Variants of human DECTIN-1 rs16910526 are linked to differential reactive oxygen species production and susceptibility to tuberculosis.

BACKGROUND: Dectin-1 is a transmembrane receptor that plays a pivotal role in recognising fungi and Mycobacterium tuberculosis (Mtb). A specific variant, DECTIN-1 rs16910526, results in a truncated receptor that disrupts membrane expression and ligand binding and is clinically associated with recurrent cutaneous mycoses. Previous research has clarified the role of Dectin-1 in boosting immune defenses against mycobacteria by enhancing reactive oxygen species (ROS) production in neutrophils (PMNs). Here, we investigated the association between the rs16910526 variant and Dectin-1 expression in PMNs, as well as intracellular ROS production in response to Mtb. Furthermore, we explored the potential link between the rs16910526 gene variant and TB outcomes in Argentina. METHODS: DNA was extracted from blood samples obtained from a cohort of 178 TB patients and healthy subjects (HS) in Argentina. PCR amplification and sequencing were performed to identify the rs16910526 variant. Flow cytometry was utilised to assess Dectin-1 expression on the PMN plasma membrane and to measure intracellular ROS levels, as indicated by the oxidation of DHR123 in response to the Mtb antigen. RESULTS: PMNs carrying the rs16910526 variant exhibited diminished Dectin-1 expression and ROS production in response to Mtb (p < 0.0001). In a case‒control study, the rs16910526 variant had an allelic frequency of 0.112 in TB patients and 0.051 in HS. Notably, 10 out of 88 HS and 18 out of 62 TB patients harboured the variant (odds ratio [OR]: 2.55 [95% CI 1.1-5.9, p = 0.03]), indicating a potential association with TB disease. Furthermore, TB patients with the rs16910526 variant exhibited a delayed sputum smear conversion time (p < 0.004) and 100% positivity for acid-fast bacilli smears (p < 0.00001). CONCLUSION: Our study identified a significant association between the SNP variant rs16910526 in the DECTIN-1 gene and Dectin-1 expression in the PMN, leading to altered ROS production. The higher frequency of this variant in TB patients compared to HS suggests a possible link with susceptibility to TB disease in Argentina.

Healthcare Provider Perceptions of the Use of Medical Interpretation in Primary Care.

OBJECTIVES: Sixty-three percent of Latinos/as/x in Alabama, speak English "not well" or "not at all." Effective provider-patient communication is the foundation of successful clinical interactions. Medical interpretation is important to the healthcare provision for patients with limited English proficiency (LEP). We examined Alabama providers' perceptions of working with medical interpreters to identify strategies to improve healthcare provision for LEP patients. METHODS: We conducted nine semistructured qualitative interviews with primary healthcare providers in western Alabama. We used NVivo to conduct thematic coding and content analysis. RESULTS: Of the nine providers, one self-identified as Latina and the others identified as White. Four participants worked in community clinics and five worked at university-based clinics. Four themes emerged: preference for in-person interpreters over technology-based interpretation; providers' perceptions and expectations of the roles of professional interpreters; challenges in the communication process; and use of family members or other ad hoc interpreters. CONCLUSIONS: To meet the needs of Latino/a/x communities, clinical settings should invest in adequate staffing of in-person interpreters, infrastructure and workflow improvements, and the hiring and training of polylingual providers. Capacity-building opportunities to establish team building between interpreters and providers could be useful tools in improving healthcare provision for LEP patients.

Apoptosis-mediated inhibition of human T-cell acute lymphoblastic leukemia upon treatment with Staphylococus Aureus enterotoxin-superantigen.

