PRPH2-Related Retinal Dystrophies: Mutational Spectrum in 103 Families from a Spanish Cohort.

PRPH2, one of the most frequently inherited retinal dystrophy (IRD)-causing genes, implies a high phenotypic variability. This study aims to analyze the PRPH2 mutational spectrum in one of the largest cohorts worldwide, and to describe novel pathogenic variants and genotype-phenotype correlations. A study of 220 patients from 103 families recruited from a database of 5000 families. A molecular diagnosis was performed using classical molecular approaches and next-generation sequencing. Common haplotypes were ascertained by analyzing single-nucleotide polymorphisms. We identified 56 variants, including 11 novel variants. Most of them were missense variants (64%) and were located in the D2-loop protein domain (77%). The most frequently occurring variants were p.Gly167Ser, p.Gly208Asp and p.Pro221_Cys222del. Haplotype analysis revealed a shared region in families carrying p.Leu41Pro or p.Pro221_Cys222del. Patients with retinitis pigmentosa presented an earlier disease onset. We describe the largest cohort of IRD families associated with PRPH2 from a single center. Most variants were located in the D2-loop domain, highlighting its importance in interacting with other proteins. Our work suggests a likely founder effect for the variants p.Leu41Pro and p.Pro221_Cys222del in our Spanish cohort. Phenotypes with a primary rod alteration presented more severe affectation. Finally, the high phenotypic variability in PRPH2 hinders the possibility of drawing genotype-phenotype correlations.

Comprehensive Genotyping and Phenotyping Analysis of GUCY2D-Associated Rod- and Cone-Dominated Dystrophies.

PURPOSE: To describe the genetic and clinical spectrum of GUCY2D-associated retinopathies and to accurately establish their prevalence in a large cohort of patients. DESIGN: Retrospective case series. METHODS: Institutional study of 47 patients from 27 unrelated families with retinal dystrophies carrying disease-causing GUCY2D variants from the Fundación Jiménez Díaz hospital dataset of 8000 patients. Patients underwent ophthalmological examination and molecular testing by Sanger or exome sequencing approaches. Statistical and principal component analyses were performed to determine genotype-phenotype correlations. RESULTS: Four clinically different associated phenotypes were identified: 66.7% of families with cone/cone-rod dystrophy, 22.2% with Leber congenital amaurosis, 7.4% with early-onset retinitis pigmentosa, and 3.7% with congenital night blindness. Twenty-three disease-causing GUCY2D variants were identified, including 6 novel variants. Biallelic variants accounted for 28% of patients, whereas most carried dominant alleles associated with cone/cone-rod dystrophy. The disease onset had statistically significant differences according to the functional variant effect. Patients carrying GUCY2D variants were projected into 3 subgroups by allelic combination, disease onset, and presence of nystagmus or night blindness. In contrast to patients with the most severe phenotype of Leber congenital amaurosis, 7 patients with biallelic GUCY2D had a later and milder rod form with night blindness in infancy as the first symptom. CONCLUSIONS: This study represents the largest GUCY2D cohort in which 4 distinctly different phenotypes were identified, including rare intermediate presentations of rod-dominated retinopathies. We established that GUCY2D is linked to about 1% of approximately 3000 molecularly characterized families of our cohort. All of these findings are critical for defining cohorts for inclusion in future clinical trials.

RPE65-related retinal dystrophy: Mutational and phenotypic spectrum in 45 affected patients.

INTRODUCTION: Biallelic pathogenic RPE65 variants are related to a spectrum of clinically overlapping inherited retinal dystrophies (IRD). Most affected individuals progress to severe disease, with 50% of patients becoming legally blind by 20 years of age. Deeper knowledge of the mutational spectrum and the phenotype-genotype correlation in RPE65-related IRD is needed. PATIENTS AND METHODS: Forty-five affected subjects from 27 unrelated families with a clinical diagnosis of RPE65-related IRD were included. Clinical evaluation consisted of self-reported ophthalmological history and objective ophthalmological examination. Patients' genotype was classified according to variant class (truncating or missense) or to variant location at different protein domains. The main phenotypic outcome measure was age at onset (AAO) of symptomatic disease and a Kaplan-Meier analysis of disease symptom event-free survival was performed. RESULTS: Twenty-nine different RPE65 variants were identified in our cohort, 7 of them novel. Patients carrying two missense alleles showed a later disease onset than those with 1 or 2 truncating variants (log-rank test p <0.05). While 60% of patients carrying a missense/missense genotype presented symptoms before or during the first year of life, almost all patients with at least 1 truncating allele (91%) had an AAO ≤1 year (p <0.05). CONCLUSION: Our findings suggest an association between the type of RPE65 variant carried and AAO. These findings provide useful data on RPE65-associated IRD phenotypes and may help improve clinical and therapeutic management of these patients.

