Comparación de frecuencias alélicas y genotípicas de los polimorfismos CAPN1-316 Y CAPN1-4751 del gen de la Calpaina en tres poblaciones de ganado criollo boliviano

La terneza de la carne está en parte determinada por el sistema proteico calpaína (CAPN1) / calpastatina (CAST). Bolivia posee en los llanos tres biotipos de ganado Criollo: los Yacumeños, los Chaqueños y los Saavedreños. El objetivo del presente trabajo fue determinar la frecuencia alélica y genotípica del gen de la CAPN1 en tres poblaciones de ganado Criollo de Bolivia. Se obtuvieron muestras de sangre de 28 Criollos del Chaco (CCH), 85 Criollos Yacumeños (CYA) y 30 Criollos Saavedreños (CSV). El ADN se extrajo utilizando el kit comercial Wizard® Genomic Purification, y posteriormente se tipificaron dos polimorfismos (CAPN1-316 y CAPN1-4751) del gen CAPN1 mediante el método ARMS-PCR. La frecuencias alélicas y genotípicas, las heterocigosidades esperadas y observadas, así como, el índice FIS y el desequilibrio de ligamiento (LD) fueron calculadas mediante los programas MS-Tools y Genepop. Las frecuencias de los alelos asociados a mayor terneza para las poblaciones de CCH, CYA y CSV fueron: 23%, 22% y 33 % para el alelo C del SNP CAPN1-316 y 75%, 76% y 60% para el alelo C del CAPN1-4751. La heterocigocidad observada en las tres poblaciones se hallan en un rango de 0,30 a 0,46 para el marcador CAPN1-316 y de 0,21 a 0,60 para el polimorfismo CAPN1-4751. Los resultados demuestran que los bovinos criollos en las poblaciones analizadas poseen altas frecuencias alélicas para las variantes asociadas a mayor terneza de la carne. Por otra parte, no se observaron valores significativos de LD (P>0,01) entre los dos polimorfismos tipificados en las poblaciones estudiadas. Sería necesario tipificar ambos polimorfismos en futuros programas de selección asistida por marcadores genéticos.Meat tenderness is in part determined by the calpain (CAPN1) / calpastatin (CAST) genes. In the lowlands of Bolivia, three well differentiated Creole cattle populations can be distinguished: the Yacumeños, Chaqueños and Saavedreños. The main objective of this research was to determine the allelic and genotypic frequencies of two polymorphisms of the calpain gene in three Creole cattle populations in Bolivia. Blood samples of 28 Creole cattle from Chaqueño cattle (CCH), 85 from Yacumeño cattle (CYA) and 30 from Saavadreño cattle (CSV) were collected. Total DNA was extracted using the commercial kit Wizard® Genomic Purification and subsequently two polymorphisms (CAPN1-316 and CAPN1- 4751) of the CAPN1 gene were genotyped by the amplification refractory mutation system (ARMS-PCR) method. Allelic and genotypic frequencies, expected and observed heterozygosities, the FIS index and the magnitude of linkage disequilibrium (LD) were calculated using the software MS-Tools and Genepop. The allelic frequencies of variants associated with tenderness in the three populations CCH, CYA and CSV were 23%, 22% and 23% for the CAPN1- 316 and 75%, 76% and 60% for the CAPN1-4751. The observed heterozygosities in the three populations fluctuated between 0.30 and 0.46 for the CAPN1-316 marker and between 0.21 and 0.60 for the CAPN1-4751 marker. The results showed that the analysed populations of Creole cattle presented high frequencies of the alleles previously associated with tenderness in meat. The analysis of LD, however, did not show evidence of linkage between the two markers. It is necessary to perform a genetic analysis for both polymorphisms if included in future selection programs.Fil: Pereira, J. A. C.. Universidad Autónoma Gabriel René Moreno; BoliviaFil: Falomir Lockhart, Agustin Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Genética Veterinaria "Ingeniero Fernando Noel Dulout"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Loza, A.. Universidad Autónoma Gabriel René Moreno; BoliviaFil: Villegas Castagnasso, Egle Etel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Genética Veterinaria "Ingeniero Fernando Noel Dulout"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Rojas, P.. Universidad Autónoma Gabriel René Moreno; BoliviaFil: Carino, M. . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Genética Veterinaria "Ingeniero Fernando Noel Dulout"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Ripoli, María Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Genética Veterinaria "Ingeniero Fernando Noel Dulout"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Giovambattista, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Genética Veterinaria "Ingeniero Fernando Noel Dulout"; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentin

