Bridges and Mechanisms: Integrating Systems Science Thinking into Implementation Research.

We present a detailed argument for how to integrate, or bridge, systems science thinking and methods with implementation science. We start by showing how fundamental systems science principles of structure, dynamics, information, and utility are relevant for implementation science. Then we examine the need for implementation science to develop and apply richer theories of complex systems. This can be accomplished by emphasizing a causal mechanisms approach. Identifying causal mechanisms focuses on the "cogs and gears" of public health, clinical, and organizational interventions. A mechanisms approach focuses on how a specific strategy will produce the implementation outcome. We show how connecting systems science to implementation science opens new opportunities for examining and addressing social determinants of health and conducting equitable and ethical implementation research. Finally, we present case studies illustrating successful applications of systems science within implementation science in community health policy, tobacco control, health care access, and breast cancer screening.

Effectiveness of trauma-focused cognitive behavioral therapy compared to psychosocial counseling in reducing HIV risk behaviors, substance use, and mental health problems among orphans and vulnerable children in Zambia: a community-based randomized controlled trial.

Orphans and vulnerable children (OVC) in sub-Saharan Africa are at high risk for HIV infection and transmission. HIV prevention and treatment efforts with OVC are hindered by mental health and substance use problems. This randomized controlled trial compared a mental health intervention, Trauma Focused Cognitive Behavioral Therapy (TF-CBT), to an enhanced version of an existing HIV Psychosocial Counseling (PC+) program among 610 adolescents who met PEPFAR criteria for OVC and had HIV risk behaviors in Lusaka, Zambia. Outcomes included HIV risk behaviors (e.g., risky sexual behaviors), mental health (internalizing symptoms, externalizing behaviors, PTSD) and substance use. At 12-month follow-up, there were significant within group reductions in both groups for all outcomes, with the only significant between group difference being for substance use, in which OVC who received TF-CBT had significantly greater reductions than OVC who received PC+. In a subgroup analysis of OVC with high levels of PTSD symptoms, TF-CBT was superior to PC + in reducing internalizing symptoms, functional impairment, and substance use. Findings support TF-CBT for reducing substance use among OVC. Subgroup analysis results suggest that a robust intervention such as TF-CBT is warranted for OVC with significant mental and behavioral health comorbidities. The similar performance of TF-CBT and PC + in the overall sample for risky sexual behavior and mild mental health problems indicates that enhancing existing psychosocial programs, such as PC, with standard implementation factors like having a defined training and supervision schedule (as was done to create PC+) may improve the efficacy of HIV risk reduction efforts.Clinical Trials Number: NCT02054780.

Why and How Epidemiologists Should Use Mixed Methods.

The field of epidemiology's current focus on causal inference follows a quantitative approach and limits research questions to those that are strictly quantifiable. How can epidemiologists study biosociocultural public health problems that they cannot easily quantify? The mixed-methods approach offers a possible solution by incorporating qualitative sociocultural factors as well as the perspective and context from the population under study into quantitative studies. After a pluralist perspective of causal inference, this article provides a guide for epidemiologists interested in applying mixed methods to their observational studies of causal identification and explanation. We begin by reviewing the current paradigms guiding quantitative, qualitative, and mixed methodologies. We then describe applications of convergent and sequential mixed-methods designs to epidemiologic concepts including confounding, mediation, effect modification, measurement, and selection bias. We provide concrete examples of how epidemiologists can use mixed methods to answer research questions of complex bio-socio-cultural health outcomes. We also include a case study of using mixed methods in an observational study design. We describe how mixed methods can enhance how epidemiologists define underlying causal structures. Our alignment of mixed-methods study designs with epidemiologic concepts addresses a major gap in current epidemiology education- how do epidemiologists systematically determine what goes into causal structures?

HIV stigma and disclosure of alcohol use to physicians: examining the mediating role of depression among persons living with HIV.

