Founder mutation in myosin-binding protein C with an early onset and a high penetrance in males.

OBJECTIVE: One of the challenges in hypertrophic cardiomyopathy (HCM) is to determine the pathogenicity of genetic variants and to establish genotype/phenotype correlations. This study aimed to: (1) demonstrate that MYBPC3 c.2149-1G>A is a founder pathogenic variant, (2) describe the phenotype and clinical characteristics of mutation carriers and (3) compare these patients with those with the most frequent pathogenic HCM variants: MYBPC3 p.Arg502Trp/Gln. METHODS: We reviewed genetic tests performed in HCM probands at our institution. We carried out transcript analyses to demonstrate the splicing effect, and haplotype analyses to support the founder effect of MYBPC3 c.2149-1G>A. Carriers with this mutation were compared with those from MYBPC3 p.Arg502Trp/Gln in terms of presentation features, imaging and outcomes. RESULTS: MYBPC3 c.2149-1G>A was identified in 8 of 570 probands and 25 relatives. Penetrance was age and sex dependent, 50.0% of the carriers over age 36 years and 75.0% of the carriers over 40 years showing HCM. Penetrance was significantly higher in males: in carriers older than 30 years old, 100.0% of males vs 50.0% of females had a HCM phenotype (p=0.01). Males were also younger at diagnosis (32±13 vs 53±10 years old, p<0.001). MYBPC3 c.2149-1G>A resulted in an abnormal transcript that led to haploinsufficiency and was segregated in two haplotypes. However, both came from one founder haplotype. Affected carriers showed a better functional class and higher left ventricular ejection fraction (LVEF) than patients with MYBPC3 p.Arg502Trp/Gln (p<0.05 for both). Nevertheless, the rate of major adverse outcomes was similar between the two groups. CONCLUSIONS: MYBPC3 c.2149-1G>A splicing variant is a founder mutation. Affected males show an early onset of HCM and with higher penetrance than women. Carriers show better functional class and higher LVEF than MYBPC3 p.Arg502Trp/Gln carriers, but a similar rate of major adverse outcomes.

Modified Oregonator: an Approach from the Complex Networks Theory / Oregonador Modificado: un Enfoque desde la Teoría de Redes Complejas

Abstract: Within the framework of Systems Biology, this paper proposes the complex network theory as a fundamental tool for determining the most critical dynamic variables in complex biochemical mechanisms. The Belousov-Zhabotinsky reaction is proposed as a study model and as a complex bipartite network. By determining the structural property authority, the most relevant dynamic variables are specified, and a mathematical model of the Belousov-Zhabotinsky reaction is obtained. The bidirectional coupling of the proposed model was made with other models associated with biological processes, finding synchronization phenomena when varying the coupling parameter. The time series obtained from the numerical solution of the coupled models were used to construct their images using the Gramian Angular Field technique. In the end, a supervised learning tool is proposed for the classification of the type of coupling by analyzing the images, obtaining score percentages above 94%. The hereby proposed methodology could be extended to the experimental field in order to determine anomalies in the coupling and synchronization of different physiological oscillators.

Resumen: En el marco de la Biología de sistemas, se propone en el presente trabajo a la teoría de redes complejas como una herramienta fundamental para la determinación de las variables dinámicas más importantes en mecanismos bioquímicos complejos. Se emplea como modelo de estudio la reacción de Belousov-Zhabotinsky y se plantea como una red compleja bipartita. Mediante la determinación de la propiedad estructural autoridad, se determinan las variables dinámicas con mayor relevancia y se obtiene un modelo matemático de la reacción de Belousov-Zhabotinsky. Se realizó el acoplamiento bidireccional del modelo planteado con otros modelos asociados a procesos biológicos, encontrándose fenómenos de sincronización al variar el parámetro de acoplamiento. Las series de tiempo obtenidas de la solución numérica de los modelos acoplados se emplearon para construir sus respectivas imágenes mediante la técnica de campo angular gramiano. Finalmente, se propone una herramienta de aprendizaje supervisado para la clasificación del tipo de acoplamiento mediante el análisis de las imágenes, obteniéndose porcentajes de exactitud por encima del 94%. La metodología propuesta en el presente trabajo podría extenderse y trasladarse al campo experimental con la finalidad de determinar anomalías en el acoplamiento y sincronización de distintos osciladores fisiológicos.

