NERNST: a genetically-encoded ratiometric non-destructive sensing tool to estimate NADP(H) redox status in bacterial, plant and animal systems.

NADP(H) is a central metabolic hub providing reducing equivalents to multiple biosynthetic, regulatory and antioxidative pathways in all living organisms. While biosensors are available to determine NADP+ or NADPH levels in vivo, no probe exists to estimate the NADP(H) redox status, a determinant of the cell energy availability. We describe herein the design and characterization of a genetically-encoded ratiometric biosensor, termed NERNST, able to interact with NADP(H) and estimate ENADP(H). NERNST consists of a redox-sensitive green fluorescent protein (roGFP2) fused to an NADPH-thioredoxin reductase C module which selectively monitors NADP(H) redox states via oxido-reduction of the roGFP2 moiety. NERNST is functional in bacterial, plant and animal cells, and organelles such as chloroplasts and mitochondria. Using NERNST, we monitor NADP(H) dynamics during bacterial growth, environmental stresses in plants, metabolic challenges to mammalian cells, and wounding in zebrafish. NERNST estimates the NADP(H) redox poise in living organisms, with various potential applications in biochemical, biotechnological and biomedical research.

The endothelial-enriched lncRNA LINC00607 mediates angiogenic function.

Long non-coding RNAs (lncRNAs) can act as regulatory RNAs which, by altering the expression of target genes, impact on the cellular phenotype and cardiovascular disease development. Endothelial lncRNAs and their vascular functions are largely undefined. Deep RNA-Seq and FANTOM5 CAGE analysis revealed the lncRNA LINC00607 to be highly enriched in human endothelial cells. LINC00607 was induced in response to hypoxia, arteriosclerosis regression in non-human primates, post-atherosclerotic cultured endothelial cells from patients and also in response to propranolol used to induce regression of human arteriovenous malformations. siRNA knockdown or CRISPR/Cas9 knockout of LINC00607 attenuated VEGF-A-induced angiogenic sprouting. LINC00607 knockout in endothelial cells also integrated less into newly formed vascular networks in an in vivo assay in SCID mice. Overexpression of LINC00607 in CRISPR knockout cells restored normal endothelial function. RNA- and ATAC-Seq after LINC00607 knockout revealed changes in the transcription of endothelial gene sets linked to the endothelial phenotype and in chromatin accessibility around ERG-binding sites. Mechanistically, LINC00607 interacted with the SWI/SNF chromatin remodeling protein BRG1. CRISPR/Cas9-mediated knockout of BRG1 in HUVEC followed by CUT&RUN revealed that BRG1 is required to secure a stable chromatin state, mainly on ERG-binding sites. In conclusion, LINC00607 is an endothelial-enriched lncRNA that maintains ERG target gene transcription by interacting with the chromatin remodeler BRG1 to ultimately mediate angiogenesis.

Endothelial deletion of the cytochrome P450 reductase leads to cardiac remodelling.

The cytochrome P450 reductase (POR) transfers electrons to all microsomal cytochrome P450 enzymes (CYP450) thereby driving their activity. In the vascular system, the POR/CYP450 system has been linked to the production of epoxyeicosatrienoic acids (EETs) but also to the generation of reactive oxygen species. In cardiac myocytes (CMs), EETs have been shown to modulate the cardiac function and have cardioprotective effects. The functional importance of the endothelial POR/CYP450 system in the heart is unclear and was studied here using endothelial cell-specific, inducible knockout mice of POR (ecPOR-/-). RNA sequencing of murine cardiac cells revealed a cell type-specific expression of different CYP450 homologues. Cardiac endothelial cells mainly expressed members of the CYP2 family which produces EETs, and of the CYP4 family that generates omega fatty acids. Tamoxifen-induced endothelial deletion of POR in mice led to cardiac remodelling under basal conditions, as shown by an increase in heart weight to body weight ratio and an increased CM area as compared to control animals. Endothelial deletion of POR was associated with a significant increase in endothelial genes linked to protein synthesis with no changes in genes of the oxidative stress response. CM of ecPOR-/- mice exhibited attenuated expression of genes linked to mitochondrial function and an increase in genes related to cardiac myocyte contractility. In a model of pressure overload (transverse aortic constriction, TAC with O-rings), ecPOR-/- mice exhibited an accelerated reduction in cardiac output (CO) and stroke volume (SV) as compared to control mice. These results suggest that loss of endothelial POR along with a reduction in EETs leads to an increase in vascular stiffness and loss in cardioprotection, resulting in cardiac remodelling.