Alcohol use among persons living with HIV (PWH) can lead to poor disease outcomes. Disclosure of alcohol consumption to physicians is critical to inform HIV care. HIV stigma is associated with poor care engagement, and this relationship is partially mediated by depression. However, less is known about how HIV stigma and depression affect reporting of alcohol use to care providers. We used baseline data from an HIV intervention trial of 330 adult PWH in Baltimore, MD. We fit a path model to examine whether HIV stigma was associated with increased depression symptoms and whether higher levels of depression were, in turn, associated with underreporting of alcohol use to physicians. Among PWH reporting past 6-month alcohol use (n = 182, 55%), 64% met symptom criteria for probable depression, 58% met criteria for hazardous drinking, and 10% reported not disclosing alcohol use to their physician. HIV stigma was associated with higher levels of depression (ß = 0.99, p < .0001); depression was associated with a lower likelihood of alcohol disclosure (ß = -0.04, p < .0001); and depression mediated the indirect pathway from stigma to alcohol disclosure (ß = -0.04, p < .01). Methods to augment or strengthen alcohol self-report may be useful in HIV care, particularly among PWH experiencing HIV stigma and depression.

Immigrant generation status and its association with pubertal timing and tempo among Hispanic girls and boys.

PURPOSE: In the United States, Hispanic-Latino children reach puberty earlier on average than non-Hispanic white children. Yet among U.S. Hispanic/Latino children, pubertal timing comparisons between immigrant generations have not been made, hence we examined whether pubertal timing differs by immigrant generational status, independent of BMI and acculturation measures. METHODS: Cross-sectional data on 724 boys and 735 girls, aged 10-15 years, from the Hispanic Community Children's Health Study/Study of Latino (SOL) Youth, were used to predict the median ages of thelarche, pubarche, and menarche in girls, and pubarche and voice change in boys, using Weibull survival models, while adjusting for SOL center, BMI, and acculturation. RESULTS: In girls, the first generation began thelarche earlier than second and third generations (median age [years] [95% confidence interval]: 7.4 [6.1, 8.8] vs. 8.5 [7.3, 9.7] and 9.1 [7.6, 10.7], respectively), but began menarche later (12.9 [12.0,137] vs. 11.8 [11.0, 12.5] and 11.6 [10.6, 12.6], respectively). Pubertal timing and tempo for boys did not differ by generational status. CONCLUSIONS: First-generation U.S. Hispanic/Latino girls had the earliest thelarche, latest menarche and longest pubertal tempo, compared to second and third generations. Factors beyond BMI and acculturation may account for the differences in pubertal timing by generational status of U.S. Hispanic/Latino girls.

Mental Health of Guatemalan Health Care Workers During the COVID-19 Pandemic: Baseline Findings From the HEROES Cohort Study.

Objectives. To assess the baseline prevalence of mental health conditions and associated exposures in a cohort of health care workers (HCWs) in Guatemala. Methods. We analyzed baseline information from the 2020 Web-based COVID-19 Health Care Workers Study (HEROES)-Guatemala. Outcomes included mental distress and depressive symptoms. Exposures included COVID-19 experiences, sociodemographic characteristics, and job characteristics. We used crude and adjusted Poisson regression models in our analyses. Results. Of the 1801 HCWs who accepted to participate, 1522 (84.5%) completed the questionnaire; 1014 (66.8%) were women. Among the participants, 59.1% (95% confidence interval [CI] = 56.6, 61.5) screened positive for mental distress and 23% (95% CI = 20.9, 25.2) for moderate to severe depressive symptoms. COVID-19 experiences, sociodemographic characteristics, and job characteristics were associated with the study outcomes. Participants who were worried about COVID-19 infection were at higher risk of mental distress (relative risk [RR] = 1.47; 95% CI = 1.30, 1.66) and depressive symptoms (RR = 1.51; 95% CI = 1.17, 1.96). Similarly, the youngest participants were at elevated risk of mental distress (RR = 1.80; 95% CI = 1.24, 2.63) and depressive symptoms (OR = 4.58; 95% CI = 1.51, 13.87). Conclusions. Mental health conditions are highly prevalent among Guatemalan HCWs. (Am J Public Health. 2022;112(S6):S602-S614. https://doi.org/10.2105/AJPH.2021.306648).

Phosphorylation of S11 in PHR1 negatively controls its transcriptional activity.

