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Background: Community-based interventions are needed to reduce the burden of childhood obesity.Purpose: To evaluate the impact of a multi-level promotora-based (Community Health Advisor) intervention to promote healthy eating and physical activity and prevent excess weight gain among Latino children.Methods: Thirteen elementary schools were randomized to one of four intervention conditions: individual/family level (Family-only), school/community level (Community-only), combined (Family + Community), or a measurement-only condition. Participants were 808 Latino parents and their children enrolled in kindergarten through 2(nd) grade. Measures included parent and child body mass index (BMI) and a self-administered parent survey that assessed several parent and child behaviors.Results: There were no significant intervention effects on children's BMI z-score. The family intervention changed several obesity-related child behaviors (e.g., fruit/vegetable consumption) and these were mediated by changes in parenting variables (e.g., parent monitoring).Conclusion: A promotora-based behavioral intervention was efficacious at changing parental factors and child obesity-related health behaviors. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate (a) the relation between frequency of church attendance, self-rated health, and health behaviors controlling for potential confounders and (b) the influence of acculturation on church attendance and health behaviors. METHODS: Physical activity and dietary patterns, demographics, and acculturation levels were compared among Latinas who attended church frequently, infrequently, and not at all. RESULTS: Church attendance was independently and positively associated with healthier dietary and physical activity behaviors, but not with self-rated health. Acculturation attenuated the relation between physical activity and church attendance. CONCLUSION: Latinas' health behaviors and self-rated health may be related to other variables that explain the salutary effects of church attendance. [ABSTRACT FROM AUTHOR]

Participants (N = 357) were randomly assigned to 1 of 3 conditions: lay health advisor (promotora) plus tailored print materials, tailored print materials only (tailored), or off-the-shelf print materials (control). The primary outcomes were calories from fat and daily grams of fiber. Secondary outcomes included total energy intake, total and saturated fat intake, and total carbohydrates. Adjusted for baseline values, calories from fat were 29%, 30%, and 30% for the promotora, tailored, and control conditions, respectively, and grams of fiber consumed were 16 g, 17 g, and 16 g. Significant Condition X Time interactions were not observed between baseline and 12-weeks postintervention. The LHA condition achieved significantly lower levels of energy intake, total fat and saturated fat, and total carbohydrates. The relative superiority of the promotora condition may derive from the personal touch achieved in the face-to-face interactions or from the women's use of print materials under the promotora's guidance. ((c) 2005 APA, all rights reserved). [ABSTRACT FROM AUTHOR]

Raj Padwal,1 Mohammad Rashead,2 Jonathan Snider,2 Louise Morrin,2 Agnes Lehman,2 Norm RC Campbell3 1Department of Medicine, Alberta Diabetes Institute and Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, 2Cardiovascular Health and Stroke Strategic Clinical Network of Alberta Health Services, 3Department of Medicine, Community Health Sciences and Physiology and Pharmacology, O’Brien Institute of Public Health and Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, AB, Canada Background: Established cardiovascular risk factors are highly prevalent and contribute substantially to cardiovascular morbidity and mortality because they remain uncontrolled in many Canadians. Worksite-based cardiovascular risk factor screening and management represent a largely untapped strategy for optimizing risk factor control.Methods: In a 2-phase collaborative demonstration project between Alberta Health Services (AHS) and the Alberta Newsprint Company (ANC), ANC employees were offered cardiovascular risk factor screening and management. Screening was performed at the worksite by AHS nurses, who collected baseline history, performed automated blood pressure measurement and point-of-care testing for lipids and A1c, and calculated 10-year Framingham risk. Employees with a Framingham risk score of ≥10% and uncontrolled blood pressure, dyslipidemia, or smoking were offered 6 months of pharmacist case management to optimize their risk factor control.Results: In total, 87 of 190 (46%) employees volunteered to undergo cardiovascular risk factor screening. Mean age was 44.5±11.9 years, 73 (83.9%) were male, 14 (16.1%) had hypertension, 4 (4.6%) had diabetes, 12 (13.8%) were current smokers, and 9 (10%) had dyslipidemia. Of 36 employees with an estimated Framingham risk score of ≥10%, 21 (58%) agreed to receive case management and 15 (42%) attended baseline and 6-month follow-up case management visits. Statistically significant reductions in left arm systolic blood pressure (−8.0±12.4 mmHg; p=0.03) and triglyceride levels (−0.8±1.4 mmol/L; p=0.04) occurred following case management.Conclusion: These findings demonstrate the feasibility and usefulness of collaborative, worksite-based cardiovascular risk factor screening and management. Expansion of this type of partnership in a cost-effective manner is warranted. Keywords: blood pressure, dyslipidemia, smoking, pharmacist, worksite

