Swordtail fish hybrids reveal that genome evolution is surprisingly predictable after initial hybridization.

Over the past 2 decades, biologists have come to appreciate that hybridization, or genetic exchange between distinct lineages, is remarkably common-not just in particular lineages but in taxonomic groups across the tree of life. As a result, the genomes of many modern species harbor regions inherited from related species. This observation has raised fundamental questions about the degree to which the genomic outcomes of hybridization are repeatable and the degree to which natural selection drives such repeatability. However, a lack of appropriate systems to answer these questions has limited empirical progress in this area. Here, we leverage independently formed hybrid populations between the swordtail fish Xiphophorus birchmanni and X. cortezi to address this fundamental question. We find that local ancestry in one hybrid population is remarkably predictive of local ancestry in another, demographically independent hybrid population. Applying newly developed methods, we can attribute much of this repeatability to strong selection in the earliest generations after initial hybridization. We complement these analyses with time-series data that demonstrates that ancestry at regions under selection has remained stable over the past approximately 40 generations of evolution. Finally, we compare our results to the well-studied X. birchmanni × X. malinche hybrid populations and conclude that deeper evolutionary divergence has resulted in stronger selection and higher repeatability in patterns of local ancestry in hybrids between X. birchmanni and X. cortezi.

2-iodohexadecanal induces autophagy during goiter involution.

BACKGROUND: Iodine plays an important role in thyroid physiology and biochemistry. The thyroid is capable of producing different iodolipids such as 2-iodohexadecanal (2-IHDA). Data from different laboratories have shown that 2-IHDA inhibits several thyroid parameters and it has been postulated as intermediary on the action of iodide function. OBJECTIVE: To explore different mechanisms involved during the involution of the hyperplastic thyroid gland of Wistar rats towards normality induced by 2-IHDA. METHODS: Goiter was induced by the administration of MMI for 10 days, then the treatment was discontinued and Wistar rats were injected with 2-IHDA or KI. RESULTS: During involution, 2-IHDA treatment reduced PCNA expression compared to spontaneous involution. KI treatment caused an increase of Caspase-3 activity and TUNEL-positive cells. In contrast, 2-IHDA failed to alter this value but induced an increase of LC3B expression. KI but not 2-IHDA led to an increase in peroxides levels, catalase and glutathione peroxidase activity. CONCLUSIONS: We demonstrated that 2-IHDA, in contrast to iodide, did not lead to an increase in oxidative stress or apoptosis induction, indicating that the involution triggered by 2-IHDA in Wistar rats, is primarily due to the inhibition of cell proliferation and the induction of autophagy.

Pregnancy homocysteine and cobalamin status predict childhood metabolic health in the offspring.

BACKGROUND: Inadequate pregnancy cobalamin status has been associated with adverse offspring metabolic health in Indian and Nepalese studies. Studies of pregnancy cobalamin status and mid-childhood health outside of Asia are scarce. METHODS: Associations between pregnancy fasting plasma total homocysteine (tHcy), cobalamin status (plasma cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA)) and mid-childhood metabolic score (MetSco) ((including fat mass index (zFMI), homeostatic model assessment of insulin resistance (zHOMA-IR) and dyslipidemia (zTG - zHDLc)/2) z-scores)) were investigated in a prospective study of 293 mother-child dyads. RESULTS: Highest versus low-mid pregnancy tHcy tertile was associated with higher mid-childhood MetSco, specifically with higher child zFMI. Stratifying by sex, the maternal tHcy-child MetSco association was limited to boys and confirmed for zFMI and zHOMA-IR. The maternal tHcy-child zFMI association was not mediated by birth weight z-score. First trimester plasma cobalamin was not associated with child outcomes, but other indicators of cobalamin status were. Lowest versus mid-high plasma holoTC tertile was associated with MetSco (specifically zFMI and zHOMA-IR) and highest versus low-mid plasma MMA tertile with higher MetSco and dyslipidemia in boys. CONCLUSIONS: Moderately elevated pregnancy tHcy and low cobalamin status were associated with mid-childhood metabolic score in boys. The pregnancy tHcy-child zFMI association was not mediated by birth weight. IMPACT: Fasting plasma total homocysteine (tHcy) during pregnancy and low cobalamin status during early pregnancy are associated with mid-childhood metabolic score and its components in the offspring. These findings were only significant in male offspring. The study provides new evidence that impaired one carbon metabolism during pregnancy is associated with negative health outcomes in the offspring, in a population with low prevalence of cobalamin deficiency. The maternal-offspring associations were observed in the functional markers of cobalamin status (holotranscobalamin and methylmalonic acid) and tHcy, not with plasma cobalamin concentration. Screening for low pregnancy cobalamin status should be considered.

