Genetic variants in KCNJ11, TCF7L2 and HNF4A are associated with type 2 diabetes, BMI and dyslipidemia in families of Northeastern Mexico: A pilot study

Abstract. The aim of the present study was to investigate whether genetic markers considered risk factors for metabolic syndromes, including dyslipidemia, obesity and type 2 diabetes mellitus (T2DM), can be applied to a Northeastern Mexican population. A total of 37 families were analyzed for 63 single nucleotide polymorphisms (SNPs), and the age, body mass index (BMI), glucose tolerance values and blood lipid levels, including those of cholesterol, low-density lipoprotein (LDL), very LDL (VLDL), high-density lipoprotein (HDL) and triglycerides were evaluated. Three genetic markers previously associated with metabolic syndromes were identified in the sample population, including KCNJ11, TCF7L2 and HNF4A. The KCNJ11 SNP rs5210 was associated with T2DM, the TCF7L2 SNP rs11196175 was associated with BMI and cholesterol and LDL levels, the TCF7L2 SNP rs12255372 was associated with BMI and HDL, VLDL and triglyceride levels, and the HNF4A SNP rs1885088 was associated with LDL levels (P<0.05)

Revisión de 13 especies de la familia Triatominae (Hemiptera: Reduviidae) vectores de la enfermedad de Chagas, en México

Vectors of Trypanosoma cruzi, parasite responsible for Chagas disease, are divided in intradomestic, peridomestic andsylvatic. The intradomestic are Triatoma barberi and Triatoma dimidiata, two species that represent the highest healthrisk among the Mexican population. Triatoma dimidiata is a species found mainly inside human habitats, but inYucatan, it corresponds to the peridomicile vectors. Also in the peridomicile most of Chagas disease vectors arefound: Meccus bassolsae, M. longipennis, M. mazzottii, M pallidipennis, M. phyllosomus, M picturata, Triatomagerstaeckeri, T mexicana, T rubida, Dipetalogaster máxima (the last two are in the process of becoming adapted tothe domicile), Panstrongylus rufotuberculatus which occasionally enters the domicile in its adult stage, and Rhodniusprolixus, which is practically controlled in the country. Peridomestic vectors are of lower risk in the transmissiondynamics, as compared to the intradomestic ones. For the control of the intradomestic vectors, health educationprograms, improvements of housing, and the use of pesticides are essential To control the peridomestic vectors, healtheducation programs are required, as well as the use of mosquito nets on doors and windows and around beds, asidefrom cementing the stone wall fences.Los transmisores de Trypanosoma cruzi, flagelado causante de la enfermedad, se dividen en intradomiciliados,peridomiciliados y silvestres. Entre los intradomiciliados se encuentran, Triatoma barberi y Triatoma dimidiata, queson los que representan un mayor riesgo para la Salud Pública, en México. Aunque Triatoma dimidiata se encuentraprincipalmente dentro de la vivienda, en Yucatán tiene un comportamiento peridomiciliar, dentro de este grupo seencuentran la mayoría de los transmisores de la enfermedad de Chagas Meccus longipennis, M. mazzottii, M.pallidipennis, M. phyllosomus, M. picturatus, Triatoma gerstaeckeri, T. mexicana, T. rubida, Dipetalogaster máxima,Panstrongylus rufotuberculatus y Rhodnius prolixus. Los transmisores peridomiciliados son de menor riesgo en ladinámica de transmisión comparados con los intradomiciliados. Para el control de los transmisores intradomiciliados,se deben emplear programas de educación para la salud, mejoramiento de vivienda e insecticidas; mientras que paralos vectores visitantes o peridomiciliados, son necesarios programas de educación para la salud, uso de mosquiteros,pabellones y cementación de las bardas de piedra

Two-center experience comparing the use of the FLOT4 and CROSS schemes for patients with gastric, esophageal, and gastroesophageal junction adenocarcinoma

