Tumor necrosis factor haplotype diversity in Mestizo and native populations of Mexico.

The so-called tumor necrosis factor (TNF) block includes the TNFA, lymphotoxin alpha and beta (LTA and LTB) genes with single-nucleotide polymorphisms (SNP) and microsatellites with an allele frequency that exhibits interpopulation variability. To date, no reports have included both SNPs and microsatellites at the TNF block to study Mestizo or Amerindian populations from Mexico. In this study, samples of five Mexican Mestizo populations (Durango, Guadalajara, Monterrey, Puebla, and Tierra Blanca) and four native-Mexican populations (North Lacandonians, South Lacandonians, Tepehuanos, and Yaquis) were genotyped for two SNPs (LTA+252A>G and TNFA-308G>A) and four microsatellites (TNFa, d, e, and f), to analyze the genetic substructure of the Mexican population. Allele and haplotype frequencies, linkage disequilibrium (LD), and interpopulation genetic relationships were calculated. There was significant LD along almost all of the TNF block but the lowest D' values were observed for the TNFf-TNFd pair. Mestizos showed higher allele and haplotype diversity than did natives. The genetic differentiation level was reduced among Mestizos; however, a slightly, but significant genetic substructure was observed between northern and southern Mexican Mestizos. Among the Amerindian populations, the genetic differentiation level was significantly elevated, particularly in both North and South Lacandonians. Furthermore, among Southern Lacandonians, inhabitants of Lacanja town were the most differentiated from all the Mexicans analyzed. The data presented here will serve as a reference for further population and epidemiological studies including these TNF polymorphisms in the Mexican population.

Neurological symptoms associated with SARS-CoV-2 infection in a tertiary hospital in Bogota, Colombia.

Introduction: SARS-CoV-2 infection is an emerging disease that represents a threat to life globally, with more than 179 million confirmed cases and 3 million deaths. In Colombia, where almost 5 million infections and approximately 127 thousand deaths have been reported, it presents a wide variety of neurological manifestations that range from mild to severe symptoms. Objective: This study describes the characteristics of neurological manifestations in patients with COVID-19 in the period March-September 2020 at a tertiary hospital in Bogota. Methods: We performed a cross-sectional descriptive study. We selected patients by non-probability sampling, including all patients attended by the neurology service at our hospital. We included all patients with infection confirmed by RT-PCR test and neurological disease confirmed by tomography, study of cerebrospinal fluid, and clinical manifestations reported in the medical history. We excluded epileptic patients who presented seizures as the only clinical manifestation. Results: In a total of 58 patients, the mean age was 58 years, with 60.3% of patients being men; 65.5% were alert at admission. The main neurological symptom was brain ischaemia, in 36.2%, followed by seizures, in 25.9%. Arterial hypertension was observed in 58.6%. We observed no alterations in the cerebrospinal fluid; the mean hospital stay was 35 days, and 41.4% of patients died. Conclusions: SARS-CoV-2 infection not only affects the respiratory system, but can also cause a range of neurological manifestations ranging from mild symptoms such as headache, dysgeusia, and anosmia to severe complications such as seizures, brain ischaemia/haemorrhage, encephalopathy, or death.

