Types of diabetes during pregnancy and risk of depression and anxiety in offspring from childhood to young adulthood.

AIMS: To assess maternal pre-existing type 1 diabetes (T1D), type 2 diabetes (T2D), gestational diabetes mellitus (GDM) during pregnancy and risk of depression and anxiety from childhood to young adulthood in offspring. MATERIALS AND METHODS: This birth cohort included singletons born during 1995-2015, followed using electronic medical records through 2020. Cox regression was used to estimate hazard ratio (HR) of depression or anxiety diagnosis during follow-up associated with in-utero exposure to maternal diabetes. RESULTS: Among 439 590 offspring, 29 891 (6.8%) had depression and 51 918 (11.8%) had anxiety. T1D, followed by T2D and GDM requiring antidiabetes medication were associated with risk of depression and anxiety in offspring. Compared with no diabetes during pregnancy, the adjusted HRs (95% confidence interval) of depression in offspring associated with T1D, T2D or GDM requiring medications were 1.44 (1.09-1.91), 1.30 (1.15-1.47) and 1.18 (1.11-1.26) respectively; conversely, HRs were 0.97 (0.82-1.15) for T2D and 0.99 (0.94-1.04) for GDM without medications. The associations with anxiety followed similar patterns. The significant associations were observed for offspring ages 5-12 and >12-18 years and attenuated for 18-25 years. CONCLUSION: These data suggest that the severity of diabetes (T1D vs. T2D requiring medications vs. GDM requiring medications) during pregnancy may increase the vulnerability of offspring for depression or anxiety.

Jackfruit Leaf Protein Hydrolysates Obtained by Enzymatic Hydrolysis of Leaf Protein Concentrate with Pepsin and Pancreatin: Molecular Weight, Cytotoxicity, Antiproliferative Activity, and Oxidative Stress.

Jackfruit leaf protein hydrolysates obtained from the enzymatic hydrolysis of leaf protein concentrate with gastrointestinal enzymes have shown good techno-functional properties and high antioxidant capacity. However, molecular weight, antiproliferative activity, cytotoxicity and the ability to reduce reactive oxygen species (ROS) are still unknown. Therefore, this study aimed to evaluate the effect of jackfruit leaf protein hydrolysates obtained by enzymatic hydrolysis with pepsin and pancreatin at different hydrolysis times (30-240 min) on molecular weights, cytotoxicity, antiproliferation of cancer cells, and the reduction of reactive oxygen species in H2O2-induced HaCaT cells. The electrophoretic profile indicated that H-Pep contains peptides with molecular weights between 25 - 20 kDa. Meanwhile, H-Pan is composed of molecular weight products between 25 - 20 kDa and < 20 kDa. H-Pan and H-Pep (125-500 µg/mL) did not show significant cytotoxicity on HaCaT (human keratinocytes) and J774A.1 (murine macrophage cells). Antiproliferative activity was achieved in human cervical, ovarian, and liver cancer cells. H-Pan-240 min (1000 µg/mL) reduced the cell viability of cervical cancer cells by 23% while H-Pan-60 min significantly reduced cell viability of ovarian and liver cancer cells by 14.5 (500 µg/mL) and 17% (1000 µg/mL), respectively (P < 0.05). The protective effect against oxidative stress on H2O2-stressed HaCaT cells was obtained with H-Pep-60 min, which reduced 25% of ROS at 250 µg/mL (P < 0.05). The findings demonstrate the safe use of green biomass as a source of plant protein hydrolysates.

Associations of Autism Spectrum Disorder with PM2.5 Components: A Comparative Study Using Two Different Exposure Models.