Epoxyeicosatrienoic Acid and Prostanoid Crosstalk at the Receptor and Intracellular Signaling Levels to Maintain Vascular Tone.

Epoxyeicosatrienoic acids (EETs) are signaling lipids produced by the cytochrome P450-(CYP450)-mediated epoxygenation of arachidonic acid. EETs have numerous biological effects on the vascular system, but aspects including their species specificity make their effects on vascular tone controversial. CYP450 enzymes require the 450-reductase (POR) for their activity. We set out to determine the contribution of endothelial CYP450 to murine vascular function using isolated aortic ring preparations from tamoxifen-inducible endothelial cell-specific POR knockout mice (ecPOR-/-). Constrictor responses to phenylephrine were similar between control (CTR) and ecPOR-/- mice. Contrastingly, sensitivity to the thromboxane receptor agonist U46619 and prostaglandin E2 (PGE2) was increased following the deletion of POR. Ex vivo incubation with a non-hydrolyzable EET (14,15-EE-8(Z)-E, EEZE) reversed the increased sensitivity to U46619 to the levels of CTR. EETs had no effect on vascular tone in phenylephrine-preconstricted vessels, but dilated vessels contracted with U46619 or PGE2. As U46619 acts through RhoA-dependent kinase, this system was analyzed. The deletion of POR affected the expression of genes in this pathway and the inhibition of Rho-GTPase with SAR407899 decreased sensitivity to U46619. These data suggest that EET and prostanoid crosstalk at the receptor level and that lack of EET production sensitizes vessels to vasoconstriction via the induction of the Rho kinase system.

Inequidades en la detección temprana del cáncer de cérvix: una realidad en la población costarricense / Inequalities in the early detection of cervical cancer: a reality in the Costa Rica

Resumen Introducción: el cáncer de cérvix es una de las enfermedades neoplásicas más frecuentes que afecta la salud de las mujeres en el mundo. Objetivo: determinar si existen diferencias entre regiones de Costa Rica en el uso del papanicoláu, con el fin de visualizar las inequidades relacionadas con la detección temprana del cáncer cérvico-uterino. Metodología: este estudio se realizó a partir de la Encuesta Nacional de Hogares de 2014, la cual es representativa en el ámbito nacional. Se utilizó R-Studio para estimar dos modelos de regresión multinomial que explican el tiempo transcurrido desde el último papanicoláu y las razones por las que las mujeres nunca se habían realizado uno. Se recurrió a datos del Registro Nacional de Tumores del Ministerio de Salud para evaluar la razón in-situ/invasor. Resultados: en comparación con las residentes de la región Central, las mujeres de las regiones Chorotega, Pacífico Central y Huetar Caribe son respectivamente un 80 % (OR=1,80; p<0,01), un 52 % (OR=1,52; p=0,031) y un 58 % (OR=1,58; p<0,01) más propensas a haberse realizado la citología vaginal por última vez hace 5 años o más que hace 1 o 2 años. Discusión: de acuerdo con los resultados de la presente investigación, la Región Chorotega presenta las condiciones más desventajosas en cuanto a la práctica de PAP, esto implica un mayor riesgo de desarrollar lesiones y cáncer de cérvix. Conclusiones: en busca de reducir las brechas y mejorar las condiciones de acceso, es necesario coordinar y articular esfuerzos institucionales tanto gubernamentales como no gubernamentales, incluyendo la participación y el protagonismo de las mujeres.