Exome sequencing identifies PEX6 mutations in three cases diagnosed with Retinitis Pigmentosa and hearing impairment.

Purpose: The aim of the present work is the molecular diagnosis of three patients with deafness and retinal degeneration. Methods: Three patients from two unrelated families were initially analyzed with custom gene panels for Usher genes, non-syndromic hearing loss, or inherited syndromic retinopathies and further investigated by means of clinical or whole exome sequencing. Results: The study allowed us to detect likely pathogenic variants in PEX6, a gene typically involved in peroxisomal biogenesis disorders (PBDs). Beside deaf-blindness, both families showed additional features: Siblings from Family 1 showed enamel alteration and abnormal peroxisome. In addition, the brother had mild neurodevelopmental delay and nephrolithiasis. The case II:1 from Family 2 showed intellectual disability, enamel alteration, and dysmorphism. Conclusions: We have reported three new cases with pathogenic variants in PEX6 presenting with milder forms of the Zellweger spectrum disorders (ZSD). The three cases showed distinct clinical features. Thus, expanding the phenotypic spectrum of PBDs and ascertaining exome sequencing is an effective strategy for an accurate diagnosis of clinically overlapping and genetically heterogeneous disorders such as deafness-blindness association.

Derivation of a human DOA iPSC line, IISHDOi006-A, with a mutation in the ACO2 gene: c.1999G>A; p.Glu667Lys.

Human iPSC line, IISHDOi006-A, was obtained from fibroblasts of a patient with Dominant Optic Atrophy (DOA) carrying a heterozygous mutation in the gene ACO2: c.1999G>A; p.Glu667Lys. Reprogramming factors Oct3/4, Sox2, Klf4, and c-Myc were delivered using a non-integrative methodology that involves the use of Sendai virus.

Genomic Landscape of Sporadic Retinitis Pigmentosa: Findings from 877 Spanish Cases.

PURPOSE: We aimed to unravel the molecular basis of sporadic retinitis pigmentosa (sRP) in the largest cohort reported to date. DESIGN: Case series. PARTICIPANTS: A cohort of 877 unrelated Spanish sporadic cases with a clinical diagnosis of retinitis pigmentosa (RP) and negative family history. METHODS: The cohort was studied by classic genotyping or targeted next-generation sequencing (NGS). Multiplex ligation-dependent probe amplification (MLPA) and array-based comparative genomic hybridization were performed to confirm copy number variations detected by NGS. Quantitative fluorescent polymerase chain reaction was assessed in sRP cases carrying de novo variants to confirm paternity. MAIN OUTCOME MEASURES: The study of the sRP cohort showed a high proportion of causal autosomal dominant (AD) and X-linked (XL) variants, most of them being de novo. RESULTS: Causative variants were identified in 38% of the patients studied, segregating recessively in 84.5% of the solved cases. Biallelic variants detected in only 6 different autosomal recessive genes explained 50% of the cases characterized. Causal AD and XL variants were found in 7.6% and 7.9% of cases, respectively. Remarkably, 20 de novo variants were confirmed after trio analysis, explaining 6% of the cases. In addition, 17% of the solved sRP cases were reclassified to a different retinopathy phenotype. CONCLUSIONS: This study highlights the clinical utility of NGS testing for sRP cases, expands the mutational spectrum, and provides accurate prevalence of mutated genes. Our findings evidence the underestimated role of de novo variants in the etiology of RP, emphasizing the importance of segregation analysis as well as comprehensive screening of genes carrying XL and AD variants in sporadic cases. Such in-depth study is essential for accurate family counseling and future enrollment in gene therapy-based treatments.

