Incidence and case-fatality rate of stroke in General Villegas, Buenos Aires, Argentina. The EstEPA population study.

OBJECTIVES: Stroke epidemiology varies among different populations. The burden of stroke is high in low- and middle-income countries. Reliable population data is needed to assess the impact of stroke and to develop policies aimed to improve stroke care in our region. EstEPA is a population-based project assessing prevalence, incidence, mortality and burden of stroke in General Villegas Department, Buenos Aires, Argentina (pop=30,864 inhabitants). We determined incidence of stroke (first-ever and recurrent stroke) and stroke case-fatality rate from 2017 to 2020. METHODS: First-ever strokes, recurrent strokes and transient ischemic attacks were ascertained and case-fatality rate was obtained. Diagnoses were based on standard AHA/WHO definitions. Study population included all persons residing in General Villegas during the three-year period. Hospitals, households, nursing homes, death certificates and several overlapping sources were surveyed. RESULTS: We assessed 92,592 person-years. There were 155 cerebrovascular events aged 70 years (SD ± 13 years), of which 115 were first-ever strokes (74%), 21 recurrent strokes (13.5%) and 19 transient ischemic attacks (12.5%). The crude overall incidence rate of first-ever strokes was 124.2 per 100,000 population (86.9 per 100,000 [95% CI 58.5-115.2] when standardized by WHO World population and 109.7 per 100,000 [95% CI 89.7-129.8] when standardized by Argentine population) and 317.0 per 100,000 population in subjects older than 40 years. Case fatality rate at 30 days of first-ever strokes was 27%. CONCLUSION: In this population-based comprehensive stroke epidemiological study in Argentina, first-ever stroke incidence in an urban population was 124.2 per 100,000 population (86.9 per 100,000 adjusted by the WHO World population). This is lower than the incidence in other countries in the region and similar to a recent incidence study in Argentina. It is also comparable to reported incidence in most middle- and high-income countries. Stroke case-fatality rate was comparable to other population-based Latin-American studies.

Control of Vascular Risk Factors and Response to Stroke Symptoms in Argentina During the COVID-19 Quarantine. The SIFHON-COVID Population Survey.

Background and Objectives: In preparation for the suspected influx of COVID-19 patients, many healthcare systems reduced or discontinued provision of "non-urgent" care. This decision had potential impact on stroke prevention and management. We conducted a large population survey to assess the effect of mandatory social isolation on routine health controls, emergency consultations and other stroke care-related behaviors of the population during the pandemic. Methods: We distributed multiple-choice anonymous questionnaires through the institutional email database and through the email database of clients of a beverage delivery company. Most respondents resided in the metropolitan area of Buenos Aires. This is the area where the infection rates were highest and restriction measures were hardest. The survey assessed demographic characteristics and actual and potential behaviors of people regarding medical checkups, risk factors control, medication provision and response to onset of symptoms consistent with stroke or TIA. Surveys were sent during May 2020, the strictest period of the quarantine in Argentina. Results: A total of 10,303 questionnaires were completed. Thirty-seven percent of the respondents were older than 60 years, 74% were women and 16% lived alone. Vascular risk factors were present in 39% of the individuals. Seventy-six percent did not continue with their regular medical checkups during the mandatory social and preventive isolation, 21% had difficulty obtaining medical prescriptions and only 38% considered that health institutions had implemented reliable safety measures to avoid exposure to COVID-19. When asked about response in case of onset of stroke symptoms, 9% would not consult given the context of the pandemic. Six percent reported having had symptoms consistent with stroke or TIA but only 35% went to a hospital. The vast majority of the respondents said they were awaiting for the end of the quarantine to resume their usual medical care. Conclusions: The implementation of a quarantine may have some serious adverse effects on the prevention, diagnosis and treatment of stroke. These undesirable aspects should be taken into consideration in the planning, communication and implementation of health policies.

MODY patients exhibit shorter telomere length than non-diabetic subjects.