The challenge of sustainability: Long-term results from the Fifty-Fifty peer group-based intervention in cardiovascular risk factors.

BACKGROUND: The Fifty-Fifty trial demonstrated that a peer-group-based intervention was able to improve healthy behaviors in individuals with cardiovascular (CV) risk factors immediately post-intervention. OBJECTIVES: To determine the long-term sustainability of a one-year peer-group-based intervention focused on CV health and behavior. METHODS: A total of 543 adults aged 25 to 50 years with at least 1 CV risk factor were screened and recruited, received initial training through workshops, and were then randomized 1:1 to a peer-group-based intervention group (IG) or a self-management control group (CG) for 12 months. At a median of 52 months from baseline, 321 participants were re-assessed (~60% retention). The primary outcome was the mean change in a composite health score related to blood pressure, exercise, weight, alimentation, and tobacco use (Fuster-BEWAT score [FBS], range 0-15). Intervention effects were assessed using linear-mixed effects models. RESULTS: The mean age of retained participants was 48.0 years (SD: 5.4), and 73% were female. Consistent with previous results, the change of overall FBS was significantly greater in the IG than in the CG at 12-month follow-up (between-group difference, 0.60 points; 95% CI, 0.08-1.12; P = .025). Assessment of long-term sustainability (52-month follow-up) showed that there were no between-group differences in the mean overall FBS (IG mean score, 8.52; 95% CI, 7.97-9.07 vs CG mean score, 8.51; 95% CI, 7.93-9.10; P = .972) or in the change of overall FBS from screening (IG mean change, 0.64; 95% CI, 0.00-1.28; CG mean change, 0.46; 95% CI, -0.20-1.12; P = .497). CONCLUSIONS: A one-year peer-group-based intervention showed favorable results at immediate post-intervention but did not demonstrate significant differences between the IG and CG at 52 months. Combination of an initial training period (workshops) with the maintenance of peer-support groups or other re-intervention strategies may be required to achieve sustained effects on healthy behaviors. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02367963. Registered (https://clinicaltrials.gov/show/NCT02367963).

Characteristics associated with time-to-treatment initiation for chronic Hepatitis C with new direct acting antivirals.

BACKGROUND: Interferon-free direct-acting antivirals (DAAs) were introduced in 2013 and have transformed the therapeutic landscape for chronic Hepatitis C (HCV). Although treatment is recommended for almost all persons infected with HCV, clinical and psychosocial factors may affect treatment initiation. METHODS: We conducted an observational cohort study of Kaiser Permanente Mid-Atlantic States members with prevalent or incident HCV infection identified from November 2013 through May 2016 to identify predictors of DAA initiation. We used Cox regression with time-dependent covariates to compare time to treatment by clinical, demographic and societal factors. RESULTS: Of 2962 patients eligible for DAA therapy, 33% (n = 980) initiated treatment over the study period. The majority of patients (97%) were persistent with therapy and most (95%) tested for sustained virologic response (SVR) achieved cure. We found no effect of race, insurance type or fibrosis stage on treatment initiation. We observed that patients aged 41-60 years (aHR: 2.014, 95% CI: 1.12, 3.60) and 61-80 years (aHR: 2.08, 95% CI: 1.15-3.75) had higher treatment rates compared to younger patients. Incident cases were more likely to be treated than prevalent cases (aHR: 3.05, 95% CI: 2.40-3.89). Patients with a history of substance use disorder (SUD) were less likely (aHR: 0.805, 95% CI: 0.680, 0.953) to be treated. CONCLUSIONS: In the first 3 years of DAA availability, one-third of patients with HCV initiated therapy, and almost all were persistent and achieved cure. While curative, DAAs remain highly priced. Triaging for non-clinical reasons or perceptions about patients will stall our ability to eradicate HCV.