Abstract Introduction. Cervical cancer is one of the most common cancer types that affects the health of women worldwide. Objective: To determine if there are differences in the use of Pap smears at the regional level in Costa Rica, in order to visualize the inequalities related to the early detection of cervical-uterine cancer. Methodology. This study was conducted based on information from the 2014 National Household Survey. This survey is representative at the national level. R-Studio was used to estimate two multinomial regression models. The first one was used to explain the time that has elapsed since the last time women had a Pap smear. The second one was used to explain the reasons why women had never had a Pap smear. Data on the incidence of cervical cancer, from the National Tumor Registry of the Ministry of Health, were used in order to estimate the in-situ/invasive ratio. Results: Women who participate less regularly in screening are those residing in the Chorotega, Central Pacific and Huetar Caribbean regions. Compared to women in the Central region, women in these three regions are 80% (OR=1.80; p<0.01), 52% (OR=1.52; p=0.031) and 58% (OR=1.58; p<0.01) respectively more likely to have had a Pap screening 5 or more years ago, as compared to 1 to 2 years ago. Discussion: According to the results of this research, the Chorotega Region presents the most disadvantageous conditions in terms of the use of PAP, which represents a higher risk for women to develop lesions and cervical cancer. Conclusions: In order to reduce gaps and improve conditions of access to prevention, it is necessary to coordinate institutional efforts, both governmental and non-governmental, as well as the participation and protagonism of women.

Corresponsabilidad en salud como base de un plan de acción interinstitucional: abordaje del sobrepeso y la obesidad en una población costarricense / Joint responsibility in health as the basis for an inter-institutional action plan: Addressing overweight and obesity in a Costa Rican population

Resumen El objetivo de este estudio fue describir el procesamiento de un plan de acción interinstitucional para el abordaje del sobrepeso y la obesidad en dos cantones urbanos de Costa Rica: Alajuelita y Escazú. Esta investigación tiene enfoque cualitativo, es de tipo descriptivo transversal y utiliza una metodología de investigación-acción, la cual toma como participantes a los actores institucionales de ambos cantones, por un lapso de seis meses. El principal resultado fue el desarrollo de un plan de acción para el abordaje del sobrepeso y la obesidad en madres de cada cantón. Además, se propusieron indicadores de proceso, producto y resultado para cada una de las cuatro áreas de trabajo que formaron parte de dicha herramienta. Se concluyó que la corresponsabilidad en salud es de vital importancia para crear acciones dirigidas a mejorar la salud de las personas, especialmente en comunidades donde, si bien existe una importante voluntad política de los actores institucionales, se cuenta con pocos recursos.

Abstract The objective of this study is to describe the process of creating an inter-institutional action plan to address overweight and obesity in the population of mothers from the urban counties of Alajuelita and Escazu in Costa Rica. This research has a qualitative approach, is a descriptive transversal study, and uses a research-action methodology, which takes as participants the institutional actors of both counties, during a six-month time frame. The main results is the creation of an action plan for in each of the two counties. Process, product and result indicators are also proposed for each of the 4 work areas that were part of the action plan, It is concluded that joint responsibility in health is of vital importance for the creation of actions that seek to improve the health of the population, especially in communities in which there is significant political will from institutional actor, but there are few resources.

Association between obesity and mortality in the Costa Rican elderly: a cohort study.

BACKGROUND: Costa Rica, along with other Latin American countries, is undergoing population aging, with an increase in the prevalence of chronic conditions, many of them resulting from a growing prevalence of obesity. As a result of the demographic and epidemiological transitions, the causes of morbidity and mortality have changed from communicable to non-communicable diseases. An increase in overweight and obesity is hypothesized to be related to premature mortality. This study assesses the association between obesity and both all-cause and cardiovascular mortality in a Costa Rican elderly population. METHODS: This is a secondary data analysis of the Costa Rican Longevity and Healthy Aging Study (CRELES, for its Spanish acronym), a longitudinal nationally representative cohort study of health and life-course experiences of the Costa Rican elderly. A baseline (n = 2827) and two subsequent 2-year follow-up interviews were conducted. Data analyses include descriptive statistics and survival models. Cox and Gompertz distributions were used to model general mortality and cardiovascular mortality as a function of obesity and controlling for confounders. Anthropometric measures used were Body Mass Index (BMI) and Waist Circumference (WC). RESULTS: Each one-unit increment in BMI was significantly associated to a 3,1% (p < 0.001) and 2,6% (p = 0.021) increment in general and cardiovascular mortality respectively. Each one-unit increment in WC was significantly associated with a 0,8% (p = 0.006) increment in general mortality, whereas WC was not significantly associated with cardiovascular mortality. CONCLUSIONS: Obesity is associated with mortality in the Costa Rican elderly. This association is strongest between obesity and all-cause mortality. As general obesity increases, all-cause and cardiovascular mortality also increase in this population. Similarly, as central obesity increases, all-cause mortality increases. Policies aimed at preventing obesity and chronic conditions are warranted for a better survival in this population.

