Individual-specific levels of CTG•CAG somatic instability are shared across multiple tissues in myotonic dystrophy type 1.

Myotonic dystrophy type 1 is a complex disease caused by a genetically unstable CTG repeat expansion in the 3'-untranslated region of the DMPK gene. Age-dependent, tissue-specific somatic instability has confounded genotype-phenotype associations, but growing evidence suggests that it also contributes directly toward disease progression. Using a well-characterized clinical cohort of DM1 patients from Costa Rica, we quantified somatic instability in blood, buccal cells, skin and skeletal muscle. Whilst skeletal muscle showed the largest expansions, modal allele lengths in skin were also very large and frequently exceeded 2000 CTG repeats. Similarly, the degree of somatic expansion in blood, muscle and skin were associated with each other. Notably, we found that the degree of somatic expansion in skin was highly predictive of that in skeletal muscle. More importantly, we established that individuals whose repeat expanded more rapidly than expected in one tissue (after correction for progenitor allele length and age) also expanded more rapidly than expected in other tissues. We also provide evidence suggesting that individuals in whom the repeat expanded more rapidly than expected in skeletal muscle have an earlier age at onset than expected (after correction for the progenitor allele length). Pyrosequencing analyses of the genomic DNA flanking the CTG repeat revealed that the degree of methylation in muscle was well predicted by the muscle modal allele length and age, but that neither methylation of the flanking DNA nor levels of DMPK sense and anti-sense transcripts could obviously explain individual- or tissue-specific patterns of somatic instability.

Myotonic dystrophy type 1 (DM1) clinical subtypes and CTCF site methylation status flanking the CTG expansion are mutant allele length-dependent.

Myotonic dystrophy type 1 (DM1) is a complex disease with a wide spectrum of symptoms. The exact relationship between mutant CTG repeat expansion size and clinical outcome remains unclear. DM1 congenital patients (CDM) inherit the largest expanded alleles, which are associated with abnormal and increased DNA methylation flanking the CTG repeat. However, DNA methylation at the DMPK locus remains understudied. Its relationship to DM1 clinical subtypes, expansion size and age-at-onset is not yet completely understood. Using pyrosequencing-based methylation analysis on 225 blood DNA samples from Costa Rican DM1 patients, we determined that the size of the estimated progenitor allele length (ePAL) is not only a good discriminator between CDM and non-CDM cases (with an estimated threshold at 653 CTG repeats), but also for all DM1 clinical subtypes. Secondly, increased methylation at both CTCF sites upstream and downstream of the expansion was almost exclusively present in CDM cases. Thirdly, levels of abnormal methylation were associated with clinical subtype, age and ePAL, with strong correlations between these variables. Fourthly, both ePAL and the intergenerational expansion size were significantly associated with methylation status. Finally, methylation status was associated with ePAL and maternal inheritance, with almost exclusively maternal transmission of CDM. In conclusion, increased DNA methylation at the CTCF sites flanking the DM1 expansion could be linked to ePAL, and both increased methylation and the ePAL could be considered biomarkers for the CDM phenotype.

Frailty as a predictor of mortality: a comparative cohort study of older adults in Costa Rica and the United States.

BACKGROUND: Frailty is a common condition among older adults that results from aging-related declines in multiple systems. Frailty increases older adults' vulnerability to negative health outcomes, including loss of mobility, falls, hospitalizations, and mortality. The aim of this study is to examine the association between frailty and mortality in older adults from Costa Rica and the United States. METHODS: This prospective cohort study uses secondary nationally-representative data of community-dwelling older adults from the Costa Rican Longevity and Healthy Aging Study (CRELES, n = 1,790) and the National Health & Aging Trends Study (NHATS, n = 6,680). Frailty status was assessed using Physical Frailty Phenotype, which includes the following five criteria: shrinking, exhaustion, low physical activity, muscle weakness, and slow gait. We used Cox proportional hazard models to examine the association between frailty and all-cause mortality, including sociodemographic characteristics and health behaviors as covariates in the models. Mortality follow-up time was right censored at 8 years from the date at baseline interview. RESULTS: The death hazard for frail compared to non-frail older adults was three-fold in Costa Rica (HR = 3.14, 95% CI: 2.13-4.62) and four-fold in the White US (HR = 4.02, 95% CI: 3.04-5.32). Older age, being male, and smoking increased mortality risk in both countries. High education was a protective factor in the US, whereas being married/in union was a protective factor in Costa Rica. In the US, White older adults had a lower risk of death compared to all other races and ethnicities. CONCLUSIONS: Results indicate that frailty can have a differential impact on mortality depending on the country. Access to universal health care across the life course in Costa Rica and higher levels of stress and social isolation in the US may explain differences observed in end-of-life trajectories among frail older adults.

