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1.
Nat Commun ; 11(1): 4799, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968074

RESUMO

Genetic association studies have identified 44 common genome-wide significant risk loci for late-onset Alzheimer's disease (LOAD). However, LOAD genetic architecture and prediction are unclear. Here we estimate the optimal P-threshold (Poptimal) of a genetic risk score (GRS) for prediction of LOAD in three independent datasets comprising 676 cases and 35,675 family history proxy cases. We show that the discriminative ability of GRS in LOAD prediction is maximised when selecting a small number of SNPs. Both simulation results and direct estimation indicate that the number of causal common SNPs for LOAD may be less than 100, suggesting LOAD is more oligogenic than polygenic. The best GRS explains approximately 75% of SNP-heritability, and individuals in the top decile of GRS have ten-fold increased odds when compared to those in the bottom decile. In addition, 14 variants are identified that contribute to both LOAD risk and age at onset of LOAD.


Assuntos
Doença de Alzheimer/genética , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Adulto , Idade de Início , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
2.
Asian Pac J Allergy Immunol ; 38(3): 170-177, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32990448

RESUMO

The disease course of coronavirus disease 2019 (COVID-19) is usually mild and self-limiting in previously healthy children, but they may also develop severe disease. Severe COVID-19 infection is especially observed in very young children or those with underlying comorbidities. Moreover, a multisystem inflammatory syndrome that mimics the Kawasaki disease shock syndrome can develop in children that are genetically predisposed to displaying an overactive immune response to SARS-CoV-2 infection. In this review, we describe the clinical phenotypes of mild and severe COVID-19 and multisystem inflammatory syndrome in children (MIS-C). We also discuss the possible immunobiological mechanisms that may be involved in the protection of children against COVID-19 and the development of multisystem inflammatory syndrome.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/virologia , Pneumonia Viral/virologia , Síndrome de Resposta Inflamatória Sistêmica/virologia , Adolescente , Idade de Início , Betacoronavirus/imunologia , Criança , Pré-Escolar , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/epidemiologia , Síndrome da Liberação de Citocina/imunologia , Citocinas/imunologia , Suscetibilidade a Doenças , Feminino , Interações Hospedeiro-Patógeno , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/virologia , Lactente , Recém-Nascido , Ativação Linfocitária , Ativação de Macrófagos , Masculino , Pandemias , Fenótipo , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia
5.
Medicine (Baltimore) ; 99(34): e21899, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846853

RESUMO

Although a strong association between idiopathic inflammatory myositis (IIM) and malignancy has been widely reported, few studies have solely focused on the concurrence of dermatomyositis (DM) and malignancies (DM-malignancy).We conducted a retrospective analysis of 37 DM-malignancy cases among 363 DM patients admitted to our hospital between January 2012 and December 2017.(1) The mean age at DM diagnosis was higher for DM-malignancy patients than for DM-non-malignancy patients [(54.76 ±â€Š9.77) years vs (48.57 ±â€Š12.82) years, t = 2.84, P = .005]. (2) Gynecological malignancies (35.90%/14 cases) were the most common malignancies. Malignancies were diagnosed before DM for 7 DM-malignancy patients. The interval between the DM and malignancy diagnoses for the remaining 32 DM-malignancy patients was less than 6 months for 18 patients (46.15%), less than 1 years for 23 patients (58.9%), and less than 2 years for 29 patients (74.26%). (3) There was no significant difference either in antinuclear antibody or anti-Ro-52 positivity between the 2 groups (P > .05). (4) Multivariate analysis demonstrated that DM onset age ≥50 years and concurrence with ILD increased the risk of death for DM patients [hazard ratio (HR): 1.62 and 2.72; 95% confidence interval (CI): (1.08-2.43) and (1.47-5.02); P = .02 and 0.001, respectively], and male gender decreased the risk of death [HR 0.66, 95% CI (0.44-0.98), P = .04]. DM-malignancy patients were older than DM-non-malignancy patients. Gynecological malignancies were the most common malignancies among these patients. A DM onset age ≥50 years, female sex and the presence of ILD were independent risk factors for death.