Loss of Endothelial Cytochrome P450 Reductase Induces Vascular Dysfunction in Mice.

BACKGROUND: POR (cytochrome P450 reductase) provides electrons for the catalytic activity of the CYP (cytochrome P450) monooxygenases. CYPs are dual-function enzymes as they generate protective vasoactive mediators derived from polyunsaturated fatty acids but also reactive oxygen species. It is not known in which conditions the endothelial POR/CYP system is beneficial versus deleterious. Here, the activity of all CYP enzymes was eliminated in the vascular endothelium to examine its impact on vascular function. METHODS: An endothelial-specific, tamoxifen-inducible POR knockout mouse (ecPOR-/-) was generated. Vascular function was studied by organ chamber experiments. eNOS (endothelial nitric oxide synthase) activity was accessed by heavy arginine/citrulline LC-MS/MS detection and phosphorylation of serine1177 in aortic rings. CYP-derived epoxyeicosatrienoic acids and prostanoids were measured by LC-MS/MS. Gene expression of aorta and endothelial cells was profiled by RNA sequencing. Blood pressure was measured by telemetry. RESULTS: Acetylcholine-induced endothelium-dependent relaxation was attenuated in isolated vessels of ecPOR-/- as compared with control mice. Additionally, ecPOR-/- mice had attenuated eNOS activity and eNOS/AKT phosphorylation. POR deletion reduced endothelial stores of CYP-derived epoxyeicosatrienoic acids but increased vascular prostanoids. This phenomenon was paralleled by the induction of genes implicated in eicosanoid generation. In response to Ang II (angiotensin II) infusion, blood pressure increased significantly more in ecPOR-/- mice. Importantly, the cyclooxygenase inhibitor Naproxen selectively lowered the Ang II-induced hypertension in ecPOR-/- mice. CONCLUSIONS: POR expression in endothelial cells maintains eNOS activity and its loss results in an overactivation of the vasoconstrictor prostanoid system. Through these mechanisms, loss of endothelial POR induces vascular dysfunction and hypertension.

Determinantes sociales de la salud y prevalencia de sobrepeso-obesidad en mujeres urbanas, según nivel socioeconómico / Social determinants of health and prevalence of overweight-obesity in urban women according to their socioeconomic level / Determinantes sociais da saúde e prevalência de sobrepeso-obesidade em mulheres urbanas, segundo nível socioeconômico

Resumen La obesidad es un factor de riesgo para diferentes enfermedades crónicas y está asociada a factores genéticos, ambientales y sociales. Objetivo: analizar la asociación entre los determinantes sociales de la salud y la prevalencia de sobrepeso y obesidad en mujeres urbanas, según nivel socioeconómico. Métodos: este estudio de corte transversal se realizó un enfoque mixto. Para el componente cuantitativo se realizan entrevistas estructuradas a una muestra de mujeres de 25 a 45 años (n=137), representativa de dos cantones urbanos en Costa Rica. Para el componente cualitativo se realizan entrevistas semiestructuradas a una muestra de 13 actores institucionales de los mismos cantones. Resultados: existen desigualdades en la prevalencia de sobrepeso y obesidad, con una mayor afectación en la población de bajo nivel socioeconómico. La inseguridad ciudadana, el nivel socioeconómico y la sobrepoblación son obstáculos para el desarrollo de prácticas saludables. Existe una asociación significativa inversa entre la actividad física regular y el sobrepeso y obesidad (OR=0,35, p=0,03). Conclusiones: estos resultados son un insumo para realizar acciones que promuevan equidad, especialmente en poblaciones que no cuenten con los recursos para llevar una vida saludable.

