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(1) Background and objectives: Maturity-onset diabetes of the young (MODY) is a group of diabetes caused by gene defects related to insulin secretion. MODY1, MODY2, and MODY3 are the most common and account for approximately 80% of all cases. Other types are relatively rare. This study describes the clinical, analytical, and genetic characteristics of a patient with MODY10, and diabetic nephropathy, retinopathy, and functional hypogonadism diagnosis. (2) Materials and methods: A clinical case was analyzed and whole exome generation sequencing (WES) was used to detect mutations related to a monogenic variant. (3) Results: A seventeen-year-old male patient, who was diagnosed with apparent type 1 diabetes at the age of eight was started with insulin therapy. He came to the emergency room with glycemic decompensation, facial, and lower limb edema. During his evaluation, he had near-nephrotic range proteinuria of 2902 mg/24 h, a kidney ultrasound showing mild pyelocalyceal dilation, proliferative diabetic retinopathy, and was also diagnosed with functional hypogonadotropic hypogonadism. These comorbidities improved with adequate glycemic control. WES showed missense variant c.94G>A (p.Gly32Ser) in the INS gene, according to Clinvar corresponding to MODY10. It was a “de novo” variant not reported in his parents. (4) Conclusions: Monogenic diabetes (MD) is rare and MODY10 is among the less frequent types. MODY should be suspected in patients with type 1 phenotype with negative autoimmunity even in the absence of a family history of diabetes. To the best of our knowledge, we present here the first patient with these phenotypic traits of MODY10 reported in Latin America.

Maturity-Onset Diabetes of the Young (MODY) comprises monogenic, non-syndromic forms of diabetes inherited in an autosomal dominant pattern. MODY is frequently misdiagnosed as type 1 diabetes (T1D), type 2 diabetes (T2D), or gestational diabetes mellitus (GDM). Studies suggest that 50-90% of MODY cases are erroneously classified as type 1 or type 2 diabetes, and up to 5% of women with GDM may have undiagnosed MODY. However, data regarding the clinical presentation and genetic characterization of MODY in Latin American populations remain scarce. This study aimed to describe the clinical, analytical, and genetic characteristics of MODY patients initially misdiagnosed as T1D, T2D, or GDM in a Latin American tertiary care center. Medical history, clinical and laboratory data were obtained from electronic medical records to assess diagnostic accuracy and identify phenotypic patterns suggestive of MODY. Whole exome sequencing (WES) was employed to detect mutations related to monogenic variants. We identified five patients with MODY. The median age at diabetes diagnosis was 13.6 years, while the median age at MODY diagnosis was 25.8 years. The average duration between the initial diabetes diagnosis and confirmation of MODY was 12.2 years. None of the patients presented with diabetic ketoacidosis at the onset of diabetes. All patients tested negative for islet cell autoimmunity. Of the five patients, two were initially misclassified as having T1D, two as T2D, and one as GDM. Whole-exome sequencing (WES) identified a pathogenic missense variant, c.94G>A (p.Gly32Ser), in the gene (MODY10) in one patient initially diagnosed with T1D. Another patient, also misclassified as T1D, carried a pathogenic missense variant, c.709A>G (p.Asn237Asp), in the gene (MODY3). Additionally, two patients initially diagnosed as T2D were found to carry missense variants: a likely pathogenic variant, c.613G>T (p.Asp205Tyr) in the gene (MODY2) and pathogenic variant, c.4135C>T (p.Arg1379Cys) in the gene (MODY12), respectively. The patient initially diagnosed with GDM was revealed to have a pathogenic frameshift variant, c.616dupC (p.His206Profs 38), in the gene (MODY6). Based on these findings, a change in therapeutic approach was implemented. MODY is often misdiagnosed, leading to delays in appropriate management. Whole-exome sequencing is crucial for identifying pathogenic variants, enabling accurate reclassification and tailored therapy.