Assuntos
Biomarcadores/sangue , Dermatomiosite/diagnóstico , Neoplasias dos Genitais Femininos/epidemiologia , Neoplasias/complicações , Neoplasias/diagnóstico , Adulto , Idade de Início , Anticorpos Antinucleares , Autoanticorpos/sangue , Estudos de Casos e Controles , Dermatomiosite/mortalidade , Feminino , Neoplasias dos Genitais Femininos/diagnóstico , Hospitalização , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
6.
Medicine (Baltimore) ; 99(34): e21733, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846794

RESUMO

Dermatomyositis (DM) is an idiopathic inflammatory myopathy that is closely related to malignant diseases. Our study aims to investigate the incidence and predictive factors for occurrence of malignancy among DM patients from Central China.We performed a retrospective, paired, case-control study of 736 DM patients admitted to the First Affiliated Hospital of Zhengzhou University between 2010 and 2017. We paired the 65 patients with malignancy with age-matched and sex-matched patients without malignancy in a ratio of 1:2. Two hundred two patients were finally enrolled and their clinical and laboratory data were collected.The incidence of malignancy in DM patients was 8.83% (65/736). Most malignancies were detected in the most recent 1 year before (9/65, 13.85%) or within 3 years after (40/65, 61.54%) the onset of DM. Males (35/65, 53.85%) and patients aged between 50 and 69 years (43/65, 66.15%) were prone to develop malignancies. Lung cancer (n = 11, 31.43%) was the most common malignancy in male patients, while for females, thyroid, breast and cervical cancer (n = 4 each, 13.33%) were more prevalent. Adenocarcinoma and squamous cell carcinoma (both 18/65, 27.69%) were the top two most common pathological types. Univariate analysis demonstrated that Gottron's sign (P = .02), dysphagia (P = .04), albumin (ALB) reduction (P = .003), aspartate aminotransferase (AST, P = .03), creatine kinase-MB (P = .02), absence of fever (P = .02), arthralgia (P = .04) and interstitial lung disease (ILD, P = .05) were closely related to the occurrence of malignancy. Multivariate analysis revealed the independent risk factors of ALB reduction (odds ratio = 1.546, P = .04) and the protective factor of ILD (odds ratio = 0.349, P = .003). There was no significant difference in the follow-up period between patients with and without ILD (P = .38).ALB reduction and the absence of ILD were the risk factors for malignancy in DM patients. The protective mechanism of ILD for DM patients needs further study.


Assuntos
Dermatomiosite/epidemiologia , Neoplasias/epidemiologia , Fatores Etários , Idade de Início , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Neoplasias/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo
7.
Georgian Med News ; (303): 79-85, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32841186

RESUMO

The purpose of the study is to examine in depth and analyze the clinical and some paraclinical characteristics for a family history of Duchenne muscular dystrophy. We analyzed the follow up clinical and laboratory data of Duchenne muscular dystrophy in two brothers-german, aged 16 and 14, respectively. The patients underwent a standardized examination, involving studying the medical case history, general clinical data, determining Sheldon's somatotype and the constitutional type, the detailed neurological status examination, testing a personality type, laboratory and instrumental examinations. Through the laboratory examination we determined the general blood test indicators, total serum protein levels, total cholesterol, the ALAT, ASAT, CPK levels, the indicators of the immunogram, myositis profile and the genetic markers of the disease. The instrumental examination included the ultrasound of the abdominal organs, muscles, as well as echo-cardiography, electroneuromyography. A complete examination fragment of 42 patients with myodystrophies is presented. The paper presents the neurological examination results, the genetic study data and the CPK level indicators in the representatives of Duchenne muscular dystrophy family history. The given family history of Duchenne muscular dystrophy showed two brothers-german to have differences both in the defective dystrophin gene exons at Xp21 and in the disease clinical picture. Thus, patient A., who is an elder brother was detected to have exon 47, 48, 50 and 52 deletion, and patient B., who is a younger brother, was found to have exon 45-43 deletion. The presented family history of Duchenne muscular dystrophy acknowledges the fact that the clinical, genetic, biochemical and other characteristics in patients with dystrophinopathies warrant further comprehensive investigations in order to update diagnostic and prognostic techniques, considering the great medical and social significance of this disabling pathology. However, the onset age of the disease, the clinical course, and the changes in the CPK level were different. Due to the muscle ultrasound both patients were detected to have degenerative changes in the proximal upper and lower limbs.