Abstract Obesity is a risk factor for different chronic diseases and is associated with genetic, environmental and social factors. Objective: To analyze the association between the social determinants of health and the prevalence of overweight and obesity in urban women, according to their socioeconomic status. Methods: This cross-sectional study used a mixed approach. For the quantitative component, structured interviews were conducted with a sample of women aged 25-45 years (n=137), representative of two urban cantons in Costa Rica. For the qualitative component, semi-structured interviews were conducted with a sample of 13 institutional actors of the same cantons. Results: There are inequalities in the prevalence of overweight and obesity, with a greater impact on the population with a low socioeconomic status. Citizen insecurity, socioeconomic status and overpopulation are obstacles to the development of healthy practices. There is a significant inverse association between regular physical activity and overweight and obesity (OR = 0.35, p = 0.03). Conclusions: These results are an input to carry out actions that promote equity, especially in populations that do not have resources for a healthy lifestyle.

Resumo A obesidade é um fator de risco para diferentes doenças crónicas e está associada a fatores genéticos, ambientais e sociais. Objetivo: analisar a associação entre os determinantes sociais da saúde e a prevalência de sobrepeso e obesidade em mulheres urbanas, segundo nível socioeconômico. Métodos: este estudo de corte transversal foi feito com um enfoque misto. Para o componente quantitativo foram feitas entrevistas estruturadas a uma amostra de mulheres de 25 a 45 anos (n=137), representativa de dois municípios urbanos em Costa Rica. Para o componente qualitativo se fizeram entrevistas semiestruturadas a uma amostra de 13 atores institucionais dos mesmos municípios. Resultados: existem desigualdades na prevalência de sobrepeso e obesidade, com uma maior afetação na população de baixo nível socioeconômico. A insegurança cidadã, o nível socioeconômico e a sobre população são obstáculos para o desenvolvimento de práticas saudáveis. Existe uma associação significativa inversa entre a atividade física regular e o sobrepeso e obesidade (OR=0,35, p=0,03). Conclusões: estes resultados são um insumo para realizar ações que promovem equidade, especialmente em populações que não contem com os recursos para levar uma vida saudável.

Women's Participation in Pap Smear Screening in a Developing Country: Evidence for Improving Health Systems.

INTRODUCTION: Every year about 83,000 women are diagnosed with cervical cancer in the Americas. Latin America and the Caribbean (LAC) has one of the highest incidence and mortality rates from cervical cancer in the world. Although incidence has decreased by half in the last 30 years, cervical cancer remains a public health concern. The detection of precursor lesions through Papanicolaou (Pap) smear remains a critical tool in the context of prevention in Costa Rica and many other LAC countries. OBJECTIVE: To determine predictors of participation in Pap smear screening among Costa Rican women, with a special focus on women who have never had a Pap smear or have had a smear 5 or more years ago. METHODS: The data source for this study is the Costa Rican Households National Survey conducted in 2014. This survey is representative at the national, urban/rural zone, and administrative region level. A subsample of women aged 20 to 69 years who responded to the survey's Papanicolaou Module were included in this study (n = 11,709). Statistical analyses were conducted in R-Studio. Statistical significance level was set at 5%. Two multinomial regression models were estimated. The first model aimed to explain the five different categories of cytology use, which were defined according to the last time women had a Pap smear. The second model aimed to explain the five different categories of reasons why women had never had a Pap smear. Both models controlled for age, educational attainment, and marital status. RESULTS: Young women with high educational attainment were more likely to have never had a cytology. Women with a lower educational attainment, married, or in domestic relationship and of older age had greater odds of having had a cytology 5 or more years ago. Each year increment in age was significantly associated with an increase in the odds of never having a Pap smear because of health care access issues or because of cultural reasons as compared to not having an active sexual life. CONCLUSIONS: Findings can inform public policy targeted to higher risk female populations where access to health services can be improved.

