Research progress on phenotype and function of microglia / 中国药理学通报

Microglia are the central nervous system's resident myeloid-derived immune cells, which play a major role in the innate and acquired immunological responses of brain. In the maintenance of brain tissue function under both healthy and pathological conditions, microglia take a protective or damaging role, depending on cell phenotypes and functions. The traditional microglia classification of pro- or anti-inflammatory phenotypes refers to the profile of macrophages, hence the term “brain macrophages:has been drawn. More microglia phenotypes are being discovered as new technologies and research methods are developed, and the newly discovered microglia phenotypes are often disease-, brain region-, and function-specific, providing an important foundation for studying the pathological processes underlying the development of specific diseases and developing appropriate interventions. Here, we provide a retrospective review of recent advances in the study of phenotype and function of microglia, and analyze the microglial cell lineage composition and its heterogeneous function.

Effects of HMGB1 on phenotypes, phagocytosis and ERK/JNK/P38 MAPK signaling pathway in dendritic cells / 中国药理学通报

Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

Research progress of targeted pulmonary vascular endothelial dysfunction in treatment of pulmonary hypertension / 中国药理学通报

Pulmonary hypertension (PH) is a progressive and fatal disease. The dysfunction of pulmonary artery endothelial cells (PAECs) is one of its important pathogenic factors. PAECs are monolayer flat epithelial cells, which play an important role in maintaining pulmonary vascular homeostasis. Studies have found that PAECs show damage and apoptosis at the early stage of PH development, while PAECs show anti-apoptotic characteristics at the late stage of PH development. The transition of PAECs into mesenchymal cells induced by hypoxic and inflammatory factors is also involved in the pathogenesis of PH. Carcinoid metabolism and mitochondrial dysfunction, bone mor- phogenic type 2 receptor mutation, epigenetic changes and inflammation of PAECs are the main pathogenesis of pulmonary vascular endothelial dysfunction in PH patients. New therapeutic measures targeting PAECs dysfunction are expected to play an important role in the treatment of PH in the future.

Genetic and phenotypic analysis of MYO15A rare variants associated with autosomal recessive hearing loss / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the phenotype and genotype characteristics of autosomal recessive hearing loss caused by MYO15A gene variants, and to provide genetic diagnosis and genetic counseling for patients and their families. Methods:Identification of MYO15A gene variants by next generation sequencing in two sporadic cases of hearing loss at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The sequence variants were verified by Sanger sequencing.The pathogenicity of these variants was determined according to the American College of Medical Genetics and Genomics（ACMG） variant classification guidelines, in conjuction with clinical data. Results:The probands of the two families have bilateral,severe or complete hearing loss.Four variants of MYO15A were identified, including one pathogenic variant that has been reported, two likely pathogenic variants,and one splicing variant of uncertain significance. Patient I carries c. 3524dupA（p. Ser1176Valfs*14）, a reported pathogenic variant, and a splicing variant c. 10082+3G>A of uncertain significance according to the ACMG guidelines. Patient I was treated with bilateral hearing aids with satisfactory effect, demonstrated average hearing thresholds of 37.5 dB in the right ear and 33.75 dB in the left ear. Patient Ⅱ carries c. 7441_7442del（p. Leu2481Glufs*86） and c. 10250_10252del（p. Ser3417del）,a pair of as likely pathogenic variants according to the ACMG guidelines. Patient Ⅱ, who underwent right cochlear implantation eight years ago, achieved scores of 9 on the Categorical Auditory Performance-Ⅱ（CAP-Ⅱ） and 5 on the Speech Intelligibility Rating（SIR）. Conclusion:This study's discovery of the rare c. 7441_7442del variant and the splicing variant c. 10082+3G>A in the MYO15A gene is closely associated with autosomal recessive hearing loss, expanding the MYO15A variant spectrum. Additionally, the pathogenicity assessment of the splicing variant facilitates classification of splicing variations.

Phenotypic plasticity in adults of Anticarsia gemmatalis exposed to sub-doses of Bt-based bioinsecticide

Abstract Anticarsia gemmatalis Hünber, 1818 is one of the main defoliating species in the soybean crop. Bacillus thuringiensis Berliner, 1915, is a bacterium used in the biological control of this pest species. Resistant populations and their sublethal effects caused by the use of the bacteria have already been reported; however, there are no studies on phenotypic plasticity in adulthood exposed to Bt-based bioinsecticide sub-doses. This study aimed to evaluate the morphometry of A. gemmatalis adults under laboratory conditions submitted to the Bt-based bioinsecticide Dipel® over the three generations. The body segments mensuread were width, length, and area of the anterior and posterior wings, the weight of the integument, chest, abdomen, wings, and the whole adult of males and females. Among the treatments, LC5 in the first generation and LC10 in the second generation were those with lower thresholds in relation to the weight of the chest and abdomen, considering the proportions of the body smaller than the females. The females weight adulthood was reduced by 10% about males, and, only in the first generation. Males have larger body size and more pronounced phenotypic plasticity than females. Here, we demonstrate the first study assessing the phenotypic plasticity of A. gemmatalis adults.