BACKGROUND: Given the increasing evidence supporting the association between telomere shortening and diabetes, the aim of the present work was to establish whether MODY patients suffer a reduction in telomere lenght (TL) due to oxidative stress produced by chronic hyperglycemia, despite not presenting insulin resistance or inflammation. METHODS: We analysed clinical and biochemical parameters in 35 MODY2 and 12 MODY3 patients compared with 48 control subjects. The absolute telomere length (aTL) of peripheral blood leukocytes was measured using the quantitative polymerase chain reaction (qPCR). RESULTS: A significant negative correlation was observed between aTL and age in the whole population, among MODY patients and in each subtype studied, MODY2 and MODY3, which allowed us to validate the method. We found, for the first time, that MODY patients have shorter aTL with respect to non-diabetic controls (6.49 ± 3.31 kbp vs 11.13 ± 7.82 kbp, p = .006). However, no differences were found between MODY2 and MODY3. In addition, aTL showed a negative correlation with duration of the disease and fasting plasma glucose (FPG) levels in MODY patients in general and also with HbA1c in MODY2 patients in particular. CONCLUSIONS: Both MODY2 and MODY3 types present telomere shortening, which, at least partly, responds to HbA1c and FPG levels. These findings suggest comparable mechanisms underlying the attrition of TL. Taken together, our results on aTL in MODY patients may provide a parameter relatively easy and inexpensive to quantify in order to measure the impact of high glucose levels and potentially carry out antidiabetic treatment with stricter targets.

[Polymorphism in CYP11alpha and CYP17 genes and the etiology of hyperandrogenism in patients with polycystic ovary syndrome]. / Polimorfismos en los genes CYP11alpha y CYP17 y etiología del hiperandrogenismo en pacientes con poliquistosis ovárica.

The polycystic ovary syndrome (PCOS) is a heterogeneous multifactorial endocrine metabolic disorder with genetic predisposition affecting 6% of women in the reproductive age. This syndrome is characterized by the presence of oligo-anovulation, hyperandrogenism and polycystic ovaries. Several genes have been postulated as responsible for the etiology of this disorder. Among these genes are those encoding the enzymes involved in the ovarian androgen biosynthesis. Two of the candidate genes are the CYP17 and the CYP11alpha, encoding the 17-alpha-hydroxylase (P45017alpha) and the cholesterol side chain cleavage (P450scc) respectively. The polymorphisms of these genes are linked to the development of an hyperandrogenic phenotype. The aim of this work was to analyze the allelic frequencies of such polymorphisms in a cohort of women with PCOS and to compare them with those of healthy women. Furthermore, the correlation between each allelic variant and the corresponding hyperandrogenic phenotype was also assessed. Therefore, 65 patients and 58 age matched healthy controls were analyzed. The serum levels of testosterone and the frequency of each polymorphism were determined. When the PCOS population was analyzed, a significant statistical difference was found when relating the group with the highest androgenemia level with the presence of A2/A2 genotype of CYP 17 gene, and a higher level of circulating androgen was found in PCO women carrying the 216- allele of CYP11alpha gene (that did not reach statistical significance). Our results suggest that both alleles play a minor role in the development of PCOS and could be a genetic risk marker of the hyperandrogenic phenotype.

Polimorfismos en los genes CYP11α y CYP17 y etiología del hiperandrogenismo en pacientes con poliquistosis ovárica / Polymorphism in CYP11alpha and CYP17 genes and the etiology of hyperandrogenism in patients with polycystic ovary syndrome

El síndrome de poliquistosis ovárica (PCOS) es un desorden endocrino-metabólico de naturaleza multifactorial, con una marcada predisposición genética, que afecta al 6% de las mujeres en edad reproductiva. Se caracteriza por la presencia de hiperandrogenismo, oligo-anovulación y ovarios poliquísticos. Entre los genes candidatos se encuentran aquellos que codifican para enzimas que actúan en la síntesis de andrógenos. Dos de los genes candidatos son el CYP17 y el CYP11alfa que codifican para la 17alfa hidroxilasa (P45017alfa) y para el P450scc (colesterol side chain cleavage) respectivamente. Los polimorfismos en estos genes están asociados al desarrollo del fenotipo hiperandrogénico. Nuestro objetivo fue analizar las frecuencias alélicas de los polimorfismos de los dos genes mencionados en población con PCOS, compararla con población normal y analizar la relación de cada variante alélica con el fenotipo hiperandrogénico correspondiente. Se analizaron 65 pacientes y 58 controles sanos en los que se determinaron niveles de testosterona y frecuencia de polimorfismos en los genes mencionados. Se observó una diferencia estadísticamente significativa cuando se asoció el grupo de mayor nivel de androgenemia con la presencia del genotipo A2/A2 del gen CYP17, y se hallaron mayores niveles de andrógenos circulantes en las pacientes con PCOS portadoras del alelo 216- del gen CYP11alfa. Nuestros resultados sugieren que ambos alelos juegan un rol menor en el desarrollo de PCOS y podrían ser considerados como potenciales marcadores de riesgo genético para el desarrollo del fenotipo hiperandrogénico.

