Association Analysis of Polymorphisms in TOMM40, CR1, PVRL2, SORL1, PICALM, and 14q32.13 Regions in Colombian Alzheimer Disease Patients.

OBJECTIVE: We evaluated the association of several single-nucleotide polymorphisms in different genes including APOE, TOMM40, CR1, PVRL2, SORL1, PICALM, and GWA_14q32.13 in a Colombian sample of Late-Onset Alzheimer disease (LOAD) patients. METHODS: A case-control study was conducted in 362 individuals (181 LOADs and 181 controls) to determine the association of single-nucleotide polymorphisms in APOE (e2, e3, and e4), TOMM40 (rs2075650), CR1 (rs665640), PVRL2 (rs6859), SORL1 (rs11218304), PICALM (rs3851179), and GWA_14q32.13 (rs11622883) with LOAD in a sample from Colombia. RESULTS: We were able to confirm the previously reported association of the APOE4 allele with AD. In addition, we report a new significant association with rs2075650 of TOMM40 for LOAD in our sample. We did not detect any significant interaction between TOMM40 and APOE4 carriers (heterozygous or homozygous) for disease risk development. However, Kaplan-Meier survival analyses suggest that AD patients with TOMM40 allele rs2075650-G have an average age of disease onset of 6 years earlier compared with carriers of the A allele. In addition, the age of disease onset is earlier if APOE4/4 is present. CONCLUSION: Our findings suggest that rs2075650 of TOMM40 could be involved in earlier presentation of LOAD in the Colombian population.

Synanthropic triatomines in Hidalgo state, Mexico: Spatial-temporal distribution, domestic transmission cycle, and natural infection with Trypanosoma cruzi.

Triatomine vectors are responsible for the main route of transmission of the protozoan Trypanosoma cruzi, the etiological agent of Chagas disease. This illness is potentially life-threatening and highly disabling and represents a major public health concern in the endemic countries in Latin America. The analysis of the spatial and temporal occurrence of triatomine insects is critical, since control strategies strongly depend on the vector species found within each area. Such knowledge is non-existent in Hidalgo state, an endemic region of Chagas disease in Mexico. A Geographic Information System (GIS) was used to analyze broad-scale spatial and temporal patterns of synanthropic triatomines collected in Hidalgo. Data was taken from the Institute of Epidemiological Diagnosis and Reference (InDRE) of Mexico and the state program of Vector Control of the Secretary of Health, covering the period of 1997-2019. Our analyses demonstrate a differential distribution of Triatoma dimidiata, T. mexicana, T. gerstaeckeri and T. barberi, which are the four predominant species, and that climate, temperature, and precipitation are some of the drivers of their distribution pattern. Notably, we report the presence of T. nitida, T. pallidipennis and T. phyllosoma for the first time in the state. In addition, we found seasonal variations of the populations of T. mexicana and T. gerstaeckeri, but not for T. dimidiata, whose population remains constant throughout the year. The insects were found mainly intradomicile (81.79%), followed by peridomicile (17.56%) and non-domestic areas (0.65%), with an average T. cruzi infection of 16.4%. Based on this evidence, priority sites for vector control intervention were identified. Our findings are very valuable for understanding the epidemiology of Chagas disease, the generation of future potential risk maps and for the development and implementation of effective and targeted vector control programs in Hidalgo state.

A Pharmacogenomic Dissection of a Rosuvastatin-Induced Rhabdomyolysis Case Evokes the Polygenic Nature of Adverse Drug Reactions.