Resumo Anticarsia gemmatalis Hünber, 1818 é uma das principais espécies desfolhadoras da cultura da soja. Bacillus thuringiensis Berliner, 1915, é uma bactéria utilizada no controle biológico dessa espécie de praga. Populações resistentes e seus efeitos subletais causados pelo uso da bactéria já foram relatados, no entanto, não há estudos sobre a plasticidade fenotípica na idade adulta exposta a subdoses de bioinseticida à base de Bt. Este trabalho teve como objetivo avaliar a morfometria de adultos de A. gemmatalis em condições de laboratório submetidos ao bioinseticida Dipel® ao longo de três gerações. Os segmentos corporais mensuráveis eram largura, comprimento e área das asas anterior e posterior, o peso do tegumento, tórax, abdômen, asas e todo o adulto de machos e fêmeas. Dentre os tratamentos, CL5 na primeira geração e CL10 na segunda geração foram aqueles com limiares mais baixos em relação ao peso do tórax e abdômen, considerando as proporções do corpo menores que as do sexo feminino. O peso da fêmea na idade adulta foi reduzido em 10% em relação aos machos e, apenas na primeira geração. Os machos têm tamanho corporal maior e plasticidade fenotípica mais pronunciada do que as fêmeas. Este estudo demonstra o primeiro estudo avaliando a plasticidade fenotípica de adultos de A. gemmatalis.

Macular dystrophies associated with Stargardt-like phenotypes / Distrofias maculares associadas a fenótipos Stargardt-like

ABSTRACT Purpose: Stargardt-like phenotype has been described as associated with pathogenic variants besides the ABCA4 gene. This study aimed to describe four cases with retinal appearance of Stargardt disease phenotypes and unexpected molecular findings. Methods: This report reviewed medical records of four patients with macular dystrophy and clinical features of Stargardt disease. Ophthalmic examination, fundus imaging, and next-generation sequencing were performed to evaluate pathogenic variants related to the phenotypes. Results: Patients presented macular atrophy and pigmentary changes suggesting Stargardt disease. The phenotypes of the two patients were associated with autosomal dominant inheritance pattern genes (RIMS1 and CRX) and in the other two patients were associated with recessive dominant inheritance pattern genes (CRB1 and RDH12) with variants predicted to be pathogenic. Conclusion: Macular dystrophies may have phenotypic similarities to Stargardt-like phenotype associated with other genes besides the classic ones.

RESUMO Objetivo: Fenótipos Stargardt-like já foram asso-ciados a variantes patogênicas no gene ABCA4. O propósito desse estudo é descrever quatro pacientes com achados retinianos semelhantes a doença de Stargardt com resultados moleculares diferentes do esperado. Métodos: Esse relato fez a revisão de prontuários médicos de quatro pacientes com distrofia macular e achados clínicos sugestivos de doença de Stargardt. Foram realizados avaliação oftalmológica, exames de imagens e testes usando next generation sequencing para avaliar variantes patogênicas associadas aos fenótipos dos pacientes. Resultados: Os pacientes apresentavam atrofia macular e alterações pigmentares sugerindo achados clínicos de doença de Stargardt. Dois pacientes foram associados a genes com herança autossômica dominante (RIMS1 e CRX) e dois pacientes foram associados a genes com herança autossômica recessiva (CRB1 e RDH12) com variantes preditoras de serem patogênicas. Conclusão: Distrofias maculares podem ter similaridades fenotípicas com fenótipo de Stargardt-like associados a outros genes além dos classicamente já descritos.

Association of dietary patterns and body phenotypes in Brazilian adolescents / Associação entre padrões alimentares e fenótipos corporais em adolescentes brasileiros

Abstract Objectives: to investigate the association between dietary patterns, physical activity, and body phenotypes in adolescents. Methods: this school-based cross-sectional study involved 1,022 adolescents aged ten to 19 years. Dietary patterns and body phenotypes were defined using a principal component analysis. Body phenotype was defined using anthropometry, body composition, biochemistry, sexual maturation, and dietary patterns from 19 food groups, using a food frequency questionnaire. The association between the dietary patterns and body phenotypes was assessed using a linear regression model. Results: five body phenotypes (BP1adiposity, BP2puberty, BP3biochemical, BP4muscular, BP5lipids_biochemical) and five dietary patterns (DP1ultraprocessed_foods, DP2fresh_foods, DP3bread_rice_beans, DP4culinary_preparations, DP5cakes_rice_beans) were identified. There were higher BP_adiposity scores for obese adolescents, but energy expenditure was similar for obese and non-obese adolescents. Physical activity was positively associated with BMI, BP_adiposity, and BP_puberty. We observed a negative association between DP_ultraprocessed_foods and BMI, and a positive association between DP_fresh_food. DP_fresh_foods was positively associated with BP_adiposity; DP_ultraprocessed_foods and DP_culinary_preparations were negatively associated with this phenotype. BP_biochemical was negatively associated with DP_fresh_foods. Conclusion: we identified a negative association between a dietary pattern composed mainly of ultra-processed foods, fresh foods, and BP_adiposity. These associations need to be better explored, especially in adolescents, as both dietary patterns and phenotypes were defined using multivariate analysis.