Assuntos
Distrofia Muscular de Duchenne/genética , Miosite , Idade de Início , Idoso , Distrofina/genética , Éxons , Humanos , Masculino
8.
Med Sci (Paris) ; 36(8-9): 763-768, 2020.
Artigo em Francês | MEDLINE | ID: mdl-32821053

RESUMO

Myopia is a refractive anomaly, a global public health issue, mainly due to an increase in axial length of the eyeball. Myopia is increasing worldwide with the appearance of a "myopia global growing epidemic". In children under 6 years old, 20 % have abnormalities, the most common of which are primarily refractive abnormalities, followed by strabismus and amblyopia. Myopia presents a major risk of complications, correlated with its severity, such as retinal detachment, retinal neovascularization, early cataracts and glaucoma. In children with high myopia, syndromic myopia must be explored. Early detection of myopia onset and progression is essential to myopia control strategies. The most promising treatments include outdoor activities, defocusing corrective lenses, defocusing contact lenses, orthokeratology and pharmacological treatments with low-dose atropine.


Assuntos
Miopia , Idade de Início , Atropina/uso terapêutico , Criança , Pré-Escolar , Lentes de Contato , Progressão da Doença , Exercício Físico/fisiologia , Humanos , Lactente , Miopia/complicações , Miopia/diagnóstico , Miopia/epidemiologia , Miopia/terapia , Parques Recreativos
9.
Rinsho Shinkeigaku ; 60(9): 581-588, 2020 Sep 29.
Artigo em Japonês | MEDLINE | ID: mdl-32779598

RESUMO

Alexander disease (ALXDRD) is a primary astrocyte disease caused by glial fibrillary acidic protein (GFAP) gene mutation. ALXDRD had been clinically regarded as a cerebral white matter disease that affects only children for about 50 years since the initial report in 1949; however, in the early part of the 21st century, case reports of adult-onset ALXDRD with medulla and spinal cord lesions increased. Basic research on therapies to reduce abnormal GFAP accumulation, such as drug-repositioning and antisense oligonucleotide suppression, has recently been published. The accumulation of clinical data to advance understanding of natural history is essential for clinical trials expected in the future. In this review, I classified ALXDRD into two subtypes: early-onset and late-onset, and detail the clinical symptoms, imaging findings, and genetic characteristics as well as the epidemiology and historical changes in the clinical classification described in the literature. The diagnostic criteria based on Japanese ALXDRD patients that are useful in daily clinical practice are also mentioned.


Assuntos
Doença de Alexander/diagnóstico , Adolescente , Adulto , Idade de Início , Doença de Alexander/tratamento farmacológico , Doença de Alexander/genética , Doença de Alexander/fisiopatologia , Animais , Criança , Imagem de Difusão por Ressonância Magnética , Reposicionamento de Medicamentos , Proteína Glial Fibrilar Ácida/genética , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Camundongos , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Mutação , Oligonucleotídeos Antissenso , Adulto Jovem
10.
Eur J Endocrinol ; 183(4): 369-379, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32621582

RESUMO

Background: The '3PAs' syndrome, associating pituitary adenoma (PA) and pheochromocytoma/paraganglioma (PPGL), is sometimes associated with mutations in PPGL-predisposing genes, such as SDHx or MAX. In '3PAs' syndrome, PAs can occur before PPGL, suggesting a new gateway into SDHx/MAX-related diseases. Objective: To determine the SDHx/MAX mutation prevalence in patients with isolated PAs and characterize PAs of patients with SDHx/MAX mutations. Design: Genes involved in PAs (AIP/MEN1/CDKN1B) or PPGLs (SDHx/MAX) were sequenced in patients with isolated PAs. We then conducted a review of cases of PA in the setting of '3PAs' syndrome. Results: A total of 263 patients were recruited. Seven (likely) pathogenic variants were found in AIP, two in MEN1, two in SDHA, and one in SDHC. The prevalence of SDHx mutations reached 1.1% (3/263). Of 31 reported patients with PAs harboring SDHx/MAX mutations (28 published cases and 3 cases reported here), 6/31 (19%) developed PA before PPGL and 8/31 (26%) had isolated PA. The age of onset was later than in patients with AIP/MEN1 mutations. PAs were mainly macroprolactinomas and showed intracytoplasmic vacuoles seen on histopathology. Conclusions: We discovered SDHx mutations in patients bearing PA who had no familial or personal history of PPGL. However, the question of incidental association remains unresolved and data to determine the benefit of SDHx/MAX screening in these patients are lacking. We recommend that patients with isolated PA should be carefully examined for a family history of PPGLs. A family history of PPGL, as well as the presence of intracytoplasmic vacuoles in PA, requires SDHx/MAX genetic testing of patients.