Comparison of allelic and genotypic frequencies of the polymorphisms CAPN1-316 and CAPN1-47151 of the calpain gene among three bolivian criollo cattle populations

La terneza de la carne está en parte determinada por el sistema proteico calpaína (CAPN1) / calpastatina (CAST). Bolivia posee en los llanos tres biotipos de ganado Criollo: los Yacumeños, los Chaqueños y los Saavedreños. El objetivo del presente trabajo fue determinar la frecuencia alélica y genotípica del gen de la CAPN1 en tres poblaciones de ganado Criollo de Bolivia. Se obtuvieron muestras de sangre de 28 Criollos del Chaco (CCH), 85 Criollos Yacumeños (CYA) y 30 Criollos Saavedreños (CSV). El ADN se extrajo utilizando el kit comercial Wizard® Genomic Purification, y posteriormente se tipificaron dos polimorfismos (CAPN1-316 y CAPN1-4751) del gen CAPN1 mediante el método ARMS-PCR. La frecuencias alélicas y genotípicas, las heterocigosidades esperadas y observadas, así como, el índice FIS y el desequilibrio de ligamiento (LD) fueron calculadas mediante los programas MS-Tools y Genepop. Las frecuencias de los alelos asociados a mayor terneza para las poblaciones de CCH, CYA y CSV fueron: 23%, 22% y 33 % para el alelo C del SNP CAPN1-316 y 75%, 76% y 60% para el alelo C del CAPN1-4751. La heterocigocidad observada en las tres poblaciones se hallan en un rango de 0,30 a 0,46 para el marcador CAPN1-316 y de 0,21 a 0,60 para el polimorfismo CAPN1-4751. Los resultados demuestran que los bovinos criollos en las poblaciones analizadas poseen altas frecuencias alélicas para las variantes asociadas a mayor terneza de la carne. Por otra parte, no se observaron valores significativos de LD (P>0,01) entre los dos polimorfismos tipificados en las poblaciones estudiadas. Sería necesario tipificar ambos polimorfismos en futuros programas de selección asistida por marcadores genéticos.Meat tenderness is in part determined by the calpain (CAPN1) / calpastatin (CAST) genes. In the lowlands of Bolivia, three well differentiated Creole cattle populations can be distinguished: the Yacumeños, Chaqueños and Saavedreños. The main objective of this research was to determine the allelic and genotypic frequencies of two polymorphisms of the calpain gene in three Creole cattle populations in Bolivia. Blood samples of 28 Creole cattle from Chaqueño cattle (CCH), 85 from Yacumeño cattle (CYA) and 30 from Saavadreño cattle (CSV) were collected. Total DNA was extracted using the commercial kit Wizard® Genomic Purification and subsequently two polymorphisms (CAPN1-316 and CAPN1- 4751) of the CAPN1 gene were genotyped by the amplification refractory mutation system (ARMS-PCR) method. Allelic and genotypic frequencies, expected and observed heterozygosities, the FIS index and the magnitude of linkage disequilibrium (LD) were calculated using the software MS-Tools and Genepop. The allelic frequencies of variants associated with tenderness in the three populations CCH, CYA and CSV were 23%, 22% and 23% for the CAPN1- 316 and 75%, 76% and 60% for the CAPN1-4751. The observed heterozygosities in the three populations fluctuated between 0.30 and 0.46 for the CAPN1-316 marker and between 0.21 and 0.60 for the CAPN1-4751 marker. The results showed that the analysed populations of Creole cattle presented high frequencies of the alleles previously associated with tenderness in meat. The analysis of LD, however, did not show evidence of linkage between the two markers. It is necessary to perform a genetic analysis for both polymorphisms if included in future selection programs.Instituto de Genética Veterinari

Genomic analysis of two phlebotomine sand fly vectors of Leishmania from the New and Old World.