Longitudinal increases in somatic mosaicism of the expanded CTG repeat in myotonic dystrophy type 1 are associated with variation in age-at-onset.

In myotonic dystrophy type 1 (DM1), somatic mosaicism of the (CTG)n repeat expansion is age-dependent, tissue-specific and expansion-biased. These features contribute toward variation in disease severity and confound genotype-to-phenotype analyses. To investigate how the (CTG)n repeat expansion changes over time, we collected three longitudinal blood DNA samples separated by 8-15 years and used small pool and single-molecule PCR in 43 DM1 patients. We used the lower boundary of the allele length distribution as the best estimate for the inherited progenitor allele length (ePAL), which is itself the best predictor of disease severity. Although in most patients the lower boundary of the allele length distribution was conserved over time, in many this estimate also increased with age, suggesting samples for research studies and clinical trials should be obtained as early as possible. As expected, the modal allele length increased over time, driven primarily by ePAL, age-at-sampling and the time interval. As expected, small expansions <100 repeats did not expand as rapidly as larger alleles. However, the rate of expansion of very large alleles was not obviously proportionally higher. This may, at least in part, be a result of the allele length-dependent increase in large contractions that we also observed. We also determined that individual-specific variation in the increase of modal allele length over time not accounted for by ePAL, age-at-sampling and time was inversely associated with individual-specific variation in age-at-onset not accounted for by ePAL, further highlighting somatic expansion as a therapeutic target in DM1.

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.

[Intake of processed meats by Costa Rican women: effect of socioeconomic status]. / Consumo de embutidos en mujeres costarricenses: efecto del nivel socioeconómico.

Introduction: Intake of processed meats has been associated with serious health problems that are common among women. In 2015, the International Agency for Research on Cancer classified processed meats as human carcinogens, associated specifically with colon cancer. The increase in intake of processed meats, which are a low-cost source of dietary protein, varies by socioeconomic status (SES) and can impact chronic disease incidence. Objective: Examine the association between processed meats intake and (a) total protein intake, (b) inadequate protein intake, by SES. Methods: This study included a representative sample (N = 135) of women age 25 to 45 years, with one to four children, from three different socioeconomic groups who were residents of two counties from the Greater Metropolitan Area of San José, Costa Rica between June 2014 and March 2015. Using photographs, we examined women's perceptions of the cost and perceived desirability of 12 different foods, including processed meats. Using 24-hour dietary recalls collected on three different days, and the ValorNut food composition database, we estimated total protein intake, in grams, and determined the intake frequency (times/day) of processed meat. Each women's dietary protein requirement was estimated based on her bodyweight. Inadequate protein intake was calculated as the difference between protein requirement and actual intake. A linear regression model was used to determine the association between total protein intake in grams and intake frequency (times/day) of processed meat. A logistic regression model was used to estimate the association between low protein intake and intake frequency (times/day) of processed meat. Results: Processed meats were perceived as the least preferred protein source but were the third most commonly consumed protein source. Consumption of processed meats differed by SES and was lower in the higher SES group (P < 0.01). The most commonly consumed processed meats by SES were "mortadella" (low-SES), sausages (middle-SES), and sliced turkey/ham (high-SES). Processed meat intake was significantly associated with an increase in protein intake. There was an inverse association between SES and inadequate protein intake. Conclusions: Processed meat intake is associated with SES. Women may consume processed meats because they are perceived to be a low-cost protein source. Educational strategies are needed to help women identify their protein needs and meet those needs with healthier and affordable dietary alternatives.

Socioeconomic inequalities in cancer mortality: Is Costa Rica an exception to the rule?