Introducción: La infección por SARS-CoV2 es una enfermedad emergente que representa un peligro para la vida a nivel mundial, con más de 179 millones de casos confirmados y 3 millones de muertes. En Colombia, se han reportado casi 5 millones de personas contagiadas y alrededor de 127 mil fallecidos, presenta una amplia variedad de manifestaciones neurológicas que van desde leves a severas. Objetivo: Describir las características de las manifestaciones neurológicas en pacientes con infección por coronavirus SARS-CoV2 (Covid19) en el periodo marzo ­ septiembre de 2020 en un Hospital de 3er nivel en Bogotá. Metodología: Se trata de un estudio descriptivo tipo corte transversal. Se realizó un muestreo no probabilístico en el que se incluyeron todos los casos atendidos por el servicio de neurología de la institución seleccionada, se incluyeron todos los pacientes con infección confirmada por prueba de RT-PCR y aquellos con enfermedad neurológica documentada por tomografía, estudio de líquido cefalorraquídeo o manifestaciones clínicas registradas en la historia clínica. Fueron excluidos los pacientes epilépticos quienes presenten convulsiones como única manifestación clínica. Resultados: En un total de 58 pacientes, se encontró media de edad de 58 años, con un 60,3% correspondiente al sexo masculino, 65,5% estuvieron alerta, la principal manifestación neurológica fue la isquemia cerebral en un 36,2%, seguida de convulsiones con un 25,9%. La hipertensión arterial estuvo en el 58,6%. No hubo alteraciones en el LCR, el promedio de estancia hospitalaria fue de 35 días y el 41,4% fallecieron. Conclusiones: La infección por SARS-CoV2 condiciona no solo una afección al sistema respiratorio, sino que presenta un amplio espectro de manifestaciones neurológicas que van desde las más leves como cefalea, disgeusia y anosmia, hasta las más graves como convulsiones, isquemia/sangrado cerebral, encefalopatía o muerte.

Five years' experience of the clinical exome sequencing in a Spanish single center.

Nowadays, exome sequencing is a robust and cost-efficient genetic diagnostic tool already implemented in many clinical laboratories. Despite it has undoubtedly improved our diagnostic capacity and has allowed the discovery of many new Mendelian-disease genes, it only provides a molecular diagnosis in up to 25-30% of cases. Here, we comprehensively evaluate the results of a large sample set of 4974 clinical exomes performed in our laboratory over a period of 5 years, showing a global diagnostic rate of 24.62% (1391/4974). For the evaluation we establish different groups of diseases and demonstrate how the diagnostic rate is not only dependent on the analyzed group of diseases (43.12% in ophthalmological cases vs 16.61% in neurological cases) but on the specific disorder (47.49% in retinal dystrophies vs 24.02% in optic atrophy; 18.88% in neuropathies/paraparesias vs 11.43% in dementias). We also detail the most frequent mutated genes within each group of disorders and discuss, on our experience, further investigations and directions needed for the benefit of patients.

Sanger sequencing is no longer always necessary based on a single-center validation of 1109 NGS variants in 825 clinical exomes.

Despite the improved accuracy of next-generation sequencing (NGS), it is widely accepted that variants need to be validated using Sanger sequencing before reporting. Validation of all NGS variants considerably increases the turnaround time and costs of clinical diagnosis. We comprehensively assessed this need in 1109 variants from 825 clinical exomes, the largest sample set to date assessed using Illumina chemistry reported. With a concordance of 100%, we conclude that Sanger sequencing can be very useful as an internal quality control, but not so much as a verification method for high-quality single-nucleotide and small insertion/deletions variants. Laboratories might validate and establish their own thresholds before discontinuing Sanger confirmation studies. We also expand and validate 23 copy number variations detected by exome sequencing in 20 samples, observing a concordance of 95.65% (22/23).

Nine-year experience in Gaucher disease diagnosis at the Spanish reference center Fundación Jiménez Díaz.