Patients with relapsed T cell acute lymphoblastic leukemia (T-ALL) have limited therapeutic options and poor prognosis. The finding of efficient strategies against this refractory neoplasm is a medical priority. Superantigens (SAgs) are viral and bacterial proteins that bind to major histocompatibility complex class II molecules as unprocessed proteins and subsequently interact with a high number of T cells expressing particular T cell receptor Vß chains. Although on mature T cells, SAgs usually trigger massive cell proliferation producing deleterious effects on the organism, in contrast, on immature T cells, they may trigger their death by apoptosis. On this basis, it was hypothesized that SAgs could also induce apoptosis in neoplastic T cells that are usually immature cells that probably conserve their particular Vß chains. In this work, we investigated the effect of the SAg Staphylococcus aureus enterotoxin E (SEE) (that specifically interacts with cells that express Vß8 chain), on human Jurkat T- leukemia line, that expresses Vß8 in its T receptor and it is a model of the highly aggressive recurrent T-ALL. Our results demonstrated that SEE could induce apoptosis in Jurkat cells in vitro. The induction of apoptosis was specific, correlated to the down regulation of surface Vß8 TCR expression and was triggered, at least in part, through the Fas/FasL extrinsic pathway. The apoptotic effect induced by SEE on Jurkat cells was therapeutically relevant. In effect, upon transplantation of Jurkat cells in the highly immunodeficient NSG mice, SEE treatment reduced dramatically tumor growth, decreased the infiltration of neoplastic cells in the bloodstream, spleen and lymph nodes and, most importantly, increased significantly the survival of mice. Taken together, these results raise the possibility that this strategy can be, in the future, a useful option for the treatment of recurrent T-ALL.

Geographic Access to Primary Healthcare Services among Latinos/as/x in Western Alabama.

OBJECTIVES: Alabama's Latino/a/x population grew 278% from 2000 to 2018. Tuscaloosa County, located in the largely rural region of western Alabama, also experienced a significant influx of Latino/as/x during this time frame. Geographic healthcare access (GHA) to primary care and hospitals is crucial for immigrant Latino/as/x to care for their health, but few studies have characterized it. The goals of this article were to describe the availability (defined as number of provider locations) and accessibility (defined as travel impedance between potential patients and provider locations) of primary healthcare services and to discuss potential strategies to address these healthcare access challenges. METHODS: We drew data from the US Census Bureau, American Community Survey 5-year estimates, Blue Cross Blue Shield national doctor and hospital finder database, the Alabama Department of Public Health, and Tuscaloosa Transit Authority. We used geographic data, geographic information systems, and spatial analyses to characterize the availability and accessibility of primary care services and hospitals for Latinos/as/x in Tuscaloosa County using ESRI, ArcGIS 10.6.1. We showed the distribution of Latinos/as/x by census tract with choropleth mapping and mapped primary healthcare providers alongside public transit routes and hospital driving times to support our findings. RESULTS: This work demonstrated that Latinos/as/x in Tuscaloosa County were concentrated in more rural areas surrounding the county's city center, presenting significant barriers to GHA. These areas had fewer primary care providers and limited public transit. Many Latinos/as/x in this county had to travel ≥45 minutes to a hospital. CONCLUSIONS: Outreach and technology-based approaches, including home visit programs, mobile health units, and telemedicine, may be particularly important in bridging the GHA gaps for this and other largely rural populations the southeastern United States. Some of this potential was unlocked during the coronavirus disease 2019 crisis. These gains should be leveraged toward sustainable healthcare access initiatives for rural Latino/a/x populations.

Rural and Racial/Ethnic Differences in Children Receiving Early Intervention Services.

A review of the literature shows that racial and ethnic minority children (eg, African American, Asian, and Hispanic) received diagnoses for developmental concerns later in life compared with their age-matched white counterparts. Research has also documented disparities in access to and receipt of health care services among children with developmental concerns as compared with children with other disabilities. OBJECTIVES: We examined health care providers' (HCPs') responses to parents' developmental concerns about their children. We looked at the association with race, ethnicity, gender, rurality, and time to diagnosis. METHODS: All data were secondary and derived from the Centers for Disease Control and Prevention's Survey of Pathways to Diagnosis and Services. Participants consisted of 1321 parents of children who had received early intervention services as reported by respondents' data collected in 2011. RESULTS: From a nationally representative sample of families receiving early intervention services, 76% were white, 10% were African American, 3% were Asian, 5% were Native American, and 9% were Hispanic. Families who were Hispanic were more likely to have received only a delaying response from HCPs. The average time to a developmental delay diagnosis was 5 months longer for families who received a delaying HCP response. CONCLUSIONS: Families who were Hispanic or who were from rural areas were most likely to receive a delayed HCP response; for parents who received a delayed HCP response, a developmental delay diagnosis took 5 months longer than for families from the other groups listed.

