Neuropsychiatric Genetics of Psychosis in the Mexican Population: A Genome-Wide Association Study Protocol for Schizophrenia, Schizoaffective, and Bipolar Disorder Patients and Controls.

No large-scale genome-wide association studies (GWASs) of psychosis have been conducted in Mexico or Latin America to date. Schizophrenia and bipolar disorder in particular have been found to be highly heritable and genetically influenced. However, understanding of the biological basis of psychosis in Latin American populations is limited as previous genomic studies have almost exclusively relied on participants of Northern European ancestry. With the goal of expanding knowledge on the genomic basis of psychotic disorders within the Mexican population, the National Institute of Psychiatry Ramón de la Fuente Muñiz (INPRFM), the Harvard T.H. Chan School of Public Health, and the Broad Institute's Stanley Center for Psychiatric Research launched the Neuropsychiatric Genetics Research of Psychosis in Mexican Populations (NeuroMex) project to collect and analyze case-control psychosis samples from 5 states across Mexico. This article describes the planned sample collection and GWAS protocol for the NeuroMex study. The 4-year study will span from April 2018 to 2022 and aims to recruit 9,208 participants: 4,604 cases and 4,604 controls. Study sites across Mexico were selected to ensure collected samples capture the genomic diversity within the Mexican population. Blood samples and phenotypic data will be collected during the participant interview process and will contribute to the development of a local biobank in Mexico. DNA extraction will be done locally and genetic analysis will take place at the Broad Institute in Cambridge, MA. We will collect extensive phenotypic information using several clinical scales. All study materials including phenotypic instruments utilized are openly available in Spanish and English. The described study represents a long-term collaboration of a number of institutions from across Mexico and the Boston area, including clinical psychiatrists, clinical researchers, computational biologists, and managers at the 3 collaborating institutions. The development of relevant data management, quality assurance, and analysis plans are the primary considerations in this protocol article. Extensive management and analysis processes were developed for both the phenotypic and genetic data collected. Capacity building, partnerships, and training between and among the collaborating institutions are intrinsic components to this study and its long-term success.

Presentación inusual de epitelioma curriculatum en escolar de 12 años / Unusual presentation of curriculatum epitelioma in a 12 years old schoolchild

Introducción: El carcinoma verrugoso es una variante inusual bien diferenciada del carcinoma epidermoide que tiende a aparecer en adultos de mediana edad o mayores. Se considera una neoplasia maligna de grado bajo con cuatro subtipos principales. Objetivo: Referir la infrecuente presentación del carcinoma verrugoso en un adolescente. Presentación de caso: Escolar masculino de 12 años de edad, de raza mestiza, que acude a Consulta Especializada de Dermatología en el Hospital Clínico Quirúrgico Docente Celia Sánchez Manduley con lesión vegetante localizada en planta de pie derecho; se realizan complementarios, biopsia excisional más injerto y se concluye el caso como epitelioma curriculatum. Conclusiones: A nivel clínico, los carcinomas verrugosos se presentan en forma de tumores exofíticos con una superficie papilomatosa o verrugosa. Se asocian con frecuencia a la infección por el virus del papiloma humano, y puede ser difícil distinguir entre un carcinoma verrugoso y una verruga. Es importante el reconocimiento temprano para guiar un diagnóstico preciso y tratamiento oportuno(AU)

Introduction: Verrucous carcinoma is a well differentiated unusual variant of squamous cell carcinoma that tends to occur in middle-aged or older adults. It is considered a low-grade malignant tumour with four main subtypes. Objective: To explain the uncommon presentation of the verrucous carcinoma in a teenager and the importance of early recognition to guide an accurate diagnosis and a timely treatment. Case presentation: 12 years old, school age male, mixed race who attends to specialized consultation of Dermatology in Celia Sánchez Manduley Surgical Clinical Hospital presenting a vegetating lesion located in the right foot´s sole; there were made complementary blood tests, an excisional biopsy plus graft and the case was finally diagnoses as curriculatum epithelioma. Conclusions: At the clinical level, the verrucous carcinomas are presented in the form of exophytic tumors with a papillomatous or verrucous surface. They are often associated with the human papilloma virus infection, and it may be difficult to distinguish between a verrucous carcinoma and a wart(AU)

Acrodermatitis enteropática en lactante femenina de 6 meses de edad / Acrodermatitis enteropathica in 6- months-old female infant

