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1.
J Assoc Physicians India ; 69(8): 11-12, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34472803

RESUMO

BACKGROUND: Family history of premature coronary artery disease as a risk factor in first degree relatives has been well established by various studies. This study aims at identification and assessment of the presence of risk factors in asymptomatic siblings of patients with documented premature coronary artery disease. Prevalence of Systemic Hypertension in siblings (both male and female) of patients with premature coronary artery disease (males <45yrs, females <55yrs, confirmed by coronary angiography) was analysed. Other risk factor prevalence estimation was also done which included, dyslipidaemia, diabetes mellitus, tobacco use, alcohol intake, obesity, passive smoke exposure, diet and exercise. The study also estimated the percentage of sibling awareness regarding the risk factors for cardiovascular disease. MATERIALS AND METHODS: This was a cross sectional study where all patients (both In and Out patient), visiting Amrita Institute of Medical Sciences, Kochi and diagnosed as having angiographically proven Premature Coronary Artery Disease from December 2014 to June 2016 were identified and risk factor screening was done for both male and female siblings of any age of these patients. Laboratory tests included fasting blood sugar and fasting lipid profile were analysed after sample collection. RESULTS: 47.6% of male siblings and 35.7% of female siblings were found to be hypertensive, 17.3% of the male siblings and 18.7% of the female siblings were found to have abnormal levels of LDL cholesterol, 22.7% of male siblings and female siblings were found to have abnormal fasting plasma sugar levels, 30.5% of male siblings and 20% of male siblings were found to be overweight. 19.1% of male siblings and 21.4% of female siblings were found to be obese. Only 18.1% of male siblings and 5.7% of female siblings performed any kind of exercise on a regular basis. Among male siblings, 21.9% of male siblings were currently using tobacco in some form. Among non-smokers in both sexes, as many as 36% were exposed to some form of passive smoke. Almost half of the male siblings (49.5%) consumed alcohol containing beverages on a regular basis. CONCLUSIONS: Previously undetected risk factors were found to be highly prevalent among the studied siblings. Significant number of siblings were was found to be hypertensive and in addition some had elevated fasting blood sugar levels. Other modifiable risk factors like obesity, alcohol consumption, tobacco use, passive smoking and lack of exercise were also found to be widely prevalent. An important aspect that the study highlighted is the widespread lack of awareness in the study population about risk factors for disease.


Assuntos
Doença da Artéria Coronariana , Irmãos , LDL-Colesterol , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Fatores de Risco
2.
Zhonghua Xue Ye Xue Za Zhi ; 42(6): 466-473, 2021 Jun 14.
Artigo em Chinês | MEDLINE | ID: mdl-34384152