This retrospective cohort study examined associations of autism spectrum disorder (ASD) with prenatal exposure to major fine particulate matter (PM2.5) components estimated using two independent exposure models. The cohort included 318 750 mother-child pairs with singleton deliveries in Kaiser Permanente Southern California hospitals from 2001 to 2014 and followed until age five. ASD cases during follow-up (N = 4559) were identified by ICD codes. Prenatal exposures to PM2.5, elemental (EC) and black carbon (BC), organic matter (OM), nitrate (NO3-), and sulfate (SO42-) were constructed using (i) a source-oriented chemical transport model and (ii) a hybrid model. Exposures were assigned to each maternal address during the entire pregnancy, first, second, and third trimester. In single-pollutant models, ASD was associated with pregnancy-average PM2.5, EC/BC, OM, and SO42- exposures from both exposure models, after adjustment for covariates. The direction of effect estimates was consistent for EC/BC and OM and least consistent for NO3-. EC/BC, OM, and SO42- were generally robust to adjustment for other components and for PM2.5. EC/BC and OM effect estimates were generally larger and more consistent in the first and second trimester and SO42- in the third trimester. Future PM2.5 composition health effect studies might consider using multiple exposure models and a weight of evidence approach when interpreting effect estimates.

Ambient Air Pollutant Exposures and COVID-19 Severity and Mortality in a Cohort of Patients with COVID-19 in Southern California.

Rationale: Ecological studies have shown air pollution associations with coronavirus disease (COVID-19) outcomes. However, few cohort studies have been conducted. Objectives: To conduct a cohort study investigating the association between air pollution and COVID-19 severity using individual-level data from the electronic medical record. Methods: This cohort included all individuals who received diagnoses of COVID-19 from Kaiser Permanente Southern California between March 1 and August 31, 2020. One-year and 1-month averaged ambient air pollutant (particulate matter ⩽2.5 µm in aerodynamic diameter [PM2.5], NO2, and O3) exposures before COVID-19 diagnosis were estimated on the basis of residential address history. Outcomes included COVID-19-related hospitalizations, intensive respiratory support (IRS), and ICU admissions within 30 days and mortality within 60 days after COVID-19 diagnosis. Covariates included socioeconomic characteristics and comorbidities. Measurements and Main Results: Among 74,915 individuals (mean age, 42.5 years; 54% women; 66% Hispanic), rates of hospitalization, IRS, ICU admission, and mortality were 6.3%, 2.4%, 1.5%, and 1.5%, respectively. Using multipollutant models adjusted for covariates, 1-year PM2.5 and 1-month NO2 average exposures were associated with COVID-19 severity. The odds ratios associated with a 1-SD increase in 1-year PM2.5 (SD, 1.5 µg/m3) were 1.24 (95% confidence interval [CI], 1.16-1.32) for COVID-19-related hospitalization, 1.33 (95% CI, 1.20-1.47) for IRS, and 1.32 (95% CI, 1.16-1.51) for ICU admission; the corresponding odds ratios associated with 1-month NO2 (SD, 3.3 ppb) were 1.12 (95% CI, 1.06-1.17) for hospitalization, 1.18 (95% CI, 1.10-1.27) for IRS, and 1.21 (95% CI, 1.11-1.33) for ICU admission. The hazard ratios for mortality were 1.14 (95% CI, 1.02-1.27) for 1-year PM2.5 and 1.07 (95% CI, 0.98-1.16) for 1-month NO2. No significant interactions with age, sex or ethnicity were observed. Conclusions: Ambient PM2.5 and NO2 exposures may affect COVID-19 severity and mortality.

Evaluation of patients´ perspective on a multimorbidity patient-centered care model piloted in the chilean public health system.

BACKGROUND: The progressive multimorbidity explosion has challenged Chile's health systems and worldwide. The Centro de Innovación en Salud ANCORA UC implemented a new Multimorbidity Patient-Centered Care Model in Chile. OBJECTIVE: Evaluate the perspective of high-risk patients about the core elements of the model. METHODOLOGY: We conducted a cross sectional telephone-based survey that considered the application of a 13 items questionnaire. Of them, nine were Likert scale questions with scores from 1 to 7, one dichotomic question, and three open-ended questions. 231 high-risk patients who received care through the model at primary care centers participated in the study. Quantitative data were encoded, consolidated, and analyzed with the SPSS software. We performed descriptive and analytic statistics techniques to assess different variables and their potential associations. Thematic analysis was conducted for qualitative data. RESULTS: The overall score was 5.84 (range: 1 to 7), with a standard deviation of 1.25. Questions with the best scores were those related with personalized care and the primary care teams. The lowest scored was for the item regarding the continuity of care between primary nurses and inpatient care at the hospital. There was a difference in patient outcomes depending on their health center. Regarding sociodemographic characteristics, age did not significantly affect the results. CONCLUSIONS: The study reveals the perceptions about a complex multimorbidity intervention from the patient's perspective. It complements the impact on health services utilization evaluation that supports decision-makers currently scaling up a similar strategy in our country and could be considered in other countries dealing with non-communicable diseases.