"I Don't Like Being Stereotyped, I Decided I Was Never Going Back to the Doctor": Sexual Healthcare Access Among Young Latina Women in Alabama.

Young Latina women (YLW) in the US and in Alabama are disproportionately affected by sexual health disparities. Our community based participatory research (CBPR) study's purpose was to examine YLW's perceptions and experiences of sexual healthcare access (SHCA) toward developing community-driven, multilevel intervention strategies. We conducted 20 semi-structured qualitative interviews with YLW between 15 and 19 years old and who had been in the US for 5 or more years. We content-analyzed the data guided by the Socioecological Model of Sexual Health (SEMSH). We began analyses by coding independently, built consensus on the codes, then finished coding transcripts independently. Sixty-five percent of participants were US-born and 60% had health insurance. Participants identified barriers/facilitators to SHCA including discrimination in clinical settings and embarrassment/stigma about SHCA. Our study is the first in AL to use CBPR to work with YLW. Interventions should consider the multi-level and intersectional nature of SHCA challenges.

No Te Tratan Bien Porque Eres Mexicana: Intersectional Systemic Violence and Precarity in Latina Adolescent Life in the U.S. South.

Young Latina women (YLW) in Alabama are disproportionately affected by sexual health disparities. However, to access needed reproductive services, YLW must navigate a healthcare landscape that restricts access for youth. YLW also face racialized immigration enforcement in their communities which is designed to attrition the region's emergent Latina/o/x immigrant population. This paper describes the intersectional, structural forces that contribute to experienced systemic violence for YLW as they try to access sexual healthcare services. In 2017, we conducted semi-structured qualitative interviews with 20 YLW and 24 key stakeholders (parents, providers, Latino/a/x community leaders etc.) in West Alabama to examine attitudes and perceptions about sexual health and healthcare access (HCA) among YLW in the region. We used purposeful convenience sampling and snowballing to recruit a community-based sample. That is, we purposefully recruited YLW, adjusting through the recruitment period for a diverse sample, who represented the various voices that we were trying to capture in the study (i.e., younger and older adolescents, adolescents born in the U.S. and those born in other countries etc.). Through a focus on YLW's access to sexual/reproductive healthcare, we conclude that YLW experience systemic violence and resulting precarity because laws and health policies restrict access to evidence-based sexual health education and reproductive healthcare services. We discuss implications for future research and policy recommendations.

Role of α-glucan-induced oxygen species in dendritic cells and its impact in immune response against tuberculosis.

With 10 million new cases and three million deaths estimated to occur yearly ̶ more than any time in history ̶ tuberculosis (TB) remains the single most widespread and deadly infectious disease. Until recently, it was thought that both latent and active TB was primarily related to host factors. Nonetheless, the participation of bacterial factors is becoming increasingly evident. Minimal variations in genes related to Mycobacterium tuberculosis (Mtb) virulence and pathogenesis can lead to marked differences in immunogenicity. Dendritic cells (DC) are professional antigen presenting cells whose maturation can vary depending on the cell wall composition of each particular Mtb strain being critical for the onset of the immune response against Mtb. Here we evaluated the role played by α-glucan, in the endogenous production of reactive oxygen species, ROS, and the impact on DC maturation and function. Results showed that α-glucans on Mtb induce ROS production leading to DC maturation and lymphocyte proliferation. Even more, α-glucans induced Syk activation but were not essential in non-opsonized phagocytosis. In summary, α-glucans of Mtb participates in ROS production and the subsequent DC maturation and antigen presentation, suggesting a relevant role of α-glucans for the onset of the protective immune response against TB.

Development of a Participatory Capacity-Building Program for Congregational Health Leaders in African American Churches in the US South.