Introducción: La acrodermatitis enteropática es una dermatosis nutricional heredada o adquirida por deficiencia de zinc que clínicamente se caracteriza por eritema, escamocostras y erosiones, especialmente en la región perioral, en zonas acras y en la región anogenital. Además de una ingesta oral inadecuada, hay causas secundarias de esta deficiencia nutricional. Objetivo: Referir una dermatosis nutricional secundaria infrecuente en lactante femenina. Presentación de caso: Pequeñita de 6 meses de edad, fototipo III, alimentada con lactancia materna exclusiva, que acude a consulta especializada de dermatología en el hospital William Soler por cuadro clínico de 3 meses de evolución caracterizado por lesiones eritematocostrosas en regiónes acrales y periorificiales. Los padres refirieron lactancia materna exclusiva. Se realizaron complementarios Conclusiones: Las deficiencias de vitaminas y oligoelementos pueden ocasionar un amplio rango de hallazgos mucocutaneos. En el caso presentado diagnosticado como acrodermatitis enteropática adquirida, hay un aporte inadecuado de zinc en la leche materna(AU)

Introduction: Acrodermatitis enteropathica is an inherited or acquired nutritional dermatosis by zinc deficiency that is clinically characterized by erythema, squamous crusts and erosions, especially in the perioral region, in acral areas and in the anogenital region. In addition to inadequate oral intake, there are secondary causes of this nutritional deficiency. Objective: To refer a nutritional dermatosis uncommon in female infants. Case presentation: 6-months-old baby girl, skin phototype III, fed with exclusive breastfeeding whom was attended in the specialized consultation in Dermatology of William Soler Pediatric Hospital due to clinical framework of 3 months of evolution characterized by eritemato crusty lesions in acral and periorifices´ regions. Parents commented on exclusive breastfeeding. There were made complementary blood tests. Conclusions: The deficiencies of vitamins and trace elements may cause a wide range of mucocutaneous findings. In the presented case diagnosed as adquired acrodermatitis enteropathica, there is an inadequate intake of zinc in breast milk(AU)

Incontinencia pigmentaria en madre e hija / Mother - daughter Incontinentia pigmenti

Introducción: La incontinencia pigmentaria es una genodermatosis poco frecuente, con herencia dominante ligada al cromosoma X, que se presenta casi exclusivamente en mujeres. Objetivo: Informar un caso de incontinencia pigmentaria familiar (madre e hija), trastorno neuroectodérmico sistémico infrecuente. Presentación del caso: Lactante femenina remitida del servicio de neurología a la consulta especializada de dermatología en el Hospital William Soler, por alteraciones en el desarrollo psicomotor y crisis epilépticas con lesiones vegetantes hiperpigmentadas que siguen las líneas de Blaschko. En la madre se detectaron lesiones atróficas con una disposición similar. Conclusiones: Esta rara enfermedad debe sospecharse por erupción cutánea que sigue las líneas de Blaschko, habitualmente presentes en el nacimiento y que evoluciona en etapas consecutivas características. Resaltamos la importancia del asesoramiento genético, con el fin de prevenir futuras generaciones afectadas, así como el manejo multidisciplinario en esta genodermatosis(AU)

Introduction: Incontinencia pigmenti is a rare genodermatoses with dominant inheritance linked to X chromosome that occurs almost exclusively in women. Objective: To report a case of family incontinentia pigmenti (mother and daughter), which is a systemic neuroectodermal disorder rare in pediatrics. Case presentation: Female infant referred from the neurology service to the dermatology specialist in William Soler Hospital due to alterations in the psychomotor development and epileptic seizures with hyperpigmented vegetative lesions that follow the Blaschko lines. In the mother, atrophic lesions were detected with a similar distribution. Conclusions: This rare disease should be suspected by rash that follows the Blaschko lines, usually present at birth and that develops in characteristic consecutive stages. We emphasize the importance of genetic counselling in order to prevent future generations to be affected, as well as the multidisciplinary management in this genodermatoses(AU)

Tratamiento de la Psoriasis vulgar con Autohemoterapia menor. Hospital "Celia Sánchez Manduley". 2016-2018 / Treatment of vulgar Psoriasis with minor autohemotherapy. Hospital "Celia Sánchez Manduley". 2016-2018 / Tratamento da psoríase vulgar com auto-hemoterapia menor. Hospital "Celia Sánchez Manduley". 2016-2018

