Avaliação da sonolência e queixas de sono dos estudantes de odontologia da Universidade Federal do Ceará / Evaluation of sleepness and sleep complaints among dentistry students from the federal University of Ceará / Evaluación de somnolencia y quejas de sueño en estudiantes de odontología de la Universidad Federal de Ceará

O sono é um estado essencial para sobrevivência humana, ele exerce função biológica, restauradora e de conservação energética do organismo, promovendo equilíbrio físico e mental. Alta prevalência da má qualidade de sono e sonolência diurna excessiva (SDE) têm sido relatadas por estudantes universitários de diversos cursos, ocasionando prejuízos na concentração e queda dos rendimentos acadêmicos. O objetivo deste trabalho foi avaliar a qualidade de sono, a SDE e suas possíveis associações com sintomas depressivos em estudantes de odontologia. Foi realizado um estudo transversal e descritivo com 251 alunos do curso de odontologia da Faculdade de Farmácia, Odontologia e Enfermagem da Universidade Federal do Ceará. Os instrumentos utilizados foram o Índice de Qualidade de Sono de Pittsburgh (IQSP), Escala de Sonolência de Epworth (ESE) e Inventário de Depressão de Beck (IDB). Verificou-se uma alta prevalência de má qualidade de sono (53,4%) e SDE (35,1%) entre os estudantes, sem diferença significante em relação ao sexo para ambas. Foi encontrada correlação positiva entre IDB com IQSP e ESE (r = 0,478; p = 0,000 e r = 0,202; p = 0,000, respectivamente). Os resultados mostraram uma alta prevalência de má qualidade de sono e SDE e ambos os achados apresentaram associação com sintomas depressivos.

Sleep is an essential state for human survival. It has a biological, restorative and energy conservation function for the organism, promoting physical and mental balance. A high prevalence of poor sleep quality and excessive daytime sleepiness (EDS) has been reported among university students from different courses, causing impaired concentration and a drop in academic performance. This study evaluates sleep quality, EDS and their possible associations with depressive symptoms in dentistry students. A cross-sectional descriptive research was conducted with 251 students from the Dentistry Course at the School of Pharmacy, Dentistry and Nursing, Federal University of Ceará. Variables of interest were assessed by Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and Beck Depression Inventory (BDI). Results show a high prevalence of poor sleep quality (53.4%) and EDS (35.1%) among students, with no significant difference regarding gender. BDI had a positive correlation with PSQI and ESS (r= 0.478, p= 0.000; and r= 0.202, p =0.000, respectively). Both findings were associated with depressive symptoms.

El sueño es un estado esencial para la supervivencia humana, tiene una función biológica, reparadora y de conservación de energía para el organismo, favoreciendo el equilibrio físico y mental. Se ha reportado una alta prevalencia de mala calidad del sueño y somnolencia diurna excesiva (SDE) en estudiantes universitarios de diferentes carreras que provoca alteración de la concentración y caída del rendimiento académico. El objetivo de este trabajo fue evaluar la calidad del sueño, la SDE y sus posibles asociaciones con síntomas depresivos en estudiantes de odontología. Se realizó un estudio descriptivo transversal con 251 estudiantes de la carrera de Odontología de la Facultad de Farmacia, Odontología y Enfermería de la Universidad Federal de Ceará. Los instrumentos utilizados fueron el Índice de Calidad del Sueño de Pittsburgh (PSQI), la Escala de Somnolencia de Epworth (ESS) y el Inventario de Depresión de Beck (BDI). Hubo una alta prevalencia de mala calidad del sueño (53,4%) y SDE (35,1%) entre los estudiantes, sin diferencia significativa en relación con el género para ambos. Se encontró una correlación positiva entre BDI con PSQI y ESS (r= 0,478; p= 0,000 y r= 0,202; p = 0,000, respectivamente). Los resultados mostraron una alta prevalencia de mala calidad del sueño y SDE, y ambos hallazgos se asociaron con síntomas depresivos.

Genotype-Phenotype Correlation Analysis of WT1 Gene Variants in Denys-Drash Syndrome and Frasier Syndrome / 罕见病研究

ObjectiveThis study aims to explore the association between different genotypes of WT1 gene variations and the phenotypes of Denys-Drash syndrome (DDS) and Frasier syndrome (FS).MethodsThrough searching and summarizing the case information of WT1 gene variations recorded in NCBI PubMed and CNKI databases from January 1, 1991 to October 31, 2023, we analyzed the association between variation types, occurrence locations, and phenotypes such as progressive renal function impairment, genitourinary developmental abnormalities, nephroblastoma, and gonadal tumors between DDS and FS.ResultsA total of 128 articles, including 304 subjects, were included in this study, and 86 pathogenic variations of the WT1 gene were detected.The distribution characteristics of these variations were as follows: the most common occurrence was in exon 9(24/86, 27.9%) and exon 8 (23/86, 26.7%); the most common variation type was missense mutation(51/86, 59.3%), followed by splice site mutation (13/86, 15.1%).The disease types caused by WT1 gene variations were as follows: DDS had the highest number of cases (174/304, 57.2%), followed by FS (83/304, 27.3%); DDS was mainly caused by missense mutations on exon 9 and exon 8 (143/174, 82.2%), while FS was mainly caused by splice site mutations on intron 9 (76/83, 91.6%).ConclusionsThe missense variants in exon 9 and exon 8 on the WT1 gene mainly resulted in DDS, while the splice variants in intron 9 mainly resulted in FS. Infants and children with progressive renal injury should undergo a comprehensive evaluation of the genitourinary system, and early genetic diagnosis should be established to improve prognosis.