BACKGROUND: Fundación Jiménez Díaz (FJD) is a reference center for genetic diagnosis of Gaucher disease (GD) in Spain. Genetic analyses of acid ß-glucosidase (GBA) gene using different techniques were performed to search for new mutations, in addition to those previously and most frequently found in the Spanish population. Additionally, the study of the chitotriosidase (CHIT1) gene was used to assess the inflammatory status of patients in the follow-up of enzyme replacement therapy (ERT). We present the genetic data gathered during the last nine years at FJD. METHODS: Blood samples from patients with suspected GD were collected for enzymatic and genetic analyses. The genetic analysis was performed on DNA from 124 unrelated suspected cases and 57 relatives from 2007 to 2015, starting with a mutational screening kit, followed by Sanger sequencing of the entire gene and other techniques to look for deletions. CHIT1 was also studied to assess the reliability of this biomarker. RESULTS: In 46 out of 93 GD patients (49.5%) the two mutant alleles were found. We detected 21 different mutations. The most common mutation was N370S (c.126A > G; p.Asp409Ser current nomenclature) (in 50.5% of patients), followed by L444P (c.1448T > C; p.Leu483Pro current nomenclature) (in 24.7%). The most common heterozygous compound genotype observed (18.3%) was c.1226A > G/c.1448T > C (N370S/L444P). Two novel mutations were found (del. Ex.4-11 and c.1296G > T; pW432C), as well as p.S146L, only once previously reported. Two patients showed the homozygous state for the duplication of CHIT1. CONCLUSION: N370S and L444P are the most common mutations and other mutations associated to Parkinson's disease have been observed. This should be taken into account in the genetic counseling of GD patients.

[Cardiac arrest in newborn of mother treated with labetalol]. / Paro cardíaco en neonato de madre tratada con labetalol.

The use of beta-adrenergic antagonists for the control of high blood pressure associated to pregnancy is frequent. Their use is related with the appearance of undesirable effects of the fetus. The case of neonatal cardiac arrest attributed, to the administration of labetalol to the mother is presented. The high transplacentary passage, the different pharmacokinetics of the drug in the newborn and the clinical evolution of the patient suggests its involvement. It is concluded that labetalol may cause severe undesirable effects in newborns and fetal heart rate of the mother and neonate should be monitored upon use of this drug.

[Thrombosis of intrathoracic veins. A complication of venous catheterization for temporary hemodialysis]. / Trombosis de las venas intratorácicas. Una complicación de la cateterización venosa para hemodiálisis temporal.

Venous thrombosis of large vessels is a common complication, generally asymptomatic, that may occur during central venous catheterization for temporal hemodialysis. We report 2 cases of intrathoracic venous thrombosis which were suspected because of the difficulties occurring during catheterization of a new venous approach during dialysis. Both cases were diagnosed by angiography.

[Effect of induced diabetes on reproduction and development]. / Efecto de la diabetes inducida sobre la reproducción y el desarrollo.

Diabetes mellitus is a major cause of morbidity and mortality and it has been studied in relation to the organs that affects, and the reproduction system is not the exception. Scientists had developed experimental animal models to investigate the effects of diabetes using different substances being streptozotocin (STZ) the most effective. STZ is natural compound produced by the Streptomyces achromogenes that selectively destroys the beta cells of the pancreas breaking the DNA. It has been proved that equilibrated solutions of STZ stored at 6 degrees C, are very effective in inducing diabetes to several animal species such as rat, mouse and hamster. In rats, the disorders in reproduction have been associated to dysfunctions in the hipotalamohipofisis-gonadal axis, given by a reduction in the secretion of GnRH, as well as of LH, FSH, prolactin and alterations in the gonadal secretion of steroids (testosterone, estrogens, progesterone). Due to this situation, male production of spermatozoids as well as its' motility is impair. In females, the principal effects are ovaric atrophy, impaired folliculogenesis, insufficiency of the corpora lutea, and problems associated with the maintenance of pregnancy. Many researchers had associated the prevalens of congenital malformation with a hiperglucemic state, being the most common retardation of the development, defects in the closure of the neural tube, micrognatias, heart malformations, etc.

Interactions between hemodynamics and pharmacology in kidney transplantation.

INTRODUCTION: Renal transplantation (RT) is considered the treatment of choice for patients with end-stage renal disease due to the improved short- and long-term survival benefits over dialysis treatment. The success of RT can be improved by working within a multidisciplinary team. OBJECTIVE: The aim of this work was to assess the anesthetic management of RT to guarantee success. DISCUSSION: Anesthesiologists who work in RT should know the interactions between hemodynamics and pharmacology in these patients. But to be able to work as a team, there are three questions that need to be answered: What do the urologist and the anesthesiologist need to know about renal transplantation? What does the urologist need to know about anesthesia? Or, in other words, what do anesthesiologists really want the urologists to know, and what does an anesthesiologist want to know about RT? CONCLUSIONS: RT is a complex procedure that needs a multidisciplinary approach, especially in patients with important comorbidities. It is necessary to learn how to look through the eyes of the rest of the team. Working within a multidisciplinary team is basic to ensure the success of the RT.