Mexico and Turkey have a not so long official diplomatic relation, as the establishment of this traces back to 1928 after a Friendship Agreement that was signed in 1927. In those first years of the 20th century the new Republic of Turkey had just ended 600 years of imperial order and was taking her first steps into becoming a democratic and westernised country, whereas Mexico was restructuring himself from the turbulent years of the Mexican Revolution. The relationship between these two countries is not commonly taught nor well documented, and it is even rarer to think about encounters before the year of 1928; nevertheless, Mexico and Turkey share various encounters -official and non-official- years before the establishment of official diplomatic relations. It is possible to trace these concurrences back to when Mexico was the so-called New Spain and Turkey was the centre of one of the most important empires to ever exist: the Ottoman Empire. Nonetheless, there were not as many encounters as there were between Mexico and other countries due to the geographical distance accentuated by the Atlantic Ocean and a whole continent in between; moreover, the societal, cultural, and historic circumstances were substantially different. During the years that Sultan Bayezid II (1481-1512), Sultan Selim I (1512-1520) and Sultan Suleiman (1520-1566) were on the throne, it was basically unimaginable to cross the Atlantic Ocean and arrive at the Americas. The geopolitical situation would not have allowed it, as many territories needed a strong presence of the Ottoman authorities as they were sources of instability; such were the cases of Eastern Europe, the southern borders of the now Republic of Turkey and the Persian lands. This, however, does not mean that the Ottoman Empire did not know about the existence of the New Spain, as a matter of fact, in the year 1513 a map made by Piri Reis was shown to Sultan Selim I; this map showed some points from the Americas to the Atlantic Ocean, nonetheless, the reasons why the Ottomans did not cross the ocean are still unclear. Later, some hypotheses and assumptions will be further discussed. Years later with the Battle of Lepanto in 1571 between the Holy League (Spain being a participant) and the Ottoman Empire the hegemony of Christianity was reaffirmed in the Mediterranean territory, of course this was a great source of pride for the Spanish Empire, resulting in King Philip II sending letters to archbishops, bishops, and religious orders of the Viceroyalty of the New Spain to celebrate the victory of Catholicism over Islam and to indeed prove that the Spanish Monarchy was the chosen one by God. There is no doubt that both sides knew about the other, but making further contact or establishing a true diplomatic relationship was an almost impossible task. The New Spain was a colony that could not take steps into developing his own international relations nor create a Ministry of Foreign Affairs; after independence, the democratic values and institutions were not solid and the years that followed were turbulent and full of uncertainties. The country oscillated between being a representative republic, having a monarchical order and even an imperial order with the first and second Mexican Empire. Moreover, Mexico suffered different invasions, hence, it was extremely difficult to establish diplomatic relations with any country, let alone with the Ottoman Empire. On the other hand, the Ottoman Empire was living his first centuries as one of the most powerful and prosperous empires to ever exist. The conquest of Constantinople, the leadership and ambition of the sultans, and the geostrategic position of the Anatolian peninsula, allowed the Ottomans to exert a great influence and to conquest nearby territories such as the ones in the Arab world, the Balkans, and Eastern Europe. The unified, but diverse empire, represented a threat to Europe; the West felt the pressure of a gigantic entity that differed completely in terms of law, culture and most importantly, religion. Nonetheless, the last years of the empire were rather turbulent and not as prosperous as in the beginning; the colonised peoples wanted their independence and so did the Turkish liberals, the aim was to transition into a modern country. During this period, which goes between the 19th Century and the first years of the 20th Century, we can find he first and most important encounters that connect Turkey and Mexico. Officially, the Ottoman Empire ceased to exist in 1922 with the abolition of the sultanate giving birth to a republic under the leadership of the father of the modern Republic of Turkey: Mustafa Kemal “Atatürk”. As can be seen, both republics faced the beginning of the 20th Century with some similarities and with great challenges ahead. The truth is that from 