Strategic Directions in Preventive Intervention Research to Advance Health Equity.

As commissioned by the Society for Prevention Research, this paper describes and illustrates strategic approaches for reducing health inequities and advancing health equity when adopting an equity-focused approach for applying prevention science evidence-based theory, methodologies, and practices. We introduce an ecosystemic framework as a guide for analyzing, designing, and planning innovative equity-focused evidence-based preventive interventions designed to attain intended health equity outcomes. To advance this process, we introduce a health equity statement for conducting integrative analyses of ecosystemic framework pathways, by describing the role of social determinants, mechanisms, and interventions as factors directly linked to specific health equity outcomes. As background, we present health equity constructs, theories, and research evidence which can inform the design and development of equity-focused intervention approaches. We also describe multi-level interventions that when coordinated can produce synergistic intervention effects across macro, meso, and micro ecological levels. Under this approach, we encourage prevention and implementation scientists to apply and extend these strategic directions in future research to increase our evidence-based knowledge and theory building. A general goal is to apply prevention science knowledge to design, widely disseminate, and implement culturally grounded interventions that incrementally attain specific HE outcomes and an intended HE goal. We conclude with recommendations for conducting equity-focused prevention science research, interventions, and training.

Ethnic Discrimination and Self-rated Health among Hispanic Emerging Adults: Examining the Moderating Effects of Self-esteem and Resilience.

Exposure to ethnic discrimination has been conceptualized as a sociocultural stressor that is associated with lower self-rated health. However, this association remains understudied among Hispanics and less is known about constructs that may mitigate the effects of ethnic discrimination on self-rated health. Accordingly, this study aimed to (a) examine the association between ethnic discrimination and self-rated health among Hispanic emerging adults (ages 18-25), and (b) examine the extent to which self-esteem and resilience may moderate this association. A convenience sample of 200 Hispanic emerging adults from Arizona (n=99) and Florida (n=101) was recruited to complete a cross-sectional survey. Data were analyzed using hierarchical multiple regression and moderation analyses. Results indicate that higher ethnic discrimination was associated with lower self-rated health. Moderation analyses indicated that self-esteem functioned as a moderator that weakened the association between ethnic discrimination and self-rated health; however, resilience did not function similarly as a moderator. This study adds to the limited literature on ethnic discrimination and self-rated health among Hispanics and highlights that psychological factors, such as enhancing self-esteem, may help buffer the adverse effects of ethnic discrimination on health outcomes.

QTOF-ESI MS Characterization and Antioxidant Activity of Physalis peruviana L. (Cape Gooseberry) Husks and Fruits from Costa Rica.

There is increasing interest in research of secondary metabolites from Physalis peruviana (Cape gooseberry) because of their potential bioactivities. In this study, the profile of compounds found in fruits and husks from Costa Rica was determined through ultra-performance liquid chromatography coupled with high-resolution mass spectrometry using a quadrupole time-of-flight analyzer (UPLC-ESI-QTOF MS) on extracts (n = 10) obtained through pressurized liquid extraction (PLE) conditions. In total, 66 different compounds were identified, comprising 34 withanolides, 23 sucrose ester derivatives and 9 flavonoids. UPLC-DAD analysis was performed to determine the ß-carotene in fruits and to quantify the flavonoids in all 10 samples, with the results showing higher contents in samples from the Dota region (58.6−60.1 µg/g of dry material versus 1.6−2.8 mg/g of dry material). The Folin−Ciocalteau total polyphenolic content (FC) and antioxidant activity using the DPPH method showed better results for the husk extracts, with the ones from the Dota region holding the best values (4.3−5.1 mg GAE/g of dry material versus IC50 = 1.6−2.3 mg of dry material/mL). In addition, a significant negative correlation was found between the RU, FC and DPPH values (r = −0.902, p < 0.05), aligning with previous reports on the role of polyphenols in antioxidant activity. Principal correlation analysis (PCoA) and hierarchical clustering (HC) analysis were performed on HRMS results, and they indicated that the D1 and D2 fruit samples from the Dota region were clustered with husks related to a higher presence of the analyzed metabolites. In turn, principal component analysis (PCA) performed on the flavonoid content and antioxidant activity yielded results indicating that the D1 and D2 husks and fruit samples from the Dota region stood out significantly, showing the highest antioxidant activity. In summation, our findings suggest that P. peruviana husks and fruits from Costa Rica constitute a substrate of interest for further studies on their potential health benefits.

