Comparative analysis of in-silico tools in identifying pathogenic variants in dominant inherited retinal diseases.

Inherited retinal diseases (IRDs) are a group of rare genetic eye conditions that cause blindness. Despite progress in identifying genes associated with IRDs, improvements are necessary for classifying rare autosomal dominant (AD) disorders. AD diseases are highly heterogenous, with causal variants being restricted to specific amino acid changes within certain protein domains, making AD conditions difficult to classify. Here, we aim to determine the top-performing in-silico tools for predicting the pathogenicity of AD IRD variants. We annotated variants from ClinVar and benchmarked 39 variant classifier tools on IRD genes, split by inheritance pattern. Using area-under-the-curve (AUC) analysis, we determined the top-performing tools and defined thresholds for variant pathogenicity. Top-performing tools were assessed using genome sequencing on a cohort of participants with IRDs of unknown etiology. MutScore achieved the highest accuracy within AD genes, yielding an AUC of 0.969. When filtering for AD gain-of-function and dominant negative variants, BayesDel had the highest accuracy with an AUC of 0.997. Five participants with variants in NR2E3, RHO, GUCA1A, and GUCY2D were confirmed to have dominantly inherited disease based on pedigree, phenotype, and segregation analysis. We identified two uncharacterized variants in GUCA1A (c.428T>A, p.Ile143Thr) and RHO (c.631C>G, p.His211Asp) in three participants. Our findings support using a multi-classifier approach comprised of new missense classifier tools to identify pathogenic variants in participants with AD IRDs. Our results provide a foundation for improved genetic diagnosis for people with IRDs.

Physicochemical, calorimetric and texture profile characteristics of various gluten-free flours.

It is important to understand how the composition and structure of proteins from other flours differ from proteins in wheat, in order to have a better option to substitute gluten products with gluten-free food products. The aim of this study was the characterization of gluten-free flours and comparison of their rheological and calorimetric properties against wheat flour, for its use as gluten-free alternative. Chemical composition analysis, water solubility index (WSI), water absorption index (WAI), texture and calorimetric profile were determined. The closest WAI to wheat flour (1.45 g gel/g sample) was corn flour (2.41 g gel/g sample), while the WSI of chickpea flour was 5.51% approaching that of wheat flour of 5.88%. The hardness and adhesiveness values closest to wheat (1.65 kgf and 0.03 mJ) were amaranth flour with 0.85 kgf and 0.01 mJ, respectively. The phenolic content and antioxidant capacity were higher in the corn and bean flours with 244.4 mg GAE/100 g, 148 mg GAE/100 g and 190 mg AAE/100 g and 170 mg AAE/100 g, respectively. The combination of these non-conventional flours can be an innovative source of gluten-free formulas.

Systematic assessment of the contribution of structural variants to inherited retinal diseases.

Despite increasing success in determining genetic diagnosis for patients with inherited retinal diseases (IRDs), mutations in about 30% of the IRD cases remain unclear or unsettled after targeted gene panel or whole exome sequencing. In this study, we aimed to investigate the contributions of structural variants (SVs) to settling the molecular diagnosis of IRD with whole-genome sequencing (WGS). A cohort of 755 IRD patients whose pathogenic mutations remain undefined was subjected to WGS. Four SV calling algorithms including include MANTA, DELLY, LUMPY, and CNVnator were used to detect SVs throughout the genome. All SVs identified by any one of these four algorithms were included for further analysis. AnnotSV was used to annotate these SVs. SVs that overlap with known IRD-associated genes were examined with sequencing coverage, junction reads, and discordant read pairs. PCR followed by Sanger sequencing was used to further confirm the SVs and identify the breakpoints. Segregation of the candidate pathogenic alleles with the disease was performed when possible. In total, sixteen candidate pathogenic SVs were identified in sixteen families, including deletions and inversions, representing 2.1% of patients with previously unsolved IRDs. Autosomal dominant, autosomal recessive, and X-linked inheritance of disease-causing SVs were observed in 12 different genes. Among these, SVs in CLN3, EYS, PRPF31 were found in multiple families. Our study suggests that the contribution of SVs detected by short-read WGS is about 0.25% of our IRD patient cohort and is significantly lower than that of single nucleotide changes and small insertions and deletions.

Systematic assessment of the contribution of structural variants to inherited retinal diseases.