Enfoque diagnóstico y terapéutico del paciente con obesidad / Diagnostic and treatment approach of obese patient / Enfoque Diagnóstico E Terapêutico Do Paciente Com Obesidade

La obesidad es un problema de salud pública, con prevalencia creciente en todo el mundo, que acarrea una importante morbimortalidad, lo cual ha llevado a su reconocimiento como entidad nosológica independiente. Colombia no escapa a esta situación y reporta una prevalencia de adultos obesos del 51.2% en 2010. Varios elementos influyen en el comportamiento epidemiológico del sobrepeso y la obesidad: aspectos genéticos, étnicos, metabólicos, ambientales, políticos y rasgos socioculturales, entre otros. La asociación de la obesidad con múltiples patologías es cada vez más evidente, no sólo porque aumenta de forma considerable el riesgo cardiovascular, sino, también, porque causa afecciones pulmonares, gastrointestinales y osteoarticulares. A la fecha, el índice de masa corporal es el parámetro que permiten la definición y clasificación del sobrepeso y la obesidad. Medidas alternas, como la circunferencia abdominal, se han planteado como predictores de morbilidad independientes. Teniendo en cuenta la alta prevalencia de la obesidad y la imprecisión de los métodos clasificatorios para estimar el riesgo cardiovascular e identificar el paciente candidato a tratamiento, es una decisión clínica importante. El enfoque terapéutico del paciente con obesidad debe dirigirse a la intervención de los factores de riesgo modificables y está basado fundamentalmente en los cambios en el estilo de vida, complementado con la farmacoterapia en algunos pacientes, sin desconocer la opción quirúrgica en pacientes que cumplan ciertos criterios. Sin embargo, sólo será la prevención multidimensional lo que combatirá la conversión de la obesidad en una verdadera pandemia.

Obesity is a public health issue with growing prevalence worldwide, which leads to morbi-mortality and has given rise to its recognition as an independent nosological entity. Colombia reports a prevalence of obese adults of 51.2% in 2010. Several elements influence the epidemiology of overweight and obesity including genetic, ethnic, metabolic, environmental, political, and social aspects, amongst many others. The association of obesity with multiple pathologies is more evident as time goes by, not only because it increases the risk of cardiovascular disease, but because it also causes pulmonary, gastrointestinal, and osteoarticular disorders. To date, body mass index is the parameter used to determine and classify overweight and obesity. Alternative measurements, such as waist circumference, have been proposed as independent predictors of morbility. Considering the high prevalence of obesity and the poor precision of the classification methods to estimate cardiovascular risk, it is an important clinical decision to identify the patient who is candidate for treatment. The therapeutic approach in obese patients should focus on correcting the modifiable risk factors, and is fundamentally based on making changes in life style, which may be complemented with medication and surgery in certain patients. However, only multidisciplinary prevention will effectively avert obesity from becoming pandemic.