Assuntos
Adenoma/genética , Mutação em Linhagem Germinativa , Neoplasias Hipofisárias/genética , Succinato Desidrogenase/genética , Adenoma/epidemiologia , Adenoma/patologia , Adolescente , Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idade de Início , Idoso , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Criança , Análise Mutacional de DNA/métodos , Feminino , França/epidemiologia , Predisposição Genética para Doença , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Isoenzimas/genética , Masculino , Pessoa de Meia-Idade , Paraganglioma/epidemiologia , Paraganglioma/genética , Paraganglioma/patologia , Feocromocitoma/epidemiologia , Feocromocitoma/genética , Feocromocitoma/patologia , Neoplasias Hipofisárias/epidemiologia , Neoplasias Hipofisárias/patologia , Prolactinoma/epidemiologia , Prolactinoma/genética , Prolactinoma/patologia , Subunidades Proteicas/genética , Estudos Retrospectivos , Adulto Jovem
11.
Eur J Endocrinol ; 183(4): 357-368, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32621587

RESUMO

Context: Accurate hydrocortisone dosing in children with adrenal insufficiency is important to avoid the risks of over and under treatment including iatrogenic Cushing's syndrome and adrenal crisis. Objective: To establish a population pharmacokinetic model of hydrocortisone in children and use this to refine hydrocortisone replacement regimens. Design and methods: Pharmacokinetic study of hydrocortisone granules, available in 0.5, 1, 2 and 5 mg dose strengths, in 24 children with adrenal insufficiency aged 2 weeks to 6 years. Cortisol concentrations quantified by LC-MS/MS were used to refine an adult pharmacokinetic model to a paediatric population model which was then used to simulate seven different hydrocortisone treatment regimens. Results: Pre-dose cortisol levels were undetectable in 54% of the 24 children. The developed pharmacokinetic model had good predictive performance. Simulations for the seven treatment regimens using either three- or four-times daily dosing showed treatment regimens delivered an AUC0-24h within the 90% reference range for healthy children except in neonates where two regimens had an AUC below the 5th percentile. Cortisol concentrations at individual time points in the 24 h were outside the 90% reference range for healthy individuals in 50%, 55-65% and 70-75% for children, infants and neonates, respectively, with low cortisol levels being most prevalent. Conclusions: Current paediatric hydrocortisone treatment regimens based on either three- or four-times daily administration replicate cortisol exposure based on AUC0-24h, but the majority of cortisol levels are above or below physiological cortisol levels with low levels very common before the next dose.


Assuntos
Insuficiência Adrenal/tratamento farmacológico , Insuficiência Adrenal/metabolismo , Cálculos da Dosagem de Medicamento , Hidrocortisona/administração & dosagem , Hidrocortisona/farmacocinética , Administração Oral , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/epidemiologia , Hiperplasia Suprarrenal Congênita/metabolismo , Insuficiência Adrenal/epidemiologia , Fatores Etários , Idade de Início , Área Sob a Curva , Pesos e Medidas Corporais , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Terapia de Reposição Hormonal/métodos , Terapia de Reposição Hormonal/normas , Humanos , Lactente , Recém-Nascido , Masculino , Modelos Teóricos
12.
Eur J Endocrinol ; 183(4): E7-E9, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32688333

RESUMO

The validity of clinical research is potentially threatened by missing data. Any variable measured in a study can have missing values, including the exposure, the outcome, and confounders. When missing values are ignored in the analysis, only those subjects with complete records will be included in the analysis. This may lead to biased results and loss of power. We explain why missing data may lead to bias and discuss a commonly used classification of missing data.