Descripción de los factores contribuyentes a las muertes secundarias a trastornos hipertensivos asociados al embarazo en Antioquia, Colombia (2012-2020) / Description of the contributing factors to deaths secondary to hypertensive disorders associated with pregnancy in Antioquia, Colombia (2012-2020)

Resumen OBJETIVO: Describir las características de la población afectada y los retrasos que contribuyeron a la mortalidad materna, secundaria a los trastornos hipertensivos del embarazo. MATERIALES Y MÉTODOS: Estudio descriptivo y retrospectivo efectuado con base en la vigilancia epidemiológica de casos centinela de muertes maternas tempranas de mujeres residentes en Antioquia, Colombia, durante el embarazo, el parto y los 42 días siguientes a éste ocurridas en el periodo 2012-2020. Se creó una base de datos en Microsoft Access 2007 (Microsoft, Redmond, WA, USA) y los datos se analizaron en Microsoft Excel y SPSS versión 22. RESULTADOS: Se registraron 266 muertes maternas, de las que 38 fueron secundarias a trastornos hipertensivos del embarazo. La eclampsia fue causa de 15 fallecimientos; 12 por síndrome HELLP, 9 por hemorragia intracerebral y 2 por desprendimiento prematuro de placenta y coagulación intravascular diseminada. En 13 de los 38 casos no hubo una pauta adecuada del sulfato de magnesio, 19 no recibieron tratamiento antihipertensivo, que estaba indicado y 17 no tuvieron un control antihipertensivo adecuado. CONCLUSIÓN: La atención prenatal es una oportunidad decisiva para la detección, prevención y estratificación del riesgo. Todos los centros de atención obstétrica deben estar preparados para gestionar urgencias asociadas con los trastornos hipertensivos del embarazo. Los desenlaces mejoran con la aplicación de protocolos de emergencia estandarizados, organizados y la participación de equipos multidisciplinarios que garanticen una atención de calidad y un efecto positivo en la morbilidad y mortalidad materna susceptible de prevención.

Abstract OBJECTIVE: To describe the characteristics of the affected population and the delays that contributed to maternal mortality secondary to hypertensive disorders of pregnancy. MATERIALS AND METHODS: Descriptive and retrospective study based on the epidemiologic surveillance of sentinel cases of early maternal deaths of women residing in Antioquia, Colombia, during pregnancy, delivery and the 42 days after delivery occurring in the period 2012-2020. A database was created in Microsoft Access 2007 (Microsoft, Redmond, WA, USA), and data were analyzed in Microsoft Excel and SPSS version 22. RESULTS: There were 266 maternal deaths, of which 38 were secondary to hypertensive disorders of pregnancy. Eclampsia was the cause of 15 deaths; 12 due to HELLP syndrome, 9 due to intracerebral hemorrhage, and 2 due to placental abruption and disseminated intravascular coagulation. In 13 of the 38 cases, there was no adequate magnesium sulfate regimen, 19 did not receive indicated antihypertensive treatment, and 17 did not have adequate antihypertensive control. CONCLUSION: Antenatal care is a critical opportunity for detection, prevention, and risk stratification. All obstetric care centers should be prepared to manage emergencies associated with hypertensive disorders of pregnancy. Outcomes improve with the use of standardized, organized emergency protocols and the participation of multidisciplinary teams that ensure quality care and a positive impact on preventable maternal morbidity and mortality.

Características clínicas del síndrome de apneas obstructivas del sueño en el adulto mayor

El síndrome de apneas obstructivas del sueño (SAOS) es un problema de salud prevalente y a menudo subdiagnosticado en el adulto mayor. Objetivos: Describir las características clínicas y trastornos del sueño en el adulto mayor de 65 años comparado con una cohorte de adultos jóvenes con SAOS (18-64 años). Métodos: Estudio clínico prospectivo realizado en sujetos roncadores atendidos en una clínica del sueño, a quienes se administraron cuestionarios de sueño y se realizó una poligrafía respiratoria o polisomnografía para confirmar el diagnóstico de SAOS. Se comparó las características clínicas y trastornos respiratorios del sueño en ambas cohortes. Resultados: Se evaluaron 1.512 pacientes, edad media: 56 ± 14 años, 70% varones, 91,2% tenían comorbilidades y 70,3% tenían SAOS moderada-severa. Los síntomas clásicos de SAOS fueron menos reportados en el adulto mayor: ronquidos (81,2% vs 86,4%, p < 0,02), apneas presenciadas (69,6% vs 79,8%, p < 0,001), fatigabilidad diurna (54,8% vs 77,3%, p < 0,001), sueño poco reparador (75,6% vs 89,6%, p < 0,001), sofocación nocturna (38,1% vs 50,7%, p < 0,001) y somnolencia diurna excesiva (43,9% vs 51,2%, p < 0,013). En el adulto mayor fueron más frecuentes las comorbilidades, especialmente cardiovascular, respiratorias y metabólicas crónicas; mientras que la obesidad objetivada por datos antropométricos (índice de masa corporal, perímetro cervical e índice cintura-cadera), índice de microdespertares, índice de desaturación (ID3%) y el índice de apneas-hipopneas fueron similares en ambos grupos. La magnitud de la hipoxemia nocturna objetivada en la oximetría de pulso (SaO2 media, SaO2 mínima y CT90%) fue superior en el adulto mayor. Conclusión: Las manifestaciones clínicas, comorbilidades y trastornos respiratorios del sueño son diferentes en el adulto mayor con síndrome de apneas obstructivas del sueño, lo cual debería ser considerado en el proceso diagnóstico y la planificación del tratamiento.