Transcriptional Response of Vitellogenin Gene in Flatfish to Environmental Pollutants from Two Regions of the Gulf of Mexico.

The present study evaluates the endocrine effect in flatfish through vitellogenin (vtg) gene expression and its association with pollutants data obtained from fish muscle and sediment from two regions in the Gulf of Mexico (GoM): Perdido Fold Belt (northwestern) and the Yucatan Peninsula (southeast). The results revealed induction of vtg in male flatfish in both geographical regions with different levels and patterns of distribution per oceanographic campaign (OC). In the Perdido Fold Belt, vtg was observed in male fish during four OC (carried out in 2016 and 2017), positively associated with Pb, V, Cd and bile metabolites (hydroxynaphthalene and hydroxyphenanthrene). In the Yucatan Peninsula, the induction of vtg in males was also detected in three OC (carried out in 2016 and 2018) mainly associated with Ni, Pb, Al, Cd, V and polycyclic aromatic hydrocarbons. Ultimately, estrogenic alterations could affect reproductive capacity of male flatfish in the GoM.

The surfactant Dioctyl Sodium Sulfosuccinate (DOSS) exposure causes adverse effects in embryos and adults of zebrafish (Danio rerio).

Dioctyl Sodium Sulfosuccinate (DOSS, CAS 577-11-7) is a chemical emulsifying surfactant that is widely used in the food and the cosmetic industry, and it is also the major component of the crude oil chemical dispersant Corexit™. Despite of its wide use, the studies related to its negative effect have been evaluated mainly in marine environments showing that DOSS is highly bioactive, extremely low volatile, and potential to persist in the environment longer than other dispersant components. Up to date, there is no available information of DOSS concentration in freshwater environments, little is known about its downstream fate after excretion and its effect on freshwater organisms. The objective of this study was to evaluate the effect of DOSS at different concentrations in embryos and adults of zebrafish Danio rerio in an acute-static bioassays of 96 h. The median lethal concentration in embryos was 33.3 mg/L. Malformations started to be observed at 10 mg/L. In adults, the gene expression analysis in gill tissues showed a deregulation in genes associated with the antioxidant system and the nucleotide excision repair mechanism. Additionally, Micronuclei (DNA damage) in erythrocytes, and fat degeneration in liver, hypertrophy and hyperplasia in gills, and hyaline drops in kidney tissues were also observed. In conclusion, the concentrations of DOSS evaluated here would be of health relevance to fish based on morphological alterations in embryos and changes in the gene expression profile, DNA damage and tissue impairment in adults.

Integrative description of changes occurring on zebrafish embryos exposed to water-soluble crude oil components and its mixture with a chemical surfactant.

The effects of crude oil spills are an ongoing problem for wildlife and human health in both marine and freshwater aquatic environments. Bioassays of model organisms are a convenient way to assess the potential risks of the substances involved in oil spills. Zebrafish embryos (ZFE) are a useful to reach a fast and detailed description of the toxicity of the pollutants, including both the components of the crude oil itself and substances that are commonly used for crude oil spill mitigation (e.g. surfactants). Here, we evaluated the survival rate, as well as histological, morphological, and proteomic changes in ZFE exposed to Water Accumulated Fraction (WAF) of light crude oil and in mixture with Dioctyl Sulfosuccinate Sodium (DOSS, e.g. CEWAF: Chemically Enhanced WAF), a surfactant that is frequently used in chemical dispersant formulations. Furthermore, we compared the hydrocarbon concentration of WAF and CEWAF of the sublethal dilution. In histological, morphological, and gene expression variables, the ZFE exposed to WAF showed less changes than those exposed to CEWAF. Proteomic changes were more dramatic in ZFE exposed to WAF, with important alterations in spliceosomal and ribosomal proteins, as well as proteins related to eye and retinal photoreceptor development and heart function. We also found that the concentration of high molecular weight hydrocarbons in water was slighly higher in presence of DOSS, but the low molecular weight hydrocarbons concentration was higher in WAF. These results provide an important starting point for identifying useful crude-oil exposure biomarkers in fish species.