The putative phosphate transporter PitB (PP1373) is involved in tellurite uptake in Pseudomonas putida KT2440.

Tellurium oxyanions are chemical species of great toxicity and their presence in the environment has increased because of mining industries and photovoltaic and electronic waste. Recovery strategies for this metalloid that are based on micro-organisms are of interest, but further studies of the transport systems and enzymes responsible for implementing tellurium transformations are required because many mechanisms remain unknown. Here, we investigated the involvement in tellurite uptake of the putative phosphate transporter PitB (PP1373) in soil bacterium Pseudomonas putida KT2440. For this purpose, through a method based on the CRISPR/Cas9 system, we generated a strain deficient in the pitB gene and characterized its phenotype on exposing it to varied concentrations of tellurite. Growth curves and transmission electronic microscopy experiments for the wild-type and ΔpitB strains showed that both were able to internalize tellurite into the cytoplasm and reduce the oxyanion to black nano-sized and rod-shaped tellurium particles, although the ΔpitB strain showed an increased resistance to the tellurite toxic effects. At a concentration of 100 µM tellurite, where the biomass formation of the wild-type strain decreased by half, we observed a greater ability of ΔpitB to reduce this oxyanion with respect to the wild-type strain (~38 vs ~16 %), which is related to the greater biomass production of ΔpitB and not to a greater consumption of tellurite per cell. The phenotype of the mutant was restored on over-expressing pitB in trans. In summary, our results indicate that PitB is one of several transporters responsible for tellurite uptake in P. putida KT2440.

Upregulation of HOX genes promotes cell migration and proliferation in head and neck squamous cell carcinoma.

BACKGROUND: Expression dysregulation of HOX homeobox genes has been observed in several cancers, including head and neck squamous cell carcinoma (HNSC). Although characterization of HOX gene roles in HNSC development has been reported, there is still a need to better understand their real contribution to tumorigenesis. OBJECTIVE: The present study aimed to evaluate the contribution of the protein-coding HOX genes (HOXA10, HOXC9, HOXC10, and HOXC13) in cellular processes related to carcinogenesis and progression of the HNSC. METHODS: Expression of HOX genes was analyzed in HNSC RNA-Seq data from The Cancer Genome Atlas (TCGA) and by RT-qPCR in different tumor cell lines. siRNA-mediated knockdown of HOXA10, HOXC9, HOXC10 or HOXC13 was performed in HNSC cell lines, and predicted transcriptional targets HOX genes was analyzed by bioinformatic. RESULTS: Thirty-one out of the 39 mammalian HOX genes were found upregulated in HNSC tissues and cell lines. The HOXC9, HOXC10 or HOXC13 knockdown attenuated cell migration, and lead to downregulation of epithelial-mesenchymal transition (EMT) markers, which were predicted as transcriptional targets of these three HOX genes. Diminished colony formation and cell cycle arrest after HOXC10 or HOXC13 knockdown were also observed, corroborating the fact that there was an enrichment for genes in proliferation/cell cycle pathways. CONCLUSIONS: In summary, we revealed roles for HOXC9, HOXC10, and HOXC13 in cell migration and proliferation/cell cycle progression in HNSC cells and suggested that those HOX members contribute to HNSC development possibly by regulating tumor growth and metastasis.

Disease burden and remaining unmet need in patients with haemophilia A treated with primary prophylaxis.