Obstructive sleep apnea syndrome (OSAS) is a prevalent and often underdiagnosed health problem in the elderly. Objectives: To describe clinical characteristics and sleep disorders in adults over 65 years-old compared to a cohort of young adults (18-64 years-old) with OSAS. Methods: Prospective clinical study carried out in snoring subjects attended in a sleep clinic, to whom sleep questionnaires were administered and respiratory polygraphy or polysomnography was performed to confirm the diagnosis of OSAS. Clinical characteristics and sleep-disordered breathing were compared among both cohorts. Results: 1,512 patients were evaluated, mean age: 56 ± 14 years, 70% male, 91.2% had comorbidities and 70.3% had moderate-severe OSAS. The classic symptoms of OSAS were less reported in older adults: snoring (81.2% vs 86.4%, p < 0.02), witnessed apneas (69.6% vs 79.8%, p < 0.001), daytime fatigue (54.8% vs 77.3%, p < 0.001), unrefreshing sleep (75.6% vs 89.6%, p < 0.001), nocturnal choking (38.1% vs 50.7%, p < 0.001) and excessive daytime sleepiness (43.9% vs 51.2%, p < 0.013). In the elderly, comorbidities were more frequent, especially chronic cardiovascular, respiratory and metabolic diseases; while obesity as measured by anthropometric data (body mass index, cervical circumference and waist-hip ratio), microarousal index, desaturation index (ID3%) and apnea-hypopnea index were similar in both groups. The magnitude of nocturnal hypoxemia observed in pulse oximetry (mean SaO2, minimum SaO2 and CT90%) was higher in the elderly. Conclusion: Clinical manifestations, comorbidities and sleep breathing disorders are different in the elderly with obstructive sleep apnea syndrome, which should be considered in the diagnostic process and treatment planning.

Encefalitis autoinmune posherpética. Caso clínico pediátrico / Autoimmune post-herpes simplex encephalitis. A pediatric clinical case report

La encefalitis por virus herpes simple (VHS) es una causa frecuente de encefalitis grave y potencialmente fatal. La encefalitis autoinmune posherpética (EAPH) afecta a un porcentaje de los pacientes que han presentado encefalitis herpética (EH) y se caracteriza por la aparición de nuevos síntomas neurológico/psiquiátricos, y/o por el empeoramiento de los déficits adquiridos durante la infección viral dentro de un lapso temporal predecible. Se produce por un mecanismo no relacionado con el VHS, sino por fenómenos autoinmunes, y es susceptible de tratamiento con inmunomoduladores. Se presenta el caso de un varón de 5 años de edad con EAPH que requirió tratamiento inmunomodulador, de primera y segunda línea, con buena evolución y remisión de los síntomas.

Herpes simplex virus (HSV) encephalitis is a common cause of severe and potentially fatal encephalitis. Autoimmune post-herpes simplex encephalitis (AIPHSE) affects a percentage of patients who developed herpes simplex encephalitis (HSE) and is characterized by the onset of new neurological/psychiatric symptoms and/or worsening of deficits acquired during the herpes infection within a predictable time frame. It is caused by a mechanism not related to HSV, but by autoimmune conditions, and is susceptible to treatment with immunomodulators. Here we describe the case of a 5-year-old boy with AIPHSE who required first- and second-line immunomodulatory treatment, with an adequate course and remission of symptoms.

Impacto econômico da implementação de políticas públicas para distúrbios de sono no Brasil: uma revisão integrativa / Economic impact of the implementation of public policies for sleep disorders in Brazil: an integrative review

Objetivo: Identificar estudos sobre políticas públicas, ações de saúde e análises econômicas relacionados aos distúrbios de sono no Brasil e discutir os seus resultados para o sistema de saúde, gestores de políticas públicas e a sociedade. Métodos: Revisão integrativa da literatura nas bases de dados Lilacs (via BVS), SciELO e PubMed (via Medline), incluindo estudos publicados nos idiomas português, inglês e espanhol, entre os anos de 1960-2023; foram excluídos estudos que não apresentaram a perspectiva brasileira ou aqueles cuja versão integral não estava disponível (seja gratuitamente ou na versão paga). Resultados: A busca retornou 536 resultados, dos quais apenas dois atendiam aos critérios de inclusão e mais cinco trabalhos foram incluídos manualmente, após consulta com especialistas de sono (todos abordaram apneia obstrutiva do sono, sendo: um relato sobre alteração na legislação de trânsito focada em prevenção de acidentes por sonolência excessiva; uma revisão de escopo sobre análises de custo-efetividade do tratamento da doença com uso de CPAP; dois relatos sobre linha de cuidado em um município e outros três em Secretarias Estaduais de Saúde). Conclusões: A revisão integrativa encontrou poucas evidências acerca do tema e aponta para a necessidade de futuros estudos que visem a suprir essa lacuna científica e de que seja necessário o desenvolvimento de futura linha de cuidado que amplie o acesso ao tratamento de doenças do sono no Sistema Único de Saúde.