Isobolographic analysis of antinociceptive effect of ketorolac, indomethacin, and paracetamol after simultaneous peripheral local and systemic administration.

This study was designed to characterize the type of interaction (subadditive, additive, or synergistic) after simultaneous administration by two different routes (intraperitoneal plus peripheral local) of the same nonsteroidal anti-inflammatory drugs (NSAID) ketorolac and indomethacin or paracetamol. The antinociceptive effects of locally or intraperitoneally delivery of NSAIDs or paracetamol, and the simultaneous administration by the two routes at fixed-dose ratio combination were evaluated using the formalin test. Pain-related behavior was quantified as the number of flinches of the injected paw. Isobolographic analysis was used to characterize the interaction between the two routes. ED30 values were estimated for individual drugs, and isobolograms were constructed. Ketorolac, indomethacin, or paracetamol and fixed-dose ratio combinations produced a dose-dependent antinociceptive effect in the second but not in the first phase of the formalin test. The analysis of interaction type after simultaneous administration by the two routes the same NSAID or paracetamol (on basis of their ED30), revealed that the simultaneous administration of ketorolac or paracetamol was additive and for indomethacin was synergistic. Since the mechanisms underlying the additive effect of ketorolac or paracetamol and the synergistic effect of indomethacin were not explored; it is possible that the peripheral and central mechanism is occurring at several anatomical sites. The significance of these findings for theory and pain pharmacotherapy practice indicates that the combination of one analgesic drug given simultaneously by two different administration routes could be an additive or it could lead to a synergistic interaction.

Ambient air pollution and COVID-19 incidence during four 2020-2021 case surges.

BACKGROUND: Air pollution exposure may make people more vulnerable to COVID-19 infection. However, previous studies in this area mostly focused on infection before May 2020 and long-term exposure. OBJECTIVE: To assess both long-term and short-term exposure to air pollution and COVID-19 incidence across four case surges from 03/1/2020 to 02/28/2021. METHODS: The cohort included 4.6 million members from a large integrated health care system in southern California with comprehensive electronic medical records (EMR). COVID-19 cases were identified from EMR. Incidence of COVID-19 was computed at the census tract-level among members. Prior 1-month and 1-year averaged air pollutant levels (PM2.5, NO2, and O3) at the census tract-level were estimated based on hourly and daily air quality data. Data analyses were conducted by each wave: 3/1/2020-5/31/2020, 6/1/202-9/30/2020, 10/1/2020-12/31/2020, and 1/1/2021-2/28/2021 and pooled across waves using meta-analysis. Generalized linear mixed effects models with Poisson distribution and spatial autocorrelation were used with adjustment for meteorological factors and census tract-level social and health characteristics. Results were expressed as relative risk (RR) per 1 standard deviation. RESULTS: The cohort included 446,440 COVID-19 cases covering 4609 census tracts. The pooled RRs (95% CI) of COVID-19 incidence associated with 1-year exposures to PM2.5, NO2, and O3 were 1.11 (1.04, 1.18) per 2.3 µg/m3,1.09 (1.02, 1.17) per 3.2 ppb, and 1.06 (1.00, 1.12) per 5.5 ppb respectively. The corresponding RRs (95% CI) associated with prior 1-month exposures were 1.11 (1.03, 1.20) per 5.2 µg/m3 for PM2.5, 1.09 (1.01, 1.17) per 6.0 ppb for NO2 and 0.96 (0.85, 1.08) per 12.0 ppb for O3. CONCLUSION: Long-term PM2.5 and NO2 exposures were associated with increased risk of COVID-19 incidence across all case surges before February 2021. Short-term PM2.5 and NO2 exposures were also associated. Our findings suggest that air pollution may play a role in increasing the risk of COVID-19 infection.

Mixed-Methods Evaluation of the Initial Implementation of Advanced Home Visits in Chile.