AIMS: There is evidence that people with haemophilia A still experience morbidity and functional limitation due to joint damage despite prophylaxis. This study aimed to compare their quality of life and work-related function with that of the general population and patients with osteoarthritis. METHODS: Data from the Cost of Haemophilia in Europe: a Socioeconomic Survey (CHESS) database were compared with published data from normative populations and patients with osteoarthritis in Europe and the United States. RESULTS: In the predominantly young (age 18-35 years) adult CHESS population treated with primary prophylaxis, about 30% reported a target joint; the average frequency of bleeds was one per year; half reported chronic pain. Levels of anxiety and depression were similar to those reported by people using on-demand treatment. Employment and productivity were lower than in the general population. The level of presenteeism (attending work with impairment) was comparable with that reported for a much older population with osteoarthritis who had more extensive joint damage and greater prevalence of pain. CONCLUSION: Compared with the general population, clinical outcomes and quality of life are indicated to be impaired for young adults whose haemophilia is managed by primary prophylaxis. Primary prophylaxis is not associated with lower levels of anxiety and depression than on-demand treatment, and pain is common. The level of presenteeism is comparable to that reported in people with osteoarthritis, an older population with more joint disease. Further studies are needed to fully assess the implications of compromised work performance among young adults with haemophilia as they seek to build a career.

Uterus procurement from deceased donor for transplantation.

Women with absolute uterine factor infertility cannot get pregnant. The current experience in uterine transplantation is limited and the use of a deceased donor uterus in this area is incipient after some initial unsuccessful attempts. The birth of healthy babies through this modality in four different centers has given a new impetus to the use of this transplantation technique. We aimed to develop a technique for uterus procurement and preparation for transplantation from a brain dead donor. Fifteen uteri were retrieved from multi-organ donor patients, 10 of these were used in bench surgeries with the proposed technique. All procedures were performed after obtaining family's consent. This study allowed the clinical use of two of the 15 organs that were procured for transplantation. One of these organs resulted in the first live birth worldwide using a uterus transplanted from a deceased donor, a landmark in reproductive medicine. Another outcome was the optimization of the surgical technique involving less manipulation of the uterine vascular pedicles. The success of this novel technique suggests that the proposed model can be replicated and optimized further to facilitate the transplantation of uterus from deceased donors.

Correction: Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study.

[This corrects the article DOI: 10.1371/journal.pgen.1006866.].

Recruitment and retention of underrepresented and vulnerable populations to research.

Per principles outlined in the Belmont Report, research involving human subjects should minimize risks to participants and maximize benefits to participants and society. Recruitment of participants should be equitable. Once enrolled, participants have the right to withdraw at any point. Researchers must balance these principles with pressures to meet enrollment goals and, in the context of repeated-measures designs, retain participants across time. The purpose of this perspective is to describe the approach and corresponding activities for recruiting and retaining underrepresented and vulnerable populations that are the focus of a transdisciplinary academic research center. To this effort, we offer diverse disciplinary backgrounds, experience working with a wide range of populations (from infants to older adults and across multiple health conditions), and spanning a variety of research designs. Effective strategies offered include partnering with community entities, approaching potential participants where they are and at a time of readiness, using population-appropriate modes of communication and data collection, conducting study activities in familiar settings and at convenient times, maintaining frequent contact, and offering meaningful incentives. These strategies are consistent with population-specific reports found in the extant literature and underscore their cross-cutting nature, with adaptations based on participant and community partner needs and preferences.

Should MASP-2 Deficiency Be Considered a Primary Immunodeficiency? Relevance of the Lectin Pathway.