Vascular biotransformation of organic nitrates is independent of cytochrome P450 monooxygenases.

BACKGROUND AND PURPOSE: Organic nitrates such as nitroglycerin (NTG) or pentaerythritol tetranitrate (PETN) have been used for over a century in the treatment of angina or ischaemic heart disease. These compounds are prodrugs which release their nitrovasodilators upon enzymic bioactivation by aldehyde dehydrogenase (ALDH2) or cytochromes P450 (CYP). Whereas ALDH2 is known to directly activate organic nitrates in vessels, the contribution of vascular CYPs is unknown and was studied here. EXPERIMENTAL APPROACH: As all CYPs depend on cytochrome P450 reductase (POR) as electron donor, we generated a smooth muscle cell-specific, inducible knockout mouse of POR (smcPOR-/- ) to investigate the contribution of POR/CYP to vascular biotransformation of organic nitrates. KEY RESULTS: Microsomes containing recombinant CYPs expressed in human vascular tissues released nitrite from NTG and PETN with CYP2C9 and CYP2C8 being most efficient. SFK525, a CYP suicide inhibitor, blocked this effect. smcPOR-/- mice exhibited no obvious cardiovascular phenotype (normal cardiac weight and endothelium-dependent relaxation) and plasma and vascular nitrite production was similar to control (CTL) animals. NTG- and PETN-induced relaxation of isolated endothelium-intact or endothelium-denuded vessels were identical between CTL and smcPOR-/- . Likewise, nitrite release from organic nitrates in aortic rings was not affected by deletion of POR in smooth muscle cells (SMCs). In contrast, inhibition of ALDH2 by benomyl (10 µM) inhibited NTG-induced nitrite production and relaxation. Deletion of POR did not modulate this response. CONCLUSIONS AND IMPLICATIONS: Our data suggest that metabolism by vascular CYPs does not contribute to the pharmacological function of organic nitrates.

Projected impact of diabetes on the Costa Rican healthcare system.

INTRODUCTION: Costa Rica, similar to many other Latin American countries is undergoing population aging at a fast pace. As a result of the epidemiological transition, the prevalence of diabetes has increased. This condition impacts not only individual lives, but also the healthcare system. The goal of this study is to examine the expected impact of diabetes, in terms of economic costs on the healthcare system and lives lost. We will also project how long it will take for the number of elderly individuals who are diabetic to double in Costa Rica. METHODS: CRELES (Costa Rican Longevity and Healthy Aging Study), a three-wave nationally representative longitudinal study, is the main source of data for this research (n = 2827). The projected impact of diabetes was estimated in three ways: length of time for the number of elderly individuals with diabetes to double; projected economic costs of diabetes-related hospitalizations and outpatient care; and years of life lost to diabetes at age 60. Data analyses and estimations used multiple regression models, longitudinal regression models, and Lee-Carter stochastic population projections. RESULTS: Doubling time of the diabetic elderly population is projected to occur in 13 calendar years. This will cause increases in hospitalization and outpatient consultation costs. The impact of diabetes on life expectancy at age 60 around the year 2035 is estimated to lead to a loss of about 7 months of life. The rapid pace at which the absolute number of elderly people with diabetes will double is projected to result in a negative economic impact on the healthcare system. Lives will also be lost due to diabetes. CONCLUSION: Population aging will inevitably lead to an increasing number of elderly individuals, who are at greater risk for diabetes due to their lifelong exposure to risk factors. Actions to increase the quality of life of diabetic elderly are warranted. Decreasing the burden of diabetes on elderly populations and the Costa Rican healthcare system are necessary to impact the quantity and quality of life of incoming cohorts. Health promotion and prevention strategies that reduce diabetes risk factors are needed to improve the health of elderly populations.

Effect of salinity on zinc toxicity (ZnCl2 and ZnO nanomaterials) in the mosquitofish (Gambusia sexradiata).