Aims: To examine the associations between the use of cannabis and arrest/conviction for cannabis related offences.Methods: Data on cannabis use and arrests/convictions for cannabis related offences were gathered during the course of a 21-year longitudinal study of a birth cohort of Christchurch (New Zealand) born children (N=983). Information on cannabis use, arrests and convictions was gathered over the period from 16 to 21 years.Results: By the age of 21, over two thirds of the cohort had used cannabis on at least one occasion with 5% using cannabis on more than 400 occasions. Amongst cannabis users, 5.1% had been arrested for a cannabis related offence and 3.6% had been convicted of an offence. There was a strong association between the extent of cannabis use and risks of arrest/conviction: over a quarter of those using cannabis on more than 400 occasions had been arrested or convicted for a cannabis related offence compared with less than 1% of those using cannabis on fewer than ten occasions. Māori, those with a previous arrest record for non cannabis related offences and those reporting involvement in violent/property offending were more likely to be arrested or convicted than other cohort members having the same level of cannabis use; in addition, males were more likely to be convicted than females with the same level of cannabis use. Arrest/conviction for a cannabis related offence did not reduce the use of cannabis: of those arrested/convicted, 95% either increased their use or continued with the same level of cannabis use subsequent to their arrest.Conclusions: The results of this study reinforce concerns about laws relating to the use and possession of cannabis. The findings show that the law was administered in an inefficient way, the application of the law was biased, and the law was ineffective in reducing cannabis use. [ABSTRACT FROM AUTHOR]

Objective: The views of consumers following contact with treatment for eating disorders represent an underresearched aspect of service provision. The aim of this paper is to examine patterns of consumer satisfaction following contact with a specialist eating- disorders service. Method: Using both a structured and an open-ended questionnaire format, consumer perspectives were sought routinely through postal survey 3 months after the point of first contact. Responses were analysed from 120 patients who returned their questionnaires during the 2-year period ending in December 1998. Results: Although the structured response format indicated high rates of satisfaction, the open-ended format revealed five categories describing the perceived best and worst aspects following consultation with the service. The category of therapeutic alliance drew the majority of positive comments, while the most frequently cited worst aspect of consultation was the category of treatment type. Conclusions: People with eating disorders form a unique group of mental health consumers to survey for satisfaction. While approval ratings prompted by both structured and open-ended questions were high, and centred around the theme of therapeutic alliance, the most frequent source of negative commentary was activities and structures considered essential by traditional treatment modalities. This provides important insights into the predicaments of people with eating disorders presenting for treatment, and the importance of developing satisfaction surveys to accommodate such predicaments and concerns. [ABSTRACT FROM AUTHOR]

Background: Parenting interventions have achieved changes in factors associated with childhood obesity but few have tested the effects on multiple parental influences.Purpose: This study examined the efficacy of an intervention aimed at improving several dimensions of parenting related to childhood obesity.Design: The study used a 2 x 2 factorial design.Setting/participants: In 2003, a sample of 13 Southern California schools was randomized to one of four conditions: micro-environment only, macro-environment only, micro-plus-macro-environment, and no treatment control condition. Participants included 811 predominantly Mexican immigrant/Mexican-American mothers with children in kindergarten through second grade.Intervention: In both micro conditions, participants received monthly home visits by a promotora over a 7-month period plus monthly mailed newsletters.Main Outcome Measures: In 2008, intervention effects were examined on (1) parenting strategies, including limit setting, monitoring, discipline, control, and reinforcement related to children's diet and physical activity; (2) parental support for physical activity; (3) parent-mediated family behaviors such as family meals eaten together and TV watching during family dinners; and (4) perceived barriers and other parent cognitions related to children's eating and activity.Results: At the 2-year follow-up, significant improvements were observed in three of five parenting strategies, parental support, and two of four parent-mediated family behaviors among parents receiving the micro intervention (i.e., those who received promotora visits and monthly newsletters), as compared with those in the macro-only and control conditions.Conclusions: Aspects of parenting related to children's risk for obesity and related health outcomes are modifiable with the support of a promotora and print media. [ABSTRACT FROM AUTHOR]