Ursodeoxycholic Acid Treatment Preferentially Improves Overall Survival Among African Americans With Primary Biliary Cholangitis.

BACKGROUND: We used data from the Fibrotic Liver Disease Consortium to evaluate the impact of ursodeoxycholic acid (UDCA) treatment across race/ethnicity, gender, and clinical status among patients with primary biliary cholangitis. METHODS: Data were collected from "index date" (baseline) through December 31, 2016. Inverse Probability of Treatment Weighting was used to adjust for UDCA treatment selection bias. Cox regression, focusing on UDCA-by-risk factor interactions, was used to assess the association between treatment and mortality and liver transplant/death. RESULTS: Among 4,238 patients with primary biliary cholangitis (13% men; 8% African American, 7% Asian American/American Indian/Pacific Island [ASINPI]; 21% Hispanic), 78% had ever received UDCA. The final multivariable model for mortality retained age, household income, comorbidity score, total bilirubin, albumin, alkaline phosphatase, and interactions of UDCA with race, gender, and aspartate aminotransferase/alanine aminotransferase ≥1.1. Among untreated patients, African Americans and ASINPIs had higher mortality than whites (adjusted hazard ratio [aHR] = 1.34, 95% confidence interval [CI] 1.08-1.67 and aHR = 1.40, 95% CI 1.11-1.76, respectively). Among treated patients, this relationship was reversed (aHR = 0.67, 95% CI 0.51-0.86 and aHR = 0.88, 95% CI 0.67-1.16). Patterns were similar for liver transplant/death. UDCA reduced the risk of liver transplant/death in all patient groups and mortality across all groups except white women with aspartate aminotransferase/alanine aminotransferase ≥1.1. As compared to patients with low-normal bilirubin at baseline (≤0.4 mg/dL), those with high-normal (1.0 > 0.7) and mid-normal bilirubin (0.7 > 0.4) had significantly higher liver transplant/death and all-cause mortality. DISCUSSION: African American and ASINPI patients who did not receive UDCA had significantly higher mortality than white patients. Among African Americans, treatment was associated with significantly lower mortality. Regardless of UDCA treatment, higher baseline bilirubin, even within the normal range, was associated with increased mortality and liver transplant/death compared with low-normal levels.

Isolation and characterization of 13 microsatellite loci for the Neotropical otter, Lontra longicaudis, by next generation sequencing.

The Neotropical otter, Lontra longicaudis, is an ecologically important species for freshwater ecosystems that is threatened due to habitat destruction and hunting. However, there is limited information regarding the population sizes, genetic diversity, genetic structure and gene flow of the species, which is crucial for the elaboration of conservation plans. The aim of this study was to isolate and characterize microsatellites for L. longicaudis, using Illumina paired-end-sequencing. Initial amplification tests were performed in 48 loci, out of which, 13 yielded high-quality PCR products and thus were further evaluated. Genetic diversity and discrimination power of the 13 microsatellite loci was assessed using 19 non-invasive samples collected in the Jamapa basin in Veracruz, Mexico and blood samples from six captive individuals. All loci were polymorphic, the number of alleles per locus ranged from 4 to 10, the observed heterozygosity from 0.21 to 0.69, and the expected heterozygosity from 0.55 to 0.82. The combined set of 13 microsatellites showed a high power for discriminating among individuals (probability of identity PID = 1.551 × 10-16) and among siblings (probability of identity of siblings PIDSIB = 3.349 × 10-06). A combination of nine loci are sufficient to discriminate among siblings with high confidence (PIDSIB < 0.0001). The new set of microsatellites for the Neotropical otter reported here will provide a useful genetic tool to assess population genetic patterns and ecological parameters of the species.