RESUMO

Objective: To explore the relationship between the reconstitution of immune cells in patients with hematological malignancies and the occurrence of chronic graft-versus-host disease (cGVHD) after treatment with unrelated cord blood transplantation (UCBT) and sibling peripheral blood stem cell transplantation (PBSCT) . Methods: A total of 124 patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) in the First Affiliated Hospital of University of Science and Technology of China from March 2018 to August 2019, including 96 patients with UCBT and 28 patients with PBSCT. Peripheral blood immune cells of patients with UCBT and PBSCT were detected at 1, 3, 6, 9, and 12 months after transplantation using flow cytometry, and both UCBT and PBSCT patients were divided into cGVHD and non-cGVHD groups based on whether cGVHD occurred to explore the correlation between the immune cells reconstitution of the two types of transplantation and cGVHD. Results: ①The cumulative incidence of the moderate to severe cGVHD in the UCBT group was significantly lower than that in the PBSCT group[9.38% (95% CI 3.35%-15.02%) vs 28.57% (95% CI 9.72%-43.50%) , P=0.008]; the 2-year cumulative incidence of cGVHD and moderate to severe cGVHD in the UCBT group was lower than that in the PBSCT group[15.60% (95% CI 9.20%-23.60%) vs 32.10% (95% CI 15.80%-49.70%) , P=0.047; 10.40% (95% CI 5.30%-17.50%) vs 28.60% (95% CI 13.30%-46.00%) , P=0.014]. ②The absolute counts of CD4(+)T cells in the UCBT group were higher than those in the PBSCT group at 6, 9, and 12 months after transplantation[59.00 (36.70-89.65) ×10(7)/L vs 31.40 (18.10-44.00) ×10(7)/L, P<0.001; 71.30 (49.60-101.45) ×10(7)/L vs 41.60 (25.82-56.27) ×10(7)/L, P<0.001; 83.00 (50.17-121.55) ×10(7)/L vs 44.85 (31.62-62.10) ×10(7)/L, P<0.001]; the proportions of CD4(+)T cells in the UCBT group were always higher than those in the PBSCT group (P<0.05) . The absolute counts and proportions of B cells in the PBSCT group were higher than those in the UCBT group at the first month after transplantation[0.70 (0.30-1.70) ×10(7)/L vs 0.10 (0-0.30) ×10(7)/L, P<0.001; 0.45% (0.30%-2.20%) vs 0.20% (0.10%-0.40%) , P=0.002]; the absolute counts and proportions of B cells in the UCBT group were higher than those in the PBSCT group at 9 and 12 months after transplantation[53.80 (28.00-103.20) ×10(7)/L vs 23.35 (5.07-35.00) ×10(7)/L, P<0.001; 21.45 (11.80-30.45) % vs 9.00% (3.08%-16.73%) , P<0.001. 66.70 (36.97-98.72) ×10(7)/L vs 20.85 (7.72-39.40) ×10(7)/L, P<0.001; 22.20% (14.93%-29.68%) vs 8.75% (5.80%-18.93%) , P<0.001]. The absolute counts and proportions of regulatory B (Breg) cells in the UCBT group were higher than those in the PBSCT group at 6, 9, and 12 months after transplantation[1.23 (0.38-3.52) ×10(7)/L vs 0.05 (0-0.84) ×10(7)/L, P<0.001; 5.35% (1.90%-12.20%) vs 1.45% (0-7.78%) , P=0.002. 2.25 (1.07-6.71) ×10(7)/L vs 0.12 (0-0.77) ×10(7)/L, P<0.001; 6.25% (2.00%-12.33%) vs 0.80% (0-5.25%) , P<0.001. 3.69 (0.83-8.66) ×10(7)/L vs 0.46 (0-0.93) ×10(7)/L, P<0.001; 6.15% (1.63%-11.75%) vs 1.40% (0.18%-5.85%) , P<0.001].The absolute counts and proportions of CD3(+)T cells, CD8(+)T cells, and Treg cells in the UCBT group were not significantly different from those in the PBSCT group. ③The absolute counts of B cells in the non-cGVHD group of UCBT patients were higher than those in the moderate to severe cGVHD group at 6 and 12 months after transplantation (P=0.038, P=0.043) ; the proportions of B cells in the non-cGVHD group were higher than those in the moderate to severe cGVHD group at 6 months after transplantation (P=0.049) . The absolute counts of Breg cells in the non-cGVHD group of patients with UCBT were higher than those in the moderate to severe cGVHD group at 6, 9, and 12 months after transplantation (P=0.006, P=0.028, P=0.050) ; the proportions of Breg cells in the non-cGVHD group were higher than those in the moderate to severe cGVHD group at 9 months after transplantation (P=0.038) . ④The absolute counts and proportions of B and Breg cells in the non-cGVHD group of patients with PBSCT were not statistically different than those in the moderate to severe cGVHD group. Conclusion: In the process of immune cell reconstitution, the Breg cells in the UCBT group were higher than those in the PBSCT group, and the Breg cells in the non-cGVHD group of the two types of transplantation were always higher than those in the moderate to severe cGVHD group, indicating that Breg cells can reduce the occurrence of cGVHD, revealing the possible reason for the lower incidence of cGVHD in the UCBT group.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Reconstituição Imune , Transplante de Células-Tronco de Sangue Periférico , Humanos , Irmãos
3.
Pan Afr Med J ; 39: 65, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34422188

RESUMO

Combined deficiency of clotting factor V and factor VIII (DF5F8) is a congenital autosomal recessive disorder. This study involved a family of four children born to consanguineous parents. The eldest daughter was referred for assessment of activated partial thromboplastin time and prothrombin time associated with hemorrhagic manifestations. Coagulation factor dosing showed combined deficiency of factor V and factor VIII as well as normal levels of other coagulation factors. DF5F8 was detected in two girls and a boy. Two protein coding genes LMAN1 (lectin, mannose binding 1) and MCFD2 (multiple coagulation factor deficiency2) were involved in the intracellular passage of Factor V and Factor VIII, including some mutations which caused deficiency of Factor V and VIII. The diagnosis of DF5F8 is routinely possible, especially in patients born to consanguineous parents with a suggestive clinico-biological condition.


