at risk for CVD living in the Washington, DC area were recruited to participate in a cross-sectional community-based study. US census-based neighborhood deprivation index (NDI) measures (at the census-tract level) were determined. Serum samples were analyzed for CVD risk factors, cytokines, and the microbial metabolite, trimethylamine-N-oxide (TMAO). Self-reported dietary intake based on food groups was collected. RESULTS: Study participants (n = 60) were predominantly female (93.3%), with a mean (SD) age of 60.83 (+/-10.52) years. Mean (SD) NDI was -1.54 (2.94), and mean (SD) TMAO level was 4.99 (9.65) µmol/L. Adjusting for CVD risk factors and BMI, NDI was positively associated with TMAO (ß = 0.31, p = 0.02). Using mediation analysis, the relationship between NDI and TMAO was significantly mediated by TNF-α (60.15%) and interleukin)-1 ß (IL; 49.96%). When controlling for clustering within neighborhoods, the NDI-TMAO association was no longer significant (ß = 5.11, p = 0.11). However, the association between NDI and IL-1 ß (ß = 0.04, p = 0.004) and TNF-α (ß = 0.17, p = 0.003) remained. Neither NDI nor TMAO was significantly associated with daily dietary intake. Conclusion and Relevance: Among a small sample of African-American adults at risk for CVD, there was a significant positive relationship with NDI and TMAO mediated by inflammation. These hypothesis-generating results are initial and need to be confirmed in larger studies.

Chronic Stress-Related Neural Activity Associates With Subclinical Cardiovascular Disease in a Community-Based Cohort: Data From the Washington, D.C. Cardiovascular Health and Needs Assessment.

Background: Psychosocial stress correlates with cardiovascular (CV) events; however, associations between physiologic measures of stressors and CVD remain incompletely understood, especially in racial/ethnic minority populations in resource-limited neighborhoods. We examined associations between chronic stress-related neural activity, measured by amygdalar 18Fluorodeoxyglucose (18FDG) uptake, and aortic vascular FDG uptake (arterial inflammation measure) in a community-based cohort. Methods: Forty participants from the Washington, DC CV Health and Needs Assessment (DC-CHNA), a study of a predominantly African-American population in resource-limited urban areas and 25 healthy volunteers underwent detailed phenotyping, including 18FDG PET/CT for assessing amygdalar activity (AmygA), vascular FDG uptake, and hematopoietic (leukopoietic) tissue activity. Mediation analysis was used to test whether the link between AmygA and vascular FDG uptake was mediated by hematopoietic activity. Results: AmygA (1.11 ± 0.09 vs. 1.05 ± 0.09, p = 0.004) and vascular FDG uptake (1.63 ± 0.22 vs. 1.55 ± 0.17, p = 0.05) were greater in the DC-CHNA cohort compared to volunteers. Within the DC-CHNA cohort, AmygA associated with vascular FDG uptake after adjustment for Framingham score and body mass index (ß = 0.41, p = 0.015). The AmygA and aortic vascular FDG uptake relationship was in part mediated by splenic (20.2%) and bone marrow (11.8%) activity. Conclusions: AmygA, or chronic stress-related neural activity, associates with subclinical CVD risk in a community-based cohort. This may in part be mediated by the hematopoietic system. Our findings of this hypothesis-generating study are suggestive of a potential relationship between chronic stress-related neural activity and subclinical CVD in an African American community-based population. Taken together, these findings suggest a potential mechanism by which chronic psychosocial stress, such as stressors that can be experienced in adverse social conditions, promotes greater cardiovascular risk amongst resource-limited, community-based populations most impacted by cardiovascular health disparities. However, larger prospective studies examining these findings in other racially and ethnically diverse populations are necessary to confirm and extend these findings.