Introduction. Gastric (GAD), gastroesophageal junction (GEJA), and esophageal adenocarcinoma (EAD) share pathophysiological features. At localized stages, FLOT is used perioperatively for the treatment of GAD and GEJA and CROSS for EAD and some GEJA. Although both therapies have been compared with MAGIC, comparative randomized data on FLOT and CROSS are not yet available. Material andmethods. We retrospectively analyzed and compared 40 patients treated with FLOT and 16 patients treated with CROSS in terms of clinical features and neoadjuvant, surgical, adjuvant, and survival outcomes. Results. At the time of analysis, 65% of patients treated with FLOT4 and 56.3% with CROSS remained in complete remission. Those who progressed after FLOT4 did so mainly at the peritoneal level (25%) and after CROSS at the bone, lymph node, and peritoneal levels (12.5% respectively). Six patients (37.5%) died after CROSS (median OS of 17.5 months; 95% CI 2–41) and 10 (25%) after FLOT4 (median OS 16.5 months; 95% CI 11–22). For the living patients, the median numbers of months from diagnosis to the follow-up cutoff date were 47.5 (95% CI 11–67) and 27 (95% CI 14–44) for CROSS and FLOT4, respectively. There were no significant differences in median OS estimated by Kaplan Meier analysis [FLOT4: 50 ± 4.6 months (95% CI 40.9–59.2); CROSS: 51.2 ± 7 months (95% CI 37.4–65.0; p = 0.79)].  Conclusions. Although we obtained lower pCR rates; TNM downstaging after neoadjuvant therapy, R0 rates, tolerance, PFS, and OS were similar in both groups and comparable with trial results. The adjuvant compliance rate was high with FLOT4. CROSS allows sequencing with nivolumab in PD-L1+ tumors

Reseñas

[ES] Seguí de la Riva , Javier. Sobre dibujar y proyectar (por Javier Seguí de la Riva) pp. 4.-- Dibujar, proyectar LVI y LVII Arte y muerte I y II ( por Javier Seguí de la Riva) pp. 6.-- dibujar, proyectar LVIII El imaginario del dibujar (por Javier Seguí de la Riva) pp. 6 y 7.-- Dibujar, proyectar LVI y LVII Diagrama, diagramar I y II ( por Javier Seguí de la Riva) pp. 7.-- DIBUJAR, proyectar LVIII El imaginario del dibujar ( por Javier Seguí de la Riva) pp. 6 y 7.-- DIBUJAR, PROYECTAR LVI y LVII Diagrama, diagramar I y II (por Javier Seguí de la Riva) pp.7.-- DIBUJAR, PROYECTAR LIX, LX y LXI Escritos críticos I, II y III ( por Javier Seguí de la Riva) pp. 7 .-- Rehabilitacion del Antiguo Hospital San Juan de Dios para Biblioteca y Archivo Historico de Orihuela (por Ana Torres Barchino) pp. 8.-- Arnau Amo, Joaquín. Arquitectura. Ritos y ritmos (por María Elia Gutiérrez Mozo) pp. 8 y 9.—Cardone, Vito. Viaggiatori d’architettura in Italia. Da Brunelleschi a Charles Garnier (por Cesare Cundari) pp. 9 y 10.-- Casado de Amezúa Vázquez, Joaquín. Las casas reales de la Alhambra. Geometría y espacio. Una aproximación al proceso de formación del espacio ( por Pilar Chías Navarro)pp. 10.-- Jaén i Urban, Gaspar; Baldomá Soto, Montserrat y Carrasco Martí, Maria Antonia. One century of photography and preservation in catalonia: the service for local architectural heritage ( por Pilar Chías Navarro) pp. 10 y 11.-- Jaén i Urban, Gaspar. El paisaje urbano de Nueva York en la obra escrita de Federico García Lorca (por Concepción López González y Jorge García valldecabres) pp. 11.—Trachana, Angelique. Urbe Ludens ( por Gonzalo García-Rosales) pp. 12.-- Fernández-Palacios, Victoria; Yanguas, Ana; Jiménez Fdez-Palacios, Luz. Manuel Aires Mateus. Cuaderno de La Alhambra ( por José Mª Gentil Baldrich) pp. 12 y 13.-- Agustín, Luis; Miret, Elena; Vallespín, Aurelio. Representación del espacio arquitectónico. 2011.12 (por Jesús Aparicio Guisado) pp. 14.—Herschdorfer, Nathalie y Lada Umstätter, Thames. Le Corbusier and the Power of Photography (por víctor A. Lafuente Sánchez) pp. 14 y 15.-- Roma en el bolsillo. Cuadernos de dibujo y aprendizaje artístico en el siglo XVIII ( por Fernando Linares García) pp. 15 y 16.-- Vicens y Hualde, Ignacio. Dicho y hecho ( por Fernando Linares García) pp 16.-- Le Corbusier. El arte decorativo de hoy ( por Carlos Montes Serrano )pp. 16 y 17.—Jenkins Birkhäuser, Eric J. Drawn to Design: Analyzing Architecture Through Freehand Drawing ( por víctor A. Lafuente Sánchez) pp. 17 y 18.—Sobrino, Miguel. Monasterios. Las biografías desconocidas de los cenobios de España ( por Javier García-Gutiérrez Mosteiro) pp. 18 y 19.-- Jiménez Martín, Alfonso. Anatomía de la Catedral de Sevilla ( por Francisco Pinto Puerto) pp. 19.-- Raposo Grau, Javier Fco; Butragueño Díaz-Guerra, Belen y Paredes Maldonado, Miguel. Dibujar, analizar, proyectar (2010) Título I. Colección dibujo, proyecto y arquitectura ( por Mariasun Salgado de la Rosa) pp. 19 y 20.-- Raposo Grau, Fco Javier; Butragueño Díaz-Guerra, Belen y Paredes Maldonado, Miguel. Dibujar, analizar, proyectar (2011) Título III. Colección dibujo, proyecto y arquitectura ( por Carlos L. Marcos Alba) pp. 20-22.-- García Doménech, Sergio. Reflexiones urbanas sobre el espacio público de Alicante. Una interpretación de la ciudad y sus escenarios ( por Juan Calduch Cervera) pp. 22 y 23.—Cundari, Casere. Il rilievo architettonico. Ragioni. Fondamenti. Applicazioni ( por Antonio Álvaro Tordesillas) pp. 23 y 24.—Autores varios. Perspectiva-Prospettiva. La práctica de la perspectiva ( por José Mª Gentil Baldrich) pp. 24 y 25.-- Soler Sanz, Felipe. Trazados Reguladores en la Arquitectura ( por Jorge García Valldecabres) pp. 25.-- Jiménez Alcañiz, Cesar. Análisis de las metodologías para la recuperación patrimonial de entornos urbanos protegidos. Propuesta metodológica: desde los valores históricos a los nuevos modelos energéticos. Russafa desde el siglo XIX( Por Pablo Navarro Esteve) pp. 26.-- de Coca Leicher, José. El recinto ferial de la Casa de Campo de Madrid (1950-75)( por Esteban Herrero Cantalapiedra) pp. 27.-- La arquitectura religiosa renacentista en tierras del Maestre: la iglesia de Nuestra Señora de la Asunción de Vistabella del Maestrazgo ( por José Teodoro Garfella Rubio) pp. 27 y 28.-- Arquitectura de los balnearios en Galicia. Cuenca del Miño. 1816-1936 ( por José Antonio Franco Taboada)pp. 28 y 29.-- Barros da Rocha e Costa. Historia de la representación gráfica del Castillo de Peñíscola. Del grafito al láser ( por Pablo Navarro Esteve) pp. 29.-- Rivas López, Esteban José. El Carmen de la fundación Rodríguez-Acosta. Una indagación gráfica ( por Joaquín Casado de Amezúa) pp.30.-- Verdejo Gimeno, Pedro. Estaciones intermedias de ferrocarril. La sección “Non nata” Teruel-Alcañiz (por Jorge Girbés Pérez) pp. 30 y 31.-- Sender Contell, Marina. El Monasterio de Santa María de la Murta. Análisis arquitectónico de un Monasterio Jerónimo ( por Pablo Navarro Esteve) pp. 32.-- Iñarra Abad, Susana. El Render de Arquitectura. Análisis de la Respuesta Emocional del Observador ( por Pablo Navarro Esteve) pp. 32 y 33.-- Fernández Morales, Angélica. De concreto a conceptual. Relaciones entre arte y arquitectura en el contexto helvético contemporáneo ( por Luis Agustín) pp. 33.—EXPOSICIÓN: Intervenciones cromáticas en los comercios del centro histórico ( por Jorge Llopis verdú) pp. 34 y 35.Seguí De La Riva, J.; Torres Barchino, A.; Gutiérrez Mozo, ME.; Cundari, C.; Chías Navarro, P.; López González, C.; García Valldecabres, J.... (2014). Reseñas. EGA. Revista de Expresión Gráfica Arquitectónica. 19(24):4-35. https://doi.org/10.4995/ega.2014.3268SWORD435192