Objective: To identify studies on public policies, health actions, and economic analyses related to sleep disorders in Brazil and discuss their results for public policy managers and society. Methods: Integrative literature review using Lilacs (via BVS), SciELO, and PubMed (via Medline) databases, including studies published in Portuguese, English, and Spanish languages, between years of 1960-2023; studies that did not present the Brazilian perspective or whose full version was not available were excluded (free or paid version). Results: The search returned 536 results, of which only two met the inclusion criteria, and five more studies were included manually after consulting sleep experts (all addressing obstructive sleep apnea, namely: a report on changes in traffic legislation focused on preventing accidents caused by excessive sleepiness; a scoping review on cost-effectiveness analysis of CPAP for sleep apnea treatment; two reports on care lines in one municipality and another three in State Secretariats). Conclusions: The integrative review found few evidences on the topic and points to the need for future studies aimed at filling this scientific gap and the development of a care line that expands access to sleep disorder treatment in Brazilian Public Health System.

Effect of Tinnitus on Sleep Quality and Insomnia

Abstract Introduction Tinnitus is a conscious perception of a sound resulting from abnormal activity within the nervous system. A relevant percentage of tinnitus patients report symptoms severe enough to significantly affect quality of life, including sleep disorders. Objectives To analyze the sleep quality, insomnia, daytime sleepiness, and risk of obstructive sleep apnea (OSA) in participants with tinnitus. Methods The sample comprised 18 adults and older adults aged between 18 and 85 years old (mean age = 58.7 ± 17.5 years old), females and males, with complaint of continuous tinnitus for > 1 month. The instruments used were the Tinnitus Handicap Inventory (THI) questionnaire, the Insomnia Severity Index, the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, and the STOP-Bang questionnaire. Results By means of the THI questionnaire, the tinnitus severity degree reported by most participants was mild (27.8%) and moderate (27.8%), having a positive (r = 0.582) and significant (0.011) correlation to sleep quality, measured by means of the Pittsburgh questionnaire. There was a positive correlation between the Insomnia Severity Index and tinnitus handicap (r = 0.499; p = 0.035). A total of 72.2% of the participants self-assessed their sleep quality as poor, in addition to moderate insomnia (27.8%), although there is low risk of OSA (66.7%), without complaints of excessive daytime sleepiness (72.2%). Conclusion Subjects with tinnitus complaint self-rated their sleep quality as poor. Moreover, the higher the reported tinnitus handicap, the greater the symptoms of insomnia. There was no influence of tinnitus in relation to daytime sleepiness and no relationship between the severity of tinnitus and the risk of OSA.

Molecular analysis of interleukin 10 promoter region-592A/C polymorphism in hypertensive disorders of pregnancy in Qinghai Han nationality / 解剖学报

Objective To investigate the association between the interleukin 10 (IL-10) gene promoter region-592A/C (rs1800872) polymorphism and hypertensive disorders of pregnancy (HDP) in Han women of Qinghai province and to determine the expression of this gene in two groups (HDP group and healthy control group) preliminarily. Methods A total of 140 HDP patients (HDP group) and 140 normal pregnant women (control group) in Qinghai Province were selected. Using blood DNA as template, the IL-10-592A/C polymorphism typing of HDP group and control group was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and verified by sequencing. The expression of IL-10 mRNA in the placental tissues of the two groups was detected by Real-time PCR. Plasma IL-10 levels of the two groups were detected by ELISA. Results The frequencies of AA, AC and CC genotypes of IL-10 gene in HDP group and control group were 24. 29%, 44. 29%, 31. 42% and 13. 57%, 41. 43%, 45. 00% respectively, the difference in genotype distribution between the two groups was statistically significant (P<0. 05);AA genotype frequency in HDP group(24. 29%)was higher than that of control group(13. 57%)(P<0. 05), CC genotype frequency in HDP group (31. 42%) was lower than that in control group (45. 00%) (P < 0. 05), while there was no significant difference in genotype frequency of AC between the two groups (P<0. 05); The distribution of A and C allele frequencies of IL-10592A/C polymorphism was different between the two groups, and the A allele frequency of HDP group was higher than that of control group (

Diagnosis and treatment of disorders of laryngeal airway in children and prospect / 临床耳鼻咽喉头颈外科杂志