Rationale and design of the SI! Program for health promotion in elementary students aged 6 to 11 years: A cluster randomized trial.

Unhealthy habits in children are increasing at an alarming rate. The school provides a promising setting for effective preventive strategies to improve children's lifestyle behaviors. The SI! Program is a multilevel multicomponent school-based educational intervention aimed at all stages of compulsory education in Spain. Here, we present the design of the SI! Program for Elementary School cluster-randomized controlled trial, targeting children aged 6 to 11 years. This trial aims to study the impact of different timings and intensities of exposure to SI! Program activities on elementary school children and their immediate environment (parents/caregivers, teachers, and school). The trial includes 1770 children from 48 public elementary schools in Madrid (Spain), together with their parents and teachers. Schools and their children were randomly assigned to the intervention group (the SI! curriculum-based educational program over 3 or 6 academic years) or to the control group (standard curriculum). The primary outcomes are the change from baseline at 3-year and 6-year follow-up in children's scores for knowledge, attitudes, and habits (KAH) and health factors (blood pressure, height, weight, waist circumference, and skinfold thickness). Secondary outcomes include 3-year and 6-year changes from baseline in lifestyle questionnaire scores for parents/caregivers and teachers, and in the school environment questionnaire. The overarching goal of the SI! Program is to provide an effective and sustainable health promotion program for the adoption of healthy behaviors in children. The present trial will address the impact and the optimal timing and duration of this educational intervention in the elementary school setting.

Rationale and design of the school-based SI! Program to face obesity and promote health among Spanish adolescents: A cluster-randomized controlled trial.

Unhealthy habits in adolescents are increasing at an alarming rate. The school offers a promising environment in which to implement effective preventive strategies to improve adolescents' lifestyle behaviors. The SI! Program is a multilevel multicomponent school-based health-promotion intervention aimed at all stages of compulsory education in Spain. We present the study design of the SI! Program for Secondary Schools, targeting adolescents aged 12 to 16 years. AIM: The main goal of this study is to evaluate the impact of the SI! Program educational intervention on adolescent lifestyle behaviors and health parameters. METHODS: The study was designed as a cluster-randomized controlled intervention trial and enrolled 1326 adolescents from 24 public secondary schools in Spain, together with their parents/caregivers. Schools and their students were randomly assigned to the intervention group (the SI! curriculum-based educational program over 2 or 4 academic years) or to the control group (usual curriculum). The primary endpoint will be the change from baseline at 2-year and 4-year follow-up in the composite Ideal Cardiovascular Health (ICH) score, consisting of four health behaviors (body mass index, dietary habits, physical activity, and smoking) and three health factors (blood pressure, total cholesterol, and glucose). Secondary endpoints will include 2-year and 4-year changes from baseline in ICH score subcomponents, the Fuster-BEWAT health scale, adiposity markers (waist circumference and body composition), polyphenol and carotenoid intake, and emotion management. DISCUSSION: The overarching goal of the SI! Program is to instill healthy behaviors in children and adolescents that can be sustained into adulthood. The SI! Program for Secondary School is a comprehensive health-promotion intervention targeting 12-16-year-old adolescents and their immediate environment. The present study addresses the optimal timing and impact of the educational intervention on health in adolescence.

Accuracy of electronic health record data for the diagnosis of chronic obstructive pulmonary disease in persons living with HIV and uninfected persons.