Objectives: Observational studies that assess the relationship between salt intake and long-term outcomes require a valid estimate of usual salt intake. The gold-standard measure in individuals is sodium excretion in multiple nonconsecutive 24-h urines. Multiple studies have demonstrated that random spot urine samples are not valid for estimating usual salt intake; however, some researchers believe that fasting morning spot urine samples produce a better measure of usual salt intake than random spot samples., Methods: We have used publicly available data from a PURE China validation study to compare estimates of usual salt intake from morning spot urine samples and three published formulae with mean of two 24-h urine samples (reference). We estimated the means and 95% confidence intervals of absolute and relative errors for each formula-led method and the degree to which estimates were able to be classified into the correct quartile of intake. Bland-Altman plots were used to test the level of agreement., Results: The results show that compared with the reference method, all formulae-led estimates from spot urine collections have high error rates: both random and systematic. This is demonstrated for individual estimates, as well as by quartiles of reference salt intake. This study conclusively demonstrates the unsuitability of morning spot urine formula-led estimates of usual salt intake., Conclusion: Our findings support international recommendations to not conduct, fund, or publish research studies that use spot urine samples with estimating equations to assess individuals' salt intake in association with health outcomes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Minimally invasive samples are often the best option for collecting genetic material from species of conservation concern, but they perform poorly in many genomic sequencing methods due to their tendency to yield low DNA quality and quantity. Genotyping-in-thousands by sequencing (GT-seq) is a powerful amplicon sequencing method that can genotype large numbers of variable-quality samples at a standardized set of single nucleotide polymorphism (SNP) loci. Here, we develop, optimize, and validate a GT-seq panel for the federally threatened northern Idaho ground squirrel ( Urocitellus brunneus ) to provide a standardized approach for future genetic monitoring and assessment of recovery goals using minimally invasive samples. The optimized panel consists of 224 neutral and 81 putatively adaptive SNPs. DNA collected from buccal swabs from 2016 to 2020 had 73% genotyping success, while samples collected from hair from 2002 to 2006 had little to no DNA remaining and did not genotype successfully. We evaluated our GT-seq panel by measuring genotype discordance rates compared to RADseq and whole-genome sequencing. GT-seq and other sequencing methods had similar population diversity and F ST estimates, but GT-seq consistently called more heterozygotes than expected, resulting in negative F IS values at the population level. Genetic ancestry assignment was consistent when estimated with different sequencing methods and numbers of loci. Our GT-seq panel is an effective and efficient genotyping tool that will aid in the monitoring and recovery of this threatened species, and our results provide insights for applying GT-seq for minimally invasive DNA sampling techniques in other rare animals., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

As the leading risk for death, population control of increased blood pressure represents a major challenge for all countries of the Americas. In the early 1990's, Canada had a hypertension control rate of 13%. The control rate increased to 68% in 2010, accompanied by a sharp decline in cardiovascular disease. The unprecedented improvement in hypertension control started around the year 2000 when a comprehensive program to implement annually updated hypertension treatment recommendations started. The program included a comprehensive monitoring system for hypertension control. After 2011, there was a marked decrease in emphasis on implementation and evaluation and the hypertension control rate declined, driven by a reduction in control in women from 69% to 49%. A coalition of health and scientific organizations formed in 2011 with a priority to develop advocacy positions for dietary policies to prevent and control hypertension. By 2015, the positions were adopted by most federal political parties, but implementation has been slow. This manuscript reviews key success factors and learnings. Some key success factors included having broad representation on the program steering committee, multidisciplinary engagement with substantive primary care involvement, unbiased up to date credible recommendations, development and active adaptation of education resources based on field experience, extensive implementation of primary care resources, annual review of the program and hypertension indicators and developing and emphasizing the few interventions important for hypertension control. Learnings included the need for having strong national and provincial government engagement and support, and retaining primary care organizations and clinicians in the implementation and evaluation.

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries., Methods: To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities., Findings: The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system., Interpretation: Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries.

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries., Methods: To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities., Findings: The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system., Interpretation: Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries.

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries., Methods: To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities., Findings: The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system., Interpretation: Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries., Funding: No funding to declare., Competing Interests: GG, MH, TM, VP and PO are staff members of the Pan American Health Organization. JB, AG, JM, GR, AR and EZ are consultants to PAHO/HEARTS in the Americas. NRCC reports personal fees from Resolve to Save Lives (RTSL), the Pan American Health Organization and the World Bank outside the submitted work; and an unpaid consultant on dietary sodium and hypertension control to numerous governmental and non-governmental organizations. MJD reports personal fees from the Ministry of Economy, Planning and Development of Dominican Republic outside the submitted work, and works as independent consultant on gender and public health to governmental and non-governmental organizations. Authors alone are responsible for the views expressed in this publication, and they do not necessarily represent those of the Pan American Health Organization. Ethics approval was not required for this study as this qualitative study reviewed existing published documents, convened a group of practitioners who participated in the Innovation Group voluntarily to select hypertension drivers and design the scorecards., (© 2022 Pan American Health Organization.)