Dolor postoperatorio: frecuencia y caracterización del manejo / Postoperative pain: frequency and management characterization

Abstract Introduction: Acute postoperative pain is a usual symptom and a surgical challenge. Objective: To determine the frequency of pain in the postoperative period of patients undergoing elective surgery and to characterize pain management at a second-level public hospital. Material and methods: A cross-section study of 175 postop patients was conducted, analyzing variables such as level of pain 24 hours after surgery according to the visual analog scale, type of surgery, use of analgesics, and anesthetic technique. Results: The findings indicate that the frequency of moderate, severe, and excruciating pain is 66.3%. In all cases, the analgesia treatment was prescribed by the treating service, and 2 to 3 nonsteroidal anti-inflammatory drugs were used in 86.4% of the cases, with a minimal use of opioids in 13% of the patients. The anesthetic techniques used included balanced general anesthesia, neuro-axial block, and a mixed technique; the latter improved pain control. Conclusion: The frequency of postoperative pain is similar to the level reported in other trials (30%-70%), pointing to the need to review our current management, with more extensive participation and training of the staff involved in pain control.

Resumen Introducción: El dolor agudo postoperatorio es un síntoma frecuente, el cual representa un reto en el ámbito quirúrgico. Objetivo: determinar la frecuencia de dolor en el paciente postoperado de cirugía electiva y caracterizar el manejo del mismo en un hospital público de segundo nivel de atención. Material y métodos: se realizó un estudio transversal en 175 pacientes postoperados, analizando las variables de grado de dolor a las 24 horas del postoperatorio con la escala visual análoga, tipo de cirugía, uso de analgésicos, técnica anestésica. Resultados: Se encontró que la frecuencia de dolor moderado, severo o insoportable es del 66.3%. El tratamiento analgésico en todos los casos fue prescrito por el servicio tratante y en el 86.4% de los casos se emplearon AINE'S, en número de uno a tres. Con un uso mínimo de opioides en el 13% de los pacientes. Las técnicas anestésicas usadas fueron AGB, BNA y técnica mixta; con mejoría en el grado de dolor con la técnica mixta. Conclusión: Existe una frecuencia de dolor postoperatorio similar a lo reportado en otros estudios (30-70%), reflejando la necesidad de revisión del manejo actual, mayor participación y capacitación del personal involucrado en su manejo.

Toward the Mutational Landscape of Autosomal Dominant Retinitis Pigmentosa: A Comprehensive Analysis of 258 Spanish Families.

Purpose: To provide a comprehensive overview of the molecular basis of autosomal dominant retinitis pigmentosa (adRP) in Spanish families. Thus, we established the molecular characterization rate, gene prevalence, and mutational spectrum in the largest European cohort reported to date. Methods: A total of 258 unrelated Spanish families with a clinical diagnosis of RP and suspected autosomal dominant inheritance were included. Clinical diagnosis was based on complete ophthalmologic examination and family history. Retrospective and prospective analysis of Spanish adRP families was carried out using a combined strategy consisting of classic genetic techniques and next-generation sequencing (NGS) for single-nucleotide variants and copy number variation (CNV) screening. Results: Overall, 60% of our families were genetically solved. Interestingly, 3.1% of the cohort carried pathogenic CNVs. Disease-causing variants were found in an autosomal dominant gene in 55% of the families; however, X-linked and autosomal recessive forms were also identified in 3% and 2%, respectively. Four genes (RHO, PRPF31, RP1, and PRPH2) explained up to 62% of the solved families. Missense changes were most frequently found in adRP-associated genes; however, CNVs represented a relevant disease cause in PRPF31- and CRX-associated forms. Conclusions: Implementation of NGS technologies in the adRP study clearly increased the diagnostic yield compared with classic approaches. Our study outcome expands the spectrum of disease-causing variants, provides accurate data on mutation gene prevalence, and highlights the implication of CNVs as important contributors to adRP etiology.

Risk factors for three-vessel coronary artery disease in patients of Northwest Mexico.