1928 until the end of the Cold War the engagements were practically inexistent, and the new approaches took place in the last decade of the century. The 21st Century brought, and has been bringing, new opportunities and means to build a stronger bond that has indeed been growing. Thus, this article will analyse in a historical and theoretical way the relationship between Mexico and Turkey since the time of the Viceroyalty of the New Spain and the existence of the Ottoman Empire. The intention is to offer a holistic view by focusing on the most important milestones considering the influence of several variables such as the role of global powers, the dynamics of the historical blocs, the guidance of certain elites, and the diplomatic processes which have settled the contacts between both countries. Based on a chronological categorization, we have considered their agency beyond the traditional geographical zones as well as the impact of the global structure towards their foreign policies, by emphasizing the deployments of collaboration at the end of the Cold War and the proliferation and potentiality of opportunities during the three decades of the twenty-first century. The conclusion will express the current state of the bilateral relations -up until the first four months of 2023-, a critical view on the selection of statements of support from one government to another, omitting positions regarding marginalized populations from both latitudes. Furthermore, the aim is to produce more knowledge and debate around this specific topic, offering some foresight of what is yet to come considering that in 2028 these two republics will commemorate 100 years of official diplomatic relations.   La relación entre México y Turquía ha sido escasamente analizada en cuanto a los estudios de política exterior e historia mexicana, de la cual se han rescatado únicamente algunos episodios muy puntuales. La distancia entre México y Turquía, acentuada por el Océano Atlántico y las diferencias en cuanto a sucesos históricos y sociales, hace pensar que los acercamientos son recientes o, por lo menos, que se despliegan a partir del establecimiento formal de las relaciones diplomáticas en 1928; no obstante, existieron contactos previos tanto de corte oficial como no oficial, que datan de la época colonial e imperial respectivamente. Para lograr un análisis histórico y holístico de esta relación bilateral, se hace un mapeo de los hitos más importantes, reconstruyendo un relato que considere variables tales como el rol de las principales potencias y sus consecuentes dinámicas, así como la influencia de determinadas élites y los procesos diplomáticos que paulatinamente han asentado los contactos entre ambas partes durante el siglo XX. Siguiendo la clasificación cronológica, se considera tanto la agencia de cada estado como el peso de la estructura global en sus políticas exteriores, particularmente debido a la fuerza gravitacional de Occidente para ambos durante la Guerra Fría y una mayor liberación de sus márgenes de maniobra hacia el final de este episodio. Asimismo, se describe la proliferación de encuentros dentro de distintos foros, el interés basado en los intercambios culturales y el potencial de oportunidades que ofrece el escenario global del siglo XXI. Finalmente, se introduce una revisión crítica que cuestiona la selección de declaraciones de respaldo de un gobierno hacia otro, omitiendo posturas respecto a poblaciones marginadas de ambas latitudes. Con todo ello, este artículo expone una historia diplomática que incluye múltiples factores y que, a su vez, aboga por mayores estudios, sobre todo a partir de la reciente rapidez en el desarrollo de las relaciones y en un momento clave que culminará en 2028 con la conmemoración del centenario de esta relación.  

Colorectal cancer (CRC) is one of the most common cancers worldwide. Lynch Syndrome (LS) is the most common form of hereditary CRC and it is caused by germline defects in the DNA-mismatch repair (MMR) pathway. It is of extreme importance for affected LS patients and their relatives to identify the germline causative alteration to provide intensified surveillance to those at risk and allow early diagnosis and cancer prevention. Current approaches for LS molecular diagnosis typically involve screening of the MMR genes by targeted gene-panel sequencing and rearrangement screening. We report the identification and characterization of a novel germline structural variant encompassing 48.757 kb, involving the 3’-ends of the MLH1 and LRRFIP2 genes, as the cause of LS in a family of Ecuador. Whole-genome sequencing and transcriptomics allowed the identification of the genomic rearrangement and highlights the importance of the use of these additional approaches to achieve a comprehensive molecular diagnosis in some LS patients.