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

Abstract The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared to information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known non-pathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification. This article is protected by copyright. All rights reserved.Peer reviewe

Main Cardiac Histopathologic Alterations in the Acute Phase of <i>Trypanosoma cruzi</i> Infection in a Murine Model

Symptoms in the acute phase of Chagas disease are usually mild and nonspecific. However, after several years, severe complications like dilated heart failure and even death may arise in the chronic phase. Due to the lack of specific symptoms in the acute phase, the aim of this work was to describe and analyze the cardiac histopathology during this phase in a CD1 mouse model by assessing parasitism, fibrotic damage, and the presence and composition of a cellular infiltrate, to determine its involvement in the pathogenesis of lesions in the cardiac tissue. Our results indicate that the acute phase lasts about 62 days post-infection (dpi). A significant increase in parasitemia was observed since 15 dpi, reaching a maximum at 33 dpi (4.1 × 106). The presence of amastigote nests was observed at 15–62 dpi, with a maximum count of 27 nests at 35 dpi. An infiltrate consisting primarily of macrophages and neutrophils was found in the cardiac tissue within the first 30 days, but the abundance of lymphocytes showed an 8 ≥ fold increase at 40–62 dpi. Unifocal interstitial fibrosis was identified after 9 dpi, which subsequently showed a 16 ≥ fold increase at 40–60 dpi, along with a 50% mortality rate in the model under study. The increased area of fibrotic lesions revealed progression in the extent of fibrosis, mainly at 50–62 dpi. The presence of perivasculitis and thrombus circulation disorders was seen in the last days (62 dpi); finally, cases of myocytolysis were observed at 50 and 62 dpi. These histopathological alterations, combined with collagen deposition, seem to lead to the development of interstitial fibrosis and damage to the cardiac tissue during the acute phase of infection. This study provides a more complete understanding of the patterns of histopathological abnormalities involved in the acute phase, which could help the development of new therapies to aid the preclinical tests of drugs for their application in Chagas disease