Despite increasing success in determining genetic diagnosis for patients with inherited retinal diseases (IRDs), mutations in about 30% of the IRD cases remain unclear or unsettled after targeted gene panel or whole exome sequencing. In this study, we aimed to investigate the contributions of structural variants (SVs) to settling the molecular diagnosis of IRD with whole-genome sequencing (WGS). A cohort of 755 IRD patients whose pathogenic mutations remain undefined were subjected to WGS. Four SV calling algorithms including include MANTA, DELLY, LUMPY and CNVnator were used to detect SVs throughout the genome. All SVs identified by any one of these four algorithms were included for further analysis. AnnotSV was used to annotate these SVs. SVs that overlap with known IRD-associated genes were examined with sequencing coverage, junction reads and discordant read pairs. Polymerase Chain Reaction (PCR) followed by Sanger sequencing was used to further confirm the SVs and identify the breakpoints. Segregation of the candidate pathogenic alleles with the disease was performed when possible. A total of 16 candidate pathogenic SVs were identified in 16 families, including deletions and inversions, representing 2.1% of patients with previously unsolved IRDs. Autosomal dominant, autosomal recessive and X-linked inheritance of disease-causing SVs were observed in 12 different genes. Among these, SVs in CLN3, EYS and PRPF31 were found in multiple families. Our study suggests that the contribution of SVs detected by short-read WGS is about 0.25% of our IRD patient cohort and is significantly lower than that of single nucleotide changes and small insertions and deletions.

[Time of care and its impact in the evolution of laryngeal cancer]. / El tiempo de atención y su impacto en la evolución del cáncer laríngeo.

Background: Laryngeal carcinoma is the 22nd most common cause of cancer in men worldwide and the second most common head and neck malignancy. The care of these patients is multidisciplinary. Factors such as tumor stage and initiation of treatment 60 days after diagnosis have been associated with worse survival. Objective: To know the overall time of care in laryngeal cancer and its impact on the outcome of patients in a tertiary health center. Material and methods: In July 2020, a retrospective study was carried out of 173 patients with laryngeal cancer diagnosed in the Department of Otorhinolaryngology from January 2014 to December 2018. Odds ratio and Fisher's exact test were calculated with a p value of 0.05. Results: 2 out of 77 patients started treatment at the recommended time. The total attention time (TAT) was 246 ± 159 days. 56% of the patients were still alive, 43% disease-free and 10% with progression. Control of the disease was achieved in 69% of early tumors and only 26% in advanced ones. Conclusions: The overall time of care impacts on the health status, affecting survival and control of disease. The stage of the tumor at the time of diagnosis is a decisive prognosis factor. Strategies towards multidisciplinary management and early detection in primary care should be created.

Introducción: el carcinoma de laringe es la vigésima segunda causa más común de cáncer en hombres a nivel mundial y la segunda malignidad más común en cabeza y cuello. La atención de estos pacientes es multidisciplinaria. Factores como el estadio del tumor y el inicio del tratamiento 60 días después del diagnóstico han sido asociados a una peor sobrevida. Objetivo: conocer el tiempo integrado de atención del cáncer de laringe y su impacto en el estado de salud de los pacientes en un centro terciario de atención. Material y métodos: en julio de 2020 se llevó a cabo un estudio retrospectivo de 173 pacientes con cáncer de laringe diagnosticados en el Servicio de Otorrinolaringología de enero de 2014 a diciembre de 2018. Se calculó la razón de momios y la prueba exacta de Fisher con valor de p = 0.05. Resultados: dos de 77 pacientes iniciaron tratamiento en tiempo recomendado. El tiempo total de atención fue de 246 +/- 159 días. El 56% de los pacientes continuaban con vida, 43% libres de enfermedad y 10% con progresión. El control de la enfermedad se logró en el 69% de los tumores tempranos y solo el 26% en los avanzados. Conclusiones: el tiempo integrado de atención impactó en el estado de salud, lo cual afectó en la sobrevida y el control de la enfermedad. El estadio de la enfermedad al momento del diagnóstico es un factor decisivo para el pronóstico. Deberán crearse estrategias para el manejo multidisciplinario y la detección temprana en la atención primaria.