A obesidade é um problema de saúde pública, com prevalência crescente em todo mundo, que arca uma importante morbimortalidade, o qual levou a seu reconhecimento como entidade nosológica independente. A Colômbia não escapa a esta situação e reporta uma prevalência de adultos obesos de 51.2% em 2010. Vários elementos influem no comportamento epidemiológico do sobrepeso e a obesidade: aspectos genéticos, étnicos, metabólicos, ambientais, políticos e rasgos socioculturais, entre outros. A associação da obesidade com múltiplas patologias é cada vez mais evidente, não só porque aumenta de forma considerável o risco cardiovascular, senão, também, porque causa afecções pulmonares, gastrointestinais e osteoarticulares. À data, o índice de massa corporal é o parâmetro que permitem a definição e classificação do sobrepeso e a obesidade. Medidas alternas, como a circunferência abdominal, propuseram-se como preditores de morbilidade independentes. Tendo em conta a alta prevalência da obesidade e a imprecisão dos métodos classificatórios para estimar o risco cardiovascular e identificar o paciente candidato a tratamento, é uma decisão clínica importante. O enfoque terapêutico do paciente com obesidade deve dirigir-se à intervenção dos fatores de risco modificáveis e está baseado fundamentalmente nas mudanças no estilo de vida, complementado com a fármaco-terapia em alguns pacientes, sem desconhecer a opção cirúrgica em pacientes que cumpram certos critérios. No entanto, só será a prevenção multidimensional o que combaterá a conversão da obesidade numa verdadeira pandemia.

Metástasis coroidea de cáncer pulmonar: reporte de un caso / Choroidal metastasis from lung cancer: case report

Introducción: El compromiso ocular en el cáncer sistémico es diverso y ampliamente conocido en la literatura internacional, pero en la nacional hay carencia de información al respecto. La coroides es la estructura ocular donde con mayor frecuencia se encuentran metástasis tumorales dentro del ojo, siendo el cáncer de pulmón el más comúnmente diagnosticado en pacientes que debutan con metástasis coroidea. En esta localización, los síntomas más frecuentes son la visión borrosa y dolor ocular, siendo la presentación asintomática infrecuente. Este tipo de lesiones se produce en la fase final de la enfermedad, donde la supervivencia no supera los 6 meses. Presentación del caso: Paciente portador de cáncer pulmonar, que debutó con metástasis coroidea, siendo la primera sintomatología compatible con desprendimiento de retina. Las claves para el diagnóstico fueron la ultrasonografía ocular, resonancia nuclear magnética, y la biopsia realizada tras la enucleación del ojo afectado que es informada como adenocarcinoma tubular y papilar. De acuerdo a este resultado, se estudia con tomografía computada (TAC) de tórax, abdomen y pelvis, cintigrama óseo, revelándose la imagen de un nódulo pulmonar sospechoso y metástasis pulmonares y extrapulmonares. Tras 8 meses desde el hallazgo de la metástasis coroidea, y 6 meses desde el diagnóstico de cáncer pulmonar, el paciente fallece. Finalmente, se revisó la bibliografía pertinente acerca de la clínica, aproximación diagnóstica, imágenes y consideraciones sobre el tratamiento de las metástasis coroideas. Discusión: Es importante conocer la aproximación diagnóstica de las metástasis coroideas de tumores primarios para tener un alto índice de sospecha.

Introduction: Ocular involvement in systemic cancer is diverse and widely known in the international literature, but in our country there is lack of information. The choroid is the structure of the eye where they most often metastatic tumor within the eye are found, being lung cancer the most commonly diagnosed in patients presenting with choroidal metastasis. At this location, the most common symptoms are blurred vision and eye pain. Asymptomatic presentation is uncommon. This type of injury occurs in the final stage of the disease, where survival does not exceed 6 months. Case report: Patient with lung cancer, which debuted with choroidal metastasis, whose first symptoms consistent in retinal detachment. The keys to diagnosis were ocular ultrasonography, magnetic resonance imaging, and biopsy performed after enucleation of the affected eye, which was reported as tubular and papillary adenocarcinoma. According to this result, he was studied with chest, abdomen and pelvis CT, bone scintigraphy, revealing the image of a suspicious lung nodule and pulmonary and extrapulmonary metastases. After 8months since the finding of choroidal metastases, and 6 months after diagnosis of lung cancer, the patient dies. Reviewed the relevant literature on the clinical diagnostic approach, images and considerations on the treatment of choroidal metastases. Discussion: It is important to know the approach to diagnosis of choroidal metastases from primary tumors to have a high index of suspicion.