Learning from history in the midst of the COVID-19: epidemics/pandemics of antiquity up to the fall of the Western Roman Empire / Aprendiendo de la historia en medio del COVID-19: epidemias/pandemias de la antigüedad hasta la caída del Imperio Romano de Occidente

Abstract When humans discovered agriculture and livestock, they ceased to be nomads and began to settle in towns until they created large cities. From the first human settlements in Egypt, Mesopotamia, and the Anatolian Peninsula, populations were exposed and susceptible to new infectious agents, leading to epidemics and pandemics. Great civilizations emerged, such as Egypt, the land of Hatti, Israel, Greece, Carthage, and Rome, among others. Contact between different populations through wars or maritime trade is well documented and has been described as a source of epidemics throughout history. Epidemics described as plagues or pestilences, such as those of Egypt, the Hebrews, or the Hittites, are based on biblical texts or evidence such as tablets or hieroglyphic writings. We also reviewed classical books by authors such as Homer, Aeschylus, Herodotus of Halicarnassus, Thucydides, Diodorus Siculus, Dionysius of Halicarnassus, Titus Livius, Suetonius, and others; and described all epidemics/pandemics chronologically. This article describes the epidemics/pandemics for which there is written evidence from ancient Egypt to the fall of the Roman Empire. We should not be surprised when new epidemics/pandemics appear as causes of political and economic collapse, as this has been common throughout history, decimating, blocking, or even destroying cultures and civilizations repeatedly.

Resumen Cuando el hombre descubrió la agricultura y la ganadería, dejó de ser nómada y empezó a asentarse en pueblos hasta crear grandes ciudades. Desde los primeros asentamientos humanos en Egipto, Mesopotamia y la península de Anatolia, las poblaciones estuvieron expuestas y susceptibles a nuevos agentes infecciosos, dando lugar a epidemias y pandemias. Aparecieron grandes civilizaciones como Egipto, la Tierra de Hatti, Israel, Grecia, Cartago y Roma, entre otras. El contacto entre las distintas poblaciones a través de las guerras o el comercio marítimo está muy bien establecido y descrito como focos de epidemias a lo largo de la historia. Las epidemias descritas como plagas o pestilencias, como las que ocurrieron a los egipcios, los judíos, o los hititas, se describen con base en textos bíblicos o mediante evidencias como tablillas o escritos jeroglíficos. También revisamos libros clásicos de autores como Homero, Esquilo, Herodoto de Halicarnaso, Tucídides, Diodoro Sículo, Dionisio de Halicarnaso, Tito Livio, Suetonio, entre otros. Este artículo describe cronológicamente todas las epidemias/pandemias de las que existe evidencia a través de la escritura desde el antiguo Egipto hasta la caída del Imperio Romano. No debemos sorprendernos cuando aparecen nuevas epidemias/pandemias como causantes del colapso político y económico, ya que ha sido algo común a lo largo de la historia, diezmando, bloqueando o incluso destruyendo culturas y civilizaciones reiteradamente.

Effectiveness of Whole-Exome Sequencing for the Identification of Causal Mutations in Patients with Suspected Inherited Ocular Diseases

ABSTRACT Background: Genetic eye disorders, affecting around one in 1000 people, encompass a diverse group of diseases causing severe visual deficiency. The recent adoption of next-generation sequencing techniques, including whole-exome sequencing (WES), in medicine has greatly enhanced diagnostic rates of genetically heterogeneous diseases. Objectives: The objectives of the study were to assess the diagnostic yield of WES in a cohort of Mexican individuals with suspected genetic eye disorders and to evaluate the improvement of diagnostic rates by reanalysis of WES data in patients without an initial molecular diagnosis. Methods: A total of 90 probands with ocular anomalies of suspected genetic origin were ascertained. Patients underwent WES in leukocytic DNA. Bioinformatics analysis and Sanger sequencing were used to confirm the disease-causing variants. Only variants identified as pathogenic or likely pathogenic were considered as causal. Results: Initial analysis revealed causal mutations in 46 cases (51%). Reanalysis of WES data 12 months after first analysis resulted in the identification of additional causal variants in 6 patients (7%), increasing the molecular diagnostic yield to 58%. The highest diagnostic rates by disease categories corresponded to hereditary retinal dystrophies (77%) and to anomalies of the anterior segment of the eye (47%). Conclusion: Our study demonstrates that WES is an effective approach for genetic diagnosis of genetic ocular diseases and that reanalysis of WES data can improve the diagnostic yield.