Mannose-binding lectin (MBL)-associated serine protease-2 (MASP-2) is an indispensable enzyme for the activation of the lectin pathway of complement. Its deficiency is classified as a primary immunodeficiency associated to pyogenic bacterial infections, inflammatory lung disease, and autoimmunity. In Europeans, MASP-2 deficiency, due to homozygosity for c.359A > G (p.D120G), occurs in 7 to 14/10,000 individuals. We analyzed the presence of the p.D120G mutation in adults (increasing the sample size of our previous studies) and children. Different groups of patients (1495 adults hospitalized with community-acquired pneumonia, 186 adults with systemic lupus erythematosus, 103 pediatric patients with invasive pneumococcal disease) and control individuals (1119 healthy adult volunteers, 520 adult patients without history of relevant infectious diseases, and a pediatric control group of 311 individuals) were studied. Besides our previously reported MASP-2-deficient healthy adults, we found a new p.D120G homozygous individual from the pediatric control group. We also reviewed p.D120G homozygous individuals reported so far: a total of eleven patients with a highly heterogeneous range of disorders and nine healthy controls (including our four MASP-2-deficient individuals) have been identified by chance in association studies. Individuals with complete deficiencies of several pattern recognition molecules of the lectin pathway (MBL, collectin-10 and collectin-11, and ficolin-3) as well as of MASP-1 and MASP-3 have also been reviewed. Cumulative evidence suggests that MASP-2, and even other components of the LP, are largely redundant in human defenses and that individuals with MASP-2 deficiency do not seem to be particularly prone to infectious or autoimmune diseases.

Clinical, molecular, and pathological findings in a Neu-Laxova syndrome stillborn: A Brazilian case report.

Neu-Laxova syndrome (NLS) is a lethal genetic multiple congenital anomaly syndrome of unknown prevalence representing the severe spectrum of serine biosynthesis defects associated with PHGDH, PSAT1, or PSP gene mutations. The purpose of this study was to describe clinical/molecular and pathologic features of a NLS case caused by novel heterozygous missense variant in PHGDH gene identified in his consanguineous parents.

Familism, Self-Esteem, and Weight-Specific Quality of Life Among Latinx Adolescents With Obesity.

OBJECTIVE: Obesity is a critical public health condition affecting Latinx adolescents and contributes to health disparities across the lifespan. Childhood and adolescent obesity is associated with reduced quality of life (QoL) and decreased self-esteem. The purpose of this study is to examine the role of cultural (e.g., familism) and psychosocial (e.g., self-esteem) factors as predictors of weight-specific QoL among Latinx adolescents with obesity. METHODS: Baseline data from 160 Latinx adolescents (ages 14-16 years) with obesity (BMI > 95th percentile for age and sex) who were recruited for a diabetes prevention intervention were used. Structural equation modeling tested the relationships between four latent constructs (familism, positive self-esteem, self-deprecation, and weight-specific QoL). RESULTS: The model tested paths from familism to positive self-esteem, self-deprecation, and weight-specific QoL, and paths from positive self-esteem and self-deprecation to weight-specific QoL. Higher familism was positively associated with positive self-esteem but not self-deprecation. In turn, positive self-esteem was positively associated with higher weight-specific QoL, whereas self-deprecation was negatively associated. Furthermore, there was an indirect effect of familism on QoL via positive self-esteem. CONCLUSIONS: These data shed light into specific cultural and psychosocial constructs that influence QoL among Latinx adolescents with obesity. This study suggests that familism and positive self-esteem can operate as protective factors associated with higher weight-specific QoL in Latinx adolescents with obesity; whereas self-deprecation may operate as a risk factor for lower weight-specific QoL.

Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study.

A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4%) of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately >7.1% risk, and those in the highest 5% have approximately >21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.

Self-regulated learning microanalysis for the study of the performance of clinical examinations by physiotherapy students.