Socioeconomic inequalities in cancer mortality have been described for a range of cancers sites worldwide, using diverse measures of socioeconomic position (SEP). These studies have shown a negative social gradient where lower SEP was associated with greater odds of having cancer, particularly in men. However, there is a lack of information regarding low and middle-income countries. The objective of our study was to analyze the relationship between the socioeconomic characteristics of patients' residential districts and mortality due to cancer in Costa Rica between 2011 and 2017. An ecological study at the level of the district of residence was conducted using the multilevel mixed-effects Poisson regression. All cancer-caused deaths between January 1, 2011 and December 31, 2017 were included (n = 32,117). Eleven cancer sites were analyzed independently. The 477 Costa Rican districts were divided by area (urban/mixed/rural) and wealth using census data. All-cancer combined a significant association between cancer mortality and wealth was found. Cancer mortality was lower in the poorest as compared to the richest districts (IRRQ4 = 0.79 [0.73-0.86]). The majority of cancer sites followed a similar pattern, showing a positive social gradient. These results contradict the international literature mostly conducted in high-income countries. These findings confirmed the importance of conducting studies in middle-income countries, since the socioeconomic and cultural contexts are different from those in high-income countries, which influence the social distribution of lifestyles and risk behaviors.

A Somatic Coliphage Threshold Approach To Improve the Management of Activated Sludge Wastewater Treatment Plant Effluents in Resource-Limited Regions.

Effective wastewater management is crucial to ensure the safety of water reuse projects and effluent discharge into surface waters. Multiple studies have demonstrated that municipal wastewater treatment with conventional activated sludge processes is inefficient for the removal of a wide spectrum of viruses in sewage. In this study, a well-accepted statistical approach was used to investigate the relationship between viral indicators and human enteric viruses during wastewater treatment in a resource-limited region. Influent and effluent samples from five urban wastewater treatment plants (WWTPs) in Costa Rica were analyzed for somatic coliphage and human enterovirus, hepatitis A virus, norovirus genotypes I and II, and rotavirus. All WWTPs provide primary treatment followed by conventional activated sludge treatment prior to discharge into surface waters that are indirectly used for agricultural irrigation. The results revealed a statistically significant relationship between the detection of at least one of the five human enteric viruses and somatic coliphage. Multiple logistic regression and receiver operating characteristic curve analysis identified a threshold of 3.0 × 103 (3.5 log10) somatic coliphage PFU per 100 ml, which corresponded to an increased likelihood of encountering enteric viruses above the limit of detection (>1.83 × 102 virus targets/100 ml). Additionally, quantitative microbial risk assessment was executed for farmers indirectly reusing WWTP effluent that met the proposed threshold. The resulting estimated median cumulative annual disease burden complied with World Health Organization recommendations. Future studies are needed to validate the proposed threshold for use in Costa Rica and other regions.IMPORTANCE Effective wastewater management is crucial to ensure safe direct and indirect water reuse; nevertheless, few countries have adopted the virus log reduction value management approach established by the World Health Organization. In this study, we investigated an alternative and/or complementary approach to the virus log reduction value framework for the indirect reuse of activated sludge-treated wastewater effluent. Specifically, we employed a well-accepted statistical approach to identify a statistically sound somatic coliphage threshold value which corresponded to an increased likelihood of human enteric virus detection. This study demonstrates an alternative approach to the virus log reduction value framework which can be applied to improve wastewater reuse practices and effluent management.

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.

Variation in dietary intake and body fatness by socioeconomic status among women in the context of Costa Rican nutrition transitions.