Expression of Proteins, Glycoproteins, and Transcripts in the Guts of Fasting, Fed, and <i>Trypanosoma cruzi</i>-Infected Triatomines: A Systematic Review

Chagas disease is caused by the hemoflagellate protozoan Trypanosoma cruzi. The main transmission mechanism for the parasite in endemic areas is contact with the feces of an infected triatomine bug. Part of the life cycle of T. cruzi occurs in the digestive tract of triatomines, where vector and parasite engage in a close interaction at a proteomic–molecular level. This interaction triggers replication and differentiation processes in the parasite that can affect its infectivity for the vertebrate host. With the aim of compiling and analyzing information from indexed publications on transcripts, proteins, and glycoproteins in the guts of fasting, fed, and T. cruzi-infected triatomines in the period 2000–2022, a systematic review was conducted following the PRISMA guidelines. Fifty-five original research articles retrieved from PubMed and ScienceDirect were selected; forty-four papers reported 1–26,946 transcripts, and twenty-one studies described 1–2603 peptides/proteins

Identification of O-Glcnacylated Proteins in Trypanosoma cruzi

International audienceOriginally an anthropozoonosis in the Americas, Chagas disease has spread from its previous borders through migration. It is caused by the protozoan Trypanosoma cruzi. Differences in disease severity have been attributed to a natural pleomorphism in T. cruzi. Several post-translational modifications (PTMs) have been studied in T. cruzi, but to date no work has focused on O-GlcNAcylation, a highly conserved monosaccharide-PTM of serine and threonine residues mainly found in nucleus, cytoplasm, and mitochondrion proteins. O-GlcNAcylation is thought to regulate protein function analogously to protein phosphorylation; indeed, crosstalk between both PTMs allows the cell to regulate its functions in response to nutrient levels and stress. Herein, we demonstrate O-GlcNAcylation in T. cruzi epimastigotes by three methods: by using specific antibodies against the modification in lysates and whole parasites, by click chemistry labeling, and by proteomics. In total, 1,271 putative O-GlcNAcylated proteins and six modification sequences were identified by mass spectrometry (data available via ProteomeXchange, ID PXD010285). Most of these proteins have structural and metabolic functions that are essential for parasite survival and evolution. Furthermore, O-GlcNAcylation pattern variations were observed by antibody detection under glucose deprivation and heat stress conditions, supporting their possible role in the adaptive response. Given the numerous biological processes in which O-GlcNAcylated proteins participate, its identification in T. cruzi proteins opens a new research field in the biology of Trypanosomatids, improve our understanding of infection processes and may allow us to identify new therapeutic targets

A revision of thirteen species of Triatominae (Hemiptera: Reduviidae) vectors of Chagas disease in Mexico

Vectors of Trypanosoma cruzi, parasite responsible for Chagas disease, are divided in intradomestic, peridomestic and sylvatic. The intradomestic are Triatoma barberi and Triatoma dimidiata, two species that represent the highest health risk among the Mexican population. Triatoma dimidiata is a species found mainly inside human habitats, but in Yucatan, it corresponds to the peridomicile vectors. Also in the peridomicile most of Chagas disease vectors are found: Meccus bassolsae, M. longipennis, M. mazzottii, M pallidipennis, M. phyllosomus, M picturata, Triatoma gerstaeckeri, T mexicana, T rubida, Dipetalogaster máxima (the last two are in the process of becoming adapted to the domicile), Panstrongylus rufotuberculatus which occasionally enters the domicile in its adult stage, and Rhodnius prolixus, which is practically controlled in the country. Peridomestic vectors are of lower risk in the transmission dynamics, as compared to the intradomestic ones. For the control of the intradomestic vectors, health education programs, improvements of housing, and the use of pesticides are essential To control the peridomestic vectors, health education programs are required, as well as the use of mosquito nets on doors and windows and around beds, aside from cementing the stone wall fences