Plant responses to phosphate starvation (-Pi) are very well characterized at the biochemical and molecular levels. The expression of thousands of genes is modified under this stress condition, depending on the action of Phosphate starvation response 1 (PHR1). Existing data indicate that neither the PHR1 transcript nor the quantity or localization of its protein increase during nutrient stress, raising the question of how its activity is regulated. Here, we present data showing that SnRK1 kinase is able to phosphorylate some phosphate starvation response proteins (PSRs), including PHR1. Based on a model of the three-dimensional structure of the catalytic subunit SnRK1α1, docking simulations predicted the binding modes of peptides from PHT1;8, PHO1 and PHR1 with SnRK1. PHR1 recombinant protein interacted in vitro with the catalytic subunits SnRK1α1 and SnRK1α2. A BiFC assay corroborated the in vivo interaction between PHR1 and SnRK1α1 in the cytoplasm and nucleus. Analysis of phosphorylated residues suggested the presence of one phosphorylated site containing the SnRK1 motif at S11, and mutation in this residue disrupted the incorporation of 32 P, suggesting that it is a major phosphorylation site. Electrophoretic mobility shift assay results indicated that the binding of PHR1 to P1BS motifs was not influenced by phosphorylation. Importantly, transient expression assays in Arabidopsis protoplasts showed a decrease in PHR1 activity in contrast with the S11A mutant, suggesting a role for Ser11 as a negative regulatory phosphorylation site. Taken together, these findings suggest that phosphorylation of PHR1 at Ser11 is a mechanism to control the PHR1-mediated adaptive response to -Pi.

Explanatory models of hypertension in Guatemala: recognizing the perspectives of patients, family members, health care providers and administrators, and national-level health system stakeholders.

BACKGROUND: Uncontrolled hypertension is a major public health burden and the most common preventable risk factor for cardiovascular diseases in Guatemala and other low- and middle-income countries. Prior to an initial trial that evaluated a hypertension intervention in rural Guatemala, we collected qualitative information on the needs and knowledge gaps of hypertension care within Guatemala's public healthcare system. This analysis applied Kleinman's Explanatory Models of Illness to capture how patients, family members, community-, district-, and provincial-level health care providers and administrators, and national-level health system stakeholders understand hypertension.  METHODS: We conducted in-depth interviews with three types of participants: 1) national-level health system stakeholders (n = 17), 2) local health providers and administrators from district, and health post levels (25), and 3) patients and family members (19) in the departments of Sololá and Zacapa in Guatemala. All interviews were conducted in Spanish except for 6 Maya-Kaqchikel interviews. We also conducted focus group discussions with auxiliary nurses (3) and patients (3), one in Maya-Tz'utujil and the rest in Spanish. Through framework and matrix analysis, we compared understandings of hypertension by participant type using the Explanatory Model of Illness domains -etiology, symptoms, pathophysiology, course of illness, and treatment. RESULTS: Health providers and administrators, and patients described hypertension as an illness that spurs from emotional states like sadness, anger, and worry; is inherited and related to advanced age; and produces symptoms that include a weakened body, nerves, pain, and headaches. Patients expressed concerns about hypertension treatment's long-term consequences, despite trying to comply with treatment. Patients stated that they combine biomedical treatment (when available) with natural remedies (teas and plants). Health providers and administrators and family members stated that once patients feel better, they often disengage from treatment. National-level health system stakeholders referred to lifestyle factors as important causes, considered patients to typically be non-compliant, and identified budget limitations as a key barrier to hypertension care. The three groups of participants identified structural barriers to limited hypertension care (e.g., limited access to healthy food and unaffordability of medications). CONCLUSION: As understandings of hypertension vary between types of participants, it is important to describe their similarities and differences considering the role each has in the health system. Considering different perceptions of hypertension will enable better informed program planning and implementation efforts.

[Mental health of Guatemalan health care workers during the COVID-19 pandemic: baseline findings from the HEROES cohort studySaúde mental dos trabalhadores da saúde guatemaltecos durante a pandemia de COVID-19: constatações basais do estudo da coorte HEROES]. / La salud mental de los trabajadores de salud en Guatemala durante la pandemia de COVID-19: resultados de base del estudio de cohortes HÉROES.