Zn is an essential trace metal in living beings. However, excessive concentrations can cause toxic effects even in the aquatic biota. Zn is widely used in different industrial sectors, which has increased its presence in aquatic environments. To assess the acute toxicity of Zn, bioassays were performed with the fish Gambusia sexradiata for a 96-h exposure using ZnCl2 (0 and 15 salinity) and ZnO nanomaterials (0 salinity). The mean lethal concentrations (LC50-96 h) for ZnCl2 were 25.36 (19.64-32.76) and 177.91 (129.39-244.63) mg Zn L-1 to 0 and 15 salinity, respectively. The increased concentration of ZnCl2 showed a dose-response relationship; similarly, the increase in salinity significantly reduces the toxicity of Zn. Characterisation of ZnO nanomaterials was carried out by FTIR, DRX, SEM, DLS and zeta potential. The FTIR spectra showed the characteristic band of Zn-O vibration at 364 cm-1, while DRX presents the hexagonal wurtzite structure with an average crystallite size of 40 nm. SEM micrographs reveal rod-like shapes with lengths and diameters of 40-350 nm and 90 nm, respectively. Agglomerates of 423 nm in water suspension were obtained by DLS and zeta potential of + 14.4 mV. Under these conditions, no mortality was observed due to the rapid flocculation/precipitation of ZnO nanomaterials, which involved brief interaction periods of Zn in the water column with the fish. Gambusia sexradiata is affected by increased Zn concentrations in hard water conditions, and salinity changes modified Zn toxicity, placing it as a suitable model for toxicity tests for this type of particles.

Online audiovisual resources for learning the disinfection protocol for dental impressions: A critical analysis.

STATEMENT OF PROBLEM: Mainly because of poor training, substandard impression disinfection practices have been reported worldwide. PURPOSE: The purpose of this cross-sectional study was to assess the extension, usefulness, and reliability of contents on this topic available on the main video websites for self-training. MATERIAL AND METHODS: An analysis of the YouTube, Vimeo, and Dailymotion websites was undertaken in February 2018. The exclusion criteria were animal procedures, non-English language videos, advertisements, videos exclusively redirecting to websites, soundless videos, duplicated videos, and videos reporting on a research project. Information extension was assessed in 6 nonmutually exclusive dimensions, and usefulness was evaluated by using a 10-item scale. Reliability was assessed on a reliable or nonreliable basis. Statistical analyses were undertaken by using the Mann-Whitney and Fisher exact tests. RESULTS: Of 386 identified videos, only 22 met the selection criteria, mostly published by health-care professionals (n=8; 36.4%). Most videos had less than 3000 views. Median usefulness score: 3 (IR: 3-3; range: 0-6). No video included all 7 topics considered in the index (median 3; IR: 2.25-3; range: 0-4). Just 5 clips (22.7%) described a procedure according to the American Dental Association and Center for Disease Control (ADA and CDC) guidelines. CONCLUSIONS: Audiovisual online resources on dental impression disinfection includes incomplete information with limited usefulness and reliability. The number of views was not related to quality, and therefore, many viewers may be obtaining knowledge from substandard material.

Diabetes epidemics: inequalities increase the burden on the healthcare system.