Oncogenic alterations to DNA are not transforming in all cellular contexts 1,2 . This may be due to pre-existing transcriptional programmes in the cell of origin. Here we define anatomic position as a major determinant of why cells respond to specific oncogenes. Cutaneous melanoma arises throughout the body, whereas the acral subtype arises on the palms of the hands, soles of the feet or under the nails 3 . We sequenced the DNA of cutaneous and acral melanomas from a large cohort of human patients and found a specific enrichment for BRAF mutations in cutaneous melanoma and enrichment for CRKL amplifications in acral melanoma. We modelled these changes in transgenic zebrafish models and found that CRKL-driven tumours formed predominantly in the fins of the fish. The fins are the evolutionary precursors to tetrapod limbs, indicating that melanocytes in these acral locations may be uniquely susceptible to CRKL. RNA profiling of these fin and limb melanocytes, when compared with body melanocytes, revealed a positional identity gene programme typified by posterior HOX13 genes. This positional gene programme synergized with CRKL to amplify insulin-like growth factor (IGF) signalling and drive tumours at acral sites. Abrogation of this CRKL-driven programme eliminated the anatomic specificity of acral melanoma. These data suggest that the anatomic position of the cell of origin endows it with a unique transcriptional state that makes it susceptible to only certain oncogenic insults., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Melanomas can have multiple coexisting cell states, including proliferative (PRO) versus invasive (INV) subpopulations that represent a "go or grow" trade-off; however, how these populations interact is poorly understood. Using a combination of zebrafish modeling and analysis of patient samples, we show that INV and PRO cells form spatially structured heterotypic clusters and cooperate in the seeding of metastasis, maintaining cell state heterogeneity. INV cells adhere tightly to each other and form clusters with a rim of PRO cells. Intravital imaging demonstrated cooperation in which INV cells facilitate dissemination of less metastatic PRO cells. We identified the TFAP2 neural crest transcription factor as a master regulator of clustering and PRO/INV states. Isolation of clusters from patients with metastatic melanoma revealed a subset with heterotypic PRO-INV clusters. Our data suggest a framework for the co-existence of these two divergent cell populations, in which heterotypic clusters promote metastasis via cell-cell cooperation., Competing Interests: Declaration of interests M.R.M. receives research funding from GRAIL. D.J.A. is a paid consultant for Microbiotica and receives researching funding from Astra Zeneca and OpenTargets. M.P.L. receives research funding from Roche and Novartis. N.A. is a paid consultant for companies with an interest in liquid biopsy. R.M.W. is a paid consultant to N-of-One Therapeutics, a subsidiary of Qiagen. R.M.W. is on the Scientific Advisory Board of Consano but receives no income for this. R.M.W. receives royalty payments for the use of the casper line from Carolina Biologicals., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Oncogenes only transform cells under certain cellular contexts, a phenomenon called oncogenic competence. Using a combination of a human pluripotent stem cell–derived cancer model along with zebrafish transgenesis, we demonstrate that the transforming ability of BRAF V600E along with additional mutations depends on the intrinsic transcriptional program present in the cell of origin. In both systems, melanocytes are less responsive to mutations, whereas both neural crest and melanoblast populations are readily transformed. Profiling reveals that progenitors have higher expression of chromatin-modifying enzymes such as ATAD2, a melanoma competence factor that forms a complex with SOX10 and allows for expression of downstream oncogenic and neural crest programs. These data suggest that oncogenic competence is mediated by regulation of developmental chromatin factors, which then allow for proper response to those oncogenes.

About 1/4th of adults have high blood pressure which is the single most important risk for death (including heart disease and stroke).There are effective policies that could facilitate people making healthy choices to prevent raised blood pressure, and if fully implemented, could largely prevent hypertension from occurring.Hypertension is easy to screen and treat for BUT only about 50% of adults with hypertension are aware of their condition and only about 1 in 7 is adequately treated.Preventing and controlling high blood pressure is the major mechanism for NCD prevention and control and a model for other NCD risks.Effective lifestyle and drug treatments could prevent and control hypertension in most individuals if systematically applied to the population, simple interventions are feasible in all settings, and can be used to enhance primary care.Urgent sustained action is needed is needed for effective public policies and health system changes to prevent and control hypertension.