Objectives: To assess the baseline prevalence of mental health conditions and associated exposures in a cohort of health care workers (HCWs) in Guatemala. Methods: We analyzed baseline information from the 2020 Web-based COVID-19 Health Care Workers Study (HEROES)-Guatemala. Outcomes included mental distress and depressive symptoms. Exposures included COVID-19 experiences, sociodemographic characteristics, and job characteristics. We used crude and adjusted Poisson regression models in our analyses. Results: Of the 1801 HCWs who accepted to participate, 1522 (84.5%) completed the questionnaire; 1014 (66.8%) were women. Among the participants, 59.1% (95% confidence interval [CI] = 56.6, 61.5) screened positive for mental distress and 23% (95% CI = 20.9, 25.2) for moderate to severe depressive symptoms. COVID-19 experiences, sociodemographic characteristics, and job characteristics were associated with the study outcomes. Participants who were worried about COVID-19 infection were at higher risk of mental distress (relative risk [RR] = 1.47; 95% CI = 1.30, 1.66) and depressive symptoms (RR = 1.51; 95% CI = 1.17, 1.96). Similarly, the youngest participants were at elevated risk of mental distress (RR = 1.80; 95% CI = 1.24, 2.63) and depressive symptoms (OR = 4.58; 95% CI = 1.51, 13.87). Conclusions: Mental health conditions are highly prevalent among Guatemalan.

Objetivos: Avaliar a prevalência basal de condições de saúde mental e exposições associadas em uma coorte de trabalhadores da saúde (TS) na Guatemala. Métodos: Analisamos as informações da linha de base do estudo on-line sobre trabalhadores da saúde e a COVID-19 (HEROES), realizado em 2020 na Guatemala. Os desfechos incluíram angústia debilitante e sintomas de depressão. As exposições incluíram experiências com a COVID-19, características sociodemográficas e características do trabalho. Usamos em nossas análises modelos de regressão bruta e ajustada de Poisson. Resultados: Dos 1801 TS que concordaram em participar, 1522 (84,5%) preencheram o questionário, sendo que 1014 (66,8%) eram mulheres. Dentre esses participantes, 59,1% (intervalo de confiança [IC] de 95%=56,6; 61,5) apresentaram resultado positivo na triagem de angústia debilitante e 23% (IC 95%=20,9, 25,2) apresentaram resultado positivo para sintomas de depressão moderados a graves. Experiências com COVID-19, e características sociodemográficas e de trabalho apresentaram associação com os resultados do estudo. Os participantes que estavam preocupados com infecção por COVID-19 apresentaram maior risco de angústia debilitante (risco relativo [RR]=1,47; IC95%=1,30; 1,66) e sintomas de depressão (RR=1,51; IC 95% =1,17; 1,96). Da mesma maneira, os participantes mais jovens apresentaram alto risco de apresentarem angústia debilitante (RR=1,80; IC 95%=1,24; 2,63) e sintomas de depressão (OR=4,58; IC 95%=1,51; 13,87). Conclusões: Condições de saúde mental são altamente prevalentes entre os guatemaltecos.

Excess Mortality During the COVID-19 Pandemic in Guatemala.

Objectives. To describe excess mortality during the COVID-19 pandemic in Guatemala during 2020 by week, age, sex, and place of death. Methods. We used mortality data from 2015 to 2020, gathered through the vital registration system of Guatemala. We calculated weekly mortality rates, overall and stratified by age, sex, and place of death. We fitted a generalized additive model to calculate excess deaths, adjusting for seasonality and secular trends and compared excess deaths to the official COVID-19 mortality count. Results. We found an initial decline of 26% in mortality rates during the first weeks of the pandemic in 2020, compared with 2015 to 2019. These declines were sustained through October 2020 for the population younger than 20 years and for deaths in public spaces and returned to normal from July onward in the population aged 20 to 39 years. We found a peak of 73% excess mortality in mid-July, especially in the population aged 40 years or older. We estimated a total of 8036 excess deaths (95% confidence interval = 7935, 8137) in 2020, 46% higher than the official COVID-19 mortality count. Conclusions. The extent of this health crisis is underestimated when COVID-19 confirmed death counts are used. (Am J Public Health. 2021;111(10): 1839-1846. https://doi.org/10.2105/AJPH.2021.306452).

Hypertension in Guatemala's Public Primary Care System: A Needs Assessment Using the Health System Building Blocks Framework.