This paper focuses on the diagnosis and treatment of disorders of laryngeal airway in children, including congenital anomalies, infection, and tumor of the larynx to provide a new technology for managing these diseases. Based on the characteristic of them, the pediatric upper airway is dedicated to the clinical evaluation of airway obstruction and the assessment of the compromised pediatric airway, including clinical evaluation of symptoms, diagnostic endoscopy, and imaging examination. Information on endoscopic techniques used for dealing with different degrees of pediatric airway comprised is provided, also this techniques could diagnose what kinds of airway disorder. For example, determining the a particular laryngeal cleft at the initial otolaryngology encounter, flexible laryngoscopy should be performed. In order to define the extent of any identified cleft, the rigid bronchoscopy should be completed to evaluate for classification of laryngeal cleft including typeⅠ, Ⅱ, Ⅲa, Ⅲb, Ⅳa, Ⅳb under general anesthesia. The decision to pursue any therapy for the disorders of laryngeal airway in children should be based on the severity of the patient's symptoms, endoscopic and imaging examination. There are two medical treatments including nonsurgical therapy and surgical therapy. For example the laryngeal cleft, approximately half of type 1 and select type 2 patients can be managed entirely with nonsurgical therapy. Medical management is multifaceted. Under recommendations from the feeding team, a modified diet with thickened feeds and possibly altered feeding position should be initiated. Endoscopic surgical repair is the current gold standard for definitive repair of type 1, the majority of type 2, and selected type 3 clefts. Finally, information on new techniques used into the future for dealing with the diagnosis and treatment of disorders of laryngeal airway in children in this paper.

"Sentinel or accomplice": gut microbiota and microglia crosstalk in disorders of gut-brain interaction

Abnormal brain-gut interaction is considered the core pathological mechanism behind the disorders of gut-brain interaction (DGBI), in which the intestinal microbiota plays an important role. Microglia are the "sentinels" of the central nervous system (CNS), which participate in tissue damage caused by traumatic brain injury, resist central infection and participate in neurogenesis, and are involved in the occurrence of various neurological diseases. With in-depth research on DGBI, we could find an interaction between the intestinal microbiota and microglia and that they are jointly involved in the occurrence of DGBI, especially in individuals with comorbidities of mental disorders, such as irritable bowel syndrome (IBS). This bidirectional regulation of microbiota and microglia provides a new direction for the treatment of DGBI. In this review, we focus on the role and underlying mechanism of the interaction between gut microbiota and microglia in DGBI, especially IBS, and the corresponding clinical application prospects and highlight its potential to treat DGBI in individuals with psychiatric comorbidities.

Clinical, genetic, and pathological analysis in 165 children with disorders of sex development / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical phenotypes, genetic characteristics, and pathological features of children with disorders of sex development (DSD).@*METHODS@#A retrospective analysis was conducted on epidemiological, clinical phenotype, chromosomal karyotype, gonadal pathology, and genotype data of 165 hospitalized children with DSD at Children's Hospital of Hebei Province and Tangshan Maternal and Child Health Hospital from August 2008 to December 2022.@*RESULTS@#Among the 165 children with DSD, common presenting symptoms were short stature (62/165, 37.6%), clitoromegaly (33/165, 20.0%), cryptorchidism (28/165, 17.0%), hypospadias (24/165, 14.5%), and skin pigmentation abnormalities/exteriorized pigmented labia majora (19/165, 11.5%). Chromosomal karyotype analysis was performed on 127 cases, revealing 36 cases (28.3%) of 46,XX DSD, 34 cases (26.8%) of 46,XY DSD, and 57 cases (44.9%) of sex chromosome abnormalities. Among the sex chromosome abnormal karyotypes, the 45,X karyotype (11/57, 19%) and 45,X/other karyotype mosaicism (36/57, 63%) were more common. Sixteen children underwent histopathological biopsy of gonadal tissues, resulting in retrieval of 25 gonadal tissues. The gonadal tissue biopsies revealed 3 cases of testes, 3 cases of dysplastic testes, 6 cases of ovaries, 11 cases of ovotestes, and 1 case each of streak gonad and agenesis of gonads. Genetic testing identified pathogenic/likely pathogenic variants in 23 cases (23/36, 64%), including 12 cases of 21-hydroxylase deficiency congenital adrenal hyperplasia caused by CYP21A2 pathogenic variants.@*CONCLUSIONS@#Short stature, clitoromegaly, cryptorchidism, hypospadias, and skin pigmentation abnormalities are common phenotypes in children with DSD. 45,X/other karyotype mosaicism and CYP21A2 compound heterozygous variants are major etiological factors in children with DSD. The most commonly observed gonadal histopathology in children with DSD includes ovotestes, ovaries, and testes/dysgenetic testes.

Clinical Decision on Disorders of Consciousness After Acquired Brain Injury: Stepping Forward / 神经科学通报·英文版

Major advances have been made over the past few decades in identifying and managing disorders of consciousness (DOC) in patients with acquired brain injury (ABI), bringing the transformation from a conceptualized definition to a complex clinical scenario worthy of scientific exploration. Given the continuously-evolving framework of precision medicine that integrates valuable behavioral assessment tools, sophisticated neuroimaging, and electrophysiological techniques, a considerably higher diagnostic accuracy rate of DOC may now be reached. During the treatment of patients with DOC, a variety of intervention methods are available, including amantadine and transcranial direct current stimulation, which have both provided class II evidence, zolpidem, which is also of high quality, and non-invasive stimulation, which appears to be more encouraging than pharmacological therapy. However, heterogeneity is profoundly ingrained in study designs, and only rare schemes have been recommended by authoritative institutions. There is still a lack of an effective clinical protocol for managing patients with DOC following ABI. To advance future clinical studies on DOC, we present a comprehensive review of the progress in clinical identification and management as well as some challenges in the pathophysiology of DOC. We propose a preliminary clinical decision protocol, which could serve as an ideal reference tool for many medical institutions.