BACKGROUND: Students require feedback on their self-regulated learning (SRL) processes to improve the performance of clinical examinations. The key SRL processes used by students can be identified by SRL-micro-analysis but, this method has not been previously applied to physiotherapy students. The aim of this pilot study was to test a research design that might allow the evaluation of the potential usefulness of SRL microanalysis for the identification of key SRL processes used by physiotherapy students during the performance of a clinical examination skill. The objectives of the pilot study were: 1) to evaluate whether SRL-microanalysis could identify differences in the use of SRL processes between successful and unsuccessful students; 2) to evaluate the reliability of SRL microanalysis ratings produced by different assessors. METHODS: SRL-microanalysis was used with second year physiotherapy students of a Spanish university (n = 26) as they performed a goniometric task. The task required students to obtain a goniometric measurement of the shoulder joint of a peer. Two assessors evaluated student performance and conducted the SRL- microanalysis with all students. An analysis of inter-rater reliability was performed to evaluate the degree of agreement between assessors. RESULTS: The SRL-microanalysis revealed differences in the use of key SRL processes between successful (n = 15: 57.0%) and unsuccessful performers (n = 11: 43.0%): The differences were particularly evident in strategic planning and self-monitoring skills. There was good inter-rater reliability for scoring of strategic planning (k = 0.792), self-monitoring (k = 0.946) and self-evaluation (k = 0.846). CONCLUSION: The use of SRL microanalysis characterized the key SRL processes of physiotherapy students performing a clinical skill with reliability between the assessors. This pilot study supports the potential usefulness of SRL-microanalysis for the identification of key SRL processes in physiotherapy education. Therefore, this study paves the way to the development of a full study, with a larger number of students and more diverse clinical tasks, to evaluate the SRL processes in successful and unsuccessful students.

Depressive Symptoms and Resilience among Hispanic Emerging Adults: Examining the Moderating Effects of Mindfulness, Distress Tolerance, Emotion Regulation, Family Cohesion, and Social Support.

Emerging adulthood has been described as a difficult stage in life and may be particularly stressful for Hispanic emerging adults who are disproportionately exposed to adversity and chronic sociocultural stressors. To better prevent and treat depressive disorders among Hispanic emerging adults, more research is needed to identify and understand modifiable determinants that can help this population enhance their capacity to offset and recover from adversity and sociocultural stressors. As such, this study aimed to (1) examine the association between resilience and depressive symptoms among Hispanic emerging adults, and (2) examine the extent to which intrapersonal resources (e.g., mindfulness, distress tolerance, emotion regulation strategies) and interpersonal resources (e.g., family cohesion, social support) moderate the association between resilience and depressive symptoms. To examine these aims, 200 Hispanic emerging adults (ages 18-25) from Arizona (n = 99) and Florida (n = 101) completed a cross-sectional survey, and data were analyzed using hierarchical multiple regression and moderation analyses. Findings from the hierarchical multiple regression indicate that higher resilience was associated with lower depressive symptoms. Findings from the moderation analyses indicate that family cohesion, social support, and emotion regulation strategies (e.g., cognitive reappraisal and expressive suppression) functioned as moderators; however, mindfulness and distress tolerance were not significant moderators. Findings from this study add to the limited literature on resilience among Hispanics that have used validated measures of resilience. Furthermore, we advance our understanding of who may benefit most from higher resilience based on levels of intrapersonal and interpersonal resources.

Associations between autoimmune conditions and hepatobiliary cancer risk among elderly US adults.

Growing evidence suggests that people with autoimmune conditions may be at increased risk of hepatobiliary tumors. In the present study, we evaluated associations between autoimmune conditions and hepatobiliary cancers among adults aged ≥66 in the United States. We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data (1992-2013) to conduct a population-based, case-control study. Cases (n = 32,443) had primary hepatobiliary cancer. Controls (n = 200,000) were randomly selected, cancer-free adults frequency-matched to cases by sex, age and year of selection. Using multivariable logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations with 39 autoimmune conditions identified via Medicare claims. We also conducted separate analyses for diagnoses obtained via inpatient versus outpatient claims. Sixteen conditions were associated with at least one hepatobiliary cancer. The strongest risk estimates were for primary biliary cholangitis with hepatocellular carcinoma (OR: 31.33 [95% CI: 23.63-41.56]) and primary sclerosing cholangitis with intrahepatic cholangiocarcinoma (7.53 [5.73-10.57]), extrahepatic cholangiocarcinoma (5.59 [4.03-7.75]), gallbladder cancer (2.06 [1.27-3.33]) and ampulla of Vater cancer (6.29 [4.29-9.22]). Associations with hepatobiliary-related conditions as a group were observed across nearly all cancer sites (ORs ranging from 4.53 [95% CI: 3.30-6.21] for extrahepatic cholangiocarcinoma to 7.18 [5.94-8.67] for hepatocellular carcinoma). Restricting to autoimmune conditions diagnosed via inpatient claims, 6 conditions remained associated with at least one hepatobiliary cancer, and several risk estimates increased. In the outpatient restricted analysis, 12 conditions remained associated. Multiple autoimmune conditions are associated with hepatobiliary cancer risk in the US Medicare population, supporting a shared immuno-inflammatory etiology to these cancers.