RESUMEN Se realizó un estudio cuasi experimental con Autohemoterapia menor a los pacientes con Psoriasis vulgar, en el hospital "Celia Sánchez Manduley" desde marzo 2016 - mayo 2018; con el objetivo de describir la respuesta de estos pacientes a dicho tratamiento. La población objeto de estudio quedó conformada por 71 pacientes que cumplieron con los criterios de inclusión/exclusión establecidos. Los datos se obtuvieron de las historias clínicas y encuestas realizadas a los pacientes y los resultados se presentaron en tablasde contingencias mediante el sistema Windows Vista. Se estudiaron las variables: respuesta clínica, tiempo de evolución de la enfermedad, número de sesiones, efectos adversos, tiempo de aparición de brotes. Se realizó el cálculo inicial del PASI y en cada consulta de evaluación y al final del tratamiento; se calculó el porciento del cambio del PASI, pues la respuesta clínica se realizó teniendo en cuenta las categorías de éste. Se concluyó que en el estudio predominaron los pacientes respondedores al tratamiento con Autohemoterapia menor, sin influir en la respuesta el tiempo de evolución de su enfermedad. Necesitó la mayoría de los psoriásicos la mayor cantidad de sesiones para la mejoría o desaparición de las lesiones y se logró con esta terapéutica espaciar los brotes sin efectos adversos en ningún enfermo.

ABSTRACT A quasi-experimental study with less autohemotherapy was performed on patients with vulgar Psoriasis, at the "Celia Sánchez Manduley" hospital from March 2016 - May 2018; with the objective of describing the response of these patients to said treatment. The study population consisted of 71 patients who met the established inclusion / exclusion criteria. The data were obtained from the clinical histories and surveys made to the patients and the results were presented in contingency tables using the Windows Vista system. The variables were studied: clinical response, time of disease evolution, number of sessions, adverse effects, time of appearance of outbreaks. The initial calculation of the PASI was performed and in each evaluation consultation and at the end of the treatment; the percentage of the PASI change was calculated, since the clinical response was made taking into account the categories of the latter. It was concluded that in the study the patients responding to treatment with minor autohemotherapy predominated, without influencing the response time of their disease evolution. The majority of psoriatics needed the most sessions for the improvement or disappearance of the lesions and this therapy was achieved by spacing the outbreaks without adverse effects in any patient.

RESUMO Um estudo quase experimental com menos auto-hemoterapia foi realizado em pacientes com psoríase vulgar, no hospital "Celia Sánchez Manduley", de março de 2016 a maio de 2018; com o objetivo de descrever a resposta desses pacientes ao referido tratamento. A população do estudo consistiu de 71 pacientes que preencheram os critérios de inclusão / exclusão estabelecidos. Os dados foram obtidos dos prontuários e levantamentos feitos aos pacientes e os resultados foram apresentados em tabelas de contingência utilizando o sistema Windows Vista. As variáveis ​​estudadas foram: resposta clínica, tempo de evolução da doença, número de sessões, efeitos adversos, tempo de aparecimento dos surtos. O cálculo inicial do PASI foi feito e em cada consulta de avaliação e no final do tratamento; o percentual de mudança do PASI foi calculado, uma vez que a resposta clínica foi feita levando-se em consideração as categorias deste último. Concluiu-se que o estudo predominou em pacientes que responderam ao tratamento com auto-hemoterapia menor, sem influenciar o tempo de resposta da evolução de sua doença. A maioria dos pacientes com psoríase precisou da maioria das sessões para a melhora ou desaparecimento das lesões e foi conseguida com essa terapia para espaçar os surtos sem efeitos adversos em nenhum paciente.

Gota tofácea crónica en un adulto / Chronic tophaceous gout in an adult

Se presenta el caso clínico de un paciente de 57 años de edad, mestizo, con antecedentes de artritis reumatoidea y gota, quien acude a la consulta especializada de Dermatología del Hospital Clinicoquirúrgico Docente Celia Sánchez Manduley de Manzanillo, provincia de Granma, por presentar lesiones nodulares dolorosas diseminadas. Se realizaron estudios complementarios y biopsia de piel, cuyos resultados permitieron diagnosticar una gota tofácea crónica. El paciente llevaba tratamiento medicamentoso con prednisona, colchicina y metrotexate, pero luego de discutir el caso con los especialistas en medicina interna y reumatología se decidió sustituir la colchicina por el alopurinol.