Epididymis cell atlas in a patient with a sex development disorder and a novel NR5A1 gene mutation / 亚洲男科学杂志(英文版)

This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development (DSD) patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene. Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1. The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development. The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis. Microfluidic-based single-cell RNA sequencing (scRNA-seq) analysis found that the fibroblast cells were significantly increased (approximately 46.5%), whereas the number of main epididymal epithelial cells (approximately 9.2%), such as principal cells and basal cells, was dramatically decreased. Bioinformatics analysis of cell-cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition (EMT) process. The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.

Application of omics in the pathogenesis and prediction of hypertensive disorders of pregnancy: a review / 预防医学

Abstract@#Hypertensive disorders of pregnancy (HDP) are a common severe complication during pregnancy, which is characterized by complex etiology, unclear pathogenesis and lack of effective tools for early diagnosis and prediction. Recently, the development of omics technology provides new insights into the research into HDP. Based on national and international publications from 2011 to 2022, this review summarizes the application of genomics, proteomics, metabolomics, and microbiomics in the pathogenesis and prediction of HDP, so as to provide insights into the prediction, prevention and precise treatment of HDP.

The Effect of SARS-CoV-2 Infection on Perinatal Outcomes in Hypertensive Disorders of Pregnancy / O efeito da infecção por SARS - CoV - 2 no perinatal resultados em distúrbios hipertensivos de gravidez

Abstract Objective To evaluate the fetal and maternal effects of the severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection in women with hypertensive disorders of pregnancy. Methods Patients with hypertensive disorders of pregnancy and SARS-CoV-2 polymerase chain reaction (PCR) positivity (n = 55) were compared with cases with similar characteristics and PCR negativity (n = 53). The study group was further divided into two groups as severe (n = 11) and nonsevere (n = 44) coronavirus disease 2019 (COVID-19). The groups were compared in terms of clinical characteristics and perinatal outcomes. Results The study and control groups were similar in terms of maternal age, parity, gestational age at diagnosis, type of hypertensive disorders, magnesium sulfate administration rate, gestational age at birth, birth weight, Apgar scores, and maternal complications. However, all cases of fetal loss (n = 6) were observed in the SARS-CoV-2 positive group (p = 0.027). From the 6 cases, there were 5 in the nonsevere group and 1 patient in the severe SARS-CoV-2 positive group. Moreover, higher rates of maternal complications, lower oxygen saturation values, and intensive care unit admissions were observed in the severe COVID-19 group. Conclusion Physicians should be cautious about the management of hypertensive disorders of pregnancy cases with SARS-CoV-2 positivity. Fetal loss seems to be more common in cases with SARS-CoV-2 positivity and severe COVID-19 seems to be associated with higher rates of maternal complications. Close follow-up for fetal wellbeing and active management of severe cases in terms of maternal complications seem to be favorable.

Hipospadias: del diagnóstico ecográfico prenatal al manejo posnatal / Hypospadias: from prenatal ultrasound diagnosis to postnatal management

El hipospadias es la localización anormal del meato urinario y es la malformación de genitales externos más frecuentemente diagnosticada. El diagnóstico prenatal es posible mediante ecografía sistemática desde la semana 20 de gestación, siendo más fácil su diagnóstico en el tercer trimestre. Las formas leves suelen ser aisladas, familiares o asociadas a disfunción placentaria o restricción de crecimiento intrauterino, mientras que las formas más graves presentan hasta un 30% de asociación a defectos fetales, anomalías cromosómicas/genéticas o anomalías del desarrollo sexual. La tríada para el diagnóstico ecográfico prenatal consiste en curvatura ventral del pene, anomalía del prepucio dorsal y punta del pene roma. La valoración de la uretra durante la micción y el aspecto del chorro miccional son de gran utilidad para clasificar el defecto. Cuando se diagnostica hipospadias peneano o escrotal es aconsejable realizar una amniocentesis para estudio genético fetal y valorar otros signos de adecuada virilización, como el descenso testicular a partir de la semana 27. El seguimiento tras el parto debe ser multidisciplinario, incluyendo urólogo y endocrinólogo infantil. En hipospadias leves el pronóstico es bueno con reparación quirúrgica en el primer año de vida, pero las formas graves pueden presentar un reto mayor para su corrección funcional y estética.

Hypospadias refers to the abnormal location of the meatus; it is the most common genital malformation detected in the fetus and newborn. Prenatal diagnosis is feasible from 20 weeks onwards with routine ultrasound; however, it is easier to diagnose during the third trimester of pregnancy. Mild defects are usually isolated, familiar o related to placental disfunction or intrauterine growth restriction, while the severe hypospadias are associated to other fetal defects, genetic or chromosomal abnormalities or disorders of sex development. In about 30% of cases. The triad of ultrasound findings prenatally is ventral curvature of the penis, redundant dorsal foreskin and blunt distal penis. The identification of the urethra during the micturition and the direction of the urinary stream help in the classification of the defect. When severe hypospadias is detected, the recommendation is to perform genetic amniocentesis and search for other ultrasound findings related to poor virilization in the fetus, as testicular descent after 27 weeks of gestation. Postnatal follow up should be multidisciplinary including infantile urologist and endocrinologist. The prognosis in distal hypospadias is usually good following surgical repair, however in severe cases surgical interventions may be more challenging in order to obtain satisfactory outcome in terms of function and esthetic.