PURPOSE: No prior studies have addressed the performance of electronic health record (EHR) data to diagnose chronic obstructive pulmonary disease (COPD) in people living with HIV (PLWH), in whom COPD could be more likely to be underdiagnosed or misdiagnosed, given the higher frequency of respiratory symptoms and smoking compared with HIV-uninfected (uninfected) persons. METHODS: We determined whether EHR data could improve accuracy of ICD-9 codes to define COPD when compared with spirometry in PLWH vs uninfected, and quantified level of discrimination using the area under the receiver-operating curve (AUC). The development cohort consisted of 350 participants who completed research spirometry in the Examinations of HIV Associated Lung Emphysema (EXHALE) study, a pulmonary substudy of the Veterans Aging Cohort Study. Results were externally validated in 294 PLWH who performed spirometry for clinical indications from the University of Washington (UW) site of the Centers for AIDS Research Network of Integrated Clinical Systems cohort. RESULTS: ICD-9 codes performed similarly by HIV status, but alone were poor at discriminating cases from non-cases of COPD when compared with spirometry (AUC 0.633 in EXHALE; 0.651 in the UW cohort). However, algorithms that combined ICD-9 codes with other clinical variables available in the EHR-age, smoking, and COPD inhalers-improved discrimination and performed similarly in EXHALE (AUC 0.771) and UW (AUC 0.734). CONCLUSIONS: These data support that EHR data in combination with ICD-9 codes have moderately good accuracy to identify COPD when spirometry data are not available, and perform similarly in PLWH and uninfected individuals.

Factors Associated With Prevalence and Treatment of Primary Biliary Cholangitis in United States Health Systems.

BACKGROUND & AIMS: Reported prevalence of primary biliary cholangitis (PBC) varies widely. Demographic features and treatment patterns are not well characterized in the United States (US). We analyzed data from the Fibrotic Liver Disease (FOLD) Consortium, drawn from 11 geographically diverse health systems, to investigate epidemiologic factors and treatment of PBC in the US. METHODS: We developed a validated electronic health record-based classification model to identify patients with PBC in the FOLD database from 2003 through 2014. We used multivariable modeling to assess the effects of factors associated with PBC prevalence and treatment with ursodeoxycholic acid (UDCA). RESULTS: We identified 4241 PBC cases among over 14.5 million patients in FOLD health systems; median follow-up was 5 years. Accuracy of the classification model was excellent, with an area under the receiver operating characteristic curve value of 93%, 94% sensitivity, and 87% specificity. The average patient age at diagnosis was 60 years; 21% were Hispanic, 8% were African American, and 7% were Asian American/American Indian/Pacific Islander. Half of the cohort (49%) had elevated levels of alkaline phosphatase, and overall, 70% were treated with UDCA. The estimated 12-year prevalence of PBC was 29.3 per 100,000 persons. Adjusted prevalence values were highest among women (42.8 per 100,000), White patients (29.6 per 100,000), and patients 60-70 years old (44.7 per 100,000). Prevalence was significantly lower among men and African Americans (10.7 and 19.7 per 100,000, respectively) than women and whites; men and African Americans were also less likely to receive UDCA treatment (odds ratios, 0.6 and 0.5, respectively; P < .05). CONCLUSIONS: In an analysis of a large cohort of patients with PBC receiving routine clinical care, we observed significant differences in PBC prevalence and treatment by gender, race, and age.

Increasing Prevalence of Primary Biliary Cholangitis and Reduced Mortality With Treatment.