La cultura del padeciente en el descontrol de la enfermedad crónica no transmisible / The Sufferer Culture in the Lack of Control of a Chronic Non-Communicable Disease

Resumen El modelo biomédico para enfermedades crónicas no transmisibles considera que los enfermos deben responder automáticamente a una prescripción. Sin embargo, esto conduce al enfermo a confrontarse con su grupo social, debido a que una fuerza invisible y controladora lo configura y conduce a desarrollar una disposición contraria a la requerida en el plan de tratamiento, este elemento se conoce como cultura. El propósito del presente artículo es exhortar a la reflexión sobre la influencia de la cultura en el descontrol de este tipo de enfermedades. Se propone diferenciar entre enfermedad y padecimiento, denominando paciente a la persona cuando se atienda la enfermedad y padeciente cuando se atienda el padecimiento. Por tanto, atender al padeciente implica considerar preocupaciones, miedos, creencias, expectativas, emociones y sentimientos, así como las repercusiones de la enfermedad en la vida. Para demostrar esta afirmación se describe cómo conceptualizamos cultura, cuál es su función y por qué es imprescindible intervenir en el contexto sociocultural del padeciente.

Abstract The biomedical model for chronic non-communicable diseases considers that people with the disease must respond automatically to their medical prescription. However, this leads to a confrontation of sick people against their social group since an invisible and controlling force shapes and leads the patient into developing a disposition opposed to their required treatment plan, this element is better known as culture. The purpose of this study is to encourage reflection about the influence of culture in the lack of control regarding this type of diseases. It is proposed to differentiate between disease and illness, calling patient when treating the disease and sufferer when treating the illness. Hence, treating the sufferer includes considering worries, fears, beliefs, expectations, emotions, and feelings, as well as repercussions of the disease on their life. To proof this statement, the concept of culture is described and conceptualized, as well as its function, and why it is of vital importance to intervene in the socio-cultural context of the sufferer.

PCDH12 variants are associated with basal ganglia anomalies and exudative vitreoretinopathy.

PCDH12 is a member of the non-clustered protocadherins that mediate cell-cell adhesion, playing crucial roles in many biological processes. Among these, PCDH12 promotes cell-cell interactions at inter-endothelial junctions, exerting essential functions in vascular homeostasis and angiogenesis. However, its exact role in eye vascular and brain development is not completely understood. To date, biallelic loss of function variants in PCDH12 have been associated with a neurodevelopmental disorder characterized by the typical neuroradiological findings of diencephalic-mesencephalic junction dysplasia and intracranial calcifications, whereas heterozygous variants have been recently linked to isolated brain calcifications in absence of cognitive impairment or other brain malformations. Recently, the phenotypic spectrum associated with PCDH12 deficiency has been expanded including cerebellar and eye abnormalities. Here, we report two female siblings harboring a novel frameshift homozygous variant (c.2169delT, p.(Val724TyrfsTer8)) in PCDH12. In addition to the typical diencephalic-mesencephalic junction dysplasia, brain MRI showed dysmorphic basal ganglia and thalamus that were reminiscent of a tubulin-like phenotype, mild cerebellar vermis hypoplasia and extensive prominence of perivascular spaces in both siblings. The oldest sister developed profound and progressive monocular visual loss and the eye exam revealed exudative vitreoretinopathy. Similar but milder eye changes were also noted in her younger sister. In summary, our report expands the clinical (brain and ocular) spectrum of PCDH12-related disorders and adds a further line of evidence underscoring the important role of PCDH12 in retinal vascular and brain development.

Caracterización de la adherencia terapéutica en adultos mayores hipertensos / Characterization of therapeutic adherence in hypertensive older adults

RESUMEN Introducción: la adherencia terapéutica es un problema multifactorial que ha generado el interés de muchos investigadores a nivel mundial. Objetivo: determinar la adherencia al tratamiento antihipertensivo en pacientes adultos mayores y los factores asociados a la no adherencia. Materiales y métodos: se realizó un estudio descriptivo longitudinal en pacientes adultos mayores hipertensos, pertenecientes al Policlínico Comunitario Sur, del municipio Morón, en la provincia de Ciego de Ávila. La adherencia al tratamiento fue evaluada por el cuestionario Martín-Bayarre-Grau y el nivel de conocimiento de la enfermedad por el Test de Batalla. Se identificaron las causas asociadas a los problemas de adherencia en dichos pacientes. Resultados: Predominó la no adherencia al tratamiento antihipertensivo en un 62 %. La adherencia parcial se constató en un 22 %. Los problemas de adherencia prevalecieron en las féminas de 60-69 años de edad. Se detectaron múltiples causas inherentes al paciente, como el olvido (48,4 %), la no disponibilidad de medicamentos (25,8 %) y el alivio de los síntomas (16,1 %). Entre otras causas se detectó el bajo nivel de conocimiento de la enfermedad y la presencia de comorbilidades. Conclusiones: se evidenció un predominio de adherencia al tratamiento antihipertensivo de los adultos mayores. Sus causas fundamentales fueron el olvido de ingerir el medicamento, la no disponibilidad de medicamentos, la falta de conocimientos sobre la enfermedad y la presencia de comorbilidades (AU).