Clinical and laboratory differences between chromosomal and undefined causes of non-obstructive azoospermia: A retrospective study

ABSTRACT BACKGROUND: Knowledge of clinical and laboratory differences between chromosomal and undefined causes aids etiological research on non-obstructive azoospermia. OBJECTIVE: Compare clinical and laboratory differences between men with non-obstructive azoospermia due to chromosomal anomalies versus undefined causes DESIGN AND SETTING: A cross-sectional retrospective study conducted at a public university hospital in Campinas (Brazil) METHODS: All men aged 20-40 years with non-obstructive azoospermia were included in the analysis. RESULTS: The 107 cases included 14 with Klinefelter syndrome (KS) (13%), 1 with mosaic KS, 4 with sex development disorders (2 testicular XX, 1 NR5A1 gene mutation, and 1 mild androgen insensitivity syndrome) (4%), 9 with other non-obstructive azoospermia etiologies (8%), and 79 with undefined causes. The 22 chromosomal anomaly cases (14 KS, 1 mosaic KS, 2 testicular XX, 4 sex chromosome anomalies, and 1 autosomal anomaly) were compared with the 79 undefined cause cases. The KS group had lower average testicular volume, shorter penile length, and lower total testosterone levels but greater height, arm span, serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, and gynecomastia frequency (absent in the undefined group and affecting more than half of the KS group). Patients with testicular XX DSD had LH, FSH, and penile length data intermediate between the KS and undefined cause groups, testicular volume similar to the KS group, and other data similar to the undefined group. CONCLUSION: Clinical and laboratory data differentiate men with non-obstructive azoospermia and chromosomal anomalies, particularly KS and testicular XX, from those with undefined causes or other chromosomal anomalies.

Congenital glycosylation disorder type Ⅱm caused by SLC35A2 mutations: a report of 3 cases and literature review / 中华神经科杂志

Objective:To summarize the clinical manifestations, gene variations, diagnosis and treatment of 3 cases with SLC35A2 variations characterized by congenital glycosylation disorder Ⅱm (CDG Ⅱm). Methods:A total of 3 patients admitted to the Department of Pediatrics of Xiangya Hospital of Central South University in China from 2018 to 2020 were examined in detail. The studies till January 2022 were searched with key words of "congenital disorders of glycosylation Ⅱm", " SLC35A2" and "CDG Ⅱm" in both English and Chinese in the databases of China National Knowledge Infrast Ructure (CNKI), Wanfang, Online Mendelian Inheritance in Man and PubMed, and the clinical manifestations, genetic variation, treatments and prognosis of patients with SLC35A2 mutation were summarized. Results:The patients all presented with intractable infantile spasm and global developmental delay, onset in infancy. A variety of antiepileptic treatments had temporary and partial efficacy. Otherwise, proband 2 and 3 presented with abnormal glutamic-pyruvic transaminase and increased platelets. Funduscopy showed dysplasia of the retinal pigment epithelium in both eyes, and they both received D-galactose treatment. A total of 22 relevant case reports, including 99 patients, were collected. The 99 patients all were heterozygous mutations, and a total of 75 different variation sites were reported. The clinical manifestations were characterized by global developmental delay or mental retardation ( n=89), epileptic seizure ( n=75), hypotonia ( n=57), facial deformity ( n=57), skeletal abnormality ( n=50), visual impairment ( n=42), elevated glutamic-pyruvic transaminase ( n=31), gastrointestinal symptoms ( n=28), skin deformity ( n=26), microcephaly ( n=23) and congenital heart disease ( n=12). Craniocerebral magnetic resonance imaging may be normal in the early stage. With age, magnetic resonance imaging may show abnormal white matter signals, brain atrophy, dysplasia of corpus callosum, delayed myelination, enlargement of lateral ventricle, brain stem atrophy and so on. Studies have shown that galactose treatment may be effective. Conclusions:SLC35A2 variants lead to CDG Ⅱm, whose clinical manifestations mainly include epileptic encephalopathy and global developmental delay. Multiple antiepileptic therapies can temporarily or partially control seizures, while oral galactose may improve the clinical symptoms, showing its prospect as a dietary therapy.

Clinical and genetic features of 5 alpha-reductase type2 deficiency caused by SRD5A2 gene variants / 中华内分泌代谢杂志