The Nutrition Transition model posits that vegetable oils, animal source foods (ASFs) and caloric sweeteners contribute to increases in adiposity and hence body mass index. Body mass index (BMI) is increasing more rapidly among Latin American populations of low versus high socioeconomic status (SES). The objectives of this study among Costa Rican women were to: (1) compare indicators of adiposity and dietary intake by SES and (2) evaluate the relationship between intake of foods high in vegetable oils, ASFs or caloric sweeteners and body fatness. This cross-sectional study, conducted in 2014-2015, included 128 low-, middle- and high-SES non-pregnant, non-lactating women aged between 25 and 45 years with 1-4 live births. Anthropometry was used to assess BMI, body composition and body fat distribution. Dietary recalls (n = 379) were used to assess dietary intake. Percentage body fat was greater in low- versus high-SES women (31.5 ± 3.9 vs 28.2 ± 4.7%). Skinfold measurements at four sites on the upper and lower body were greater in low- versus high-SES women. Body mass index did not vary in low- versus high-SES women. Intake frequency of foods high in vegetable oils was greater in low- and middle- (1.8 and 1.8 times/day, respectively) versus high- (1.1 times/day) SES women. For individual foods, intake frequency varied significantly by SES for high-fat condiments, fried vegetables, dairy, sweetened coffee/tea and pastries and desserts. Intake frequency of Nutrition Transition food categories was not associated with percentage body fat after adjustment for energy intake. Indicators of body composition provide additional information beyond BMI that are useful in understanding SES-adiposity associations in Latin America. Approaches to understanding diet and adiposity in Latin America that focus on vegetable oils, ASFs and caloric sweeteners should consider within-country variation in the pace of the Nutrition Transition, especially when explaining variation in adiposity by SES.

Costa Rican Mortality 1950-2013: An Evaluation of Data Quality and Trends Compared with Other Countries.

BACKGROUND: Mortality estimates from various sources suggest that Costa Ricans experience record-high life expectancy at birth in Latin America and higher longevity than the populations of many high-income countries, although there is some uncertainty as to the reliability of those estimates. OBJECTIVE: We construct a life table series for Costa Rica to assess the quality of national demographic statistics for the period 1950-2013 and to determine whether reliable mortality estimates can be directly calculated from these data. METHODS: We apply the methods from the Human Mortality Database (HMD) to national statistics to construct the Costa Rica life table series without adjusting for data quality, and we validate our results through internal consistency by evaluating the plausibility of the mortality patterns and its change over time and through external consistency by comparing our results with those from other sources. RESULTS: Our mortality estimates for Costa Rica tend to be lower than others, especially for the period before 1970. They also produce a suspicious age pattern of mortality, with low adult and old-age mortality relative to the infant and child mortality, casting doubt on the quality of national demographic data. CONCLUSIONS: Other organizations have produced mortality estimates for Costa Rica that are higher than our unadjusted estimates, but it is difficult to evaluate the accuracy of the available estimates. CONTRIBUTION: This analysis provides a more thorough evaluation of data quality issues regarding Costa Rica mortality than previously available. Unadjusted life tables by sex for 1950-2013 are included as supplemental material, together with the raw data upon which those life tables are based and with links to the detailed methods protocol implemented.

Using the protein leverage hypothesis to understand socioeconomic variation in obesity.

OBJECTIVES: The protein leverage hypothesis (PLH) predicts that protein appetite will stimulate excess energy intake, and consequently obesity, when the proportion of protein in the diet is low. Experimental studies support the PLH, but whether protein leverage can be used to understand socioeconomic (SES) variation in obesity is unknown. The objective of this study was to test two hypotheses from the PLH under non-experimental conditions. Consistent with the PLH, we expect that (1) absolute protein intake will be similar across populations, here defined as SES groups and, (2) the proportion of protein in the diet will be inversely associated with energy intake. METHODS: This was a cross-sectional study conducted in a random sample of 135 low-, middle-, and high-SES women in Costa Rica. Anthropometry was used to calculate body mass index (BMI). Twenty-four-hour dietary recalls were used to measure dietary intake. RESULTS: The prevalence of obesity varied between low- (38.8%), middle- (43.9%), and high- (17.8%) SES women. Absolute protein intake was similar across low- (58.5 g), middle- (59.4 g), and high- (65.6 g) SES women (p = 0.12). Protein intake as a proportion of total energy intake was inversely associated with total energy intake only among middle- (r = -0.37, p = 0.02) and high- (r = -0.36, p = 0.01) SES women. CONCLUSIONS: Consistent with the PLH, absolute protein intake was similar across SES groups. The relationship between the proportion of protein in the diet and total energy intake should be studied further in the context of real world conditions that may influence protein leverage.

Challenges detecting SARS-CoV-2 in Costa Rican domestic wastewater and river water.