ABSTRACT Introduction: therapeutic adherence is a multifactorial problem that has generated the interest of many researchers worldwide. Objective: to determine adherence to antihypertensive therapy in older adult patients and the factors associated with no adherence. Materials and methods: a longitudinal descriptive study was carried out in hypertensive elderly patients belonging to the South Community Polyclinic, in the municipality of Moron, in the province of Ciego de Avila. The adherence to treatment was evaluated by the Martín-Bayarre-Grau questionnaire and the level of knowledge of the disease by the Batalla test. The causes associated with adherence problems in these patients were identified. Results: non-adherence to antihypertensive therapy predominated in 62%. Partial adherence was found to be 22%. Adherence problems prevailed in women aged 60-69 years. Multiple causes related with the patient were detected, such as forgetfulness (48.4%), non-availability of medicines (25.8%) and relief of symptoms (16.1%). Among other causes, the low level of knowledge on the disease and the presence of comorbidities were detected. Conclusions: a predominance of adherence to antihypertensive treatment in older adults was evidenced. Its main causes were the forgetfulness of taking the medicine, the non-availability of medicines, the lack of knowledge about the disease and the presence of comorbidities (AU).

[Clinical-pathological characterization of laryngeal cancer in the Mexican population]. / Caracterización clínico-patológica del cáncer de laringe en la población mexicana.

Background: Cancer of the larynx occupies the first frequency site of cancer of the upper digestive tract and represents 42% of malignant neoplasms of the upper aero-digestive tract. It is a potentially curable entity if it is diagnosed in early stages. Objective: Characterize the clinical pathological features of patients with laryngeal cancer, which can serve as a guide for diagnostic suspicion in primary and secondary care. Method: Descriptive study. All the records of patients with an initial diagnosis of primary laryngeal carcinoma undergoing direct micro-laryngoscopy plus biopsy from January 1, 2014 to December 31, 2018 were analyzed. Results: 173 new cases of laryngeal carcinoma were diagnosed, the male sex predominated (86%). With an average age of presentation of 65 ± 11 years and a history of smoking in 78.6% (n 136). Dysphonia was the initial symptom in 81% (140) of the patients. Conclusions: The profile of the patient with laryngeal cancer corresponds to a patient older than 60 years, male, a history of smoking and a history of dysphonia greater than 30 days. Clinically, we will find an epithelial epidermoid moderately differentiated tumor limited to the glottis.

Introducción: El cáncer de laringe ocupa el primer lugar en frecuencia entre los cánceres del tracto aéreo-digestivo superior, y representa el 42% de las neoplasias malignas de las vías aéreo-digestivas superiores. Es una enfermedad potencialmente curable si se diagnostica en estadios tempranos. Objetivo: Conocer las características clínico-patológicas de los pacientes con cáncer de laringe, mismas que puedan ayudar como guía para la sospecha diagnóstica en el primer y el segundo niveles de atención. Método: Estudio descriptivo en el que se analizaron todos los expedientes de pacientes con diagnóstico inicial de carcinoma primario de laringe intervenidos con microlaringoscopia directa más biopsia del 1 de enero de 2014 al 31 de diciembre de 2018. Resultados: Se diagnosticaron 173 casos nuevos de carcinoma de laringe. Predominó el sexo masculino (86%). La edad promedio de presentación fue de 65 ± 11 años. Hubo antecedente de tabaquismo en el 78.6% (136). La disfonía fue el síntoma inicial en el 81% (140) de los pacientes. Conclusiones: El perfil del paciente con cáncer de laringe corresponderá a un paciente mayor de 60 años, de sexo masculino, con antecedente de tabaquismo y disfonía de más de 30 días. Clínicamente se encontrará un tumor epitelial del tipo epidermoide moderadamente diferenciado confinado en la glotis.

SARS-CoV-2 Direct Detection Without RNA Isolation With Loop-Mediated Isothermal Amplification (LAMP) and CRISPR-Cas12.