Objective:To explore the clinical and genetic characteristics of 5α-reductase 2 deficiency syndrome(5α-RD2).Methods:Retrospective analysis of three cases of 5α-RD2 to summarize clinical data. Genetic testing was conducted using chromosome karyotyping analysis, whole-exome sequencing(WES), Sanger sequencing, and bioinformatics analysis. The effect of the novel variant on the structure of the 5α-reductase was evaluated by studying the homology modeling structure using SWISSMODEL and PyMoL.Results:The patients of all three cases have social gender as female. In Case 1, a 6-year-old patient sought medical attention due to abnormal external genitalia development. In Cases 2 and 3, 15-year-old patients presented with primary amenorrhea, and they showed masculinization of secondary sexual characteristics during puberty. In all three cases, the external genitalia exhibited varying degrees of masculinization, with clitoromegaly resembling a small penis and accompanying cryptorchidism. In Case 2, an hCG stimulation test was performed, and the testosterone/dihydrotestosterone(DHT) ratio was found to be 17.4. The karyotype of all three patients was 46, XY. Whole-exome sequencing(WES) detected SRD5A2 gene variants in all cases, with genotypes being p. Gln6Ter/p.Arg227Gln, p. Gln6Ter/p.Pro250Ala, and p. Arg227Ter/p.His89Tyr, respectively. Parental validation confirmed compound heterozygous mutations in all cases. The novel variant p. Pro250Ala was identified and classified as a likely pathogenic variant according to ACMG guidelines. Protein modeling analysis indicated that this variant may affect the binding of 5α-reductase 2 to NADPH. In Case 1, male gender was chosen, and a laparoscopic bilateral orchiopexy was performed. In Case 2, female gender was chosen, and testectomy and vaginoplasty were performed. The gender selection for Case 3 has not been definitively determined yet.Conclusions:Abnormal external genitalia is a common phenotype of 5α-RD2. After hCG stimulation test, there is a significant increase in the testosterone/dihydrotestosterone(DHT) ratio, which indicates that Sanger sequencing of the SRD5A2 gene can be directly performed. 5α-RD2 exhibits significant clinical heterogeneity, and WES can facilitate the differential diagnosis of 46, XY disorders of sex development. The study also reported a novel variant, p. Pro250Ala, which enriches the SRD5A2 gene variant database.

Evaluation of left atrial function and predictive value of risk stratification in patients with hypertensive disorder of pregnancy by four-dimensional automatic left atrial quantitative analysis / 中华超声影像学杂志

Objective:To investigate the change of left atrial volume and function in patients with hypertensive disorders of pregnancy (HDPs) by four-dimensional automatic left atrial quantitative analysis (4D LAQ) and analyze the predictive value of risk stratification.Methods:A total of 60 patients diagnosed with hypertensive disorder of pregnancy in Henan Provincial People′s Hospital from March to December 2021 were randomly enrolled, which were divided into gestational hypertension group (low risk group, n=30) and preeclampsia group (medium and high risk group, n=30) according to the disease development and risk stratification method reported in the literature; another 30 healthy pregnant women matched for age, gestational weeks and body mass index were selected as the control group. Left atrial anteroposterior diameter (LAd), interventricular septum thickness (IVSd), left ventricular end diastolic diameter (LVd), left ventricular ejection fraction (LVEF), left ventricular myocardial mass index (LVMI), peak early diastolic (E) and late diastolic (A) velocities of mitral inflow, and e′ values on the septal and lateral mitral annulus sides were routinely measured to calculate E/A and E/e′ values. Left atrial volume and strain parameters were obtained using 4D LAQ technique, including left atrial minimum volume (LAVmin), left atrial maximum volume (LAVmax), left atrial presystolic volume (LAVpreA), left atrial maximum volume index (LAVImax), left atrial inflation index (LAEI), left atrial stroke volume (LAEV), left atrial fraction (LAEF), longitudinal strain of left atrial reserve, conduit and systolic period (LASr, LAScd, LASct), circumferential strain of left atrial reserve, conduit and systolic period(LASr-c, LAScd-c, LASct-c). The differences among the three groups were compared. Multiple Logistics regression analysis was used to obtain the relevant indicators of risk stratification of HDPs and ROC curves were used for assessment. Results:Compared with the control group, E/e′, LAVmin, LAVpreA, LAScd, and LAScd-c increased, and LAEI, LAEF, LApEF, LASr, and LASr-c decreased in the gestational hypertension group (all P<0.05). Compared with the control group and gestational hypertension group, LAd, IVSd, LVd, LVMI, E/e′ LAVmin, LAVmax, LAVpreA, LAVImax, LAEV, LAScd, and LAScd-c increased, and LVEF, LAEF, LAEI, LApEF, LASr, and LASr-c decreased in the preeclamptic group, and the differences were statistically significant (all P<0.05). The results of multiple Logistics regression showed that LAVmax, LAScd-c and LASr were the indicators relevant to risk stratification of HDPs(β=0.344, 0.216 and -0.249, respectively, all P<0.05). ROC analysis showed when the cut-off value of left atrial strain parameter LASr was 30.5%, the AUC, sensitivity, and specificity were 0.725, 0.58, 0.90, respectively; when the cut-off value of LAVmax was 44.5 ml, the AUC, sensitivity, and specificity were 0.662, 0.80, and 0.56, respectively; and when the cut-off value of LAScd-c was -17.5%, the AUC, sensitivity, and specificity were 0.706, 0.56, and 0.78, respectively. Conclusions:Left atrial remodeling occured in pregnant women with hypertensive disorders, their reserve and conduit function were impaired, and aggravated with the progress of the disease. The four-dimensional parameters LASr, LAVmax, and LAScd-c were relevant indicators for risk stratification of HDPs. In predicting the severity of HDPs, LASr has high diagnostic value and good specificity; LAVmax and LAScd-c can be considered as supplementary parameters to predict the risk stratification of HDPs.