Assuntos
Viés , Reprodutibilidade dos Testes , Projetos de Pesquisa/normas , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Terapia de Reposição Hormonal , Humanos , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/epidemiologia , Modelos Logísticos , Razão de Chances , Avaliação de Resultados em Cuidados de Saúde , Placebos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Tamanho da Amostra , Tiroxina/uso terapêutico
13.
Eur J Endocrinol ; 183(4): P11-P18, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32698145

RESUMO

Background: Currently, there are no European recommendations for the management of pediatric thyroid cancer. Other current international guidelines are not completely concordant. In addition, medical regulations differ between, for instance, the US and Europe. We aimed to develop new, easily accessible national recommendations for differentiated thyroid carcinoma (DTC) patients <18 years of age in the Netherlands as a first step toward a harmonized European Recommendation. Methods: A multidisciplinary working group was formed including pediatric and adult endocrinologists, a pediatric radiologist, a pathologist, endocrine surgeons, pediatric surgeons, pediatric oncologists, nuclear medicine physicians, a clinical geneticist and a patient representative. A systematic literature search was conducted for all existing guidelines and review articles for pediatric DTC from 2000 until February 2019. The Appraisal of Guidelines, Research and Evaluation (AGREE) instrument was used for assessing quality of the articles. All were compared to determine dis- and concordances. The American Thyroid Association (ATA) pediatric guideline 2015 was used as framework to develop specific Dutch recommendations. Discussion points based upon expert opinion and current treatment management of DTC in children in the Netherlands were identified and elaborated. Results: Based on the most recent evidence combined with expert opinion, a 2020 Dutch recommendation for pediatric DTC was written and published as an online interactive decision tree (www.oncoguide.nl). Conclusion: Pediatric DTC requires a multidisciplinary approach. The 2020 Dutch Pediatric DTC Recommendation can be used as a starting point for the development of a collaborative European recommendation for treatment of pediatric DTC.


Assuntos
Adenocarcinoma/terapia , Pediatria/normas , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/normas , Neoplasias da Glândula Tireoide/terapia , Adenocarcinoma/epidemiologia , Adenocarcinoma/patologia , Idade de Início , Diferenciação Celular , Criança , Humanos , Comunicação Interdisciplinar , Países Baixos/epidemiologia , Pediatria/organização & administração , Pediatria/estatística & dados numéricos , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia
14.
PLoS Genet ; 16(6): e1008725, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32603359

RESUMO

Risk factors that contribute to inter-individual differences in the age-of-onset of allergic diseases are poorly understood. The aim of this study was to identify genetic risk variants associated with the age at which symptoms of allergic disease first develop, considering information from asthma, hay fever and eczema. Self-reported age-of-onset information was available for 117,130 genotyped individuals of European ancestry from the UK Biobank study. For each individual, we identified the earliest age at which asthma, hay fever and/or eczema was first diagnosed and performed a genome-wide association study (GWAS) of this combined age-of-onset phenotype. We identified 50 variants with a significant independent association (P<3x10-8) with age-of-onset. Forty-five variants had comparable effects on the onset of the three individual diseases and 38 were also associated with allergic disease case-control status in an independent study (n = 222,484). We observed a strong negative genetic correlation between age-of-onset and case-control status of allergic disease (rg = -0.63, P = 4.5x10-61), indicating that cases with early disease onset have a greater burden of allergy risk alleles than those with late disease onset. Subsequently, a multivariate GWAS of age-of-onset and case-control status identified a further 26 associations that were missed by the univariate analyses of age-of-onset or case-control status only. Collectively, of the 76 variants identified, 18 represent novel associations for allergic disease. We identified 81 likely target genes of the 76 associated variants based on information from expression quantitative trait loci (eQTL) and non-synonymous variants, of which we highlight ADAM15, FOSL2, TRIM8, BMPR2, CD200R1, PRKCQ, NOD2, SMAD4, ABCA7 and UBE2L3. Our results support the notion that early and late onset allergic disease have partly distinct genetic architectures, potentially explaining known differences in pathophysiology between individuals.