Resumo Objetivos: investigar associação entre padrão alimentar (PA), atividade física (AF) e fenótipos corporais (FC) em adolescentes. Métodos: estudo transversal de base escolar com 1.022 adolescentes de dez a 19 anos. Padrão alimentar e fenótipo corporal foram definidos por meio da análise de componentes principais. O fenótipo corporal foi definido usando antropometria, composição corporal, bioquímica e maturação sexual, e padrão alimentar a partir de 19 grupos de alimentos de um questionário de frequência alimentar. A associação entre padrão alimentar e fenótipo corporal foi avaliada por modelo de regressão linear. Resultados: foram identificados cinco fenótipos corporais (FC1adiposidade, FC2puberdade, FC3bioquímico, FC4muscular, FC5lipídios_bioquímico) e cinco padrões alimentares (PA1alimentos_ultraprocessados, PA2alimentos_frescos, PA3pão_arroz_feijão, PA4preparações_culinárias, PA5bolos_arroz_feijão). Há maiores escores de FC_adiposidade para adolescentes com obesidade, mas o gasto energético foi semelhante para adolescentes com e sem diagnóstico de obesidade. Atividade física associou-se positivamente com IMC, FC_adiposidade e FC_puberdade. Observamos associação negativa entre PA_ultraprocessados e IMC, e positiva entre PA_alimentos_frescos. PA_alimentos_frescos associou-se positivamente com FC_adiposidade; PA_ultraprocessados e PA_preparações_culinárias se associaram negativamente a este fenótipo. FC_bioquímico associou-se negativamente com PA_alimentos_frescos. Conclusão: identificamos associação negativa entre padrão alimentar composto principalmente por alimentos ultraprocessados e alimentos in natura e FC_adiposidade. Essas associações devem ser exploradas com o mesmo público em estudos futuros, principalmente em adolescentes, pois tanto o padrão alimentar quanto o fenótipo foram definidos por meio de análise multivariada.

Phenotypic plasticity in adults of Anticarsia gemmatalis exposed to sub-doses of Bt-based bioinsecticide / Plasticidade fenotípica morfométrica em adultos de Anticarsia gemmatalis Hübner, 1818 expostos a subdoses de Bacillus thuringiensis Berliner, 1911

Anticarsia gemmatalis Hünber, 1818 is one of the main defoliating species in the soybean crop. Bacillus thuringiensis Berliner, 1915, is a bacterium used in the biological control of this pest species. Resistant populations and their sublethal effects caused by the use of the bacteria have already been reported; however, there are no studies on phenotypic plasticity in adulthood exposed to Bt-based bioinsecticide sub-doses. This study aimed to evaluate the morphometry of A. gemmatalis adults under laboratory conditions submitted to the Bt-based bioinsecticide Dipel® over the three generations. The body segments mensuread were width, length, and area of the anterior and posterior wings, the weight of the integument, chest, abdomen, wings, and the whole adult of males and females. Among the treatments, LC5 in the first generation and LC10 in the second generation were those with lower thresholds in relation to the weight of the chest and abdomen, considering the proportions of the body smaller than the females. The female's weight adulthood was reduced by 10% about males, and, only in the first generation. Males have larger body size and more pronounced phenotypic plasticity than females. Here, we demonstrate the first study assessing the phenotypic plasticity of A. gemmatalis adults.

Anticarsia gemmatalis Hünber, 1818 é uma das principais espécies desfolhadoras da cultura da soja. Bacillus thuringiensis Berliner, 1915, é uma bactéria utilizada no controle biológico dessa espécie de praga. Populações resistentes e seus efeitos subletais causados pelo uso da bactéria já foram relatados, no entanto, não há estudos sobre a plasticidade fenotípica na idade adulta exposta a subdoses de bioinseticida à base de Bt. Este trabalho teve como objetivo avaliar a morfometria de adultos de A. gemmatalis em condições de laboratório submetidos ao bioinseticida Dipel® ao longo de três gerações. Os segmentos corporais mensuráveis eram largura, comprimento e área das asas anterior e posterior, o peso do tegumento, tórax, abdômen, asas e todo o adulto de machos e fêmeas. Dentre os tratamentos, CL5 na primeira geração e CL10 na segunda geração foram aqueles com limiares mais baixos em relação ao peso do tórax e abdômen, considerando as proporções do corpo menores que as do sexo feminino. O peso da fêmea na idade adulta foi reduzido em 10% em relação aos machos e, apenas na primeira geração. Os machos têm tamanho corporal maior e plasticidade fenotípica mais pronunciada do que as fêmeas. Este estudo demonstra o primeiro estudo avaliando a plasticidade fenotípica de adultos de A. gemmatalis.

Phenotypic and genotypic characterization of Colombian clinical isolates of Sporothrix spp

Introduction. For over a century, Sporothrix schenckii was considered the sole species responsible for sporotrichosis. In 2007, scientific community confirmed the disease could be caused by various Sporothrix species. These species differed in their virulence factors and their antifungal sensitivity. Objective. This study aims to characterize 42 Colombian clinical isolates of Sporothrix spp. phenotypically and genotypically. Material and methods. Forty-two clinical isolates were characterized using phenotypic methods. It involved various culture media to determine their growth range at different temperatures and to assess the type and distribution of pigment and colony texture. Microscopic morphology was evaluated through microcultures, as well as the conidia diameter, type of sporulation, and morphology. Additionally, the assimilation of carbohydrates was selected as a physiological trait for species identification. Genotyping of 40 isolates was performed through partial amplification of the calmodulin gene, followed by sequence analysis. Results. Molecular studies enabled the identification of 32 isolates of S. schenckii and 8 isolates of S. globosa. The combination of phenotypic and genotypic methods eased these species characterizations and the recognition keys development based on parameters such as growth diameter at 25 and 30 °C, colony texture (membranous or velvety) on potato dextrose agar, and microscopic morphology with predominance of pigmented triangular, elongated oval globose, or subglobose conidia. Conclusions. Confirmation of the phenotypic characteristics and molecular analysis is crucial for identifying Sporothrix species and determining adequate treatment. This study represents the first phenotypical and genotypical characterization of clinical isolates of Sporothrix spp. reported in Colombia.