BACKGROUND: Uncontrolled hypertension represents a substantial and growing burden in Guatemala and other low and middle-income countries. As a part of the formative phase of an implementation research study, we conducted a needs assessment to define short- and long-term needs and opportunities for hypertension services within the public health system. METHODS: We conducted a multi-method, multi-level assessment of needs related to hypertension within Guatemala's public system using the World Health Organization's health system building blocks framework. We conducted semi-structured interviews with stakeholders at national (n = 17), departmental (n = 7), district (n = 25), and community (n = 30) levels and focus groups with patients (3) and frontline auxiliary nurses (3). We visited and captured data about infrastructure, accessibility, human resources, reporting, medications and supplies at 124 health posts and 53 health centers in five departments of Guatemala. We conducted a thematic analysis of transcribed interviews and focus group discussions supported by matrix analysis. We summarized quantitative data observed during visits to health posts and centers. RESULTS: Major challenges for hypertension service delivery included: gaps in infrastructure, insufficient staffing and high turnover, limited training, inconsistent supply of medications, lack of reporting, low prioritization of hypertension, and a low level of funding in the public health system overall. Key opportunities included: prior experience caring for patients with chronic conditions, eagerness from providers to learn, and interest from patients to be involved in managing their health. The 5 departments differ in population served per health facility, accessibility, and staffing. All but 7 health posts had basic infrastructure in place. Enalapril was available in 74% of health posts whereas hydrochlorothiazide was available in only 1 of the 124 health posts. With the exception of one department, over 90% of health posts had a blood pressure monitor. CONCLUSIONS: This multi-level multi-method needs assessment using the building blocks framework highlights contextual factors in Guatemala's public health system that have been important in informing the implementation of a hypertension control trial. Long-term needs that are not addressed within the scope of this study will be important to address to enable sustained implementation and scale-up of the hypertension control approach.

Human Rickettsiosis Caused by Rickettsia parkeri Strain Atlantic Rainforest, Urabá, Colombia.

We describe the clinical, serologic, and molecular findings of a new human rickettsiosis in Colombia. Antibodies against Rickettsia spp. were detected. PCR showed amplification of genes for R. parkeri strain Atlantic Rainforest. This new rickettsiosis of minor virulence could explain some of the undifferentiated acute febrile diseases in Colombia.

Reliability and Validity of an Adapted and Translated Version of the Mullen Scales of Early Learning (AT-MSEL) in Rural Guatemala.

BACKGROUND: A growing literature base supports the use of tests developed in high-income countries to assess children in low resource settings when carefully translated, adapted, and applied. Evaluation of psychometric properties of adapted and translated measures within populations is necessary. The current project sought to evaluate the reliability and validity of an adapted and translated version of the Mullen Scales of Early Learning (AT-MSEL) in rural Guatelama. METHODS: The reliability and validity of the AT-MSEL in rural Guatemala were analyzed for children ages 0-5 years. RESULTS: Interrater reliability coefficients (ICC = 0.99-1.0) and internal consistency (Cronbach's alpha = 0.91-0.93) were excellent for all subscales. General linear models utilizing paired data showed consistency between standard scores (p < 0.0001). Mean raw scores increased with chronological age, as expected. Across age groups, subscales were significantly, positively correlated with one another (p < 0.05 - < 0.001) with one exception, visual reception and expressive language at the 0-10 month age range (p = 0.43). CONCLUSIONS: The AT- MSEL showed strong psychometric properties in a sample of young children in rural Guatemala. Findings demonstrate that the AT-MSEL can be used validly and reliably within this specific population of children. This work supports the concept that tests developed in high-income countries can be used to assess children in low resource settings when carefully translated, adapted and applied.

Receptive language skills among young children in rural Guatemala: The relationship between the Test de Vocabulario en Imagenes Peabody and a translated and adapted version of the Mullen Scales of Early Learning.

BACKGROUND: Children in low- and lower middle income countries (LMICs) often have poorer language skills compared with children from high-income countries. Limited availability of culturally and linguistically appropriate assessment measures in LMICs, especially for young children, can hinder early identification and prevention efforts. Here, we describe receptive language (RL) skills among young children in rural Guatemala and report on the validity of a translated and culturally adapted developmental measure of RL. METHODS: Children (n = 157; m = 53.6 months, range = 42-68 months) enrolled in a prospective cohort study of postnatally acquired Zika virus infection were administered the Test de Vocabulario en Imagenes Peabody (TVIP) and the RL scale from a translated and adapted version of the Mullen Scales of Early Learning (MSEL). Performance on the TVIP was compared with the Latin American normative sample. Correlational analysis examined the relationship between performance on the TVIP and the MSEL-RL. RESULTS: Mean scores were significantly below the normative sample mean on the TVIP, t(126) = -11.04, p < .001; d = 1.00. Performance on the TVIP among children who passed the practice items (n = 127) was significantly positively associated with performance on the MSEL-RL (r = .50, p < .001), but not significantly associated with age or gender. Older age (p < .0001) and female gender (p = .018) were associated with passing the TVIP practice items. CONCLUSIONS: Delays in RL vocabulary were identified among young children in rural Guatemala on the TVIP. The association between scores on the TVIP and the RL scale of the MSEL provides preliminary support for the construct validity of this translated and adapted version of the MSEL.