The polycystic ovary syndrome (PCOS) is a heterogeneous multifactorial endocrine metabolic disorder with genetic predisposition affecting 6% of women in the reproductive age. This syndrome is characterized by the presence of oligo-anovulation, hyperandrogenism and polycystic ovaries. Several genes have been postulated as responsible for the etiology of this disorder. Among these genes are those encoding the enzymes involved in the ovarian androgen biosynthesis. Two of the candidate genes are the CYP17 and the CYP11alpha, encoding the 17-alpha-hydroxylase (P45017alpha) and the cholesterol side chain cleavage (P450scc) respectively. The polymorphisms of these genes are linked to the development of an hyperandrogenic phenotype. The aim of this work was to analyze the allelic frequencies of such polymorphisms in a cohort of women with PCOS and to compare them with those of healthy women. Furthermore, the correlation between each allelic variant and the corresponding hyperandrogenic phenotype was also assessed. Therefore, 65 patients and 58 age matched healthy controls were analyzed. The serum levels of testosterone and the frequency of each polymorphism were determined. When the PCOS population was analyzed, a significant statistical difference was found when relating the group with the highest androgenemia level with the presence of A2/A2 genotype of CYP 17 gene, and a higher level of circulating androgen was found in PCO women carrying the 216- allele of CYP11alpha gene (that did not reach statistical significance). Our results suggest that both alleles play a minor role in the development of PCOS and could be a genetic risk marker of the hyperandrogenic phenotype.

Bayesian network multi-classifiers for protein secondary structure prediction.

Successful secondary structure predictions provide a starting point for direct tertiary structure modelling, and also can significantly improve sequence analysis and sequence-structure threading for aiding in structure and function determination. Hence the improvement of predictive accuracy of the secondary structure prediction becomes essential for future development of the whole field of protein research. In this work we present several multi-classifiers that combine the predictions of the best current classifiers available on Internet. Our results prove that combining the predictions of a set of classifiers by creating composite classifiers is a fruitful one. We have created multi-classifiers that are more accurate than any of the component classifiers. The multi-classifiers are based on Bayesian networks. They are validated with 9 different datasets. Their predictive accuracy results outperform the best secondary structure predictors by 1.21% on average. Our main contributions are: (i) we improved the best know predictive accuracy by 1.21%, (ii) our best results have been obtained with a new semi naïve Bayes approach named Pazzani-EDA and (iii) our multi-classifiers combine results of previously build classifiers predictions obtained through Internet, thanks to our development of a Java application.

17alpha-hydroxylase deficiency : biochemical and molecular findings in two sisters and their family.

OBJECTIVE: To search for molecular changes in two Argentinian sisters with a clinical and biochemical diagnosis of 17alpha-hydroxylase deficiency. SUBJECTS: Both patients had 46 XX karyotype, with sexual infantilism, primary amenorrhea, and hypertension. Other member of the first degree family did not have this deficiency. HORMONAL RESULTS: The patients showed high levels of gonadotrophins and progesterone along with very low cortisol and androgen levels. Basal levels of corticosterone were very high, but aldosterone was normal. Both steroids had a high response after adrenocorticotropic hormone (ACTH) stimulation, with no changes in 17-hydroxyl progesterone and cortisol levels. Progesterone, corticosterone, and aldosterone decreased with the dexamethasone test, without modifications in 17-hydroxyl progesterone and cortisol levels. A corticosterone/aldosterone ratio was calculated from the results of the stimulation test; the ratios were similar in both patients. On administration of the ACTH test, both parents and one sister (S2) showed a marked response in corticosterone levels, their corticosterone/aldosterone ratios were also similar to each other and similar to the patients. MOLECULAR RESULTS: Molecular studies in the cytochrome P450 17 (CYP17) gene showed that exon 8 had a 4 bp duplication at codon 480 (CATC) in the two patients and their mother and in exon 1, a C to T transition at codon 96 was identified, changing CGG into TGG in the two patients, S2, and their father. CONCLUSIONS: Both patients were shown to be compound heterozygous, carrying different alleles in exon 1 and exon 8, inherited from their father and mother, respectively. The molecular results obtained on S2 confirmed the heterozygosity suggested by the stimulated hormonal test and corticosterone/aldosterone ratio.