As to date, more than 49 million confirmed cases of Coronavirus Disease 19 (COVID-19) have been reported worldwide. Current diagnostic protocols use qRT-PCR for viral RNA detection, which is expensive and requires sophisticated equipment, trained personnel and previous RNA extraction. For this reason, we need a faster, direct and more versatile detection method for better epidemiological management of the COVID-19 outbreak. In this work, we propose a direct method without RNA extraction, based on the Loop-mediated isothermal amplification (LAMP) and Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated protein (CRISPR-Cas12) technique that allows the fast detection of SARS-CoV-2 from patient samples with high sensitivity and specificity. We obtained a limit of detection of 16 copies/µL with high specificity and at an affordable cost. The diagnostic test readout can be done with a real-time PCR thermocycler or with the naked eye in a blue-light transilluminator. Our method has been evaluated on a small set of clinical samples with promising results.

Criterios de medicación potencialmente inapropiada para el anciano: una propuesta cubana / Medication approaches potentially inappropriate for the elderly: a Cuban proposal

Introducción: El impacto de la prescripción inapropiada de fármacos en el anciano ha llevado al desarrollo de métodos para su reducción en varias partes del mundo. Objetivo: Diseñar y validar los criterios de medicación potencialmente inapropiada en el anciano, adaptados al entorno sociosanitario de Cuba. Métodos: Se realizó una investigación cualitativa, en la cual los criterios fueron validados por medio de la metodología Delphi, por un comité de expertos (especialistas en medicina geriátrica y clínica de diferentes zonas geográficas del país), y se les calculó la consistencia interna mediante el coeficiente alfa de Cronbach. Resultados: Los criterios quedaron estructurados en tres listas: 1) medicación potencialmente inapropiada, medicamento indicado no prescripto, cuando no existe contraindicación para su uso; 2) medicación potencialmente inapropiada independiente del diagnóstico o la condición clínica; 3) medicación potencialmente inapropiada dependiente del diagnóstico o la condición clínica. Conclusiones: Se demostró la validez del contenido y la adecuada consistencia interna de los criterios diseñados para la identificación de medicación potencialmente inapropiada en el anciano.

Introduction: The impact of inappropriate prescription of medication in the elderly has led to the development of methods for its reduction in several parts of the world. Objective: To design and validate the medication approaches potentially inappropriate in the elderly, adapted to the socio-sanitary environment of Cuba. Methods: A qualitative investigation was carried out, in which the approaches were validated by means of the Delphi methodology, by an experts committee (specialists in geriatrics medicine and clinic from different geographical areas of the country), and the internal consistency was calculated by means of the alpha coefficient of Cronbach. Results: The approaches were structured in three lists: 1) potentially inappropriate medication, advised medication non prescribed, when contraindication doesn't exist for its use; 2) medication potentially inappropriate, independent from the diagnosis or clinical condition; 3) potentially inappropriate medication, depending on the diagnosis or clinical condition. Conclusions: The validity of the content and the appropriate internal consistency of the designed approaches for the medication identification potentially inappropriate in the elderly were demonstrated.

Manejo de la COVID-19 en Cuba. Su relación con la inmunología / Management of COVID -19 in Cuba. Its relation with immunology

Introducción: Se viven momentos críticos en la historia de la humanidad. En Cuba se procura el distanciamiento para frenar la propagación del SARS‐CoV‐2. Objetivo: Describir las nuevas terapéuticas para combatir esta enfermedad y relacionarlas con los mecanismos inmunológicos. Métodos: Se realizó una revisión bibliográfica integradora. El criterio de selección fue la literaturareciente y novedosa, se trató la vinculación básica clínica entre la disciplina de Inmunología y los protocolos. Se consultaron: el Centro Nacional de Información de Ciencias Médicas, los sitios web de la Organización Mundial de la Salud; las revistas nacionales e internacionales en bases de datos como Pubmed/Medline, Elsevier y en Google Scholar. Conclusiones: No hay tratamiento específico establecido,a partir de experiencias internacionales ynacionales, Cuba aprueba protocolos y medidas que responden a la interacción básica clínica en el desarrollo profesional.(AU)

Introduction: Critical moments are lived in the history of humanity. In Cuba, isolation has been tried to stop transmission by SARS‐CoV‐2. Objective: To describe new treatments to fight this disease and relate them with immunologic mechanisms. Methods: An integrated library research was performed. The criterion of selection was the updatedcurrent literature, a basic clinical link between the discipline Immunology and protocols was treated. The National Medical Sciences Information Center, the WHO web sites; national and international on line magazines on data Bases such as Pubmed/Medline, Elsevier and inGoogle Scholar were consulted. Conclusions: Not there is specific established treatment, taking national and international experiences, Cuba approves protocols and measures that respond to the basic clinical interaction in the professional development.(AU)

Occurrence of zoonotic gastrointestinal parasites of rodents and the risk of human infection in different biomes of Brazil.