Rosuvastatin, is a widely-used statin for the treatment of hypercholesterolemia and the prevention of cardiovascular diseases. Although rosuvastatin is well tolerated, about 3/10.000 patients can suffer severe myopathy. Rhabdomyolysis is a severe medical condition that causes injury to the skeletal muscle, electrolyte imbalances, acute renal failure and extreme creatine kinase (CK) elevation. Little is known regarding the molecular involvement of rosuvastatin-induced rhabdomyolysis (RIR). It has been demonstrated that genomic variants associated with decreased enzymatic activity of proteins are important determinants in plasmatic and skeletal muscle distribution of rosuvastatin and its toxicity. Until now, no interactions of ticagrelor, ezetimibe and rosuvastatin have been described with the consideration of pharmacogenomics predisposition. The present report involves a whole-exome sequencing (WES), in a patient affected by rosuvastatin-induced rhabdomyolysis. A pharmacogenomic dissection was performed by analyzing a comprehensive subset of candidate genes (n=160) potentially related to RIR. The genes were selected according to their implication in drug metabolism or inherited myopathies. Using an innovative approach of bioinformatics analysis, considering rare and common variants, we identified 19 genomic variations potentially related to the pharmacokinetic/pharmacodynamic modifications of rosuvastatin, ezetimibe and ticagrelor. The affected genes are involved in Phase I metabolism (CYP2C19, CYP2E1, CYP1A1, CYP2D6 and CYP2C9), Phase II metabolism (UGT2B15 and UGT2B7), influx transportation (SLCO1B3 and SLCO2B1), efflux transportation (ABCG8, ABCB11, ABCC4 and ABCB1), drug targeting (NPC1L1) and inherited myopathy etiology (OBSCN). We report three rare, potentially pathogenic molecular variants in CYP2C19, NPC1L1 and OBSCN genes. Pharmacogenetic analysis indicated that the patient was a carrier of inactivating alleles in several pharmacogenes involved in drug toxicity. The whole-exome sequencing and bioinformatics analysis presented here represents an innovative way to identify genomic variants contributing with RIR´s origin and evokes the polygenic nature of adverse drug reactions.

Valoración de la seguridad del paciente en la práctica clínica de terapia renal sustitutiva en las unidades de vigilancia intensiva / Patient safety assessment in the clinical practice of renal replacement therapy in intensive care unit

Introducción: La seguridad del paciente en unidades de vigilancia intensiva, con terapia renal sustitutiva intermitente, está influenciada por diversos factores: los inherentes al paciente, humanos y técnicos.Objetivo: Identificar los factores de riesgo y principales incidencias presentes en la práctica clínica, que interfieren en la seguridad del paciente al que se le realiza terapia sustantiva renal intermitente.Material y Método: Estudio descriptivo y retrospectivo de 413 sesiones de terapia sustitutiva renal intermitente. Se obtuvieron datos demográficos, clínicos, complicaciones clínicas, técnicas, controles de monitores, medidas correctivas y factores de riesgo relacionados con las enfermeras mediante un cuestionario de experteza en diálisis. Resultados: 413 sesiones; (52,1%) hemodiálisis intermitente. Edad media 65 años; 78,7% sexo masculino; motivo de ingreso shock séptico (35,1%).Incidencias: error en la asignación de la modalidad (33,2%), pautas sin actualizar (30,5%), disfunción del acceso vascular (15,7%). Complicaciones clínicas: 47,6 en hemodiálisis intermitente, destacando hipotensión en 41,2%.Complicaciones técnicas en el 37,7% de las sesiones, coagulación total o parcial del circuito extracorpóreo (16,7%). Relacionados con el personal: falta de un programa estandarizado de formación (57,1%), variabilidad de personal (81%) y no asistencia a la capacitación programada (52,4%). Conclusión: La seguridad del paciente con terapia sustitución renal en unidades de vigilancia intensiva, es un proceso multifactorial: relacionados con aspectos no modificables (asociados al paciente), incidencias durante el procedimiento y complicaciones. Aunque no se produjeron efectos adversos mayores en la evolución clínica del paciente, éstos son considerados potenciales y algunos previsibles, controlables y evitables.(AU)

Introduction: Patient safety in intensive care units with intermittent renal replacement therapy is influenced by different factors; including patient-related, human, and technical factors.Objective: Identify risk factors and major incidences present in clinical practice affecting the patient safety on intermittent renal replacement therapy.Material and Method: Descriptive and retrospective study of 413 sessions of intermittent renal replacement therapy. Demographic and clinical data, clinical and technical complications, monitor controls, corrective measures, and nurse-related risk factors were obtained using a dialysis expert questionnaire. Results: Out of the 413 sessions, 52.1% were intermittent hemodialysis. Patients had a mean age of 65 years and 78.7% were male. 35.1% were admitted by septic shock. Incidences include error in modality assignment (33.2%), outdated protocols (30.5%) and vascular access dysfunction (15.7%). As clinical complications found 47.6% in intermittent hemodialysis and 41.2% had hypotension. Technical complications in 37.7% of sessions, with total or partial extracorporeal circuit coagulation (16.7%). As personnel related factors highlighted the lack of standardized training program (57.1%), personnel variability (81%), and not attending scheduled training (52.4%).Conclusions: Patient safety with renal replacement therapy in intensive care units is a multifactorial process involving non-modifiable patient-related aspects, incidences during the procedure, and complications. Although no major adverse effects were produced in the patient’s clinical evolution, risk factors are considered potential and some of them predictable, controllable, and avoidable.(AU)

Global long interspersed nuclear element 1 DNA methylation in a Colombian sample of patients with late-onset Alzheimer's disease.