Assuntos
Asma/genética , Eczema/genética , Polimorfismo de Nucleotídeo Único , Rinite Alérgica Sazonal/genética , Adolescente , Adulto , Idade de Início , Idoso , Asma/patologia , Criança , Eczema/patologia , Feminino , Loci Gênicos , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Rinite Alérgica Sazonal/patologia
15.
PLoS One ; 15(7): e0236241, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716957

RESUMO

BACKGROUND: Early-Onset Schizophrenia (EOS) is rare but severe mental health disorder in children and adolescents. Diagnosis of schizophrenia before the age of 18 years remains complex and challenging, especially in young children. In France, there are no recent reliable epidemiological data about the prevalence of EOS. The present study evaluates the EOS rate in a target clinical population of children and adolescents in psychiatric and medico-social care centres in the South-East of France. METHODS: Psychiatric and medico-social centres for children and adolescent in the geographical area have been contacted, and after receiving their agreement to participate in the study, eligible patients corresponding to inclusion criteria were selected based on patients' medical records. Main inclusion criteria were age 7 to 17 years and intelligence quotient > 35. EOS categorical diagnosis was assessed by Kiddie-SADS Present and Lifetime psychosis section. RESULTS: 37 centres participated and 302 subjects have been included in the study. The main result was the categorical diagnosis of EOS in 27 subjects, corresponding to a rate of 8.9% in the study population. Half of the patients presented mild to moderate intellectual deficiency. Interestingly, only 2.3% had a diagnosis of schizophrenia spectrum disorder noted in their medical records before standardized assessment. CONCLUSIONS: The results of the study highlight the importance of using a standardized diagnostic tool for the diagnosis of schizophrenia in the paediatric population. In fact, EOS might be underdiagnosed in children and adolescents with neurodevelopmental disorders and subnormal cognitive functioning. TRIAL REGISTRATION: NCT01512641. Registered 19 January 2012; https://clinicaltrials.gov/ct2/show/NCT01512641.


Assuntos
Assistência à Saúde , Esquizofrenia/epidemiologia , Psicologia do Esquizofrênico , Idade de Início , Criança , Cognição , Estudos Transversais , Escolaridade , Feminino , França/epidemiologia , Geografia , Humanos , Recém-Nascido , Testes de Inteligência , Classificação Internacional de Doenças , Masculino , Gravidez , Esquizofrenia/tratamento farmacológico , Esquizofrenia/reabilitação , Fatores Socioeconômicos
16.
Artigo em Inglês | MEDLINE | ID: mdl-32645841

RESUMO

Breast cancer is the most frequently diagnosed malignant neoplasm among females. The proportion of women diagnosed in the premenopausal period is relatively small. Nevertheless, this is the most commonly diagnosed cancer among young women. The aim of the study was to analyze the incidence rate of breast cancer in a group of young women based on data obtained in the Lower Silesian Voivodeship between 1984 and 2016. A total of 34,251 women with a diagnosis of invasive breast cancer were analyzed. The median age of diagnosis exhibited an upward trend from 57 to 63. The youngest age of breast cancer diagnosis did not decrease. Women up to the age of 24 were sporadically diagnosed. Given the total number of cases, the proportion of women under the age of 39 was approximately 5%, and it did not increase throughout the entire examination period. The major increase in the growth trend during the analyzed period was observed in a group of women aged of 50-69 (regression coefficient: +24.9) and above 70 (regression coefficient +21.2). In a group of women under 40 the regression coefficient was only +4. It seems that breast cancer does not increasingly affect younger women since the risk in this age group remains low. However, an increasing incidence rate of breast cancer is more commonly observed in premenopausal women.


Assuntos
Neoplasias da Mama/epidemiologia , Adulto , Distribuição por Idade , Idade de Início , Idoso , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Polônia/epidemiologia , Pré-Menopausa , Adulto Jovem
17.
BMC Neurol ; 20(1): 258, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600288