Rodents are synanthropic mammals adapted to several ecosystems, where they can contribute to the transmission of zoonotic pathogens, including gastrointestinal parasites. The aim of this study was to study the occurrence of gastrointestinal parasites from rodents and discuss the risk of transmission to humans. Fecal samples (n = 110) from different rodent species, namely, Cerradomys subflavus (n = 4), Mus musculus (n = 14), Rattus norvegicus (n = 80), Rattus rattus (n = 8) and Thrichomys apereoides (n = 4), were analyzed using the FLOTAC technique. Of the samples examined, 73.6% (81/110) tested positive for at least one gastrointestinal parasite. The most commonly identified parasites were Aspiculuris sp., Hymenolepis nana, Moniliformis sp., Syphacia sp., Strongyloides spp., Taenia spp., and Trichuris spp. eggs, Angiostrongylus cantonensis larvae and Entamoeba spp. cysts. The findings of this study demonstrate that rodents living in different Brazilian biomes are parasitized by a wide range of parasites, including some of public health concern. Therefore, the proximity of rodents to human settlements may represent a tangible risk of infection for people living in these areas.

Roedores são mamíferos sinantrópicos adaptados a vários ecossistemas, onde podem contribuir para a transmissão de patógenos zoonóticos, incluindo parasitas gastrointestinais. O objetivo deste estudo foi descrever a ocorrência de parasitos gastrointestinais de roedores e discutir o risco de transmissão ao ser humano. Amostras fecais (n = 110) de diferentes espécies de roedores, a saber, Cerradomys subflavus (n = 4), Mus musculus (n = 14), Rattus norvegicus (n = 80), Rattus rattus (n = 8) e Thrichomys apereoides (n = 4), foram analisados pela técnica FLOTAC. Das amostras examinadas, 73,6% (81/110) apresentaram resultado positivo para pelo menos um parasito gastrointestinal. Os parasitos mais comumente identificados foram ovos de Aspiculuris sp., Hymenolepis nana, Moniliformis sp., Syphacia sp., Strongyloides spp., Taenia spp., Trichuris spp., larvas de Angiostrongylus cantonensis e cistos de Entamoeba spp. Os resultados deste estudo demonstraram que os roedores que vivem em diferentes biomas brasileiros são parasitados por uma ampla variedade de parasitos, incluindo alguns problemas de saúde pública. Portanto, a proximidade de roedores com assentamentos humanos pode representar um risco de infecção nessas áreas.

Olfactory Dysfunction in a Mexican Population Outside of COVID-19 Pandemic: Prevalence and Associated Factors (the OLFAMEX Study).

PURPOSE OF REVIEW: To study the prevalence of olfactory loss and its associated factors in a Mexican population a cross-sectional analytical study based on a population interviewed about health, epidemiologic aspects, and sense of smell (tested with four scents: rose, banana, perfume, and gas) was conducted to evaluate olfactory detection, memory, and identification. Levels of sense of smell perception were determined when the participants detected, recognized, or identified all (normosmia), 1-3 (hyposmia), or none (anosmia) of the odorants. Associated factors of olfactory dysfunction were identified by multivariate analysis (odds ratio, 95%CI). RECENT FINDINGS: Olfactory dysfunction is a prevalent disorder affecting up to 20% of the general population. In addition to viral infection, including COVID-19, a number of other causes and factors may also be involved. 1,956 surveys were conducted and 1,921 were analyzed. Most of the participants (62.1%) were women. The general prevalence of olfactory dysfunction, regarding detection, was 7.2% (7.1% hyposmia, 0.1% anosmia). Age-related olfactory deterioration was observed in both sexes from the 5th decade of life (OR 2.74, p = 0.0050). Women showed better olfactory identification (OR 0.73, p = 0.0010). Obesity (OR 1.97, p = 0.0070), low educational level, bad/very bad self-perceived olfactory function (OR 2.74, p = 0.0050), olfactory loss for less than one week (OR 1.35, p = 0.0030), exposure to toxics/irritants (OR 1.31, p = 0.0030), active smoking (OR 1.58, p < 0.0010), and type 2 diabetes mellitus (OR 2.68, 95%CI 1.74-4.10, p < 0.0001) were identified as factors associated with olfactory dysfunction. These results in a Mexican population suggest better olfactory identification (verbalization) in females. Age was a determining factor in the olfactory deterioration process and obesity and diabetes mellitus were also associated with olfactory disorders. Finally, these findings reinforce the differential diagnosis with other potential causes of sense of smell loss, during the COVID-19 outbreak.