Home visiting programs are evidence-based interventions that have a myriad outcomes for mothers and newborns. Chile offers these services as part of the Chile Crece Contigo, a nationwide program. However, implementing home visiting programs in community settings is difficult. In this study, we report clinic, provider, and participant engagement with the implementation of advanced home visits (ViDAs) in Chilean primary care clinics. ViDAs include a high number of visits, external supervision, and the use of technology. In this study, qualitative and quantitative data were collected to assess the initial implementation of the home visiting strategy. Qualitative data consisted of individual interviews and focus groups with directors of city health departments, clinic managers, and providers conducting home visits. Quantitative data included clinic, provider, and participant recruitment. City health departments were approached to authorize the participation of primary care clinics in the ViDAs program. Then, clinic directors were invited to approve the implementation of the home visiting program at their health centers. In total, 16 clinics, 42 practitioners, and 185 participants were recruited. A large amount of resources was needed to recruit clinics, providers, and participants. The intervention had low acceptability, low adoption, and a high implementation cost. Initial program implementation experienced several challenges. Identified facilitators and barriers both highlighted the need for community engagement at all levels for the successful implementation of an innovation in Chilean primary care clinics. In addition, this article provides recommendations for practitioners and researchers regarding the conduct of research in community-based settings.

[Contribution of a multimorbidity person-centered care strategy to the Comprehensive Family and Community Healthcare Model in Chile]. / Contribución de una estrategia de atención centrada en la persona con multimorbilidad al Modelo de Atención Integral de Salud Familiar y Comunitario en Chile.

BACKGROUND: The Multimorbidity Person-Centered Care Model allows to customize care according the needs of each person. AIM: To characterize the perception of health teams about the contribution of the Multimorbidity Person-Centered Care Model (MACEP) to the development of the key principles of the Comprehensive Family and Community Health Care Model (MAIS). MATERIAL AND METHODS: A qualitative collaborative study with 35 interviews and the participation of 67 professionals from the primary healthcare network. Content analysis using mixed code system with MAXQDA2020 program. RESULTS: The innovations and complex interventions that positively affect the development and implementation of the essential principles of MAIS were recognized by participants as a contribution of the central elements of MACEP. CONCLUSIONS: This contribution is an opportunity for the expeditious implementation of Family Health principles in the health network. Incorporating the vision of implementers and users, who are part of these changes, is essential. It is necessary to establish, project and evaluate innovations to identify, implement and promote learning at Health Services throughout the country.

Acute Exposure to Crude Oil Induces Epigenetic, Transcriptional and Metabolic Changes in Juvenile Sciaenops ocellatus.

In this study, we report molecular and metabolic responses of Sciaenops ocellatus during an acute oil exposure bioassay (100, 800 and 8000 mg 1-1 of crude oil). The global DNA methylation and expression profiles of key genes of the xenobiotic biotransformation system (cytochrome P450 1A [cyp1a] and glutathione S-tranferase [gst]), oxidative stress system (glutathione peroxidase [gpx], catalase [cat], aldehyde dehydrogenase [aldh]) and reproductive system (vitellogenin [vtg]) were evaluated. At the metabolic level, we evaluated the concentration of four polycyclic aromatic hydrocarbon (PAH) metabolites -hydroxybenzo[a]pyrene, hydroxypyrene, hydroxynaphthalene and hydroxyphenanthrene- in fish bile. The results of this study revealed that fish exposed to crude oil exhibited hypomethylation of DNA, up-regulation of cyp1a and gst and down-regulation of gpx, cat, aldh and vtg and high concentrations of PAH metabolites with respect to the control.

Morphological Alterations in the Early Developmental Stages of Zebrafish (Danio rerio; Hamilton 1822) Induced by Exposure to Polystyrene Microparticles.

Microplastics (MPs) are emerging pollutants of widespread concern in aquatic environments. The aim of this study was to evaluate the negative impact of pristine MPs of polystyrene of 100 µm on embryo and larvae of Danio rerio exposed to three environmentally relevant concentrations of polystyrene (3.84 × 10- 6, 3.84 × 10- 7, and 3.84 × 10- 8 g/mL). The exposure effect was evaluated through the general morphology score, biometrics, and integrated biomarker response version 2 index. No mortality was observed but the anatomical structure of fishes was affected showing pigmentation deficiency and alterations in the head region as the main affected endpoints. The general morphology score and the integrated biomarker response values were highly sensitive to address the effect of the three concentrations of MPs used here. Our results provide solid evidence of the negative impact of 100 µm pristine polystyrene MPs exposure on early stages of zebrafish.