African Americans are disproportionately affected by diabetes and colorectal cancer. Although studies have shown the effectiveness of spiritually based health interventions delivered by community health workers to African Americans, few have described the development of the capacity-building component. This article describes this process. The development of the Healthy Congregations Healthy Communities Program (HCHC) was guided through a community-based participatory research lens and included: 1) establishment of a community coalition; 2) identification by coalition members of churches as the best venues for health promotion strategies among African Americans; 3) recruitment of churches; 4) development of a training manual; 5) recruitment and training of congregational health leaders (CHLs); and 6) "Passing of the torch" from the coalition to the CHLs who implemented the intervention in their congregations. We trained 35 CHLs to promote awareness about diabetes and colorectal cancer using a culturally relevant, spiritually based curriculum. Pre- and post-test paired t-tests showed significant increases in CHLs' knowledge of wellness (P<.001), colorectal cancer (P<.002), nutrition (P<.004), and lifestyle changes (P<.005). The community-academic partnership was successful in developing a culturally relevant, spiritually based capacity-building program for African American CHLs to implement health promotion strategies in their congregations and communities.

Disparities in Retention in HIV Care Among HIV-Infected Young Men Who Have Sex with Men in the District of Columbia, 2013.

PURPOSE: Among young men who have sex with men (YMSM), aged 13-24 years, Blacks/African Americans and Hispanics/Latinos are disproportionately affected by HIV, accounting for 58% and 21%, respectively, of diagnoses of HIV infection in the United States. In the District of Columbia (DC), YMSM of color are also disproportionately affected by HIV. National goals are that 80% of HIV-infected persons be retained in HIV care. We analyzed DC surveillance data to examine retention among YMSM living with HIV infection in DC. METHODS: We characterized correlates of retention in HIV care (≥2 clinical visits, ≥3 months apart, within 12 months of diagnosis) among YMSM in DC to inform and strengthen local HIV care efforts. We analyzed data from DC HIV surveillance system for YMSM aged 13-29 years diagnosed between 2005 and 2012 and alive in 2013. We also combined demographic and clinical variables with sociodemographic data from the U.S. American Community Survey (ACS) by census tracts. RESULTS: From 2005 to 2012, 1034 YMSM were diagnosed and living with HIV infection in DC; 83% were Black or Latino. Of the 1034 YMSM, 910 (88%) had census tract data available and were included in analyses (72% Black, 10% Latino, and 17% White); among the 854 (94%) linked to care, 376 (44%) were retained in care. In multivariate analyses, retention in care was less likely among 19-24 year YMSM compared with 13-18-year-old YMSM (adjusted prevalence ratios [aPR] = 0.89, 95% confidence intervals [CI] 0.80-0.99). CONCLUSION: Retention in HIV care was suboptimal for YMSM. Increased retention efforts are warranted to improve outcomes and reduce age and racial/ethnic disparities.

Sowing the Seeds of Health: Training of Community Health Advisors to Promote Breast and Cervical Cancer Screening among Latina Immigrants in Alabama.

Latinas in the U.S. are disproportionately affected by breast and cervical cancer. This project sought to develop and evaluate a culturally relevant training for Community Health Advisors (CHA) to promote breast and cervical cancer screening among Latina immigrants in Alabama. The Empowerment Model guided training development and implementation supported by a formative evaluation and a Community Advisory Committee. The 16-hour CHA training included two intertwined components: knowledge and skills.Fifty-six (56) Latinas participated in the CHA training in six Alabama counties. The training increased the CHAs' (1) knowledge of cancer screening and other health topics and (2) their perceived confidence to communicate with women in their communities about cancer screening and to motivate them to attain cancer screenings. This work demonstrates the application of a transformative philosophical framework to promote capacity-building among CHAs toward the development and implementation of strategies to promote breast and cervical cancer screening among Latina immigrants.

Correlates and predictors of sexual health among adolescent Latinas in the United States: A systematic review of the literature, 2004-2015.