Applicability of FLOTAC® technique in recovering equine strongyle larvae in the pasture: A comparison study.

The FLOTAC® technique represents a highly sensitive method for the isolation of oocysts, eggs, and larvae of parasites in faeces. This assay could be used for detecting free-living stages of nematodes in the pasture but no attempt has been assessed so far. Therefore, the performance of FLOTAC® technique for isolating infective larvae of nematodes in the environment was investigated and compared with the spontaneous sedimentation (SST) and centrifugal sedimentation (CST) techniques. The study was conducted in a horse farm located in northeastern Brazil, where the occurrence of strongyle larvae had been previously reported. Pasture samplings were collected monthly from January to May 2016 in a 376 m2 crop area harvested with the Guinea grass Panicum cultivar Massai. The recovery of third-stage larvae (L3) was performed using the FLOTAC®, SST and CST techniques. Values of Cohen's kappa coefficient, sensitivity, specificity, positive and negative predictive values, and accuracy of each technique were assessed. Although strongyle larvae were evenly detected, with the FLOTAC® technique yielded the highest number of positive samples (i.e., 41%, 41/100, p < .0001). The main parasites isolated belonged to the Cyathostominae and Strongylinae subfamilies. Based on these results, the FLOTAC® technique should be considered as practical and safe method for the isolation of nematode larvae in the pasture, thus opening a new potential use for this tool in the field.

The Genetic Causes of Nonsyndromic Congenital Retinal Detachment: A Genetic and Phenotypic Study of Pakistani Families.

Purpose: To evaluate consanguineous pedigrees from Pakistan with a clinical diagnosis of nonsyndromic congenital retinal nonattachment (NCRNA) and identify genes responsible for the disease as currently only one NCRNA gene is known (atonal basic helix-loop-helix transcription factor 7: ATOH7). Methods: We implemented a three-step genotyping platform: single nucleotide polymorphism genotyping to identify loss of heterozygosity regions in patients, Retinal Information Network panel screening for mutations in currently known retinal genes. Negative patients were then subjected to whole exome sequencing. Results: We evaluated 21 consanguineous NCRNA pedigrees and identified the causal mutations in known retinal genes in 13 out of our 21 families. We found mutations in ATOH7 in three families. Surprisingly, we then found mutations in familial exudative vitreoretinopathy (FEVR) genes; low-density lipoprotein receptor-related protein 5 mutations (six families), tetraspanin 12 mutations (two families), and NDP mutations (two families). Thus, 62% of the patients were successfully genotyped in our study with seven novel and six previously reported mutations in known retinal genes. Conclusions: Although the clinical diagnosis of all children was NCRNA with severe congenital fibrotic retinal detachments, the molecular diagnosis determined that the disease process was in fact a very severe form of FEVR in 10 families. Because severe congenital retinal detachment has not been previously associated with all the FEVR genes, we have thus expanded the phenotypic spectrum of FEVR, a highly variable retinal detachment phenotype that has clinical overlap with NCRNA. We identified seven novel mutations. We also established for the first time genetic overlap between the Iranian and Pakistani populations. We identified eight NCRNA families that do not harbor mutations in any known retinal genes, suggesting novel causal genes in these families.

[Imploding antrum syndrome: three cases with different management approaches]. / Síndrome de implosión maxilar: tres casos y sus diferentes abordajes de tratamiento.