INTRODUCTION: Three-vessel coronary artery disease is an advanced manifestation of atherosclerosis, with high prevalence in Mexico. OBJECTIVE: The aim of this study was to describe coronary risk factors in a group of patients with three-vessel coronary artery disease in Northwest Mexico. METHODS: A cross sectional study was conducted on a population with three-vessel coronary artery disease from May 2015 to February 2016. The disease was defined when ≥70% stenosis was present in each major epicardial coronary artery. Anthropometric and biochemical parameters were measured in each patient. Ankle-Brachial Index was measured with vascular ultrasound, and Syntax score calculation with an on-line application. Statistical analysis for qualitative differences was performed using Pearson X2 test, with p<0.05 being considered as significant. RESULTS: The study included 100 patients, of whom 75 were male (mean age 63±9 years) and 25 female (mean age 69±9 years). The coronary risk factors observed were diabetes (58%), hypertension (86%), smoking (68%), dyslipidaemia (100%), metabolic syndrome (71%), and obesity/overweight (75%). Diabetes and metabolic syndrome prevalence was higher in women (p=0.03), but smoking was higher in men (76%, p=0.003). Ankle-Brachial Index was abnormal in 58% of patients, the mean Syntax score was in 36.9±11.5, and the prevalence of left main coronary heart disease was 36%. CONCLUSIONS: This group of patients with complex coronary lesions has a high prevalence of coronary risk factors, which could represent a worse prognosis.

Combining targeted panel-based resequencing and copy-number variation analysis for the diagnosis of inherited syndromic retinopathies and associated ciliopathies.

Inherited syndromic retinopathies are a highly heterogeneous group of diseases that involve retinal anomalies and systemic manifestations. They include retinal ciliopathies, other well-defined clinical syndromes presenting with retinal alterations and cases of non-specific multisystemic diseases. The heterogeneity of these conditions makes molecular and clinical characterization of patients challenging in daily clinical practice. We explored the capacity of targeted resequencing and copy-number variation analysis to improve diagnosis of a heterogeneous cohort of 47 patients mainly comprising atypical cases that did not clearly fit a specific clinical diagnosis. Thirty-three likely pathogenic variants were identified in 18 genes (ABCC6, ALMS1, BBS1, BBS2, BBS12, CEP41, CEP290, IFT172, IFT27, MKKS, MYO7A, OTX2, PDZD7, PEX1, RPGRIP1, USH2A, VPS13B, and WDPCP). Molecular findings and additional clinical reassessments made it possible to accurately characterize 14 probands (30% of the total). Notably, clinical refinement of complex phenotypes was achieved in 4 cases, including 2 de novo OTX2-related syndromes, a novel phenotypic association for the ciliary CEP41 gene, and the co-existence of biallelic USH2A variants and a Koolen-de-Vries syndrome-related 17q21.31 microdeletion. We demonstrate that combining next-generation sequencing and CNV analysis is a comprehensive and useful approach to unravel the extensive phenotypic and genotypic complexity of inherited syndromic retinopathies.

Chitosan treatment for skin ulcers associated with diabetes.

Infections, ulcerations, gangrene and, in severe cases, extremity amputation, are common complications among diabetic subjects. Various biomaterials have been utilized for the treatment of these lesions. Chitosan is an amino sugar with a low risk of toxicity and immune response. In this study, we evaluated chitosan topical gel and film treatments for subjects with diabetic ulcerations and wounds associated with diabetes mellitus. In a pre-experimental design, we described the result of chitosan gel and film treatment for wounds and skin ulcers among patients with long-standing diabetes mellitus. We studied 8 diabetic patients with wounds and skin ulcers (long duration and Wagner degree 1-2). Initially, most lesions had some degree of infection, tissue damage and ulceration. At the end of the treatment (topical chitosan) period, the infections were cured. All patients experienced a significant improvement in the initial injury and developed granulation tissue and a healthy skin cover. This report represents one of the few published clinical experience regarding the chitosan for the treatment of skin lesions among diabetic subjects. These results are relevant and promising for the treatment of this disease.