Distribution of the pilS gene in Escherichia coli pathovars, its transfer ability and influence in the typical enteropathogenic E. coli adherence phenotype.

Typical enteropathogenic Escherichia coli strains (tEPEC) cause attaching/effacing lesions in eukaryotic cells and produce the bundle-forming pilus (BFP), which interweaves and aggregates bacteria, resulting in the localized adherence (LA) pattern on eukaryotic cells. Previously, we identified tEPEC strains (serotype O119:H6) that exhibited LA simultaneously with an aggregative adherence (AA)-like pattern (LA/AA-like+). Remarkably, AA is characteristically produced by strains of enteroaggregative E. coli (EAEC), another diarrheagenic E. coli pathovar. In one LA/AA-like + strain (Ec404/03), we identified a conjugative plasmid containing the pil operon, which encodes the Pil fimbriae. Moreover, a pil operon associated with an AA pattern and plasmid transfer had been previously described in the EAEC C1096 strain. In this study, we investigated the occurrence of the two pilS alleles (pilSEc404 and pilSC1096) in tEPEC strains of different serotypes, origins and years of isolation. We also examined the potential relationship of pilS with the AA-like phenotype, its ability to be transferred by conjugation, and occurrence among strains of the other E. coli pathovars. The pilS alleles were found in 90 (55.2%) of 163 tEPEC strains, with pilSEc404 occurring more often (30.7%) than pilSC1096 (25.1%). About 21 tEPEC serotypes carried pilS. The pilS alleles were found in tEPEC strains from Chile, Peru and different Brazilian cities, with the oldest strain being isolated in 1966. No absolute correlation was found between the presence of pilS and the AA-like pattern. Conjugative pilS transfer was detected in 26.2% of pilSEc404+ strains and in 65.1% of pilSC1096+ strains, but only pilSEc404+ transconjugants were AA-like+, thus suggesting that the latter allele might need a different genetic background to express this phenotype. pilS was found in all other E. coli pathovars, where it was most prevalent in enterotoxigenic E. coli. More studies are needed to understand the mechanisms involved in the regulation of Pil expression and production.

Gut bacterial diversity and physiological traits of Anastrepha fraterculus Brazilian-1 morphotype males are affected by antibiotic treatment.

BACKGROUND: The interaction between gut bacterial symbionts and Tephritidae became the focus of several studies that showed that bacteria contributed to the nutritional status and the reproductive potential of its fruit fly hosts. Anastrepha fraterculus is an economically important fruit pest in South America. This pest is currently controlled by insecticides, which prompt the development of environmentally friendly methods such as the sterile insect technique (SIT). For SIT to be effective, a deep understanding of the biology and sexual behavior of the target species is needed. Although many studies have contributed in this direction, little is known about the composition and role of A. fraterculus symbiotic bacteria. In this study we tested the hypothesis that gut bacteria contribute to nutritional status and reproductive success of A. fraterculus males. RESULTS: AB affected the bacterial community of the digestive tract of A. fraterculus, in particular bacteria belonging to the Enterobacteriaceae family, which was the dominant bacterial group in the control flies (i.e., non-treated with AB). AB negatively affected parameters directly related to the mating success of laboratory males and their nutritional status. AB also affected males' survival under starvation conditions. The effect of AB on the behaviour and nutritional status of the males depended on two additional factors: the origin of the males and the presence of a proteinaceous source in the diet. CONCLUSIONS: Our results suggest that A. fraterculus males gut contain symbiotic organisms that are able to exert a positive contribution on A. fraterculus males' fitness, although the physiological mechanisms still need further studies.