About 1/4th of adults have high blood pressure which is the single most important risk for death (including heart disease and stroke).There are effective policies that could facilitate people making healthy choices to prevent raised blood pressure, and if fully implemented, could largely prevent hypertension from occurring.Hypertension is easy to screen and treat for BUT only about 50% of adults with hypertension are aware of their condition and only about 1 in 7 is adequately treated.Preventing and controlling high blood pressure is the major mechanism for NCD prevention and control and a model for other NCD risks.Effective lifestyle and drug treatments could prevent and control hypertension in most individuals if systematically applied to the population, simple interventions are feasible in all settings, and can be used to enhance primary care.Urgent sustained action is needed is needed for effective public policies and health system changes to prevent and control hypertension.

Transcriptional profiling of tumors has revealed a stress-like state among the cancer cells with the concerted expression of genes such as fos, jun, and heat-shock proteins, though this has been controversial given possible dissociation-effects associated with single-cell RNA sequencing. Here, we validate the existence of this state using a combination of zebrafish melanoma modeling, spatial transcriptomics, and human samples. We found that the stress-like subpopulation of cancer cells is present from the early stages of tumorigenesis. Comparing with previously reported single-cell RNA sequencing datasets from diverse cancer types, including triple-negative breast cancer, oligodendroglioma, and pancreatic adenocarcinoma, indicated the conservation of this state during tumorigenesis. We also provide evidence that this state has higher tumor-seeding capabilities and that its induction leads to increased growth under both MEK and BRAF inhibitors. Collectively, our study supports the stress-like cells as a cancer cell state expressing a coherent set of genes and exhibiting drug-resistance properties., Competing Interests: Declaration of Interests R.M.W. is a paid consultant to N-of-One, Inc., a subsidiary of QIAGEN. None of the work described in this manuscript is related to this work. He serves on the Scientific Advisory Board of Consano, a non-profit crowdfunding company and receives no compensation for this work., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Polymorphic chromosomal inversions have been implicated in local adaptation. In anopheline mosquitoes, inversions also contribute to epidemiologically relevant phenotypes such as resting behavior. Progress in understanding these phenotypes and their mechanistic basis has been hindered because the only available method for inversion genotyping relies on traditional cytogenetic karyotyping, a rate-limiting and technically difficult approach that is possible only for the fraction of the adult female population at the correct gonotrophic stage. Here, we focus on an understudied malaria vector of major importance in sub-Saharan Africa, Anopheles funestus . We ascertain and validate tag single nucleotide polymorphisms (SNPs) using high throughput molecular assays that allow rapid inversion genotyping of the three most common An. funestus inversions at scale, overcoming the cytogenetic karyotyping barrier. These same inversions are the only available markers for distinguishing two An. funestus ecotypes that differ in indoor resting behavior, Folonzo and Kiribina. Our new inversion genotyping tools will facilitate studies of ecotypic differentiation in An. funestus and provide a means to improve our understanding of the roles of Folonzo and Kiribina in malaria transmission.

Chromosomal inversion polymorphisms have special importance in the Anopheles gambiae complex of malaria vector mosquitoes, due to their role in local adaptation and range expansion. The study of inversions in natural populations is reliant on polytene chromosome analysis by expert cytogeneticists, a process that is limited by the rarity of trained specialists, low throughput, and restrictive sampling requirements. To overcome this barrier, we ascertained tag single nucleotide polymorphisms (SNPs) that are highly correlated with inversion status (inverted or standard orientation). We compared the performance of the tag SNPs using two alternative high throughput molecular genotyping approaches vs. traditional cytogenetic karyotyping of the same 960 individual An. gambiae and An. coluzzii mosquitoes sampled from Burkina Faso, West Africa. We show that both molecular approaches yield comparable results, and that either one performs as well or better than cytogenetics in terms of genotyping accuracy. Given the ability of molecular genotyping approaches to be conducted at scale and at relatively low cost without restriction on mosquito sex or developmental stage, molecular genotyping via tag SNPs has the potential to revitalize research into the role of chromosomal inversions in the behavior and ongoing adaptation of An. gambiae and An. coluzzii to environmental heterogeneities., (Copyright © 2020 Love et al.)