Whole sequencing of the mitochondrial genome of breast cancer tissue in Mexican-mestizo postmenopausal women with different body mass index

Abstract Background Mitochondrial and oxidative stress has been related to obesity and breast cancer being this cancer more frequent and more aggressive in postmenopausal women with obesity. Objective The objective of this study was to investigate whether Mexican-Mestizo postmenopausal women with breast cancer and obesity present different somatic mutations in the mitochondrial DNA (mtDNA) when compared to women with normal body mass index (BMI). Subjects and Methods We included six Mexican-Mestizo postmenopausal women bearing breast cancer and who underwent mastectomy or breast-conserving surgery. BMI was determined in each case. Patients’ genomic DNA was isolated from blood leukocytes and tumor tissue samples. Whole mtDNA sequence was determined by MitoChip v2.0 mitochondrial resequencing array, and data were analyzed using the GeneChip Sequence Analysis Software. Tumor mtDNA sequence was compared with matched leukocyte mtDNA sequence. Results Three women had a normal BMI and three presented obesity. Overall, we found 64 genetic variants: 53.1% were somatic mutations and 46.9% were polymorphisms; 44.1% were in the non-coding region and 55.9% were in genes that encode for mitochondrial proteins. Among the somatic mutations, 67.7% were in patients with normal BMI and 32.3% in patients with obesity. Conclusions We did not find a higher frequency of mitochondrial somatic mutations in postmenopausal women with breast cancer and obesity compared to those with normal BMI. However, results could be due to the small number of women studied.

A recurrent de novo mutation in ATP1A3 gene in a Mexican patient with alternating hemiplegia of childhood detected by massively parallel sequencing / Mutación de novo recurrente en el gen ATP1A3 en una paciente mexicana con hemiplejia alternante de la infancia detectada por secuenciación masiva en paralelo

Abstract Background: Pediatric movement disorders represent a diagnostic challenge for pediatricians and pediatric neurologists due to their high clinical heterogeneity and shared common features. Therefore, specific diagnoses require different approaches including metabolic work-up and specific tests for frequent genetic conditions. Alternating hemiplegia of childhood (AHC) is an ultra-rare pediatric movement disorder, characterized by paroxysmal alternating hemiplegia, dystonia, and seizure-like episodes that can be misleading during the evaluation of a child with a movement disorder. Case report: We present a Mexican patient with abnormal movements referred to the Genetics clinic because of hyperammonemia and a possible organic acidemia. Our assessment did not find clinical features compatible with an inborn error of metabolism. A massively parallel sequencing approach with targeted panel sequencing was used to get a final diagnosis. A missense variant c.2839G>A (p.Gly947Arg) located at exon 21 of ATP1A3 gene was demonstrated. This variant (rs398122887) has been previously reported as de novo producing alternating hemiplegia of childhood (AHC). Conclusions: AHC is an ultra-rare syndrome presented as a movement disorder with seizure-like episodes and a unique facial phenotype. Clinicians should be aware of this combination in order to diagnose this condition in a timely manner. Massive parallel sequencing panels are emerging as the best approach to diagnose rare movement disorders and simultaneously rule out metabolic disorders and common epileptic syndromes.

Resumen Introducción: Los trastornos pediátricos del movimiento representan un reto diagnóstico para pediatras y neurólogos pediatras debido a su gran heterogeneidad clínica y características comunes compartidas. Por lo tanto, los diagnósticos específicos requieren de diferentes abordajes que incluyen la búsqueda de desórdenes metabólicos y pruebas específicas para condiciones genéticas frecuentes. La hemiplejia alternante de la infancia (AHC) es un trastorno pediátrico del movimiento poco común, caracterizado por cuadros paroxísticos de hemiplejia alternante, distonía y episodios semejantes a crisis epilépticas, que pueden resultar desorientadores durante el abordaje diagnóstico de un infante con un desorden del movimiento. Caso clínico: Presentamos una paciente mexicana con movimientos anormales referida a la Clínica de Genética por hiperamonemia y una posible acidemia orgánica. Nuestro abordaje no identificó características clínicas compatibles con un error innato del metabolismo. Se utilizó un abordaje basado en secuenciación masiva en paralelo para obtener un diagnóstico final. Se demostró una variante de sentido equivocado c.2839G>A (p.Gly947Arg) localizada en el exón 21 del gen ATP1A3. Esta variante (rs398122887) ha sido previamente reportada como de novo, ocasionando AHC. Conclusiones: La AHC es un síndrome excepcionalmente raro que se presenta con un trastorno del movimiento con cuadros semejantes a crisis epilépticas y un fenotipo facial particular. Los médicos deben ser conscientes de esta combinación con el fin de diagnosticar oportunamente esta condición. Los paneles de secuenciación masiva están emergiendo como el mejor abordaje para diagnosticar trastornos del movimiento raros y, simultáneamente, descartar trastornos metabólicos y síndromes epilépticos comunes.

16S rRNA gene-based identification of bacteria in postoperative endophthalmitis by PCR- Denaturing Gradient Gel Electrophoresis (PCR-DGGE) fingerprinting

Conventional microbiological culture techniques are frequently insufficient to confirm endophthalmitis clinical cases which could require urgent medical attention because it could lead to permanent vision loss. We are proposing PCR-DGGE and 16S rRNA gene libraries as an alternative to improve the detection and identification rate of bacterial species from endophthalmitis cases.