Risk factors for three-vessel coronary artery disease in patients of Northwest Mexico / Factores de riesgo para la enfermedad arterial coronaria de tres vasos en pacientes del noroeste de México

Abstract Introduction: Three-vessel coronary artery disease is an advanced manifestation of atherosclerosis, with high prevalence in Mexico. Objective: The aim of this study was to describe coronary risk factors in a group of patients with three-vessel coronary artery disease in Northwest Mexico. Methods: A cross sectional study was conducted on a population with three-vessel coronary artery disease from May 2015 to February 2016. The disease was defined when ≥70% stenosis was present in each major epicardial coronary artery. Anthropometric and biochemical parameters were measured in each patient. Ankle-Brachial Index was measured with vascular ultrasound, and Syntax score calculation with an on-line application. Statistical analysis for qualitative differences was performed using Pearson X2 test, with p < 0.05 being considered as significant. Results: The study included 100 patients, of whom 75 were male (mean age 63 ± 9 years) and 25 female (mean age 69 ± 9 years). The coronary risk factors observed were diabetes (58%), hypertension (86%), smoking (68%), dyslipidaemia (100%), metabolic syndrome (71%), and obesity/overweight (75%). Diabetes and metabolic syndrome prevalence was higher in women (p = 0.03), but smoking was higher in men (76%, p = 0.003). Ankle-Brachial Index was abnormal in 58% of patients, the mean Syntax score was in 36.9 ± 11.5, and the prevalence of left main coronary heart disease was 36%. Conclusions: This group of patients with complex coronary lesions has a high prevalence of coronary risk factors, which could represent a worse prognosis.

Resumen Introducción: La enfermedad coronaria de tres vasos (ECTV) es una manifestación avanzada de aterosclerosis, con alta prevalencia en el noroeste de México. Objetivo: Describir los factores de riesgo coronario (FRC) en un grupo de enfermos con ECTV en el noroeste de México. Métodos: De mayo de 2015 a febrero de 2016 se realizó un estudio transversal en una población del noroeste de México diagnosticada con ECTV. Se definió ECTV cuando existía estenosis ≥70% en cada una de las arterias coronarias epicárdicas mayores. Se midieron parámetros antropométricos y bioquímicos en cada paciente. Los parámetros para el índice tobillo-brazo (ITB) se obtuvieron con ultrasonido vascular (Edan SonoTrax 8 Hz) y un cálculo de puntaje Syntax con una aplicación en línea. Análisis estadístico con 32 de Pearson para diferencias cualitativas Se consideró significativo cuando p ≤ 0.05. Resultados: Se estudiaron 25 mujeres (edad 69 ± 9 años) y 75 varones (edad 63 ± 9 años). Los FRC observados fueron diabetes (58%), hipertensión (86%), antecedente de tabaquismo (68%), dislipidemia (100%), síndrome metabólico (71%) y sobrepeso/obesidad (75%). En las mujeres la prevalencia de diabetes y síndrome metabólico fue mayor que en los varones (p = 0.03), pero el tabaquismo fue más prevalente en los varones (76%, p = 0.003). El ITB se encontró anormal en el 58% de los pacientes, el puntaje Syntax promedio fue de 36.9 ± 11.5 y la prevalencia de la enfermedad del tronco de la arteria coronaria izquierda fue del 36%. Conclusión: En este grupo de estudio con lesiones coronarias complejas existe alta prevalencia de FRC que se refleja en y posiblemente un peor pronóstico.

Aterosclerosis placentaria y marcadores de disfunción endotelial en neonatos hijos de madres con diabetes gestacional / Placental atherosclerosis and markers of endothelial dysfunction in infants born to mothers with gestational diabetes