Performance of a Mobile Phone App-Based Participatory Syndromic Surveillance System for Acute Febrile Illness and Acute Gastroenteritis in Rural Guatemala.

BACKGROUND: With their increasing availability in resource-limited settings, mobile phones may provide an important tool for participatory syndromic surveillance, in which users provide symptom data directly into a centralized database. OBJECTIVE: We studied the performance of a mobile phone app-based participatory syndromic surveillance system for collecting syndromic data (acute febrile illness and acute gastroenteritis) to detect dengue virus and norovirus on a cohort of children living in a low-resource and rural area of Guatemala. METHODS: Randomized households were provided with a mobile phone and asked to submit weekly reports using a symptom diary app (Vigilant-e). Participants reporting acute febrile illness or acute gastroenteritis answered additional questions using a decision-tree algorithm and were subsequently visited at home by a study nurse who performed a second interview and collected samples for dengue virus if confirmed acute febrile illness and norovirus if acute gastroenteritis. We analyzed risk factors associated with decreased self-reporting of syndromic data using the Vigilant-e app and evaluated strategies to improve self-reporting. We also assessed agreement between self-report and nurse-collected data obtained during home visits. RESULTS: From April 2015 to June 2016, 469 children in 207 households provided 471 person-years of observation. Mean weekly symptom reporting rate was 78% (range 58%-89%). Households with a poor (<70%) weekly reporting rate using the Vigilant-e app during the first 25 weeks of observation (n=57) had a greater number of children (mean 2.8, SD 1.5 vs mean 2.5, SD 1.3; risk ratio [RR] 1.2, 95% CI 1.1-1.4), were less likely to have used mobile phones for text messaging at study enrollment (61%, 35/57 vs 76.7%, 115/150; RR 0.6, 95% CI 0.4-0.9), and were less likely to access care at the local public clinic (35%, 20/57 vs 67.3%, 101/150; RR 0.4, 95% CI 0.2-0.6). Parents of female enrolled participants were more likely to have low response rate (57.1%, 84/147 vs 43.8%, 141/322; RR 1.4, 95% CI 1.1-1.9). Several external factors (cellular tower collapse, contentious elections) were associated with periods of decreased reporting. Poor response rate (<70%) was associated with lower case reporting of acute gastroenteritis, norovirus-associated acute gastroenteritis, acute febrile illness, and dengue virus-associated acute febrile illness (P<.001). Parent-reported syndromic data on the Vigilant-e app demonstrated agreement with nurse-collected data for fever (kappa=.57, P<.001), vomiting (kappa=.63, P<.001), and diarrhea (kappa=.61, P<.001), with decreased agreement as the time interval between parental report and nurse home visit increased (<1 day: kappa=.65-.70; ≥2 days: kappa=.08-.29). CONCLUSIONS: In a resource-limited area of rural Guatemala, a mobile phone app-based participatory syndromic surveillance system demonstrated a high reporting rate and good agreement between parental reported data and nurse-reported data during home visits. Several household-level and external factors were associated with decreased syndromic reporting. Poor reporting rate was associated with decreased syndromic and pathogen-specific case ascertainment.

Leuprolide acetate-stimulated androgen response during female puberty.