Alterations in DNA methylation have implicated as an epigenetic event in the pathogenesis of late-onset Alzheimer's disease (LOAD). The objective of this work was to evaluate global DNA methylation levels for long interspersed nuclear element 1 (LINE-1) repetitive sequences in Colombian patients with LOAD and controls. The LINE-1 DNA methylation levels in peripheral blood samples from 28 Colombian patients with LOAD and 30 healthy participants were assessed using a methylation-sensitive high-resolution melting (MS-HRM) quantitative assay. We did not find differences in LINE-1 methylation levels between patients with Alzheimer's disease (AD; median 76.2%, interquartile range [IQR]: 69.8-81.9) and control participants (median 79.8%, IQR: 73.2-83.8; P = .3). Additional stratified analyses did not show differences in LINE-1 methylation levels for male or female patients versus controls nor for apolipoprotein E4 carriers and noncarriers. This is the first report of LINE-1 methylation levels in patients with LOAD using the cost-effective MS-HRM technique, and this is the first global DNA methylation study in Latin American patients with AD.

Enfermedad de Castleman multicéntrica en una paciente postrasplantada de médula ósea / Multicentric Castleman's disease in a patient post-transplanted of bone marrow

Resumen La enfermedad de Castleman es un grupo heterogéneo de trastornos linfoproliferativos con dos formas de manifestación: variedad unicéntrica y multicéntrica. En términos histológicos se caracteriza por ganglios linfáticos con hiperplasia del centro germinal y aumento en la vascularidad. Se comunica el caso de una paciente de 70 años de edad con antecedente de trasplante autólogo de células troncales y progenitoras hematopoyéticas, que acudió a consulta por padecer astenia, pérdida de peso, dolor abdominal y disnea de evolución progresiva; a la que se le encontró un tumor retroperitoneal y derrame pleural derecho. Se plantea el abordaje del caso y se revisa la bibliografía, ya que se estima la incidencia en 21-25 casos por un millón de habitantes, sólo 14% de los casos reportados con manifestación retroperitoneal.

Abstract Castleman's disease is a heterogeneous group of lymphoproliferative disorders (LPD'S), which has two types of presentation, unicentric (UCD) and multicentric (MCD) variety. Histologically it is characterized by lymph nodes with hyperplasia of germinal centers and increased vascularity. This article reports the clinical case of a 70-year-old female with previous autologous haematopoietic stem cell transplant. She arrived with asthenia, weight loss, abdominal pain and progressive dyspnea. A retroperitoneal tumor and right pleural effusion were found. Clinical approach and bibliographic review are reported, the incidence estimation for this disorder is 21-25 cases per million population, and only 14% of reported cases had a retroperitoneal presentation.

Molecular interactions of progesterone derivatives with 5 alpha-reductase types 1 and 2 and androgen receptors.

The aim of this study was to ascertain the inhibitory effect of several progesterone derivatives for 5 alpha-reductase types 1 and 2 isozymes and to determine the binding to the androgen receptor. The 3,20-dioxopregna-4-ene-17 alpha-yl acetate 4 containing an acetoxy group in C-17 and steroid 17 alpha-hydroxypregn-4-ene-3,20-dione 5 having a hydroxyl group in the same position inhibited both isozymes. On the other hand, 17 alpha-hydroxy-4,5-epoxypregnan-3,20-dione 6 with an epoxy function at C-4, inhibited only the type 1 enzyme. Steroid 4-chloro-17 alpha-hydroxypregn-4-ene-3,20-dione 7a and 4-bromo-17 alpha-hydroxypregn-4-ene-3,20-dione 7b having the C-4 conjugated system and a chlorine or a bromine atom at C-4 respectively, inhibited both types of 5 alpha-reductase. These results indicate that an increase in the electronegativity of ring A produces a major inhibitory activity for 5 alpha-reductase type 1; however this increase was not observed for type 2 enzyme. When the free hydroxyl group of 7a or 7b was esterified, compounds 3,20-dioxo-4-chloropregn-4-ene-17 alpha yl-4-ethylbenzoate 8a and 3,20-dioxo-4-bromopregn-4-ene-17 alpha yl-4-ethylbenzoate 8b were obtained; these steroids inhibited only the 5 alpha-reductase type 2 enzyme. Finasteride and steroids 4, 5, 7b, 8a showed a comparable in vivo pharmacological activity, however the IC(50) values of these compounds were higher as compared to that of finasteride. These results indicated also that steroids 4, 5, 7a, and 7b bind to the androgen receptor whereas compounds 6, 8a and 8b failed to do so. The overall data from this study showed that steroids 5 and 7b bind to the AR and decreased of the growth of prostate and seminal vesicles. Moreover, 4 decreased also the growth of seminal vesicles.