The case report of a 57 year-old mestizo patient, is presented with a history of rheumatoid arthritis and gout who visited the specialized Dermatology department of Celia Sánchez Manduley Teaching Clinical-Surgical Hospital in Manzanillo, Granma province, for presenting disseminated painful nodular lesions. Complementary studies and skin biopsy were carried out which results allowed to diagnose a chronic . The patient was under drugs treatment with prednisona, colchicina and metrotexate, but after discussing the case with the specialists in internal medicine and rheumatology it was decided to sustitute colchicina by alopurinol.

Gota tofácea crónica en un adulto / Chronic tophaceous gout in an adult

Se presenta el caso clínico de un paciente de 57 años de edad, mestizo, con antecedentes de artritis reumatoidea y gota, quien acude a la consulta especializada de Dermatología del Hospital Clinicoquirúrgico Docente Celia Sánchez Manduley de Manzanillo, provincia de Granma, por presentar lesiones nodulares dolorosas diseminadas. Se realizaron estudios complementarios y biopsia de piel, cuyos resultados permitieron diagnosticar una gota tofácea crónica. El paciente llevaba tratamiento medicamentoso con prednisona, colchicina y metrotexate, pero luego de discutir el caso con los especialistas en medicina interna y reumatología se decidió sustituir la colchicina por el alopurinol(AU)

The case report of a 57 year-old mestizo patient, is presented with a history of rheumatoid arthritis and gout who visited the specialized Dermatology department of Celia Sánchez Manduley Teaching Clinical-Surgical Hospital in Manzanillo, Granma province, for presenting disseminated painful nodular lesions. Complementary studies and skin biopsy were carried out which results allowed to diagnose a chronic . The patient was under drugs treatment with prednisona, colchicina and metrotexate, but after discussing the case with the specialists in internal medicine and rheumatology it was decided to sustitute colchicina by alopurinol(AU)

Fenómeno de Lucio: a propósito de un caso / Lucio's phenomenon: a case report

Se presenta caso de paciente masculino de 67 años de edad, fototipo III, con antecedentes patológicos personales de lepra lepromatosa en tratamiento, que acude a consulta especializada de Dermatología en el Hospital Guillermo Fernández Baquero (La Habana, Cuba) por lesiones ulcerosas diseminadas. Se realizan complementarios y se concluye caso como fenómeno de Lucio. Resaltando la infrecuencia de este eritema necrosante y la severidad de los estados reactivos de la lepra pues son procesos distintos pero destructores de los tejidos, supuestamente dirigidos por el sistema inmunológico que aumentan en gran medida la morbimortalidad de esta enfermedad

A case of a 67 year old male patient, phototype III, with a personal pathological history of lepromatous leprosy in treatment is presented at a specialized dermatology clinic at Guillermo Fernández Vaquero hospital for disseminated ulcerative lesions. Complementary are performed and case is concluded as a phenomenon of Lucio. Highlighting the infrequency of this necrotizingerythema and the severity of the reactive states of leprosy are different but destructive processes of the tissues, supposedlydirected by the immune system that greatly increase the morbidity and mortality of this disease.

Síndrome de Jackson-Lawler. A propósito de un caso / Jackson-Lawler síndrome. A case report

Se presenta paciente masculino de 27 años de edad, de raza mestiza, con antecedentes de queratodermia plantar, que acude a consulta especializada de dermatología en el hospital clínico quirúrgico docente Celia Sánchez Manduley por exacerbación de las lesiones, acompañadas de dolor intenso al caminar; evidenciándose al examen físico la presencia de lesiones quísticas diseminadas, hipertrofia ungueal y alopecia. Se concluye caso como síndrome de Jackson-Lawler, resaltando su infrecuencia en el medio, la afectación de calidad de vida e impacto psicológico generada al paciente y la importancia del asesoramiento genético al mismo, con el fin de prevenir futuras generaciones afectadas(AU)

We present a 27-year-old male patient of mixed race, with a history of plantar keratoderma, who attended a specialized in the Celia Sánchez Manduley clinical teaching hospital due to exacerbation of the lesions, accompanied by severe pain when walking; the physical examination revealed the presence of disseminatedcystic lesions, nail hypertrophy and alopecia. The case is concluded as a Jackson-Lawler syndrome, highlighting its infrequence in the environment, the impact on the quality of life and the psychological impact generated on the patient and the importance of genetic counseling to them, in order to prevent future generations affected(EU)

Animal Models of Diabetic Retinopathy.