Assuntos
Deficiência do Fator V/diagnóstico , Hemofilia A/diagnóstico , Adulto , Criança , Pré-Escolar , Deficiência do Fator V/genética , Feminino , Hemofilia A/genética , Humanos , Masculino , Lectinas de Ligação a Manose/genética , Proteínas de Membrana/genética , Mutação , Irmãos , Proteínas de Transporte Vesicular/genética
4.
Sensors (Basel) ; 21(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34372306

RESUMO

Accurate identification of siblings through face recognition is a challenging task. This is predominantly because of the high degree of similarities among the faces of siblings. In this study, we investigate the use of state-of-the-art deep learning face recognition models to evaluate their capacity for discrimination between sibling faces using various similarity indices. The specific models examined for this purpose are FaceNet, VGGFace, VGG16, and VGG19. For each pair of images provided, the embeddings have been calculated using the chosen deep learning model. Five standard similarity measures, namely, cosine similarity, Euclidean distance, structured similarity, Manhattan distance, and Minkowski distance, are used to classify images looking for their identity on the threshold defined for each of the similarity measures. The accuracy, precision, and misclassification rate of each model are calculated using standard confusion matrices. Four different experimental datasets for full-frontal-face, eyes, nose, and forehead of sibling pairs are constructed using publicly available HQf subset of the SiblingDB database. The experimental results show that the accuracy of the chosen deep learning models to distinguish siblings based on the full-frontal-face and cropped face areas vary based on the face area compared. It is observed that VGGFace is best while comparing the full-frontal-face and eyes-the accuracy of classification being with more than 95% in this case. However, its accuracy degrades significantly when the noses are compared, while FaceNet provides the best result for classification based on the nose. Similarly, VGG16 and VGG19 are not the best models for classification using the eyes, but these models provide favorable results when foreheads are compared.


Assuntos
Aprendizado Profundo , Reconhecimento Facial , Bases de Dados Factuais , Humanos , Redes Neurais de Computação , Irmãos
5.
BMJ Open ; 11(8): e043202, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380712

RESUMO

OBJECTIVES: To investigate the association between breast feeding and infant development during the first year of life using sibling comparison. DESIGN: Nationwide prospective birth cohort study with sibling pair analysis. SETTING: 15 regional centres that participated in the Japan Environment and Children's Study. PARTICIPANTS: This study included 77 119 children (singleton, term birth and no malformation/severe diseases) whose mothers were registered between January 2011 and March 2014, including 3521 duos or trios of siblings. PRIMARY OUTCOME MEASURES: The primary outcome was developmental delay at 6 and 12 months of age, assessed using the Japanese translation of the Ages and Stages Questionnaires, third edition. Multivariable regression analyses adjusted for confounders were performed to estimate the risk ratios of delay associated with any or exclusive breast feeding. Pairs of siblings discordant for statuses were selected, and conditional regression analyses were conducted with a matched cohort design. RESULTS: Developmental delay was identified in 6162 (8.4%) and 10 442 (14.6%) children at 6 and 12 months of age, respectively. Any breast feeding continued until 6 months or 12 months old was associated with reduced developmental delay at 12 months of age (adjusted risk ratio (95% CI): 0.81 (0.77 to 0.85) and 0.81 (0.78 to 0.84), respectively). Furthermore, exclusive breast feeding until 3 months was associated with reduced developmental delay at 12 months of age (adjusted risk ratio, 0.86 (95% CI 0.83 to 0.90)). In sibling pair analysis, the association between any breast feeding until 12 months and reduced developmental delay at 12 months of age persisted (adjusted risk ratio, 0.64 (95% CI 0.43 to 0.93)). CONCLUSIONS: The present study demonstrated the association of continuous breast feeding with reduced developmental delay at 1 year of age using sibling pair analysis, in which unmeasured confounding factors are still present but less included. This may provide an argument to promote breastfeeding continuation.


Assuntos
Aleitamento Materno , Irmãos , Criança , Desenvolvimento Infantil , Estudos de Coortes , Feminino , Humanos , Lactente , Japão/epidemiologia , Estudos Prospectivos
6.
Res Dev Disabil ; 117: 104046, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34388576

RESUMO

BACKGROUND: Developmental disabilities (DD) in close family members have profound effects on psychological adjustment of siblings of individuals with DD. One factor that influences the psychological adjustment of siblings is emotions. However, little is known about emotions among siblings of individuals with DD. AIMS: This study sought to examine negative emotions of adolescent siblings of individuals with DD and focus on the roles of individual- and system-related factors, namely early maladaptive schemas (EMS) and system justification. METHODS AND PROCEDURES: A cross-sectional study including adolescent 72 siblings of individuals with DD and 109 adolescent siblings of individuals without DD was conducted. OUTCOMES AND RESULTS: The siblings of individuals with DD had higher scores on the Other-Directedness schema domain and system justification than the siblings of individuals without DD. However, the frequency of negative emotions did not differ between groups. Lower scores on EMS and higher scores on system justification were associated with less frequent negative emotions. CONCLUSIONS AND IMPLICATIONS: Negative emotions seem to be common in adolescents regardless of having a sibling with DD or not. Nevertheless, EMS and system justification tendencies in siblings of individuals with DD may act as vulnerability factors for negative emotions.