Introducción. Por más de un siglo se creyó que Sporothrix schenckii era la única especie responsable de la esporotricosis. Sin embargo, en el 2007, se consideró que podría ser causada por diferentes especies de Sporothrix, que difieren en sus factores de virulencia y su sensibilidad a los antifúngicos. Objetivo. Caracterizar fenotípica y genotípicamente 42 aislamientos clínicos colombianos de Sporothrix spp. Materiales y métodos. Se caracterizaron 42 aislamientos clínicos mediante métodos fenotípicos. Se usaron varios medios de cultivo para determinar el rango de crecimiento a diferentes temperaturas, el tipo y la distribución del pigmento, y la textura de las colonias. Se evaluó la morfología microscópica por microcultivos mediante la determinación del diámetro, el tipo de esporulación y la morfología de las conidias. La asimilación de carbohidratos se usó como una característica fisiológica para identificar las especies. La genotipificación de los 40 aislamientos se llevó a cabo mediante la amplificación parcial del gen que codifica para la calmodulina y se confirmó por secuenciación. Resultados. Mediante estudios moleculares, se identificaron 32 aislamientos de S. schenckii y ocho de S. globosa. La combinación de métodos fenotípicos y genotípicos permitió caracterizar las especies y construir claves para su reconocimiento, con base en parámetros como el diámetro de crecimiento a 25 y 30 °C, la textura de las colonias (membranosa, aterciopelada) en agar papa dextrosa y la morfología microscópica con predominio de conidias (triangulares pigmentadas, ovales globosas elongadas, subglobosas). Conclusiones. La caracterización fenotípica y los análisis moleculares son necesarios para identificar las especies de Sporothrix y, de esta forma, elegir el tratamiento indicado. Esta es la primera caracterización fenotípica y genotípica reportada de aislamientos clínicos colombianos de Sporothrix spp.

Relación entre biometría fetal, producto de acumulación de los lípidos y condición trófica al nacer / Relationship between fetal biometry, lipid accumulation product and the trophic condition at birth

Fundamento: Las alteraciones del estado nutricional materno generalmente se relacionan con desviaciones del crecimiento fetal, que pueden detectarse por los parámetros biofísicos fetales e identifican la posible condición trófica al nacer. Objetivo: Determinar la posible relación entre los parámetros biométricos fetales, la condición trófica al nacer y el producto de acumulación de los lípidos. Metodología: Se realizó un estudio transversal en el Policlínico Chiqui Gómez Lubian del municipio Santa Clara, durante el año 2019, en una población de 253 gestantes normopeso supuestamente sanas al inicio de la gestación. La muestra no probabilística fue de 144 gestantes. Las variables de estudio fueron: producto de acumulación de los lípidos, biometría fetal y condición trófica al nacer. Se utilizaron métodos teóricos, empíricos y estadísticos. Resultados: En el segundo trimestre ningún parámetro biométrico coincidió con la condición al nacer de pequeño, mientras que para el grande coincidieron las circunferencias cefálica y abdominal. En el tercer trimestre la longitud del fémur y la circunferencia abdominal coinciden en la identificación del pequeño y del grande. El PAL se correlacionó con la circunferencia abdominal del tercer trimestre y con el peso al nacer; presentando mayor frecuencia de valores en el tercer tertil para los nacimientos grandes. Conclusiones: La circunferencia abdominal fue el parámetro biométrico con mayor coincidencia con la condición trófica al nacer, la que se asoció con valores en el tercer tertil del PAL para la detección de nacimientos grandes, relacionándose el fenotipo normopeso metabólicamente obeso con el crecimiento fetal por exceso.

Background: Maternal nutritional status disorders are usually related to fetal growth deviations, which can be detected by fetal biophysical parameters and identify the possible trophic condition at birth. Objective: To determine the possible relationship between fetal biometric parameters, the birth trophic state and lipid accumulation product. Methodology: A cross-sectional study was conducted at the Chiqui Gómez Lubian Polyclinic in Santa Clara municipality, during 2019, in a population of 253 normal-weight pregnant women who were apparently healthy at the beginning of their gestation. The non-probability sample was made up of 144 pregnant women. Study variables were: lipid accumulation product, fetal biometry and trophic condition at birth. Theoretical, empirical and statistical methods were used. Results: In the second trimester, none of the biometric parameters matched the condition at birth as a small child, while in the large one the head and abdominal circumferences matched. In the third trimester, femoral length and abdominal circumference coincide in identifying the small one and the large one. LAP correlated with third trimester abdominal circumference and birth weight, presenting higher frequency of values in the third tertile for large births. Conclusions: Abdominal circumference was the biometric parameter with the highest coincidence with trophic condition at birth, associated with values in the third tertile of the LAP for detecting large births, relating the metabolically obese normal weight phenotype with excessive fetal growth.