Antecedentes y objetivo: La fisiopatología de la diabetes gestacional provoca por sí misma una hiperestimulación del tejido adiposo y de las células placentarias que aumenta la producción de citocinas inflamatorias, las cuales provocan cambios en los tejidos expuestos como la placenta y el feto, por lo que en este estudio el objetivo fue comparar los marcadores metabólicos y de disfunción endotelial en sangre de cordón umbilical, así como determinar la presencia de aterosclerosis en las placentas de hijos neonatos de pacientes con diabetes gestacional y en pacientes con embarazo normoevolutivo. Pacientes y método: Se realizó un estudio transversal analítico en 84 pacientes, de las cuales se obtuvieron datos como edad, tabaquismo y ganancia de peso en el embarazo; del recién nacido se determinó la edad gestacional por Capurro, el peso y el destino posterior al nacimiento. Además se utilizaron las placentas para la búsqueda de aterosclerosis mediante estudio anatomopatológico y en las muestras sanguíneas obtenidas de cordón umbilical se determinaron glucosa, insulina, colesterol, c-VLDL, c-HDL, triglicéridos, fibrinógeno, PCR y los marcadores de disfunción endotelial (adiponectina, VCAM-1, ICAM-1 e IL-6). Resultados: La aterosclerosis placentaria se presentó en un 28,94% del grupo que cursó con diabetes gestacional frente a un 10,52% del grupo con embarazo normoevolutivo (p=0,044); se encontraron diferencias en glucosa, colesterol, triglicéridos, fibrinógeno, HOMA-IR, PCR-us y c-HDL, no encontrándose en c-VLDL. El 21,05% de los recién nacidos de las pacientes con diabetes gestacional requirieron hospitalización frente al 5,2% del grupo control. Conclusiones: Los embarazos que cursan con diabetes presentan una mayor proporción de aterosclerosis, de hospitalización en el recién nacido, de resistencia a la insulina, así como de elevación de marcadores relacionados con inflamación y disfunción endotelial en sangre de cordón umbilical (AU)

Background and objective: The pathophysiology of gestational diabetes itself causes hyperstimulation of adipose tissue and of the placenta cells increasing the production of inflammatory cytokines, which cause changes in the tissues exposed such as the placenta and foetus. Therefore, the objective of this study was to compare metabolic markers and endothelial dysfunction in umbilical cord blood, as well as to determine the presence of atherosclerosis in the placentas of newborn infants of patients with gestational diabetes and in patients with normally progressing pregnancies. Patients and method: An analytical cross-sectional study was carried out in 84 patients, obtaining data such as age, smoking and weight gain in pregnancy; the gestational age of the newborns was determined by Capurro, and their weight and destination subsequent to birth, the placentas were also collected in order to look for atherosclerosis through histological studies and glucose, insulin, VLDL-C, HDL-C, triglycerides, cholesterol, fibrinogen, PCR and markers of endothelial dysfunction (adiponectin, VCAM-1, ICAM-1 and IL-6) were determined in blood samples obtained from the umbilical cord. Results: Placental atherosclerosis presented in 28.94% of the group with gestational diabetes compared to 10.52% of the group with normally progressing pregnancies (P=.044); differences were found in glucose, cholesterol, triglycerides, fibrinogen, HOMA-IR, PCR-us, HDL-C, not in VLDL-C. Twenty-one point five percent of the newborns of the gestational diabetes patients required hospitalization, against 5.2% in the control group, Conclusions: Pregnancies that involve diabetes have higher proportion of atherosclerosis, hospitalization of the newborn, insulin resistance, as well as elevation of markers associated with inflammation and endothelial dysfunction in umbilical cord blood (AU)

[Placental atherosclerosis and markers of endothelial dysfunction in infants born to mothers with gestational diabetes]. / Aterosclerosis placentaria y marcadores de disfunción endotelial en neonatos hijos de madres con diabetes gestacional.