BACKGROUND & AIMS: There are few data from longitudinal studies of trends in primary biliary cholangitis (PBC) among patients under routine clinical care in the United States. We collected data from the Fibrotic Liver Disease consortium to investigate changes in the incidence and prevalence of PBC and the effects of patient demographics, clinical features, and treatment on mortality. METHODS: We collected demographic and clinical data for the general patient population as well as PBC patients receiving care from 11 health systems in different regions of the United States (Northeast, Midwest, Northwest, and South) from January 1, 2003, through December 31, 2014. Annual percentage changes in PBC prevalence and incidence were estimated using join-point Poisson regression. Differences based on race, age, and gender were calculated with rate ratios. All-cause mortality was estimated using Cox regression with adjustment for patient characteristics and treatment with ursodeoxycholic acid (UDCA). Propensity scores were used to adjust for treatment selection bias. Analyses were adjusted by geographic regions. RESULTS: In our racially diverse cohort of 3488 patients with PBC (21% Hispanic, 8% African American, 7% Asian American), 70% had ever received UDCA. From 2006 through 2014, the prevalence of PBC increased from 21.7 to 39.2 per 100,000 persons. Adjusted annual percentage changes in prevalence differed among age groups (≤40 y, 41-50 y, 51-60 y, 61-70 y, and >70 y), ranging from 3.0% to 7.5% (P < .05). Incidence did not change significantly during the study period (4.2 vs 4.3 per 100,000 person-years in 2006 and 2014, respectively; P = .98). Ratios of prevalence for women vs men (3.9:1) and incidence for women vs men (3.2:1) were consistent over the study period. Among African Americans, the prevalence of PBC increased from 16.9 to 30.8 per 100,000 during the study period, and annual incidence ranged from 2.6 to 6.6 per 100,000 person-years. In adjusted analyses, an increased level of alkaline phosphatase at baseline was associated with significantly higher mortality (adjusted hazard ratios [aHR], 1.24; 95% CI, 1.04-1.48 for patients with levels 1-2 times the upper limit of normal and aHR, 2.27; 95% CI, 1.88-2.73 for patients with levels more than 3 times the upper limit of normal). UDCA treatment was associated with significantly reduced mortality (aHR, 0.57; 95% CI, 0.52-0.64). CONCLUSIONS: In an analysis of data from patients receiving routine clinical care in Fibrotic Liver Disease Consortium health systems, we found that the prevalence of PBC increased from 2004 through 2014, despite steady incidence. Patient demographic and clinical characteristics, as well as UDCA treatment, affected mortality.

Sensitive and non-invasive method for the in vivo analysis of membrane permeability in small animals.

Tissue membranes are boundaries that isolate organs or cavities in the body. These semi-permeable membranes are responsible for passive protection that acts through the regulation of nutrient absorption, secretion and filtration of small molecules. These functions could be altered as a consequence of inflammation or trauma, which in turn could lead to changes in permeability, allowing the entrance of toxins, antigens, proteins or facilitating the spread of tumors. Membrane permeability therefore plays an important role in numerous diseases. However, current experimental techniques that are available to quantify membrane permeability in small animals have limited precision and temporal specificity. Improvements in such measurements would lead to a deeper understanding of disease pathogenesis and this may accelerate the development of specific therapies. The study reported here concerns the efficacy of a novel, non-invasive imaging analysis-based measurement method that significantly improves the quantification of tissue membrane permeability in small animals, while at the same time mitigating the adverse effects experienced by the animals under study.

HIV Provider Documentation and Actions Following Patient Reports of At-risk Behaviors and Conditions When Identified by a Web-Based Point-of-Care Assessment.

We compared same-day provider medical record documentation and interventions addressing depression and risk behaviors before and after delivering point-of-care patient-reported outcomes (PROs) feedback for patients who self-reported clinically relevant levels of depression or risk behaviors. During the study period (1 January 2006-15 October 2010), 2289 PRO assessments were completed by HIV-infected patients. Comparing the 8 months before versus after feedback implementation, providers were more likely to document depression (74% before vs. 87% after feedback, p = 0.02) in patients with moderate-to-severe depression (n = 317 assessments), at-risk alcohol use (41 vs. 64%, p = 0.04, n = 155) and substance use (60 vs. 80%, p = 0.004, n = 212). Providers were less likely to incorrectly document good adherence among patients with inadequate adherence after feedback (42 vs. 24%, p = 0.02, n = 205). While PRO feedback of depression and adherence were followed by increased provider intervention, other domains were not. Further investigation of factors associated with the gap between awareness and intervention are needed in order to bridge this divide.