BACKGROUND: Silent sinus or imploding antrum syndrome is a very rare condition, consisting of a usually asymptomatic spontaneous collapse of the sinus walls and floor of the orbit. It is associated with negative pressures, and when this occurs, it presents with manifestations such as enophthalmos, hypoglobus, and tilt flow orbital floor. As its incidence is very low, it is frequently missed as a diagnosis, and in fact there are currently fewer than 150 cases reported in the literature. CLINICAL CASES: Three patients have been identified in our practice over a period of two years, with different symptoms that influenced the decision of the treatment modality, which were: watch and wait, endoscopic sinus surgery, or endoscopic sinus surgery plus orbitoplasty. CONCLUSIONS: Despite being a rare entity, it stills catches the attention of the ENT, OMF surgery and Ophthalmologist. The diagnosis is mainly radiological, due to the late clinical manifestations and symptomatology. The treatment should be individualised and based on the symptoms and the individual decision of each patient, firstly by Functional Endoscopic sinus surgery, and once sinus permeability is restored, it may require augmentation surgery of the orbital floor, either with autologous bone implant, titanium or other material. It is important to be aware of this pathology, to know and to suspect it, avoiding misdiagnosis.

Content design and validation of a Standard Operating Procedure to provide pharmacotherapy follow-up for the elderly in Cuba

ABSTRACT Incorporating methodological tools that allow uniform and standardized development from the clinical pharmacy services to the Pharmaceutical Care practice, is nowadays a necessity. Considering the importance of pharmaceutical care provision to elderly patients, this manuscript introduces the design and content validation of a standard operating procedure to provide pharmacotherapy follow-up to the elderly in nursing homes in Cuba. The procedure was designed based on a deep analysis of documents relative to experiences focused on holistic care to elderly patients, criteria for the identification and assessment of potentially inappropriate prescriptions and the relationship between functional geriatric evaluation and the use of drugs. The content validation was conducted by a panel of experts, using the Delphi methodology, through two working sessions. In addition, we used Likert-type scale to evaluate the procedure by experts, in line with the indicators described. In general, the criteria issued by the experts were very appropriate and allowed us to modify, add or keep several elements of the instrument for the final version. The findings demonstrated that the instrument can be used at any level of health care.

Mutations in POMGNT1 cause non-syndromic retinitis pigmentosa.

A growing number of human diseases have been linked to defects in protein glycosylation that affects a wide range of organs. Among them, O-mannosylation is an unusual type of protein glycosylation that is largely restricted to the muscular and nerve system. Consistently, mutations in genes involved in the O-mannosylation pathway result in infantile-onset, severe developmental defects involving skeleton muscle, brain and eye, such as the muscle-eye-brain disease (MIM no. 253280). However, the functional importance of O-mannosylation in these tissues at later stages remains largely unknown. In our study, we have identified recessive mutations in POMGNT1, which encodes an essential component in O-mannosylation pathway, in three unrelated families with autosomal recessive retinitis pigmentosa (RP), but without extraocular involvement. Enzymatic assay of these mutant alleles demonstrate that they greatly reduce the POMGNT1 enzymatic activity and are likely to be hypomorphic. Immunohistochemistry shows that POMGNT1 is specifically expressed in photoreceptor basal body. Taken together, our work identifies a novel disease-causing gene for RP and indicates that proper protein O-mannosylation is not only essential for early organ development, but also important for maintaining survival and function of the highly specialized retinal cells at later stages.

Hypomorphic mutations identified in the candidate Leber congenital amaurosis gene CLUAP1.

PURPOSE: Leber congenital amaurosis (LCA) is an early-onset form of retinal degeneration. Six of the 22 known LCA genes encode photoreceptor ciliary proteins. Despite the identification of 22 LCA genes, the genetic basis of ~30% of LCA patients remains unknown. We sought to investigate the cause of disease in the remaining 30% by examining cilia-associated genes. METHODS: Whole-exome sequencing was performed on an LCA cohort of 212 unsolved probands previously screened for mutations in known retinal-disease genes. Immunohistochemistry using mouse retinas was used to confirm protein localization and zebrafish were used to perform rescue experiments. RESULTS: A homozygous nonsynonymous mutation was found in a single proband in CLUAP1, a gene required for ciliogenesis and cilia maintenance. Cluap1 knockout zebrafish exhibit photoreceptor cell death as early as 5 days after fertilization, and rescue experiments revealed that our proband's mutation is significantly hypomorphic. CONCLUSION: Consistent with the knowledge that CLUAP1 plays an important role in cilia function and that cilia are critical to photoreceptor function, our results indicate that hypomorphic mutations in CLUAP1 can result in dysfunctional photoreceptors without systemic abnormalities. This is the first report linking mutations in CLUAP1 to human disease and establishes CLUAP1 as a candidate LCA gene.Genet Med 18 10, 1044-1051.