BACKGROUND: A physiological increase in androgen levels occurs during adolescence. Measuring androgen concentrations is the best method to distinguish normal evolution processes from hyperandrogenic disorders. HYPOTHESIS: The increase in circulating androgens during puberty is inversely associated with insulin sensitivity in normal weight girls. OBJECTIVE: To assess circulating levels of ovarian androgens and anti-Müllerian hormone (AMH) at baseline and after GnRH analogue (GnRH-a) stimulation in normal pubertal girls across different Tanner stages. We also studied the association between this response and insulin sensitivity. DESIGN: Prospective study of healthy girls (6-12 years) from the local community (n = 63). METHODS: Tanner I (n = 23) subjects were assessed cross-sectionally, and Tanner II girls (n = 40) were evaluated every 6 months until they reached Tanner V. Early morning dehydroepiandrosterone sulphate (DHEA-S), AMH, sex hormone-binding globulin (SHBG), androstenedione, glucose and insulin levels were measured. A GnRH-a test (500 µg/m(2) ; sc) and oral glucose intolerance test (OGTT) were performed. Differences throughout puberty were evaluated. RESULTS: Basal and/or stimulated Testosterone DHEA-S and 17-hydroxyprogesterone (17OHP) were inversely associated with insulin sensitivity (WIBSI) from the beginning of puberty, whereas androstenedione was directly associated with gonadotrophins. AMH was inversely associated with basal and stimulated gonadotrophins and directly with insulin area under the curve (AUC) only in the early stages of puberty. 17OHP and testosterone responsiveness increased significantly during puberty in all subjects, whereas testosterone levels changed less consistently. This pattern of ovarian-steroidogenic response was most evident during mid- and late puberty. Moreover, during late puberty only, basal 17OHP, testosterone and DHEA-S were positively associated with gonadotrophins. CONCLUSION: In normal nonobese girls born appropriate for gestational age, androgen synthesis was associated with insulin sensitivity in early puberty and with LH only in late puberty.

Dermoscopic structures and patterns used in melanoma detection.

Melanoma is the leading cause of skin cancer-related deaths. Yet, early detection remains the most cost-effective means of preventing death from melanoma. Early detection can be achieved by a physician and/or the patient (also known as a self-skin exam). Skin exams performed by physicians are further enhanced using dermoscopy. Dermoscopy is a non-invasive technique that allows for the visualization of subsurface structures that are otherwise not visible to the naked eye. Evidence demonstrates that dermoscopy improves the diagnostic accuracy for skin cancer, including melanoma; it decreases the number of unnecessary skin biopsies of benign lesions and improves the benign-to-malignant biopsy ratio. Yet, these improvements are contingent on acquiring dermoscopy training. Dermoscopy is used by clinicians who evaluate skin lesions and perform skin cancer screenings. In general, under dermoscopy nevi tend to appear as organized lesions, with one or two structures and colors, and no melanoma-specific structures. In contrast, melanomas tend to manifest a disorganized pattern, with more than two colors and, usually, at least one melanoma-specific structure. This review is intended to familiarize the reader with the dermoscopic structures and patterns used in melanoma detection.

Spanish translation of the Expert Recommendations for Implementing Change (ERIC) compilation.

BACKGROUND: Most implementation science resources (e.g., taxonomies) are published in English. Linguistic inaccessibility creates a barrier to the conduct of implementation research among non-English-speaking populations, so translation of resources is needed. Translation into Spanish can facilitate widespread reach, given the large proportion of Spanish speakers around the world. This research aimed to systematically translate the Expert Recommendations for Implementation Change (ERIC) compilation into Spanish as an exemplar for the linguistic translation process. METHODS: Using the World Health Organization guidelines, this work translated the ERIC compilation strategy names, short definitions, and thematic clusters through a three-step process: 1) forward translation into Spanish by a native Spanish-speaking implementation scientist, 2) back-translation into English by a bilingual global health researcher, and 3) piloting via virtual focus group discussions with bilingual researchers not conducting implementation research. To achieve a generalizable translation, recruitment targeted a multicultural group of Spanish-speaking researchers. At the conclusion of each step, the transdisciplinary research team (N = 7) met to discuss discrepancies and refine translations. The Spanish version of the ERIC compilation was finalized through group consensus. Reflections from research team meetings and focus group discussions were synthesized qualitatively. RESULTS: Given that dialectical nuances exist between Spanish-speaking regions, efforts prioritized universally accepted terminology. Team discussions focused on difficult translations, word choice, and clarity of concepts. Seven researchers participated in two focus groups, where discussion surrounded clarity of concepts, alternative word choice for Spanish translations, linguistic formality, grammar, and conciseness. Translation difficulties highlighted lack of precision in implementation science terminology, and the lack of conceptual clarity of words underscored limitations in the application of the compilation. CONCLUSIONS: The work demonstrated the feasibility of translating implementation science resources. As one of the first systematic efforts to translate implementation resources, this study can serve as a model for additional efforts, including translation into other languages and the expansion to conceptual modifications. Further, this work yielded insights into the need to provide conceptual clarity in implementation science terminology. Importantly, the development of Spanish resources will increase access to conduct implementation research among Spanish-speaking populations.