This study presents the development of a SARS-CoV-2 detection method for domestic wastewater and river water in Costa Rica, a middle-income country in Central America. Over a three-year period (November to December 2020, July to November 2021, and June to October 2022), 80 composite wastewater samples (43 influent and 37 effluent) were collected from a Wastewater Treatment Plant (SJ-WWTP) located in San José, Costa Rica. Additionally, 36 river water samples were collected from the Torres River near the SJ-WWTP discharge site. A total of three protocols for SARS-CoV-2 viral concentration and RNA detection and quantification were analyzed. Two protocols using adsorption-elution with PEG precipitation (Protocol A and B, differing in the RNA extraction kit; n = 82) were used on wastewater samples frozen prior to concentration, while wastewater (n = 34) collected in 2022 were immediately concentrated using PEG precipitation. The percent recovery of Bovine coronavirus (BCoV) was highest using the Zymo Environ Water RNA (ZEW) kit with PEG precipitation executed on the same day as collection (mean 6.06 % ± 1.37 %). It was lowest when samples were frozen and thawed, and viruses were concentrated using adsorption-elution and PEG concentration methods using the PureLink™ Viral RNA/DNA Mini (PLV) kit (protocol A; mean 0.48 % ± 0.23 %). Pepper mild mottle virus and Bovine coronavirus were used as process controls to understand the suitability and potential impact of viral recovery on the detection/quantification of SARS-CoV-2 RNA. Overall, SARS-CoV-2 RNA was detected in influent and effluent wastewater samples collected in 2022 but not in earlier years when the method was not optimized. The burden of SARS-CoV-2 at the SJ-WWTP decreased from week 36 to week 43 of 2022, coinciding with a decline in the national COVID-19 prevalence rate. Developing comprehensive nationwide surveillance programs for wastewater-based epidemiology in low-middle-income countries involves significant technical and logistical challenges.

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.

Social inequalities in cancer survival: A population-based study using the Costa Rican Cancer Registry.

BACKGROUND: Social inequalities in survival after cancer diagnosis have been described in several high-income countries, all cancer sites combined and for several specific cancer sites. The objective of this study was to analyze 5-year net survival after cancer diagnosis in a middle-income country (Costa Rica), according to the characteristics at the district level. METHODS: Costa Rican Cancer Registry is a national population-based registry. All cases diagnosed between January 1, 2011 and December 31, 2015 were included (N = 46,904). Deaths that occurred before December 31, 2018 were identified. An ecological study was implemented. The 477 districts were described using the 2011 Census. Urbanity and wealth was assessed. Socioeconomic inequalities in cancer survival were measured using multivariable flexible parametric models. Life tables by socio-economic status were used. RESULTS: 5-year net survival ranged from 9% for liver cancer to 98 % for in situ cervical cancer. Patients living in socioeconomically disadvantaged districts experienced poorer cancer survival at 5 years, after taking into account the inequalities in survival in the general population (HR = 1.23, p < 0.01). This result was robust and was found at 1, 2 and 5 years, in all-cancer combined, and in low-, medium- and high-lethality cancers. There was no difference according to the area, except for low-lethality cancers at 1 year. DISCUSSION: Despite its universal and solidarity-based health system, Costa Rica is experiencing social inequalities in survival after cancer diagnosis.

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.

Analysis of mutational dynamics at the DMPK (CTG)n locus identifies saliva as a suitable DNA sample source for genetic analysis in myotonic dystrophy type 1.

Genotype-to-phenotype correlation studies in myotonic dystrophy type 1 (DM1) have been confounded by the age-dependent, tissue-specific and expansion-biased features of somatic mosaicism of the expanded CTG repeat. Previously, we showed that by controlling for the confounding effects of somatic instability to estimate the progenitor allele CTG length in blood DNA, age at onset correlations could be significantly improved. To determine the suitability of saliva DNA as a source for genotyping, we used small pool-PCR to perform a detailed quantitative study of the somatic mutational dynamics of the CTG repeat in saliva and blood DNA from 40 DM1 patients. Notably, the modal allele length in saliva was only moderately higher in saliva and not as large as previously observed in most other tissues. The lower boundary of the allele distribution was also slightly higher in saliva than it was in blood DNA. However, the progenitor allele length estimated in blood explained more of the variation in age at onset than that estimated from saliva. Interestingly, although the modal allele length was slightly higher in saliva, the overall degree of somatic variation was typically lower than in blood DNA, revealing new insights into the tissue-specific dynamics of somatic mosaicism. These data indicate that saliva constitutes an accessible, non-invasive and suitable DNA sample source for performing genetic studies in DM1.