The Role of Current and Historical Alcohol Use in Hepatic Fibrosis Among HIV-Infected Individuals.

We examined risk factors for advanced hepatic fibrosis [fibrosis-4 (FIB)-4 >3.25] including both current alcohol use and a diagnosis of alcohol use disorder among HIV-infected patients. Of the 12,849 patients in our study, 2133 (17%) reported current hazardous drinking by AUDIT-C, 2321 (18%) had a diagnosis of alcohol use disorder, 2376 (18%) were co-infected with chronic hepatitis C virus (HCV); 596 (5%) had high FIB-4 scores >3.25 as did 364 (15%) of HIV/HCV coinfected patients. In multivariable analysis, HCV (adjusted odds ratio (aOR) 6.3, 95% confidence interval (CI) 5.2-7.5), chronic hepatitis B (aOR 2.0, 95% CI 1.5-2.8), diabetes (aOR 2.3, 95% CI 1.8-2.9), current CD4 <200 cells/mm3 (aOR 5.4, 95% CI 4.2-6.9) and HIV RNA >500 copies/mL (aOR 1.3, 95% CI 1.0-1.6) were significantly associated with advanced fibrosis. A diagnosis of an alcohol use disorder (aOR 1.9, 95% CI 1.6-2.3) rather than report of current hazardous alcohol use was associated with high FIB-4. However, among HIV/HCV coinfected patients, both current hazardous drinkers (aOR 1.6, 95% CI 1.1-2.4) and current non-drinkers (aOR 1.6, 95% CI 1.2-2.0) were more likely than non-hazardous drinkers to have high FIB-4, with the latter potentially reflecting the impact of sick abstainers. These findings highlight the importance of using a longitudinal measure of alcohol exposure when evaluating the impact of alcohol on liver disease and associated outcomes.

Streamlining Screening to Treatment: The Hepatitis C Cascade of Care at Kaiser Permanente Mid-Atlantic States.

Hepatitis C virus (HCV) screening is recommended for patients at risk and/or born during 1945-1965, but screening gaps persist. This new program screens target populations and enhances care linkage for chronically HCV-infected patients. Kaiser Permanente Mid-Atlantic States created a comprehensive HCV screening pathway, supported by a HCV care coordinator. The testing pathway includes HCV antibody (Ab), automatic HCV RNA for Ab-positive patients, coinfection and liver health tests, vibration-controlled transient elastography (VCTE), and a physician referral. A total of 11 200 patients were screened; 3.25% were HCV Ab positive, and 100% of Ab-positive patients received HCV RNA testing. Of HCV Ab-positive patients, 75.9% had chronic HCV, of which 80.8% underwent VCTE. HCV diagnosis was communicated to 94% of patients, and 70.9% had HCV documented in the electronic health record. The pathway shows promise in closing gaps, including improving HCV RNA testing, communicating diagnoses, and assessing liver fibrosis. Improved testing and linkage could increase curative treatment access.

Genetic divergence in the common bush-tanager Chlorospingus ophthalmicus (Aves: Emberizidae) throughout Mexican cloud forests: The role of geography, ecology and Pleistocene climatic fluctuations.

By integrating mitochondrial DNA (mtDNA), microsatellites and ecological niche modelling (ENM), we investigated the phylogeography of Mexican populations of the common bush-tanager Chlorospingus ophthalmicus to examine the relative role of geographical and ecological features, as well as Pleistocene climatic oscillations in driving the diversification. We sequenced mtDNA of individuals collected throughout the species range in Mexico and genotyped them at seven microsatellite loci. Phylogeographic, population genetics and coalescent methods were used to assess patterns of genetic structure, gene flow and demographic history. ENM was used to infer contractions and expansions at different time periods as well as differences in climatic conditions among lineages. The retrieved mitochondrial and microsatellite groups correspond with the fragmented cloud forest distribution in mountain ranges and morphotectonic provinces. Differing climatic conditions between mountain ranges were detected, and palaeodistribution modelling as well as demographic history analyses, indicated recent population expansions throughout the Sierra Madre Oriental (SMO). The marked genetic structure of C. ophthalmicus was promoted by the presence of ecological and geographical barriers that restricted the movement of individuals among mountain ranges. The SMO was mainly affected by Pleistocene climatic oscillations, with the moist forests model best fitting the displayed genetic patterns of populations in this mountain range.