Phenotyping of clinically significant blood group antigens among the South Indian donor population

ABSTRACT Introduction: Data on the prevalence of clinically significant antigens (Rh, Kell, Kidd, Duffy, MNSs, Lewis, P and Lutheran) among the Indian donor population is sparse. Objective: This prospective study was aimed at determining the prevalence of 21 clinically significant antigens for the first time in the South Indian donor population. Method: A total of 672 regular O group blood donors were enrolled for Rh (C, c, E, e) and Kell (K) antigens typing. Of these, 188 donors were typed for other clinically significant antigens (k, Kpa, Kpb, Jka, Jkb, Fya, Fyb, M, N, S, s, P1, Lea, Leb, Lua and Lub). Results: Antigen frequencies were expressed in percentages. In our study, R1R1 and rr were the most common phenotypes among D+ and D− donors, respectively. Among the Rh antigens, the e antigen was expressed by 97.5% and 100% of D+ and D− donors, respectively. The K antigen was found in only 0.15% of donors. In the Duffy and Kidd blood group system, Fy (a+b+) and Jk (a+b+) were the most frequent phenotypes, respectively. In the MNSs blood group system, M+N+ and S−s+ were the most common phenotypes reported. The Le (a−b+) was found to be the phenotype with the highest prevalence in the Lewis blood group system. The Lu (a−b+) was the only phenotype found in the Lutheran blood group system. Conclusion: Knowledge regarding the prevalence of antigens in a given population is essential in developing cost-effective in-house panels and a rare donor registry comprising donors typed negative for a high-frequency antigen or a combination of common multiple antigens.

Infección por SARS-CoV-2 y grupos sanguíneos en pacientes cubanos diagnosticados con la COVID-19

Introducción: Diferentes estudios han propuesto la relación entre los grupos sanguíneos del sistema ABO y la susceptibilidad a la COVID-19 y su importancia en el curso de la enfermedad. Objetivo: Determinar la frecuencia fenotípica de grupos sanguíneos ABO y RhD en un grupo de pacientes con infección activa por SARS-CoV-2. Métodos: Se realizó un estudio descriptivo, transversal y caso control en el Hospital Docente Clínico Quirúrgico "Freyre Andrade" de La Habana, para determinar la frecuencia fenotípica ABO y RhD en un grupo de pacientes con enfermedad activa por la COVID-19. Se estudiaron 928 muestras de sangre de pacientes con diagnóstico de COVID-19 y 1050 muestras pertenecientes a individuos sanos como grupo control. El grupo sanguíneo ABO y RhD se determinó por método de aglutinación en tubo con sueros hemoclasificadores anti-A, anti-B, anti-A+B, yanti-D. Los resultados fueron expresados en frecuencias absolutas y relativas y se determinó la asociación del grupo sanguíneo con la gravedad de la enfermedad por medio de la prueba no paramétrica de χ2 con un nivel de significación de p ≤ 0,05. Resultados: Se observó predominio del fenotipo O (49,24 %) seguido del A (35,79 %), B (12,68 %) y AB (2,27 %) respectivamente. Los fenotipos O y B presentaron significación estadística para la ocurrencia de la COVID-19, con valores de p < 0,05. No se encontró significación estadística en cuanto al predominio de un fenotipo particular y la necesidad de cuidados intensivos. Conclusiones: La relación del grupo sanguíneo ABO en la infectividad por SARS-CoV-2 y la gravedad de la enfermedad por la COVID-19 requiere estudios adicionales ya que los actuales no son concluyentes.

Introduction: Different studies have proposed the relationship between the blood groups of ABO system and the susceptibility to COVID-19 and its importance in the course of the disease. Objective: To determine the phenotypic frequency of ABO and RhD blood groups in a group of patients with active SARS-CoV-2 infection. Methods: A descriptive, cross-sectional, case-control study was conducted to determine the ABO and RhD phenotypic frequency in a group of patients with COVID-19 active disease. Nine hundred twenty eight blood samples and 1050 samples belonging to healthy individuals as control group were studied. The ABO and RhD blood group was determined by the tube agglutination method with anti-A, anti-B, anti-A+B, and anti-D blood classifying sera. The results were expressed in absolute and relative frequencies and the association of the blood group with the severity of the disease was determined by the non-parametric χ2 test with a significance level of p ≤ 0.05. Results: A predominance of phenotype O (49.24%) was observed, followed by A (35.79%), B (12.68%) and AB (2.27%) respectively. The O and B phenotypes showed statistical significance for the occurrence of COVID-19, with p values < 0.05. No statistical significance was found regarding the prevalence of a particular phenotype and the need for intensive care. Conclusions: The relationship of the ABO blood group in the infectivity of SARS-CoV-2 and the severity of the disease by COVID-19 requires additional studies, since the current ones are not conclusive.