RESUMO

BACKGROUND: Leukodystrophies are familial heterogeneous disorders primarily affecting the white matter, which are defined as hypomyelinating or demyelinating based on disease severity as assessed at MRI. Recently, a group of clinically overlapping hypomyelinating leukodystrophies (HL) has been associated with mutations in RNA polymerase III enzymes (Pol III) subunits. CASE PRESENTATION: In this manuscript, we describe two Italian siblings carrying a novel POLR3A genotype. MRI imaging, genetic analysis, and clinical data led to diagnosing HL type 7. The female sibling, at the age of 34, is tetra-paretic and suffers from severe cognitive regression. She had a disease onset at the age of 19, characterized by slow and progressive cognitive impairment associated with gait disturbances and amenorrhea. The male sibling was diagnosed during an MRI carried out for cephalalgia at the age of 41. After 5 years, he developed mild cognitive impairment, dystonia with 4-limb hypotonia, and moderate dysmetria with balance and gait impairment. CONCLUSIONS: The present study provides the first evidence of unusually late age of onset in HL, describing two siblings with a novel POLR3A genotype which showed the first symptoms at the age of 41 and 19, respectively. This provides a powerful insight into clinical heterogeneity and genotype-phenotype correlation in POLR3A related HL.


Assuntos
Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , RNA Polimerase III/genética , Adulto , Idade de Início , Encéfalo/patologia , Feminino , Genótipo , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Mutação , Irmãos , Substância Branca/patologia
18.
J Stroke Cerebrovasc Dis ; 29(8): 104957, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689603

RESUMO

INTRODUCTION: Clinical spectrum of Moyamoya angiopathy (MMA) differs across populations with different ethnicity. This study, the largest one done among Indian population was undertaken to assess clinico-radiological profile of MMA patients in eastern India. METHODS: A single centre cross-sectional study was undertaken among 76 MMA cases. Each patient was evaluated for epidemiological, clinical and radiological characteristics. SPSS 25 was used for statistical analysis. P < 0.05 was taken as statistically significant. RESULTS: 36 (47.4%) were children without gender preponderance. There were female predominance among adults (male:female = 1:2.33). Mean age at onset of first neurological symptoms for children was 4.2 ± 2.0years, followed by 34.9 ± 58.2months of latency with final diagnosis at the mean age of 7.4 ± 3.5years. For adults, mean age of onset of first neurological symptoms was 31.5 ± 12.3years, followed by 14.7 ± 41.7months time gap and diagnosed at the mean age of 33.5 ± 12.5years. There was a statistically significant difference between child and adult regarding the diagnostic latency (p = 0.035). Fixed motor weakness (FMW) was the predominant symptom across the whole disease course. Among children predominant first neurological symptom was fixed motor weakness (FMW) (52.8%), followed by seizures (22.2%). FMW was predominant (55%) first neurological complaint, followed by headache (22.5%) among adults. Seizure was more prevalent among children both as first (p = 0.002) and presenting symptom at the time of diagnosis (p = 0.048). Over the course of the disease seizure was more common among children (p = 0.001), while headache was more common among adults (p = 0.017). Recurrence of symptoms was more common among children (p = 0.059). Infarcts were more common among children (91.7%) than adults (72.5%), while hemorrhage was seen only among adults (25%) (p = 0.004). Isolated cerebral cortex was involved more commonly among children (59.4%) than adults (36.1%), while isolated subcortical involvement was seen only among adults (19.4%) (p = 0.016). Majority of the MMA cases were of Suzuki stage 4 (39.5%) and 5 (27.6%). Brain atrophy was associated with diagnostic latency (p = 0.009). CONCLUSION: Indian Moyamoya presents similar to disease presentation in Caucasian and Japanese patients. It is a frequently overlooked cause of stroke in young, often with various non-motor presentations, failure to recognize which leads to delay in diagnosis. Radiological burden disproportionate to number of acute vascular events, with subtle neurological manifestations like headache or seizure, often with cognitive decline, should raise suspicion of MMA.