A Cohort Study of the Prognostic Impact of Exon-16 EZH2 Mutations in a Mexican-Mestizo Population of Patients with Diffuse Large B-Cell Lymphoma.

BACKGROUND: Novel prognostic factors in patients with diffuse large B-cell lymphoma (DLBCL) are required in the era of Rituximab. OBJECTIVE: The objective of the study was to study the prognostic impact of exon-16 enhancer-of-zeste homolog-2 (EZH2) mutations in patients with DLBCL. METHODS: In a cohort of patients with DLBCL treated between 2015 and 2017, we analyzed the presence of EZH2 mutations and their association with clinical response (CR), relapse, progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 198 patients were included; of them, 30 (15.2%) had mutations at codon 641, in exon 16 of EZH2. Response was achieved in 151 patients (76.3%), and 43 (21.7%) relapsed or progressed during follow-up. EZH2 mutations were associated with relapse/progression (risk ratio [RR] 1.18; 95% confidence interval [CI] 0.98-1.42; p = 0.031), while a trend for not achieving a complete response was observed (RR: 0.876; 95%CI 0.74-1.038; p = 0.071). Of note, Tyr641His and Tyr641Ser EZH2 mutations were associated with shorter PFS (hazard ratio 3.234; 95% CI 1.149-9.1; p = 0.026). CONCLUSION: The presence of EZH2 mutations was negatively associated with relapse/progression and showed a trend for lack of complete response. Further studies are needed to define better the prognostic significance of these mutations in Mexican-Mestizo DLBCL patients.

Maternal Gestational Diabetes and Type 2 Diabetes During Pregnancy and Risk of Childhood Asthma in Offspring.

OBJECTIVE: To examine maternal preexisting type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) on risk of childhood asthma. STUDY DESIGN: This retrospective birth cohort study included 97 554 singletons born in 2007-2011 within hospitals from a single integrated healthcare system. Children were prospectively followed from age 5 until December 31, 2017, using electronic medical records. Relative risks of childhood asthma associated with maternal diabetes in utero were estimated by hazard ratios using Cox regression adjusting for potential confounders. RESULTS: There were 3119 children (3.2%) who were exposed to preexisting T2D and 9836 (10.1%) to GDM. Among mothers with GDM, 3380 (34.4%) were dispensed antidiabetic medication during pregnancy. During a median of 7.6 years (IQR, 6.3-9.0 years) after birth, 15 125 children (15.5%) were diagnosed with asthma after age 5. Maternal diabetes interacted with maternal asthma history to affect child's asthma risk (P = .05). Among children without maternal asthma (n = 89 487), the adjusted hazard ratios for childhood asthma were 1.21 (95% CI, 1.08-1.36; P < .001) for exposure to T2D, 1.12 (95% CI, 1.01-1.25; P = .04) for GDM requiring antidiabetic medications, and 1.01 (95% CI, 0.93-1.10; P = .82) for GDM not requiring medications compared with no diabetes during pregnancy. The corresponding hazard ratios were 1.53 (95% CI, 1.19-1.96; P < .001), 1.11 (95% CI, 0.65-1.46; P = .44), and 0.84 (95% CI, 0.66-1.08; P = .17) among children without maternal asthma (n = 8067). Gestational age at GDM diagnosis was not associated with childhood asthma (P = .27). CONCLUSIONS: The risk of childhood asthma was predominately observed for exposure to preexisting T2D, small for GDM requiring medication, and not increased for GDM not requiring medication during pregnancy, compared with no diabetes during pregnancy.

Linearolactone and Kaempferol Disrupt the Actin Cytoskeleton in Entamoeba histolytica: Inhibition of Amoebic Liver Abscess Development.