A Broken Heart: Takotsubo Cardiomyopathy.

This case illustrates the unusual presentation of Takotsubo cardiomyopathy in an elderly male patient with characteristic chest pain and dyspnea associated with electrocardiographic changes of biphasic T wave inversions and QT-interval prolongation on anterior segment, mimicking acute coronary syndrome. Takotsubo cardiomyopathy is a transient systolic dysfunction of the apical and/or mid and anterior segments of left ventricle most frequently seen in post- menopausal women, up to 80 to 100% of cases. Often there is a history of a recent (within the previous two months) episode of severe emotional or physical stress associated with the event.

High-Risk Congenital Heart Disease in Pregnancy.

High-risk congenital heart disease (CHD) in pregnancy presents a complex clinical challenge. With improved medical care and increased survival rates, a growing population of adults with complex CHD are surviving to adulthood, including women of reproductive age. This chapter focuses on risk stratification and management of pregnant women with high-risk CHD, emphasizing the importance of considering both anatomical and physiological complexity. Maternal physiological changes, such as blood volume increase, cardiac output changes, and alterations in vascular resistance, can significantly impact high-risk CHD patients. Management of high-risk CHD in pregnancy necessitates a multidisciplinary approach and individualized care.

Selenium bioavailability modulates the sensitivity of thyroid cells to iodide excess.

INTRODUCTION: Iodide is an essential micronutrient for the synthesis of thyroid hormones and its imbalance is involved in the origin of different thyroid pathological processes. Selenium (Se) is another essential trace element that contributes to thyroid preservation through the control of the redox homeostasis. Different studies have demonstrated that sodium-iodide-symporter (NIS) is downregulated in the presence of iodide excess and Se supplementation reverses this effect. We also demonstrated that NOX4-derived ROS are involved in NIS repression induced by iodide excess. The aim of this study was to investigate how Se bioavailability is decisive in the sensitivity to iodide excess on a differentiated rat thyroid cell line (FRTL-5). RESULTS: We demonstrated that siRNA-mediated silencing of Nox4 suppressed AKT phosphorylation induced by iodide excess. Iodide increases TGF-ß1 mRNA expression, AKT phosphorylation, ROS levels and decreases GPX1 and TXRND1 mRNAs expression while Se reversed these effects. Furthermore, iodide induced Nrf2 transcriptional activity only in Se-supplemented cultures, suggesting that Se positively influences Nrf2 activation and selenoenzyme response in FRTL-5. Se, also inhibited NF-κB phosphorylation induced by iodide excess. In addition, we found that iodide excess decreased total phosphatase activity and PTP1B and PTEN mRNA expression. Se supply restored only PTEN mRNA expression. Finally, we studied the 2-α-iodohexadecanal (2-IHD) effects since it has been proposed as intermediary of iodide action on thyroid autoregulation. 2-IHD stimulated PI3K/AKT activity and reduced NIS expression by a ROS-independent mechanism. Also, we found that 2-IHD increased TGF-ß1 mRNA and TGF-ß inhibitor (SB431542) reverses the 2-IHD inhibitory effect on NIS mRNA expression, suggesting that TGF-ß1 signaling pathway could be involved. Although Se reduced 2-IHD-induced TGFB1 levels, it could not reverse its inhibitory effect on NIS expression. CONCLUSION: Our study suggests that Se bioavailability may improve the expression of antioxidant genes through the activation of Nrf2, interfere in PI3K/AKT signaling and NIS expression by redox modulation.