The DNA polymerase Polκ plays a key role in translesion synthesis, an error-prone replication mechanism. Polκ is overexpressed in various tumor types. Here, we found that melanoma and lung and breast cancer cells experiencing stress from oncogene inhibition up-regulated the expression of Polκ and shifted its localization from the cytoplasm to the nucleus. This effect was phenocopied by inhibition of the kinase mTOR, by induction of ER stress, or by glucose deprivation. In unstressed cells, Polκ is continually transported out of the nucleus by exportin-1. Inhibiting exportin-1 or overexpressing Polκ increased the abundance of nuclear-localized Polκ, particularly in response to the BRAF V600E -targeted inhibitor vemurafenib, which decreased the cytotoxicity of the drug in BRAF V600E melanoma cells. These observations were analogous to how Escherichia coli encountering cell stress and nutrient deprivation can up-regulate and activate DinB/pol IV, the bacterial ortholog of Polκ, to induce mutagenesis that enables stress tolerance or escape. However, we found that the increased expression of Polκ was not excessively mutagenic, indicating that noncatalytic or other functions of Polκ could mediate its role in stress responses in mammalian cells. Repressing the expression or nuclear localization of Polκ might prevent drug resistance in some cancer cells., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Developmental processes underlying normal tissue regeneration have been implicated in cancer, but the degree of their enactment during tumor progression and under the selective pressures of immune surveillance, remain unknown. Here we show that human primary lung adenocarcinomas are characterized by the emergence of regenerative cell types, typically seen in response to lung injury, and by striking infidelity among transcription factors specifying most alveolar and bronchial epithelial lineages. In contrast, metastases are enriched for key endoderm and lung-specifying transcription factors, SOX2 and SOX9, and recapitulate more primitive transcriptional programs spanning stem-like to regenerative pulmonary epithelial progenitor states. This developmental continuum mirrors the progressive stages of spontaneous outbreak from metastatic dormancy in a mouse model and exhibits SOX9-dependent resistance to natural killer cells. Loss of developmental stage-specific constraint in macrometastases triggered by natural killer cell depletion suggests a dynamic interplay between developmental plasticity and immune-mediated pruning during metastasis.

Objective: To assess agreement between established methods of estimating salt intake from spot urine collections and 24 h urinary Na (24hUNa) and then to develop a valid formula that can be used in the Iranian population to estimate salt intake from spot urine samples., Design: A validation study. Three spot urine samples were collected (fasting second-void morning; afternoon; evening) on the same day as a 24 h urine collection. We estimated 24hUNa from spot specimens using the Kawasaki, Tanaka and INTERSALT equations. Two new formulas were developed, the Iran formula 1 (Iran 1) and Iran formula 2 (Iran 2), based on our population characteristics., Setting: Iranian adults recruited in 2014-2015., Participants: Healthy volunteer adults aged ≥18 years., Results: With all three spot urine specimens, predicted population 24hUNa was underestimated based on the INTERSALT equation (-469 to -708 mg/d; all P < 0·05) and conversely overestimation occurred with the Kawasaki equation (926 to 1080 mg/d; all P < 0·01). The Tanaka equation produced comparable estimates to measured 24hUNa (-151 to 86 mg/d; all P > 0·49). The newly derived formulas, Iran 1 and Iran 2, showed less mean bias than the established equations (Iran 1: 43 to 80 mg/d, all P > 0·55; Iran 2: 22 to 90 mg/d, all P > 0·50)., Conclusions: In this Iranian sample, the Tanaka equation and newly derived formulas produced group-level estimates comparable to measured 24hUNa. The newly developed formulas showed less mean bias than established equations; however, they need to be tested for generalization in a larger sample.

Minimally invasive sampling (MIS) is widespread in wildlife studies; however, its utility for massively parallel DNA sequencing (MPS) is limited. Poor sample quality and contamination by exogenous DNA can make MIS challenging to use with modern genotyping-by-sequencing approaches, which have been traditionally developed for high-quality DNA sources. Given that MIS is often more appropriate in many contexts, there is a need to make such samples practical for harnessing MPS. Here, we test the ability for Genotyping-in-Thousands by sequencing (GT-seq), a multiplex amplicon sequencing approach, to effectively genotype minimally invasive cloacal DNA samples collected from the Western Rattlesnake (Crotalus oreganus), a threatened species in British Columbia, Canada. As there was no previous genetic information for this species, an optimized panel of 362 SNPs was selected for use with GT-seq from a de novo restriction site-associated DNA sequencing (RADseq) assembly. Comparisons of genotypes generated within and among RADseq and GT-seq for the same individuals found low rates of genotyping error (GT-seq: 0.50%; RADseq: 0.80%) and discordance (2.57%), the latter likely due to the different genotype calling models employed. GT-seq mean genotype discordance between blood and cloacal swab samples collected from the same individuals was also minimal (1.37%). Estimates of population diversity parameters were similar across GT-seq and RADseq data sets, as were inferred patterns of population structure. Overall, GT-seq can be effectively applied to low-quality DNA samples, minimizing the inefficiencies presented by exogenous DNA typically found in minimally invasive samples and continuing the expansion of molecular ecology and conservation genetics in the genomics era., (© 2019 John Wiley & Sons Ltd.)