Caries dental y enfermedad periodontal en un grupo de personas de 60 o más años de edad de la Ciudad de México / Dental caries and periodontal disease in a group of persons with 60 year-old or more living in Mexico city

Los cambios demográficos de nuestro país indican que la proporción guardada por el grupo de la tercera edad con respecto al resto de la población está en aumento. En México no se cuenta con suficiente información sobre el estado de salud bucal de este grupo de población. El propósito del presente trabajo fue estimar la prevalencia y severidad de caries dental así como el estado de salud periodontal en personas de 60 o más años de edad de la Ciudad de México. Se utilizaron los criterios de la Organización Mundial de la Salud para el levantamiento del índice de caries (CPOD) y del estado parodontal (CPITN). Se examinó a un total de 161 personas, el promedio de edad de la población fue de 69.6 (d.e. 6.9) años. El 23.6 por ciento de la población era edéntula. El índice de caries dental CPOD fue de 16.3 (d.e. 6.7). El índice CPITN mostró que aproximadamente el 50 por ciento de la población tenía bolsas parodontales. Los resultados del presente estudio muestran un importante deterioro en la salud bucal de la población examinada

Trombofilia: ana historia para volver a contar / Thromnophilia: a history for back and talk

El mayor conocimiento de la trombosis como un fenómeno poligénico se ha dado gracias tanto a la biología molecular como a la genética,permitiendo dilucidar con mayor claridad la interacción entre defectos heredados y condiciones externas que actúan como desencadenantes.Estos avances permiten al clínico sopesar el riesgo individual de trombosis en los pacientes con trombofilia heredada, de acuerdo con la situación de riesgo a que se exponga y por ende, tomar las medidas antitrombóticas necesarias.Conclusión: La relevancia clínica de este tópico se ha incrementado con la nueva evidencia de genes mutantes que aumentan la susceptibilidad a la trombosis, permitiendo entender el fenómeno como un trastorno poligénico en el que la interacción con alteraciones adquiridas, ya sean transitorias como también permanentes, aumenta la frecuencia de los episodios. A medida que el avance de la genética y el de la biología molecular amplíen nuestro conocimiento sobre el delicado equilibrio entre los factores procoagulantes y anticoagulantes plasmáticos, se ampliará la compresión del clínico de los fenómenos trombóticos, permitiéndole una más efectiva intervención tanto preventiva como terapéutica.

Correlacion entre los niveles de citoquinas en el lavado broncoalveolar en una cohorte de pacientes del Hospital Militar Central con esclerosis sistemica (SS), con y sin alveolitis / Cytokines in bronchoalveolar lavage in systemic sclerosis patient

Debido a la preocupación que produce la osteomielitis crónica y los problemas sociales y laborales que conlleva esta enfermedad, nos propusimos sacar adelante un protocolo de tratamiento médico-ortopédico que hemos implementando y desarrollado con la colaboración del Dr. Cesar Arango (Medico Infectólogo) en nuestros pacientes durante 20 años. Hemos utilizado esta metodología en 180 pacientes, 100 de sexo masculino y 80 de sexo femenino. Los segmentos anatómicos afectados fueron: tibia 56 por ciento, fémur 33 por ciento, antebrazo 6 por ciento, pie 4 por ciento y dedos de pie 1 por ciento. La base fundamental del tratamiento es el desbridamiento seriado de las lesiones con el paciente hospitalizado, la toma de cuatro cultivos en la primera intervención, la administración de antibióticos se lleva a cabo de acuerdo a determinación del medico infectólogo que se modifica según el resultado de los cultivos, y el cuidado postoperatorio domiciliario hasta obtener una granulación adecuada de las zonas desbridadas con cultivos negativos. Se rellena el espacio vado producido por los desbridamientos con injertos óseos extraídos de las espinas ilíacas provista la estabilización de la fractura. De estos 180 pacientes, el 97 por ciento se encuentra hasta el momento libre de recidivas, 5 pacientes no cumplieron con las expectativas del tratamiento y 1 paciente fue amputado. Consideramos que esta forma de tratamiento es adecuada para nuestro medio y mejora el pronóstico de los pacientes que sufren esta penosa enfermedad