Background An annual incidence of pheochromocytoma (PHEO) has been reported between 0.4 to 9.5 cases per million inhabitants and a prevalence of 2.13 per 100 000 people. More than 40% of patients have a genetic predisposition, and its presentation is heterogeneous, from incidental findings (10-49%) to prominent clinical pictures attributable to hypersecretion of catecholamines. The epidemiological and descriptive studies referring to pheochromocytomas in South America are scarce. This study aimed to show a retrospective analysis of patients with pheochromocytomas attending in a cancer referral center to determine the clinical, histology, and surgery outcomes. Methods From January 2015 to December 2021, a cross-sectional study was conducted in a regional reference public hospital for endocrine neoplasia in adults. We identified the clinical manifestations, pharmacologic and surgical treatment modalities from a patient interview and review of clinical records. Results Twelve patients were included, with a mean age of 44.9 (SD 10.5) years old. Around 58.3% (n=7) of the patients were male, and 16.6% (n=2) had a family history of MEN2A. Clinical characteristics of PHEO were identified in 83.3% (n=10) of the patients. The most common clinical presentation included: hypertension 10/12, palpitations and headache 9/12, diaphoresis and dyspnea 8/12, abdominal pain, nausea, and vomiting 7/12, and sensation of heat and dizziness 6/12. The classic triad of headache, palpitations, and sweating was observed in 8 patients. The CT image revealed adrenal tumors in the left (n=7/12), right (n=4/12), and one bilateral. The mean tumor diameter was 70.5 mm (SD +39.8 range 38 - 180 mm), and 91.7% of the patients (n=11/12) had tumors ≥ 4 cm. Most of the patients, 54.5%, underwent a laparoscopy procedure (n=6/11). In 2 cases, the procedure was converted to open surgery. The mean operative time was 201 ± 77.2 min. After surgery, all patients were admitted to the intensive care unit, where 75% (n=9/11) required vasoactive therapy with satisfactory recovery. The postoperative outcome showed 81.8% with normal blood pressure (n=9/11). Conclusion Most patients presenting to our hospital had large intra-abdominal tumors with a high cure rate and low mortality. Accurate diagnosis and optimal treatment are best achieved at 'centers of excellence' with expert multidisciplinary teams. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Introducción: el síndrome de quilomicronemia familiar se considera un trastorno autosómico recesivo, poco frecuente, que puede presentarse clínicamente desde la infancia, pero se manifiesta después de su debut a cualquier edad. Clínicamente se presenta con dolor abdominal, pancreatitis aguda recurrente, xantomas cutáneos y hepatoesplomegalia. Por NGS su confirmación precisa que la variante encontrada siempre es bialélica; los progenitores por definición son heterocigotos para la misma variante y no presentan la enfermedad, solo portan la mutación sin presentar síntomas. Objetivo: investigar la presencia de la quilomicronemia y determinar su patrón de herencia, ya sea como una forma familiar con un patrón monogénico bialélico o como una condición de naturaleza multifactorial. Presentación del caso: se presenta el caso de un paciente con múltiples comorbilidades que acude por dolor abdominal e hipertrigliceridemia de etiología no filiada, al cual se le envían estudios genéticos para filiar la etiología y establecer un tratamiento adecuado. Discusión y conclusión: se realiza un estudio genético de análisis molecular por secuenciación de nueva generación, identificado en homocigosis en el gen LMF1. Esta variante se caracteriza por ser patogénica. Para diagnosticar el síndrome de quilomicronemia se deben identificar variantes bialélicas no patogénicas en el complejo LPL y proteínas relacionadas. El tratamiento consiste en la restricción de grasa en la dieta para reducir la morbilidad y mortalidad, así como el seguimiento por parte de genética para el estudio de familiares con riesgo.