Adolescent Latinas in the United States (US) are disproportionately affected by early pregnancy, sexually transmitted infections (STIs) and human immunodeficiency virus (HIV) in comparison to their non-Hispanic white counterparts. However, only a few studies have sought to understand the multi-level factors associated with sexual health in adolescent Latinas. Adhering to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, we conducted a systematic literature review to better understand the correlates and predictors of sexual health among adolescent Latinas in the US, identify gaps in the research, and suggest future directions for empirical studies and intervention efforts. Eleven studies were identified: five examined onset of sexual intercourse, nine examined determinants of sexual health/risk behaviors (e.g., number of sexual partners and condom use), and three examined determinants of a biological sexual health outcome (i.e., STIs or pregnancy). Two types of variables/factors emerged as important influences on sexual health outcomes: proximal context-level variables (i.e., variables pertaining to the individual's family, sexual/romantic partner or peer group) and individual-level variables (i.e., characteristics of the individual). A majority of the studies reviewed (n=9) examined some aspect of acculturation or Latino/a cultural values in relation to sexual health. Results varied widely between studies suggesting that the relationship between individual and proximal contextual variables (including acculturation) and sexual health may be more complex than previously conceived. This review integrates the findings on correlates and predictors of sexual health among adolescent Latinas, and supports the need for strengths-based theoretically guided research on the mechanisms driving these associations.

Reactive oxygen species production by human dendritic cells involves TLR2 and dectin-1 and is essential for efficient immune response against Mycobacteria.

Tuberculosis remains the single largest infectious disease with 10 million new cases and two million deaths that are estimated to occur yearly, more than any time in history. The intracellular replication of Mycobacterium tuberculosis (Mtb) and its spread from the lungs to other sites occur before the development of adaptive immune responses. Dendritic cells (DC) are professional antigen-presenting cells whose maturation is critical for the onset of the protective immune response against tuberculosis disease and may vary depending on the nature of the cell wall of Mtb strain. Here, we describe the role of the endogenous production of reactive oxygen species (ROS) on DC maturation and expansion of Mtb-specific lymphocytes. Here, we show that Mtb induces DC maturation through TLR2/dectin-1 by generating of ROS and through Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN) in a ROS independently manner. Based on the differences observed in the ability to induce DC maturation, ROS production and lymphocyte proliferation by those Mtb families widespread in South America, i.e., Haarlem and Latin American Mediterranean and the reference strain H37Rv, we propose that variance in ROS production might contribute to immune evasion affecting DC maturation and antigen presentation.

Oxidative stability of a heme iron-fortified bakery product: Effectiveness of ascorbyl palmitate and co-spray-drying of heme iron with calcium caseinate.

Fortification of food products with iron is a common strategy to prevent or overcome iron deficiency. However, any form of iron is a pro-oxidant and its addition will cause off-flavours and reduce a product's shelf life. A highly bioavailable heme iron ingredient was selected to fortify a chocolate cream used to fill sandwich-type cookies. Two different strategies were assessed for avoiding the heme iron catalytic effect on lipid oxidation: ascorbyl palmitate addition and co-spray-drying of heme iron with calcium caseinate. Oxidation development and sensory acceptability were monitored in the cookies over one-year of storage at room temperature in the dark. The addition of ascorbyl palmitate provided protection against oxidation and loss of tocopherols and tocotrienols during the preparation of cookies. In general, ascorbyl palmitate, either alone or in combination with the co-spray-dried heme iron, prevented primary oxidation and hexanal formation during storage. The combination of both strategies resulted in cookies that were acceptable from a sensory point of view after 1year of storage.

Neutrophil apoptosis in the context of tuberculosis infection.

Polymorphonuclear neutrophils comprise two-thirds of peripheral blood leukocytes and are key components of innate immunity as a first line of defense against bacterial and fungal pathogens. Their microbicidal mechanisms are essential for bacterial killing, the enhancement of inflammatory reactions and also comprise signaling molecules which have been implicated in signal transduction cascades. In tuberculosis, the number of neutrophils increases in the affected lung. In addition, they become activated and apoptotic due the bacterial burden. As apoptosis is promoted by reactive oxygen species (ROS) during phagocytosis, the advantages and benefits to the host as well as the strategies displayed by the pathogen to avoid or retard apoptosis are discussed in this review.