Background: Obesity disproportionately affects Latino youth. Community clinics are an important resource, yet there is little evidence for the efficacy of clinic-based approaches in this population., Objective: The purpose of this study was to test the efficacy of a clinic-based intervention to lower body mass index (BMI) and improve body composition among overweight Latino children., Methods: A randomized trial (2 group × 3 repeated measures) was conducted among 297 randomly sampled, overweight paediatric patients (5-10 years old) and their parents. The 12-month family-based culturally tailored behavioural intervention (Luces de Cambio) was based on the 'traffic light' concepts to address behaviour change and was delivered by clinic health educators and mid-level providers. The primary study outcome was child BMI (kg m -2 ) assessed at baseline, 6-month (n = 191) and 12-month (n = 201) post-baseline. A subsample of the children was examined for overall and site-specific adiposity using dual-energy X-ray absorptiometry (n = 79)., Results: There were no significant intervention effects on child BMI (p > 0.05); however, intervention children showed significantly (p < 0.05) lower total and trunk per cent fat compared with the usual care condition., Conclusions: The Luces intervention did not reduce child BMI, yet small but significant reductions were observed for child per cent body fat. Further research is needed to identify and reduce barriers to recruitment and participation among Latino families., (© 2018 World Obesity Federation.)

Transgenic animals are invaluable for modeling cancer genomics, but often require complex crosses of multiple germline alleles to obtain the desired combinations. Zebrafish models have advantages in that transgenes can be rapidly tested by mosaic expression, but typically lack spatial and temporal control of tumor onset, which limits their utility for the study of tumor progression and metastasis. To overcome these limitations, we have developed a method referred to as Transgene Electroporation in Adult Zebrafish (TEAZ). TEAZ can deliver DNA constructs with promoter elements of interest to drive fluorophores, oncogenes or CRISPR-Cas9-based mutagenic cassettes in specific cell types. Using TEAZ, we created a highly aggressive melanoma model via Cas9-mediated inactivation of Rb1 in the context of BRAF V600E in spatially constrained melanocytes. Unlike prior models that take ∼4 months to develop, we found that TEAZ leads to tumor onset in ∼7 weeks, and these tumors develop in fully immunocompetent animals. As the resulting tumors initiated at highly defined locations, we could track their progression via fluorescence, and documented deep invasion into tissues and metastatic deposits. TEAZ can be deployed to other tissues and cell types, such as the heart, with the use of suitable transgenic promoters. The versatility of TEAZ makes it widely accessible for rapid modeling of somatic gene alterations and cancer progression at a scale not achievable in other in vivo systems., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Advanced, metastatic melanomas frequently grow in subcutaneous tissues and portend a poor prognosis. Though subcutaneous tissues are largely composed of adipocytes, the mechanisms by which adipocytes influence melanoma are poorly understood. Using in vitro and in vivo models, we find that adipocytes increase proliferation and invasion of adjacent melanoma cells. Additionally, adipocytes directly transfer lipids to melanoma cells, which alters tumor cell metabolism. Adipocyte-derived lipids are transferred to melanoma cells through the FATP/SLC27A family of lipid transporters expressed on the tumor cell surface. Among the six FATP/SLC27A family members, melanomas significantly overexpress FATP1/SLC27A1. Melanocyte-specific FATP1 expression cooperates with BRAF V600E in transgenic zebrafish to accelerate melanoma development, an effect that is similarly seen in mouse xenograft studies. Pharmacologic blockade of FATPs with the small-molecule inhibitor Lipofermata abrogates lipid transport into melanoma cells and reduces melanoma growth and invasion. These data demonstrate that stromal adipocytes can drive melanoma progression through FATP lipid transporters and represent a new target aimed at interrupting adipocyte-melanoma cross-talk. Significance: We demonstrate that stromal adipocytes are donors of lipids that mediate melanoma progression. Adipocyte-derived lipids are taken up by FATP proteins that are aberrantly expressed in melanoma. Inhibition of FATPs decreases melanoma lipid uptake, invasion, and growth. We provide a mechanism for how stromal adipocytes drive tumor progression and demonstrate a novel microenvironmental therapeutic target. Cancer Discov; 8(8); 1006-25. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 899 ., (©2018 American Association for Cancer Research.)