Diabetes is a major cause of morbidity and mortality and represents a source of demands on already constrained healthcare systems in Latin America and the Caribbean. We estimate inequalities in diabetes incidence, prevalence and mortality and assess the economic burden on the healthcare system in Costa Rica. The main source of data is the Costa Rican Longevity and Healthy Aging Study, a longitudinal nationally representative survey of the elderly population (n = 2827). Data analyses include descriptive statistics, multiple regression models and survival analysis models. More than a fifth of Costa Rican elderly experience diabetes. Incidence is estimated at 5 per 1000 person-years in the population 30+. Gender and geographical inequalities were found. Men have a significantly lower prevalence (16.51% vs 24.02%, P < 0.05) and incidence (4.3 vs 6.0 per 1000 person-years, P < 0.05), but higher mortality (hazard ratio = 1.31, P < 0.01). Longer time to the closest facility translates into a lower probability of having the condition diagnosed [odds ratio (OR) = 0.77, P < 0.05]. The diabetic as compared to the non-diabetic population imposes a larger economic burden on the healthcare system with a higher probability of using outpatient care (OR = 3.08, P < 0.01), medications (OR = 3.44, P < 0.01) and hospitalizations (OR = 1.24, P > 0.05). Individuals living in the Metro Area have a significantly lower probability of being hospitalized (OR = 0.72, P < 0.05), which may be evidence of better access to primary care that prevents hospitalization. Along the same line, women have higher utilization rates of outpatient care (OR = 2.02, P < 0.01) and medications (OR = 1.73, P < 0.01), which may contribute to lower odds of hospitalization (OR = 0.61, P < 0.01). Aligned with the aim of attaining Sustainable Development Goals, this study highlights the importance of generating health policies focused on prevention of diabetes that take into consideration gender and geographical inequalities. Strategies should booster preventive healthcare utilization by men and aim to make healthcare services accessible to all, regardless of geographical location.

Addressing gaps in transversal educational contents in undergraduate dental education. The audio-visual 'pill of knowledge' approach.

INTRODUCTION: Training on impression disinfection is often limited to brief explanations in the clinic. This investigation assessed knowledge on this topic amongst clinical students in our university, produced a pill of knowledge to suit their needs, and evaluated its impact and acceptance. MATERIAL AND METHODS: A pre-post study was designed to identify knowledge gaps using an anonymous, voluntary self-applied questionnaire before and after watching an audio-visual clip (pill of knowledge). All 136 students in the school were invited to enter the study (estimated sample size: 116). RESULTS: Participants: 109 (26.6% in 3rd year; 37.6% in 4th year and 39.4% in 5th year). Participation dropped 10.29% (n = 95) in the post-intervention survey. Knowledge improvement was higher for those impression materials included in the pill. Most students (68.4%) reported to know more about impression disinfection after the pill and 70.5% felt more able to achieve correct disinfection. The pill was particularly well received (86.3%). All students would recommend it to their peers, and 93.5% are willing to receive pills on other topics. DISCUSSION: Our results disclosed an important gap in knowledge, which can be filled by a single, brief and concise pill adapted to the intended audience. Once made readily available through digital repositories, it may help solve this problem, given the ubiquitous presence of mobile devices. CONCLUSIONS: Our results found pills of knowledge as a useful approach to facilitating undergraduates' learning process. This method, using suitable information and communication technologies, has the potential to improve the performance on certain clinical tasks.

Global Assessment of Schistosomiasis Control Over the Past Century Shows Targeting the Snail Intermediate Host Works Best.

BACKGROUND: Despite control efforts, human schistosomiasis remains prevalent throughout Africa, Asia, and South America. The global schistosomiasis burden has changed little since the new anthelmintic drug, praziquantel, promised widespread control. METHODOLOGY: We evaluated large-scale schistosomiasis control attempts over the past century and across the globe by identifying factors that predict control program success: snail control (e.g., molluscicides or biological control), mass drug administrations (MDA) with praziquantel, or a combined strategy using both. For data, we compiled historical information on control tactics and their quantitative outcomes for all 83 countries and territories in which: (i) schistosomiasis was allegedly endemic during the 20th century, and (ii) schistosomiasis remains endemic, or (iii) schistosomiasis has been "eliminated," or is "no longer endemic," or transmission has been interrupted. PRINCIPAL FINDINGS: Widespread snail control reduced prevalence by 92 ± 5% (N = 19) vs. 37 ± 7% (N = 29) for programs using little or no snail control. In addition, ecological, economic, and political factors contributed to schistosomiasis elimination. For instance, snail control was most common and widespread in wealthier countries and when control began earlier in the 20th century. CONCLUSIONS/SIGNIFICANCE: Snail control has been the most effective way to reduce schistosomiasis prevalence. Despite evidence that snail control leads to long-term disease reduction and elimination, most current schistosomiasis control efforts emphasize MDA using praziquantel over snail control. Combining drug-based control programs with affordable snail control seems the best strategy for eliminating schistosomiasis.