Antioxidative effect of lipophilized caffeic acid in fish oil enriched mayonnaise and milk.

The antioxidative effect of lipophilized caffeic acid was assessed in two different fish oil enriched food products: mayonnaise and milk. In both emulsion systems, caffeic acid esterified with fatty alcohols of different chain lengths (C1-C20) were better antioxidants than the original phenolic compound. The optimal chain length with respect to protection against oxidation was, however, different for the two food systems. Fish oil enriched mayonnaise with caffeates of medium alkyl chain length (butyl, octyl and dodecyl) added resulted in a better oxidative stability than caffeates with shorter (methyl) or longer (octadecyl) alkyl chains. Whereas in fish oil enriched milk emulsions the most effective caffeates were those with shorter alkyl chains (methyl and butyl) rather than the ones with medium and long chains (octyl, dodecyl, hexadecyl and eicosyl). These results demonstrate that there might be an optimum alkyl chain length for each phenolipid in each type of emulsion systems.

Intimate partner violence and human immunodeficiency virus risk among black and Hispanic women.

BACKGROUND: Approximately 80% of new HIV infections among U.S. women are among black/African American and Hispanic women. HIV risk may be associated with intimate partner violence (IPV); data regarding IPV for women in high-HIV prevalence areas are scarce. PURPOSE: To examine prevalence and correlates of IPV among women. METHODS: Heterosexual women and their male partners in cities with high HIV prevalence were enrolled. During 2006-2007, participants completed interviews about HIV risk factors and IPV (physical violence or forced sex) experiences. Data were analyzed during 2012-2013 using multivariate logistic regression to identify individual- and partner-level IPV correlates. RESULTS: Of 1,011 female respondents, 985 (97.4%) provided risk factor and demographic data. Most were non-Hispanic black/African American (82.7%); living at or below poverty (86.7%); and tested HIV-negative (96.8%). IPV-physical violence was reported by 29.1%, and IPV-forced sex by 13.7%. Being married/living with a partner (AOR=1.60, 95% CI=1.06, 2.40); non-injection drug use (AOR=1.74, 95% CI=1.22, 2.48); and ever discussing male partners' number of current sex partners (AOR=1.60, 95% CI=1.15, 2.24) were associated with IPV-physical violence. Women reporting concurrent sex partners (AOR=1.80, 95% CI=1.04, 3.13) and ever discussing number of male partners' past sex partners (AOR=1.85, 95% CI=1.13, 3.05) were associated with IPV-forced sex. Feeling comfortable asking a male partner to use condoms was associated with decreased IPV-physical violence (AOR=0.32, 95% CI=0.16,0.64) and -forced sex (AOR=0.37, 95% CI=0.16, 0.85). CONCLUSIONS: Prevention interventions that enhance women's skills to decrease HIV and IPV risk are important strategies for decreasing racial/ethnic disparities among women.

Urban adolescent girls' perspectives on romantic relationships: initiation, involvement, negotiation, and conflict.

The purpose of this paper was to describe romantic relationships from the perspective of urban, adolescent girls, to address gaps in our understanding of their relationship dimensions. Minority adolescent girls (n  =  17) participated in private semi-structured interviews aimed to elicit the understanding of the adolescents' perspectives on their own relationship experiences and dynamics. The research team conducted conventional content analysis of the interview transcripts. Four major themes emerged about romantic relationships: (1) influence of male pursuit and social norms on relationship initiation factors; (2) a romantic partner is a confidant, friend, and companion; (3) negotiating intimacy respectfully; and (4) relationship conflict through control and abuse. Adolescents described sub-themes of social norms of male pursuit and relationship pressures that dictated relationship initiation. Relationships were depicted by emotional support, caring, and companionship. Adolescents described positive negotiation skills. However, relationship conflict, including controlling behaviors and violence, was illustrated in these same relationships. This study provides a rich description of romantic relationships from the perspectives of urban, adolescent girls. Most salient findings included social pressures and a combination of both positive and negative attributes. Implications include the need for intervention development at the community level to address social pressures, recognition of positive adolescent relationship attributes, and facilitation of skills to identify and address low-quality relationship characteristics.