Factors associated with hypertension prevalence, unawareness and treatment among Costa Rican elderly.

BACKGROUND: Reliable information on the prevalence of hypertension is crucial in the development of health policies for prevention, control, and early diagnosis of this condition. This study describes the prevalence of hypertension among Costa Rican elderly, and identifies co-factors associated with its prevalence, unawareness and treatment. METHODS: The prevalence of hypertension is estimated for the Costa Rican elderly. Measurement error is assessed, and factors associated with high blood pressure are explored. Data for this study came from a nationally representative sample of about 2,800 individuals from CRELES (Costa Rica: Longevity and Healthy Aging Study). Two blood pressure measures were collected using digital monitors. Self reports of previous diagnosis, and medications taken were also recorded as part of the study. RESULTS: No evidence of information bias was found among interviewers, or over time. Hypertension prevalence in elderly Costa Ricans was found to be 65% (Males = 60%, Females = 69%). Twenty-five percent of the studied population did not report previous diagnoses of hypertension, but according to our measurement they had high blood pressure. The proportion of unaware men is higher than the proportion of unaware women (32% vs. 20%). The main factors associated with hypertension are: age, being overweight or obese, and family history of hypertension. For men, current smokers are 3 times more likely to be unaware of their condition than non smokers. Both men and women are less likely to be unaware of their condition if they have a family history of hypertension. Those women who are obese, diabetic, have suffered heart disease or stroke, or have been home visited by community health workers are less likely to be unaware of their hypertension. The odds of being treated are higher in educated individuals, those with a family history of hypertension, elderly with diabetes or those who have had heart disease. CONCLUSION: Sex differences in terms of hypertension prevalence, unawareness, and treatment in elderly people have been found. Despite national programs for hypertension detection and education, unawareness of hypertension remains high, particularly among elderly men. Modifiable factors identified to be associated with prevalence such as obesity and alcohol intake could be used in educational programs aimed at the detection and treatment of those individuals who have the condition.

Inequality in the Incidence of Cervical Cancer: Costa Rica 1980-2010.

Introduction: Cervical cancer is the third most incident and the fourth most lethal cancer among Costa Rican women. The purpose of this study was to quantify incidence inequality along three decades and to explore its determinants. Materials and Methods: This is a population-based study. Main data sources were the National Tumor Registry (1980-2010), CRELES (Costa Rican Longevity and Healthy Aging Study) longitudinal survey (2013), and published indices of economic condition (2007) and access to healthcare (2000). Cartography was made with QGIS software. Inequality was quantified using the Theil-T index. With the purpose of detecting differences by tumor's behavior, inequality was estimated for "in situ" and invasive incidence. In Situ/Invasive Ratios were estimated as an additional marker of inequality. Poisson and spatial regression analyses were conducted with Stata and ArcMap software, respectively, to assess the association between incidence and social determinants such as economic condition, access to healthcare and sub-utilization of Papanicolaou screening. Results: As measured by Theil-T index, incidence inequality has reached high (83 to 87%) levels during the last three decades. For invasive cervical cancer, inequality has been rising especially in women aged 50-59; increasing from 58% in the 1980's to 66% in 2000's. Poisson regression models showed that sub-utilization of Papanicolaou smear was associated with a significant decrease in the probability of early diagnosis. Costa Rican guidelines establish a Pap smear every 2 years; having a Pap smear every 3 years or longer was associated with a 36% decrease in the probability of early "in situ" diagnosis (IRR = 0.64, p = 0.003) in the last decade. Spatial regression models allowed for the detection of specific areas where incidence of invasive cervical cancer was higher than expected. Conclusion: Results from this study provide evidence of inequality in the incidence of cervical cancer, which has been high over three decades, and may be explained by sub-utilization of Papanicolaou smear screening in certain regions. The reasons why women do not adequately use screening must be addressed in future research. Interventions should be developed to stimulate the utilization of screening especially among women aged 50 to 59 where inequality has been rising.