[Post-traumatic femoral arteriovenous fistula, endovascular treatment]. / Fístula arteriovenosa femoral postraumática, tratamiento endovascular.

BACKGROUND: Arteriovenous fistulas secondary to gunshot wounds have been increasing due to military activities, with endovascular treatment showing better results in haemodynamically stable patients. CLINICAL CASE: A 16 year-old male with diagnosis of femoral arteriovenous fistula in the left lower extremity was admitted to general surgery for endovascular management. A procedure with stent was performed without complications, and is currently on anticoagulant and antiplatelet treatment. CONCLUSION: Arteriovenous fistulas under the inguinal region can be safely treated with endovascular treatment (embolisation or stent) on stable patients. The objective of this therapy is to close the defect between artery and vein. This is the case of a patient with great results due to endovascular treatment, decreasing complications of the surgical treatment.

[Hemangiolymphangioma of the spermatic cord in a 17 year-old: A case report]. / Hemangiolinfangioma de cordón espermático en adolescente de 17 años, reporte de caso.

BACKGROUND: Hemangiolymphangiomas are extremely rare tumours arising from blood and lymphatic vessels. It is a benign disorder, and 95% are of the neck and axilla. OBJECTIVE: To present a case of hemangiolymphangioma of the spermatic cord with contralateral recurrence. CLINICAL CASE: A 17-year-old patient with a progressively growing tumour in the right inguinoscrotal region. Examination revealed a painless, movable and soft right inguinoscrotal tumour, mobile and soft. Surgical resection showed a 25×25cm tumour from spermatic cord, right testicle, and subcutaneous cellular tissue. Histopathological study reported a hemangiolymphangioma. CONCLUSIONS: The spermatic cord is an unusual location of hemangiolymphangiomas with contralateral recurrence. Surgical treatment, with histopathological diagnosis, is associated with good prognosis.

Apical meristem organization and lack of establishment of the quiescent center in Cactaceae roots with determinate growth.

Some species of Cactaceae from the Sonoran Desert are characterized by a determinate growth pattern of the primary root, which is important for rapid lateral-root formation and seedling establishment. An analysis of the determinate root growth can be helpful for understanding the mechanism of meristem maintenance in plants in general. Stenocereus gummosus (Engelm.) Gibson & Horak and Pachycereus pringlei (S. Watson) Britton & Rose are characterized by an open type of root apical meristem. Immunohistochemical analysis of 5-bromo-2'-deoxyuridine incorporation into S. gummosus showed that the percentage of cells passing through the S-phase in a 24-h period is the same within the zone where a population of relatively slowly proliferating cells could be established and above this zone in the meristem. This indicated the absence of the quiescent center (QC) in S. gummosus. During the second and the third days of growth, in the distal meristem portion of P. pringlei roots, a compact group of cells that had a cell cycle longer than in the proximal meristem was found, indicating the presence of the QC. However, later in development, the QC could not be detected in this species. These data suggest that during post-germination the absence of the establishment of the QC within the apical meristem and limited proliferative activity of initial cells are the main components of a determinate developmental program and that establishment of the QC is required for maintenance of the meristem and indeterminate root growth in plants.

Dispersión de sustancias contaminantes en cursos de agua

En el presente trabajo se presenta una metodología de resolucíon de la ecuación de convección-difusión a traves de esquemas que minimizan problemas de estabilidad y difusión numerica frecuentes en este tipo de ecuaciones. Se describe su implementación computacional y se realizan aplicaciones a situaciones teóricas y reales. Se concluye sobre el comportamiento del modelo matemático en base a los resultados obtenidos

Dispersión de sustancias contaminantes en cursos de agua

En el presente trabajo se presenta una metodología de resolucíon de la ecuación de convección-difusión a traves de esquemas que minimizan problemas de estabilidad y difusión numerica frecuentes en este tipo de ecuaciones. Se describe su implementación computacional y se realizan aplicaciones a situaciones teóricas y reales. Se concluye sobre el comportamiento del modelo matemático en base a los resultados obtenidos