Fenotipos hipertrigliceridemia e hipertensión-cintura abdominal alterada y su asociación con factores de riesgo cardiovascular en mujeres atendidas en Consulta Provincial de Climaterio

Fundamento: la presencia de fenotipos hipertensión- circunferencia abdominal aumentada se considera un índice pronóstico de deterioro cardiometabólico. Objetivo: determinar la frecuencia de mujeres con fenotipos cintura alterada y establecer la asociación entre estos y los principales factores de riesgo cardiovascular, así como estimar el riesgo cardiovascular global a los 10 años. Métodos estudio descriptivo, correlacional, transversal, que incluyó a 100 mujeres que asistieron a Consulta Provincial de Climaterio, del Hospital Gustavo Aldereguìa, de Cienfuegos, desde marzo 2016 a 2020. Variables analizadas: edad, color de piel, tabaquismo, hipertensión arterial, obesidad, actividad física, diabetes mellitus, índice de masa corporal, circunferencia abdominal, colesterol total, ácido úrico y triglicéridos. Se determinó la razón de prevalencia con un nivel de significación del 95 %. Resultados: la razón de probabilidad demostró mayor riesgo de presentar el fenotipo en mayores de 45 años (1,47), obesas (5,57), hipertensas (3,71) y diabéticas (1,67). Se evidenció asociación significativa entre hábito de fumar y actividad física con razón de probabilidad de 5,80 y 18 respectivamente. Conclusiones: existe una relación significativa entre fenotipos cintura abdominal alterada y los principales factores de riesgo cardiovasculares, como incremento de la edad, riesgo cardiovascular, diabetes mellitus, hipertensión arterial, tabaquismo, inactividad física y obesidad.

Background: the presence of hypertension-increased abdominal circumference phenotypes is considered a cardiometabolic deterioration prognostic index. Objective: to determine the frequency of women with altered waist phenotypes and to establish the association between these and the main cardiovascular risk factors, as well as to estimate the global cardiovascular risk at 10 years. Methods: descriptive, correlational, cross-sectional study, which included 100 women who attended the Provincial Climacteric Consultation, at the Gustavo Aldereguía Lima Cienfuegos Hospital, from March 2016 to 2020. The analyzed variables were: age, skin color, smoking, arterial hypertension, obesity, physical activity, diabetes mellitus, body mass index, abdominal circumference, total cholesterol, uric acid, and triglycerides. The prevalence ratio was determined with a significance level of 95%. Results: the likelihood ratio showed a higher risk of presenting the phenotype in people over 45 years of age (1.47), obese (5.57), hypertensive (3.71) and diabetic (1.67). A significant association was found between smoking and physical activity with a probability ratio of 5.80 and 18, respectively. Conclusions: there is a significant relationship between altered abdominal waist phenotypes and the main cardiovascular risk factors, such as increased age, cardiovascular risk, diabetes mellitus, arterial hypertension, smoking, physical inactivity and obesity.

Next-generation sequencing-based genetic testing and phenotype correlation in retinitis pigmentosa patients from India

Purpose: Inherited retinal dystrophies (IRD) are a heterogeneous group of retinal diseases leading to progressive loss of photoreceptors through apoptosis. Retinitis pigmentosa (RP) is considered the most common form of IRD. Panel?based testing in RP has proven effective in identifying the causative genetic mutations in 70% and 80% of the patients. This is a retrospective, observational, single?center study of 107 RP patients who had undergone next?generation sequencing?based targeted gene panel testing for IRD genes. These patients were inspected for common phenotypic features to arrive at meaningful genotype–phenotype correlation. Methods: Patients underwent complete ophthalmic examination, and blood was collected from the proband for DNA extraction after documenting the pedigree. Targeted Next Generation Sequencing (NGS) was done by panel?based testing for IRD genes followed by co?segregation analysis wherever applicable. Results: Of the 107 patients, 72 patients had pathogenic mutations. The mean age of onset of symptoms was 14 ± 12 years (range: 5–55). Mean (Best Corrected Visual Acuity) BCVA was 6/48 (0.9 logMAR) (range 0.0–3.0). At presentation, over one?third of eyes had BCVA worse than 6/60 (<1 logMAR). Phenotype analysis with the gene defects showed overlapping features, such as peripheral well?defined chorioretinal atrophic patches in patients with CERKL, PROM1, and RPE65 gene mutations and large macular lesions in patients with RDH12 and CRX gene mutations, respectively. Nummular or clump?like pigmentation was noted in CRB1, TTC8, PDE6A, and PDE6B. Conclusion: NGS?based genetic testing can help clinicians to diagnose RP more accurately, and phenotypic correlations can also help in better patient counselling with respect to prognosis and guidance regarding ongoing newer gene?based therapies.

Patrón inflamatorio de las vías aéreas en pacientes fumadores con enfermedad pulmonar obstructiva crónica / Inflammatory pattern of the airways in COPD smokers

Introducción: La enfermedad pulmonar obstructiva crónica cursa con un patrón inflamatorio en la vía aérea que incluye neutrófilos, macrófagos, linfocitos, los cuales se pueden obtener mediante un cepillado bronquial citológico. Objetivos: Identificar patrón inflamatorio según células inflamatorias presentes en la vía aérea, mediante el cepillado bronquial citológico e índice tabáquico de paquetes/año en pacientes con enfermedad pulmonar obstructiva crónica. Métodos: Se realizó un estudio descriptivo transversal en pacientes con enfermedad pulmonar obstructiva crónica, que concurrieron al Hospital Neumológico Benéfico-Jurídico, en el período comprendido de junio de 2018 a junio de 2019, con indicación para la realización de fibrobroncoscopía con cepillado bronquial. Resultados: El 53,1 por ciento de los pacientes corresponden al sexo masculino. Un 46,1 por ciento presentó un índice tabáquico de paquetes/año entre 21-40. Predominaron las criptas y estrías como hallazgos broncoscópicos con un 51 por ciento y 40,8 por ciento respectivamente en pacientes con índice paquetes/año mayor que 40. De los pacientes con índice paquetes/año mayor de 40 (13 para un 26,5 por ciento) presentaron hiperplasia de células basales. El 46,9 por ciento de los pacientes presentaron un patrón inflamatorio neutrofílica. Conclusiones: Se identificaron a los pacientes con EPOC que presentaron patrón inflamatorio neutrofílica en la vía aérea y elevado índice tabáquico y desde el punto de vista broncoscópico tienen varios hallazgos que sugieren cronicidad(AU)