BACKGROUND AND OBJECTIVE: The pathophysiology of gestational diabetes itself causes hyperstimulation of adipose tissue and of the placenta cells increasing the production of inflammatory cytokines, which cause changes in the tissues exposed such as the placenta and foetus. Therefore, the objective of this study was to compare metabolic markers and endothelial dysfunction in umbilical cord blood, as well as to determine the presence of atherosclerosis in the placentas of newborn infants of patients with gestational diabetes and in patients with normally progressing pregnancies. PATIENTS AND METHOD: An analytical cross-sectional study was carried out in 84 patients, obtaining data such as age, smoking and weight gain in pregnancy; the gestational age of the newborns was determined by Capurro, and their weight and destination subsequent to birth, the placentas were also collected in order to look for atherosclerosis through histological studies and glucose, insulin, VLDL-C, HDL-C, triglycerides, cholesterol, fibrinogen, PCR and markers of endothelial dysfunction (adiponectin, VCAM-1, ICAM-1 and IL-6) were determined in blood samples obtained from the umbilical cord. RESULTS: Placental atherosclerosis presented in 28.94% of the group with gestational diabetes compared to 10.52% of the group with normally progressing pregnancies (P=.044); differences were found in glucose, cholesterol, triglycerides, fibrinogen, HOMA-IR, PCR-us, HDL-C, not in VLDL-C. Twenty-one point five percent of the newborns of the gestational diabetes patients required hospitalization, against 5.2% in the control group, CONCLUSIONS: Pregnancies that involve diabetes have higher proportion of atherosclerosis, hospitalization of the newborn, insulin resistance, as well as elevation of markers associated with inflammation and endothelial dysfunction in umbilical cord blood.

[Family structure of obese/overweight and normal weight adolescents in México]. / Estructura familiar y estado de nutrición en adolescentes de Sonora, México.

BACKGROUND: Feeding modes and appetence toward certain foods are usually conditioned by the family. Obesity during adolescence usually persists during adulthood. AIM: To determine differences in family structure of adolescents according to their nutritional status. MATERIAL AND METHODS: A cross-sectional study was conducted in 60 overweight-obese and 60 normal weight adolescents. Family type was determined based on their conformation (kinship and cohabitation), development (if the mother had a remunerated job), demography (geographical area), integration (functions of the couple); life cycle stage and functionality. RESULTS: Fifty eight percent of normal weight adolescents had simple nuclear families and 47% of overweight-obese adolescents had an extended family. Thirty one and 21% of overweight/obese and normal weight adolescents lived with an overweight/obese individual, respectively. CONCLUSIONS: There are differences in the family structure of overweight/obese and normal weight adolescents.

A Comprehensive Analysis of Choroideremia: From Genetic Characterization to Clinical Practice.

Choroideremia (CHM) is a rare X-linked disease leading to progressive retinal degeneration resulting in blindness. The disorder is caused by mutations in the CHM gene encoding REP-1 protein, an essential component of the Rab geranylgeranyltransferase (GGTase) complex. In the present study, we evaluated a multi-technique analysis algorithm to describe the mutational spectrum identified in a large cohort of cases and further correlate CHM variants with phenotypic characteristics and biochemical defects of choroideremia patients. Molecular genetic testing led to the characterization of 36 out of 45 unrelated CHM families (80%), allowing the clinical reclassification of four CHM families. Haplotype reconstruction showed independent origins for the recurrent p.Arg293* and p.Lys178Argfs*5 mutations, suggesting the presence of hotspots in CHM, as well as the identification of two different unrelated events involving exon 9 deletion. No certain genotype-phenotype correlation could be established. Furthermore, all the patients´ fibroblasts analyzed presented significantly increased levels of unprenylated Rabs proteins compared to control cells; however, this was not related to the genotype. This research demonstrates the major potential of the algorithm proposed for diagnosis. Our data enhance the importance of establish a differential diagnosis with other retinal dystrophies, supporting the idea of an underestimated prevalence of choroideremia. Moreover, they suggested that the severity of the disorder cannot be exclusively explained by the genotype.

Efectos de la educación comunitaria sobre factores de riesgo en adultos mayores prediabéticos / Effects of community-based education on the risk factors in prediabetic older adults