Phlebotomine sand flies are of global significance as important vectors of human disease, transmitting bacterial, viral, and protozoan pathogens, including the kinetoplastid parasites of the genus Leishmania, the causative agents of devastating diseases collectively termed leishmaniasis. More than 40 pathogenic Leishmania species are transmitted to humans by approximately 35 sand fly species in 98 countries with hundreds of millions of people at risk around the world. No approved efficacious vaccine exists for leishmaniasis and available therapeutic drugs are either toxic and/or expensive, or the parasites are becoming resistant to the more recently developed drugs. Therefore, sand fly and/or reservoir control are currently the most effective strategies to break transmission. To better understand the biology of sand flies, including the mechanisms involved in their vectorial capacity, insecticide resistance, and population structures we sequenced the genomes of two geographically widespread and important sand fly vector species: Phlebotomus papatasi, a vector of Leishmania parasites that cause cutaneous leishmaniasis, (distributed in Europe, the Middle East and North Africa) and Lutzomyia longipalpis, a vector of Leishmania parasites that cause visceral leishmaniasis (distributed across Central and South America). We categorized and curated genes involved in processes important to their roles as disease vectors, including chemosensation, blood feeding, circadian rhythm, immunity, and detoxification, as well as mobile genetic elements. We also defined gene orthology and observed micro-synteny among the genomes. Finally, we present the genetic diversity and population structure of these species in their respective geographical areas. These genomes will be a foundation on which to base future efforts to prevent vector-borne transmission of Leishmania parasites

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: A systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1-4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0-8·4) while the total sum of global YLDs increased from 562 million (421-723) to 853 million (642-1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6-9·2) for males and 6·5% (5·4-7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782-3252] per 100 000 in males vs 1400 [1279-1524] per 100 000 in females), transport injuries (3322 [3082-3583] vs 2336 [2154-2535]), and self-harm and interpersonal violence (3265 [2943-3630] vs 5643 [5057-6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Impact of common cardio-metabolic risk factors on fatal and non-fatal cardiovascular disease in Latin America and the Caribbean: an individual-level pooled analysis of 31 cohort studies

Background: Estimates of the burden of cardio-metabolic risk factors in Latin America and the Caribbean (LAC) rely on relative risks (RRs) from non-LAC countries. Whether these RRs apply to LAC remains un- known. Methods: We pooled LAC cohorts. We estimated RRs per unit of exposure to body mass index (BMI), systolic blood pressure (SBP), fasting plasma glucose (FPG), total cholesterol (TC) and non-HDL cholesterol on fatal (31 cohorts, n = 168,287) and non-fatal (13 cohorts, n = 27,554) cardiovascular diseases, adjusting for regression dilution bias. We used these RRs and national data on mean risk factor levels to estimate the number of cardiovascular deaths attributable to non-optimal levels of each risk factor. Results: Our RRs for SBP, FPG and TC were like those observed in cohorts conducted in high-income countries; however, for BMI, our RRs were consistently smaller in people below 75 years of age. Across risk factors, we observed smaller RRs among older ages. Non-optimal SBP was responsible for the largest number of attributable cardiovascular deaths ranging from 38 per 10 0,0 0 0 women and 54 men in Peru, to 261 (Dominica, women) and 282 (Guyana, men). For non-HDL cholesterol, the lowest attributable rate was for women in Peru (21) and men in Guatemala (25), and the largest in men (158) and women (142) from Guyana. Interpretation: RRs for BMI from studies conducted in high-income countries may overestimate disease burden metrics in LAC; conversely, RRs for SBP, FPG and TC from LAC cohorts are similar to those esti- mated from cohorts in high-income countries