Introduction: Chronic obstructive pulmonary disease presents with an inflammatory pattern in the airway that includes neutrophils, macrophages, and lymphocytes, which can be obtained by cytological bronchial brushing. Objectives: To identify inflammatory pattern according to inflammatory cells present in the airway, through cytological bronchial brushing and smoking rate of packs/year in patients with chronic obstructive pulmonary disease. Methods: A cross-sectional descriptive study was carried out in patients with chronic obstructive pulmonary disease, who attended Benefico-Jurídico Pneumological Hospital, from June 2018 to June 2019, with an indication for fiberoptic bronchoscopy with bronchial brushing. Results: 53.1percent of the patients correspond to the male sex. 46.1percent ad a smoking rate of packs/year between 21-40. Crypts and striae predominated as bronchoscopic findings with 51percent and 40.8percent respectively in patients with a pack/year index greater than 40. Patients with a pack/year index greater than 40 (13 for 26.5percent) showed basal cell hyperplasia. 46.9percent of the patients had a neutrophilic inflammatory pattern. Conclusions: Patients with COPD who had a neutrophilic inflammatory pattern in the airway and high smoking index were identified, and from the bronchoscopic point of view they have several findings that suggest chronicity(AU)

Evaluation and prognostic significance of tumor budding in pancreatic ductal adenocarcinomas

Aim: In this study, it was aimed to investigate the prognostic importance of Tumor budding (TB) in Pancreatic ductal adenocarcinomas(PDAC) and its correlation with histopathological findings according to the International Tumor Budding Consensus Conference(ITBCC) grading. Material and Methods: A total of 75 patients diagnosed with PDAC were included in this study. The demographic features of the cases (age, sex) and the macroscopic features of the tumors (localization,size) were obtained from the electronic archive system. All Hematoxylin-Eosin-stained sections were re-evaluated in terms of differentiation, presence of lymphovascular (LVI) and perineural invasion(PNI), surgical margin positivity, primary tumor(pT), lymph node metastasis(LNM) and tumor budding. Statistically, Chi-square test, cox-regression and Kaplan-Meier test were performed. Results:Thirty four of the cases were female and 41 were male. The mean age was 64.21±9.71years. The degree of TB was TB-few in 17 cases, TB-moderate in 25cases, and TB-high in 33cases. LVI, PNI, LNM and TB-high were poor prognostic factors. Moreover, TB-high was related with poor differantiation,LVI,PNI,LNM and short survival time. Tumor budding was independent negative prognostic factor in multivariable model analyzes. Conclusion: ITBCC scoring can also be used in PDACs. In addition, high tumor budding was a poor prognostic feature and might be a target for tumor-specific treatments as it could be a predictive finding for the locally invasive character of the tumor. Evaluation and grading of TB thought to represent EMT may be a histological feature that can be used in tumor selection for advanced molecular methods to identify subtypes that may be associated with poor prognosis and drug resistance.

Growth phenotypes of very low birth weight infants for prediction of neonatal outcomes from a Brazilian cohort: comparison with INTERGROWTH

Abstract Objective: To assess the predictive value of selected growth phenotypes for neonatal morbidity and mortality in preterm infants < 30 weeks and to compare them with INTERGROWTH-21st (IG21). Methods: Retrospective analysis of data from the Brazilian Neonatal Research Network (BNRN) database for very low birth weight (VLBW) at 20 public tertiary-care university hospitals. Outcome: the composite neonatal morbidity and mortality (CNMM) consisted of in-hospital death, oxygen use at 36 weeks, intraventricular hemorrhage grade 3 or 4, and Bell stage 2 or 3 necrotizing enterocolitis. Selected growth phenotypes: small-for-gestational-age (SGA) defined as being < 3rd (SGA3) or 10th (SGA10) percentiles of BW, and large-for-gestational-age (LGA) as being > 97th percentile of BW. Stunting as being < 3rd percentile of the length and wasting as being < 3rd percentile of BMI. Single and multiple log-binomial regression models were fitted to estimate the relative risks of CNMM, comparing them to IG21. Results: 4,072 infants were included. The adjusted relative risks of CNMM associated with selected growth phenotypes were (BNRN/IG21): 1.45 (0.92-2.31)/1.60 (1.27-2.02) for SGA; 0.90 (0.55-1.47)/1.05 (0.55-1.99) for LGA; 1.65 (1.08-2.51)/1.58 (1.28-1.96) for stunting; and 1.48 (1.02-2.17) for wasting. Agreement between the two references was variable. The growth phenotypes had good specificity (>95%) and positive predictive value (70-90%), with poor sensitivity and low negative predictive value. Conclusion: The BNRN phenotypes at birth differed markedly from the IG21 standard and showed poor accuracy in predicting adverse neonatal outcomes.