El presente estudio tiene por objetivo motivar la reflexión sobre uno de los conceptos más utilizados y polisémicos en el campo de las Relaciones Internacionales como ciencia: la seguridad nacional. Apartándose del enfoque tradicional que considera a ésta únicamente como la seguridad del Estado, el artículo contribuye a entender cómo la identidad de un Estado-Nación puede formar parte de sus políticas de seguridad y qué estrategias son comúnmente utilizadas por los gobiernos cuando dicha identidad se ve amenazada en el escenario nacional. Para poder realizar este análisis se plantea una revisión sobre el concepto de seguridad ontológica situándolo desde un enfoque más nacional y menos estatal, tanto en el orden externo como interno de los Estados-Nación. Además, se hace uso del caso turco para ilustrar diversos fenómenos que versan sobre la importancia que tiene para los Estados el mantenimiento de sus identidades, aun en el actual sistema internacional.

El presente artículo tiene por objetivo analizar la incidencia del factor identitario en las actividades paradiplomáticas. Para ello, se ha desarrollado un marco de pensamiento a partir de la adaptación de ciertas teorías de las Relaciones Internacionales al campo de la paradiplomacia. Asimismo, se introduce una propuesta metodológica por medio de categorías analíticas, la cual ha sido aplicada a tres casos de estudio que, debido a sus particularidades, sirven para ilustrar este fenómeno: la relación de Quebec con Francia, las colectividades vascas francesas con respecto al País Vasco y Navarra, y el Gobierno Regional de Kurdistán en relación con las localidades kurdas de los Estados vecinos a Iraq. Así, el análisis teórico-empírico ayudará a entender de qué modo la elección del actor con el que se pretende colaborar parte de una identificación recíproca, esto es que se sienten parte de una misma colectividad. Lo anterior no sólo puede motivar la relación paradiplomática sino que incluso puede ser una finalidad, la cual se traduce en acuerdos de preservación respecto a la cultura compartida por ambas partes. Sin embargo, las peculiaridades de cada caso evidenciarán que, aunque la identidad sirva como motor paradiplomático, existen otros factores que reducen su potencial de cooperación.

Background: Dyggve–Melchior–Clausen syndrome (DMC) is a rare autosomal recessive skeletal dysplasia characterized by dwarfism, coarse facial features, and intellectual disability. Caused by loss-of-function variants in the DYM gene, which encodes dymeclin, DMC is predominantly reported in consanguineous populations but remains poorly studied in South America. Methods: We report a 21-year-old Ecuadorian male with clinical features suggestive of DMC. Comprehensive clinical, radiological, and genetic evaluations were conducted, including clinical exome sequencing and Sanger sequencing, followed by an in silico analysis to assess the structural and functional consequences of the identified variant. Results: Exome sequencing identified a homozygous c.1878delA (p.Lys626fs) frameshift variant in the DYM gene, which was confirmed by Sanger sequencing as inherited from heterozygous parents. Variants of uncertain significance were detected in other skeletal dysplasia-related genes but did not correlate with the phenotype. A comprehensive review of reported DYM variants was also conducted. Conclusions: This report documents the first case of DMC in Ecuador and the second in South America, expanding the global understanding of DMC’s genetic diversity. It underscores the value of next-generation sequencing in rare disease diagnostics and highlights the critical need for inclusive genomic research in underrepresented populations to improve the understanding of genetic heterogeneity and rare disease epidemiology.

Resumen La hegemonía ha pasado de ser un fenómeno de estudio a una de las principales herramientas analíticas en el campo de las ciencias sociales. Su abordaje ha sido popularizado por Laclau y Mouffe, quienes propusieron una visión contingente y discursiva de esta noción. Sin embargo, el arribo de los teóricos de la poshegemonía −Lash, Arditi, Beasley-Murray, entre otros− ha ocasionado una multiplicidad de debates. Este artículo propone la identificación de cuatro ejes de discusión y su análisis: el contexto temporal, la (in)mediación, las vías de acción y la cuestión ontológica, rechazando una visión paradigmática del estado de la cuestión.