Linearolactone (1) and kaempferol (2) have amebicidal activity in in vitro studies. The type of cell death induced by 1 and 2 and their effects on the virulence of E. histolytica were analyzed by transmission and confocal electron microscopy, reactive oxygen species (ROS) production, and apoptosis, detected by flow cytometry with dichlorofluorescein 2',7'-diacetate and annexin-V binding, respectively, and confirmed by TUNEL. The interaction of 1 and 2 with actin was analyzed by docking, and the in vivo amoebicidal activity was established with the Mesocricetus auratus model; amebic liver abscess (ALA) development was evaluated by magnetic resonance (MR) and validated post mortem. In vitro, compounds 1 and 2 caused chromatin condensation, intracellular ROS, and loss of actin structures. Coupling analysis showed that they bind to the allosteric and catalytic sites of actin with binding energies of -11.30 and -8.45 kcal/mol, respectively. Treatments with 1 and 2 induced a decrease in ALA formation without toxic effects on the liver and kidney. Thus, compound 1, but not 2, was able to induce apoptosis-like effects in E. histolytica trophozoites by intracellular production of ROS that affected the actin cytoskeleton structuration. In vivo, compound 1 was more active than compound 2 to reduce the development of ALA.

Breastfeeding Persistence at 6 Months: Trends and Disparities from 2008 to 2015.

OBJECTIVE: To assess trends and disparities in breastfeeding by maternal characteristics (race and ethnicity, age at delivery, obesity, parity, and level of education) and the relative importance among these for breastfeeding at 6 months. STUDY DESIGN: This retrospective birth cohort study included 195 861 live singleton children born at 32-42 weeks of gestation from 2008 to 2015 within a single integrated healthcare system. All children had healthcare coverage during the first year of life. Maternal characteristics and breastfeeding status at 6 months of age were extracted from electronic medical records. Trends over time of any breastfeeding ≥6 months were evaluated for the 5 maternal characteristics. Robust Poisson regression models were used to estimate breastfeeding rate differences associated with each of the 5 characteristics. The relative importance among them associated with breastfeeding ≥6 months was assessed by comparing model quasi-likelihood information criteria. RESULTS: Rates of breastfeeding ≥6 months significantly increased overall and among groups defined by the maternal characteristics. However, there was little improvement over time in closing disparities associated with maternal race and ethnicity, age at delivery, prepregnancy obesity status, and level of education. Education level contributed to the greatest disparity in breastfeeding ≥6 months. Maternal age was the second factor, followed by prepregnancy obesity and maternal race and ethnicity. CONCLUSIONS: Breastfeeding outreach programs focusing on women with less than a college education, women <25 years old, and women from non-Hispanic black or Hispanic race and ethnicity may help to reduce disparities and improve breastfeeding persistence rates within integrated healthcare systems.

Teaching the Social Determinants of Health in Undergraduate Medical Education: a Scoping Review.

BACKGROUND: To provide optimal care, medical students should understand that the social determinants of health (SDH) impact their patients' well-being. Those charged with teaching SDH to future physicians, however, face a paucity of curricular guidance. OBJECTIVE: This review's objective is to map key characteristics from publications about teaching SDH to students in undergraduate medical education (UME). METHODS: In 2016, the authors searched PubMed, Embase, Web of Science, the Cochrane and ERIC databases, bibliographies, and MedEdPORTAL for articles published between January 2010 and November 2016. Four reviewers screened articles for eligibility then extracted and analyzed data descriptively. Scoping review methodology was used to map key concepts and curricular logistics as well as educator and student characteristics. RESULTS: The authors screened 3571 unique articles of which 22 were included in the final review. Many articles focused on community engagement (15). Experiential learning was a common instructional strategy (17) and typically took the form of community or clinic-based learning. Nearly half (10) of the manuscripts described school-wide curricula, of which only three spanned a full year. The majority of assessment was self-reported (20) and often related to affective change. Few studies objectively assessed learner outcomes (2). CONCLUSIONS: The abundance of initial articles screened highlights the growing interest in SDH in medical education. The small number of selected articles with sufficient detail for abstraction demonstrates limited SDH curricular dissemination. A lack of accepted tools or practices that limit development of robust learner or program evaluation was noted. Future research should focus on identifying and evaluating effective instructional and assessment methodologies to address this gap, exploring additional innovative teaching frameworks, and examining the specific contexts and characteristics of marginalized and underserved populations and their coverage in medical education.