Frailty as a predictor of outcome in heart failure in the elderly: An observational study at a tertiary care center

Introduction: Heart failure is the leading contributor to global morbidity and mortality. Frailty is an emerging prognostic factor in heart failure. There is little data on the prognostic role of frailty in patients admitted for acute heart failure as most studies have been done on stable heart failure patients. Methodology: The study included elderly (age ≥60 years) patients admitted with acute heart failure at a tertiary care center in India. Patients with dementia, cognitive impairment, and documented terminal illness were excluded. The sample size was 85 patients. Frailty assessment was done using short performance physical battery (SPPB) and Fried phenotype scales and follow‑up data was collected at 3 months postdischarge telephonically. The primary objective of the study was to determine the proportion of frailty in elderly in‑hospital heart failure patients. The secondary objectives were to see the agreement between the frailty assessment tools used (SPPB and Fried phenotype). Results: Eighty seven patients were included in the study. The majority were male (n = 45) and had heart failure with reduced ejection fraction (n = 56). Coronary artery disease (CAD) (n = 60) was the most common cause of heart failure. Eighty-two patients had at least one comorbidity. The proportion of frailty as per the SPPB was 43.67%, and as per the Fried phenotype was 68.9%. A total of 4 deaths and 15 re-admissions occurred during the follow-up period of 3 months. The majority belonged to the frail category as per both the frailty scales (P < 0.001 for SPPB, P = 0.087 for Fried phenotype). Fleiss’s kappa coefficient for agreement between the scales was 0.373 (SE = 0.106, P < 0.001), which signifies that there was a fair agreement between the two scales. The Spearman Rank correlation coefficient was −0.691 (P < 0.01) between the two scales. Hence, the SPPB score inversely correlated with the Fried phenotype. Conclusion: Frailty is largely prevalent in elderly heart failure patients. It can be used to predict poor outcomes in these patients. Clinicians should identify these high-risk patients at the time of discharge from their facility and consider interventions (tailored rehabilitation programs) to minimize the adverse outcomes.

Isolated ocular colobomas caused by a novel variant of the YAP1 gene / 中华眼底病杂志

Objective:To identify the causative gene and observe the phenotypic characteristics of a family with isolated microphthalmia-anophthalmia-coloboma (MAC).Methods:A retrospective clinical study. One patient (proband) and 3 family members of a family with MAC visited the Henan Eye Hospital from May 2019 to May 2022 were included in the study. The patient's medical history and family history were inquired in detail, and the best corrected visual acuity (BCVA), slit lamp microscope, fundus photography, optical coherence tomography (OCT), ophthalmological B mode ultrasound and axial length (AL) measurement were performed. The peripheral venous blood of the proband, his parents and brother was collected for Trio whole-exome sequencing and pathogenic gene screening. Fluorescence quantitative Polymerase chain reaction was used to verify the suspicious variations. The clinical features of the patient's ocular and systemic also were observed.Results:The proband, male, was 3 years old at the first visit. The horizontal pendular nystagmus was detected in both eyes. Vertical elliptical microcornea and keyhole-shaped iris colobomas were detected in both eyes. The objective refraction at first visit (3 years old) was -4.00 DS/-0.50 DC×105° (OD) and -3.50 DS/-1.25 DC×80° (OS). Refraction and BCVA at 6 years old: -6.50 DS/-2.00 DC×110°→0.05 (OD) and -6.00 DS/-1.50 DC×80°→0.2 (OS). The AL at 4 years and 10 months old was 24.62 mm (OD) and 23.92 mm (OS), respectively. The AL at 5 years and 7 months old was 25.24 mm (OD) and 24.36 mm (OS), respectively. Ultrasonography shows tissue defects in both eyes. Fundus photography showed the inferior choroidal coloboma involving optic disc. OCT showed the optic disc in both eyes was abnormal with colobomas around, and the retinal neurosensory layer in colobomas area was disordered and thin; the retinoschisis was visible in the left eye. The proband's parents and siblings have normal phenotypes. Whole exome sequencing reveals a denovo heterozygous deletion of YAP1 gene: YAP1, chr11: 10280247-102100671, NM_ 001130145, loss 1 (EXON: 6-9). The results of bioinformatics analysis were pathogenic variants. Parents and siblings were of the wild type. Conclusions:Loss of heterozygosity in exons 6-9 of YAP1 gene is the pathogenic variation in this family. It can cause abnormal development of anterior segment, chorioretinal colobomas, deepening of axial myopia, even severe macular colobomas and retinoschisis.

Atopic dermatitis with typical and atypical manifestations / 中华皮肤科杂志

Atopic dermatitis (AD) is a highly heterogeneous skin disease with various clinical manifestations. Early studies mainly focused on infant-onset AD, which is characterized by typical skin lesions such as eczematous dermatitis on the flexor sites accompanied by genetic predisposition to other allergic diseases; however, atypical manifestations and distributions of skin lesions are common among adult AD and elderly AD, e.g., distribution mainly on the extensor sites and polymorphic rashes such as prurigo nodularis. Many dermatologists are not familiar with atypical manifestations of AD, including atypical manifestations and distributions of skin lesions as well as atypical age at onset, which decreases the diagnostic rate of AD to a certain extent. This article delineates clinical features of AD with typical and atypical manifestations, in order to promote the understanding of AD among Chinese dermatologists.