Patterning of vertebrate melanophores is essential for mate selection and protection from UV-induced damage. Patterning can be influenced by circulating long-range factors, such as hormones, but it is unclear how their activity is controlled in recipient cells to prevent excesses in cell number and migration. The zebrafish wanderlust mutant harbors a mutation in the sheddase bace2 and exhibits hyperdendritic and hyperproliferative melanophores that localize to aberrant sites. We performed a chemical screen to identify suppressors of the wanderlust phenotype and found that inhibition of insulin/PI3Kγ/mTOR signaling rescues the defect. In normal physiology, Bace2 cleaves the insulin receptor, whereas its loss results in hyperactive insulin/PI3K/mTOR signaling. Insulin B, an isoform enriched in the head, drives the melanophore defect. These results suggest that insulin signaling is negatively regulated by melanophore-specific expression of a sheddase, highlighting how long-distance factors can be regulated in a cell-type-specific manner., (Published by Elsevier Inc.)

The 2013 Institute of Medicine report entitled "Sodium Intake in Populations: Assessment of Evidence" found inconsistent evidence of health benefit with dietary sodium intake <2300 mg/d. Different studies reported benefit and harm of population dietary intake <2300 mg/d. The Institute of Medicine committee, however, did not assess whether the methodology used in each of the studies was appropriate to examine dietary sodium and health outcomes. This review investigates the association of methodological rigor and outcomes of studies in the Institute of Medicine report. For the 13 studies that met all methodological criteria, nine found a detrimental impact of high sodium consumption on health, one found a health benefit, and in three the effect was unclear (P = .068). For the 22 studies that failed to meet all criteria, 11 showed a detrimental impact, four a health benefit, and seven had unclear effects from increasing dietary sodium (P = .42)., (©2018 Wiley Periodicals, Inc.)

Coho salmon were extirpated in the mid-20th century from the interior reaches of the Columbia River but were reintroduced with relatively abundant source stocks from the lower Columbia River near the Pacific coast. Reintroduction of Coho salmon to the interior Columbia River (Wenatchee River) using lower river stocks placed selective pressures on the new colonizers due to substantial differences with their original habitat such as migration distance and navigation of six additional hydropower dams. We used restriction site-associated DNA sequencing (RAD-seq) to genotype 5,392 SNPs in reintroduced Coho salmon in the Wenatchee River over four generations to test for signals of temporal structure and adaptive variation. Temporal genetic structure among the three broodlines of reintroduced fish was evident among the initial return years (2000, 2001, and 2002) and their descendants, which indicated levels of reproductive isolation among broodlines. Signals of adaptive variation were detected from multiple outlier tests and identified candidate genes for further study. This study illustrated that genetic variation and structure of reintroduced populations are likely to reflect source stocks for multiple generations but may shift over time once established in nature.

The purpose of this review was to identify, summarize, and critically appraise studies on dietary salt relating to health outcomes that were published from December 2015 to March 2016. The search strategy was adapted from a previous systematic review on dietary salt and health. Overall, 13 studies were included in the review: one study assessed cardiovascular events, nine studies assessed prevalence or incidence of blood pressure or hypertension, one study assessed kidney disease, and two studies assessed other health outcomes (obesity and nonalcoholic fatty liver disease). Four studies were selected for detailed appraisal and commentary. One study met the minimum methodologic criteria and found an increased risk associated with lower sodium intake in patients with heart failure. All other studies identified in this review demonstrated positive associations between dietary salt and adverse health outcomes., (© 2017 Wiley Periodicals, Inc.)

The objective of this periodic review was to identify, summarize, and appraise studies relating to the implementation of salt reduction strategies that were retrieved between November 2015 and February 2016. From the established MEDLINE search, 56 studies were identified as relevant to the implementation of salt reduction initiatives. Detailed appraisal was performed on seven studies that evaluated the impact of salt reduction interventions. While study quality varied, all had one or more risks related to bias. There was consistent evidence, from three studies, demonstrating that setting-based structural interventions to improve the nutritional composition of foods were effective in reducing salt but mixed evidence in relation to the effectiveness of behavioral interventions. The development of an evaluation guidance framework that supports scientific rigor and external validity would aid future design and interpretation of studies evaluating salt reduction interventions, particularly for low-resource countries., (©2016 Wiley Periodicals, Inc.)