Assuntos
Doença de Moyamoya/diagnóstico , Sistema Nervoso/fisiopatologia , Exame Neurológico , Avaliação de Sintomas , Adolescente , Adulto , Idade de Início , Criança , Pré-Escolar , Estudos Transversais , Diagnóstico Tardio , Feminino , Humanos , Índia/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Doença de Moyamoya/epidemiologia , Doença de Moyamoya/fisiopatologia , Sistema Nervoso/diagnóstico por imagem , Valor Preditivo dos Testes , Prevalência , Prognóstico , Fatores de Risco , Adulto Jovem
19.
Neurology ; 95(9): e1163-e1173, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32727836

RESUMO

OBJECTIVE: To examine the relationship between neonatal inflammatory cytokines and perinatal stroke using a systems biology approach analyzing serum and blood-spot cytokines from 47 patients. METHODS: This was a population-based, controlled cohort study with prospective and retrospective case ascertainment. Participants were recruited through the Alberta Perinatal Stroke Project. Stroke was classified as neonatal arterial ischemic stroke (NAIS), arterial presumed perinatal ischemic stroke (APPIS), or periventricular venous infarction (PVI). Biosamples were stored blood spots (retrospective) and acute serum (prospective). Controls had comparable gestational and maternal ages. Sixty-five cytokines were measured (Luminex). Hierarchical clustering analysis was performed to create heat maps. The Fisher linear discriminant analysis was used to create projection models to determine discriminatory boundaries between stroke types and controls. RESULTS: A total of 197 participants were analyzed (27 with NAIS, 8 with APPIS, 12 with PVI, 150 controls). Cytokines were quantifiable with quality control measures satisfied (standards testing, decay analysis). Linear discriminant analysis had high accuracy in using cytokine profiles to separate groups. Profiles in participants with PVI and controls were similar. NAIS separation was accurate (sensitivity 77%, specificity 97%). APPIS mapping was also distinguishable from NAIS (sensitivity 86%, specificity 99%). Classification tree analysis generated similar diagnostic accuracy. CONCLUSIONS: Unique inflammatory biomarker signatures are associated with specific perinatal stroke diseases. Findings support an acquired pathophysiology and suggest the possibility that at-risk pregnancies might be identified to develop prevention strategies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that differences in acute neonatal serum cytokine profiles can discriminate between patients with specific perinatal stroke diseases and controls.


Assuntos
Isquemia Encefálica/imunologia , Citocinas/imunologia , Inflamação/imunologia , Acidente Vascular Cerebral/imunologia , Adulto , Idade de Início , Infarto Encefálico/classificação , Infarto Encefálico/diagnóstico por imagem , Infarto Encefálico/imunologia , Infarto Encefálico/fisiopatologia , Isquemia Encefálica/classificação , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Análise por Conglomerados , Análise Discriminante , Teste em Amostras de Sangue Seco , Feminino , Humanos , Recém-Nascido , Infarto da Artéria Cerebral Média/classificação , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/imunologia , Infarto da Artéria Cerebral Média/fisiopatologia , Doenças Arteriais Intracranianas/classificação , Doenças Arteriais Intracranianas/diagnóstico por imagem , Doenças Arteriais Intracranianas/imunologia , Doenças Arteriais Intracranianas/fisiopatologia , Modelos Lineares , Imagem por Ressonância Magnética , Masculino , Idade Materna , Paresia/fisiopatologia , Pré-Eclâmpsia/epidemiologia , Gravidez , Convulsões/fisiopatologia , Fumar/epidemiologia , Acidente Vascular Cerebral/classificação , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Substância Branca/diagnóstico por imagem , Adulto Jovem
20.
Anticancer Res ; 40(8): 4465-4469, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727776

RESUMO

BACKGROUND/AIM: The roles of microRNAs (miRNAs) in tumorigenesis have attracted a lot of attention. The current study aimed at examining the association of the miR-196a-2 rs11614913 genotypes with susceptibility to childhood acute lymphoblastic leukemia (ALL) in Taiwan. MATERIALS AND METHODS: This case-control investigation recruited 266 patients with childhood ALL and 266 healthy controls, and the miR-196a-2 rs11614913 genotypes of each participant were examined via the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The frequency of miR-196a-2 C allele in controls was 0.440 compared with 0.423 in ALL patients. In addition, there was no significant association between CT or CC genotypes with susceptibility to childhood ALL (OR=0.89 and 0.89, 95%CI=0.60-1.30 and 0.54-1.45, p=0.5427 and 0.6302). Furthermore, the frequencies of miR-196a-2 polymorphisms were not associated with age, gender and clinical outcomes in ALL cases. CONCLUSION: The miR-19a-2 genotypes are not associated with susceptibility to childhood ALL in Taiwan.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Idade de Início , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Taiwan
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