Introducción: la educación es piedra angular en la prevención, atención y tratamiento de la diabetes mellitus. Promueve efectos positivos en la salud de los enfermos y sus familiares a través del conocimiento, con la finalidad de prevenir o retardar las complicaciones de la diabetes, por lo que ningún grupo etario debe ser excluido de este beneficio. Objetivo: determinar el efecto de la educación comunitaria sobre el sedentarismo, los hábitos alimentarios y la glucemia, en adultos mayores con prediabetes. Métodos: estudio cuasi experimental en 20 adultos mayores de ambos géneros, con glucemia capilar de 100 mg/dL a 125 mg/dL, derechohabientes del Instituto Mexicano del Seguro Social, adscritos a la Unidad de Medicina Familiar No. 17 del Instituto Mexicano del Seguro Social, en Villa Juárez, Sonora, México. Resultados: el promedio de edad fue 67 ± 6 años, con predominio del género femenino (60 %) y escolaridad baja. El 72 % de la población tenía familiares directos con diabetes mellitus. Luego de la estrategia educativa, mejoraron los conocimientos sobre diabetes, y hubo cambios significativos antes-después en la evaluación global (p= 0,0001), glucemia capilar (p= 0,0001) y hemoglobina glucosilada (p= 0,003). Así mismo, mejoraron los hábitos dietéticos y de ejercicio físico. Conclusiones: la estrategia educativa tiene un efecto benéfico sobre variables metabólicas y favorece cambios en el estilo de vida(AU)

Introduction: education is the milestone in the prevention, care and treatment of diabetes mellitus. It promotes positive effects for the patient's and the relatives' health through acquisition of knowledge for the purpose of preventing or delaying the diabetes complications, so any age group should be excluded from this benefit. Objective: to determine the effect of community-based education on sedentary and feeding habits and glycemia in pre-diabetic older adults. Methods: quasi-experimental study of 20 older adults of both sexes with capillary glycemia of 100 mg/dL a 125 mg/dL, rightful owners of the Instituto Mexicano del Seguro Social and ascribed to the family medicine unit no. 17 of Instituto Mexicano del Seguro Social in Villa Juarez, Sonora, Mexico. Results: the average age was 67 ± 6 years, females (60 percent) and low schooling prevailed. Seventy two percent of the population had first-line relatives with diabetes. After the educational strategy implementation, knowledge on diabetes improved and significant changes occurred when comparing before and after this intervention in terms of global assessment (p= 0.0001), capillary glycemia (p= 0.0001), and glycosylate hemoglobin (p= 0.003). Feeding habits and physical exercising showed some improvement. Conclusions: educational strategy has beneficial effects on the metabolic parameters and encourages lifestyle changes(AU)

Estructura familiar y estado de nutrición en adolescentes de Sonora, México / Family structure of obese/overweight and normal weight adolescents in México

Background: Feeding modes and appetence toward certain foods are usually conditioned by the family. Obesity during adolescence usually persists during adulthood. Aim: To determine differences in family structure of adolescents according to their nutritional status. Material and Methods: A cross-sectional study was conducted in 60 overweight-obese and 60 normal weight adolescents. Family type was determined based on their conformation (kinship and cohabitation), development (if the mother had a remunerated job), demography (geographical area), integration (functions of the couple); life cycle stage and functionality. Results: Fifty eight percent of normal weight adolescents had simple nuclear families and 47% of overweight-obese adolescents had an extended family. Thirty one and 21% of overweight/obese and normal weight adolescents lived with an overweight/obese individual, respectively. Conclusions: There are differences in the family structure of overweight/obese and normal weight adolescents.

Panel-based NGS Reveals Novel Pathogenic Mutations in Autosomal Recessive Retinitis Pigmentosa.

Retinitis pigmentosa (RP) is a group of inherited progressive retinal dystrophies (RD) characterized by photoreceptor degeneration. RP is highly heterogeneous both clinically and genetically, which complicates the identification of causative genes and mutations. Targeted next-generation sequencing (NGS) has been demonstrated to be an effective strategy for the detection of mutations in RP. In our study, an in-house gene panel comprising 75 known RP genes was used to analyze a cohort of 47 unrelated Spanish families pre-classified as autosomal recessive or isolated RP. Disease-causing mutations were found in 27 out of 47 cases achieving a mutation detection rate of 57.4%. In total, 33 pathogenic mutations were identified, 20 of which were novel mutations (60.6%). Furthermore, not only single nucleotide variations but also copy-number variations, including three large deletions in the USH2A and EYS genes, were identified. Finally seven out of 27 families, displaying mutations in the ABCA4, RP1, RP2 and USH2A genes, could be genetically or clinically reclassified. These results demonstrate the potential of our panel-based NGS strategy in RP diagnosis.