PURPOSE OF REVIEW: Diabetic retinopathy (DR) is one of the most common complications associated with chronic hyperglycemia seen in patients with diabetes mellitus. While many facets of DR are still not fully understood, animal studies have contributed significantly to understanding the etiology and progression of human DR. This review provides a comprehensive discussion of the induced and genetic DR models in different species and the advantages and disadvantages of each model. RECENT FINDINGS: Rodents are the most commonly used models, though dogs develop the most similar morphological retinal lesions as those seen in humans, and pigs and zebrafish have similar vasculature and retinal structures to humans. Nonhuman primates can also develop diabetes mellitus spontaneously or have focal lesions induced to simulate retinal neovascular disease observed in individuals with DR. DR results in vascular changes and dysfunction of the neural, glial, and pancreatic ß cells. Currently, no model completely recapitulates the full pathophysiology of neuronal and vascular changes that occur at each stage of diabetic retinopathy; however, each model recapitulates many of the disease phenotypes.

The nuclear hormone receptor gene Nr2c1 (Tr2) is a critical regulator of early retina cell patterning.

Nuclear hormone receptors play a major role in the development of many tissues. This study uncovers a novel role for testicular receptor 2 (Tr2, Nr2c1) in defining the early phase of retinal development and regulating normal retinal cell patterning and topography. The mammalian retina undergoes an overlapping yet biphasic period of development to generate all seven retinal cell types. We discovered that Nr2c1 expression coincides with development of the early retinal cells. Loss of Nr2c1 causes a severe vision deficit and impacts early, but not late retina cell types. Retinal cone cell topography is disrupted with an increase in displaced amacrine cells. Additionally, genetic background significantly impacts phenotypic outcome of cone photoreceptor cells but not amacrine cells. Chromatin-IP experiments reveal NR2C1 regulates early cell transcription factors that regulate retinal progenitor cells during development, including amacrine (Satb2) and cone photoreceptor regulators thyroid and retinoic acid receptors. This study supports a role for Nr2c1 in defining the biphasic period of retinal development and specifically influencing the early phase of retinal cell fate.

Whole-Exome Sequencing in a South American Cohort Links ALDH1A3, FOXN1 and Retinoic Acid Regulation Pathways to Autism Spectrum Disorders.

Autism spectrum disorders (ASDs) are a range of complex neurodevelopmental conditions principally characterized by dysfunctions linked to mental development. Previous studies have shown that there are more than 1000 genes likely involved in ASD, expressed mainly in brain and highly interconnected among them. We applied whole exome sequencing in Colombian-South American trios. Two missense novel SNVs were found in the same child: ALDH1A3 (RefSeq NM_000693: c.1514T>C (p.I505T)) and FOXN1 (RefSeq NM_003593: c.146C>T (p.S49L)). Gene expression studies reveal that Aldh1a3 and Foxn1 are expressed in ~E13.5 mouse embryonic brain, as well as in adult piriform cortex (PC; ~P30). Conserved Retinoic Acid Response Elements (RAREs) upstream of human ALDH1A3 and FOXN1 and in mouse Aldh1a3 and Foxn1 genes were revealed using bioinformatic approximation. Chromatin immunoprecipitation (ChIP) assay using Retinoid Acid Receptor B (Rarb) as the immunoprecipitation target suggests RA regulation of Aldh1a3 and Foxn1 in mice. Our results frame a possible link of RA regulation in brain to ASD etiology, and a feasible non-additive effect of two apparently unrelated variants in ALDH1A3 and FOXN1 recognizing that every result given by next generation sequencing should be cautiously analyzed, as it might be an incidental finding.

Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases.

The nuclear hormone receptor (NHR) superfamily is composed of a wide range of receptors involved in a myriad of important biological processes, including development, growth, metabolism, and maintenance. Regulation of such wide variety of functions requires a complex system of gene regulation that includes interaction with transcription factors, chromatin-modifying complex, and the proper recognition of ligands. NHRs are able to coordinate the expression of genes in numerous pathways simultaneously. This review focuses on the role of nuclear receptors in the central nervous system and, in particular, their role in regulating the proper development and function of the brain and the eye. In addition, the review highlights the impact of mutations in NHRs on a spectrum of human diseases from autism to retinal degeneration.