Assuntos
Deficiências do Desenvolvimento , Irmãos , Adaptação Psicológica , Adolescente , Criança , Estudos Transversais , Emoções , Humanos
7.
Int J Mol Sci ; 22(11)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34199759

RESUMO

The TWIK-related spinal cord potassium channel (TRESK) is encoded by KCNK18, and variants in this gene have previously been associated with susceptibility to familial migraine with aura (MIM #613656). A single amino acid substitution in the same protein, p.Trp101Arg, has also been associated with intellectual disability (ID), opening the possibility that variants in this gene might be involved in different disorders. Here, we report the identification of KCNK18 biallelic missense variants (p.Tyr163Asp and p.Ser252Leu) in a family characterized by three siblings affected by mild-to-moderate ID, autism spectrum disorder (ASD) and other neurodevelopment-related features. Functional characterization of the variants alone or in combination showed impaired channel activity. Interestingly, Ser252 is an important regulatory site of TRESK, suggesting that alteration of this residue could lead to additive downstream effects. The functional relevance of these mutations and the observed co-segregation in all the affected members of the family expand the clinical variability associated with altered TRESK function and provide further insight into the relationship between altered function of this ion channel and human disease.


Assuntos
Alelos , Deficiência Intelectual/genética , Mutação/genética , Transtornos do Neurodesenvolvimento/genética , Canais de Potássio/genética , Adolescente , Adulto , Sequência de Aminoácidos , Animais , Sequência de Bases , Calcineurina/metabolismo , Feminino , Genoma Humano , Humanos , Ativação do Canal Iônico/efeitos dos fármacos , Ionomicina/farmacologia , Masculino , Linhagem , Canais de Potássio/química , Irmãos , Xenopus laevis/metabolismo , Adulto Jovem
9.
J Med Case Rep ; 15(1): 375, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34315532

RESUMO

BACKGROUND: Non-Hodgkin lymphoma is the fourth most common malignancy in children, and it is not considered to be a hereditary disorder. However, it could affect members from the same family. CASE PRESENTATION: We are presenting two cases of Caucasian female siblings who were diagnosed with mediastinal lymphoblastic lymphoma in the same year. The two young females were presented to the emergency department with respiratory symptoms. After doing radiological investigations and biopsies, they were diagnosed with lymphoblastic lymphoma. The elder sister died before confirming the diagnosis, and the other is on chemotherapy now, with good treatment outcomes. CONCLUSIONS: This case emphasizes the crucial role of precursor genetics in lymphoblastic lymphomas and suggests a strong relation between these genetics and age at symptom presentation. This is the first report of non-Hodgkin lymphoma in a pair of siblings in the pediatric population.


Assuntos
Linfoma não Hodgkin , Linfoma , Neoplasias do Mediastino , Leucemia-Linfoma Linfoblástico de Células Precursoras , Pré-Escolar , Feminino , Humanos , Lactente , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Irmãos
10.
J Dent Child (Chic) ; 88(2): 134-139, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34321146

RESUMO

GAPO syndrome is a rare autosomal recessive genetic disorder, characterized by growth retardation, alopecia, pseudoanodontia, and progressive ocular changes. This disorder is caused by recessive mutations in the ANTXR1 gene and has characteristic dysmorphic facial features along with connective tissue changes, cardiomyopathy, gonadal dysfunction and craniosynostosis. The most common dental implication of GAPO syndrome is pseudoanodontia caused by eruption failure of the primary and permanent dentition. Currently, there is no standard treatment for patients with GAPO syndrome. Management often includes multidisciplinary care in the surveillance of syndromic sequelae and supportive treatment of symptomatic health concerns, which are unique to each patient. The purpose of this paper is to describe the dental rehabilitation of two brothers with GAPO syndrome.


Assuntos
Anodontia , Irmãos , Alopecia , Assistência Odontológica , Transtornos do Crescimento , Humanos , Masculino , Proteínas dos Microfilamentos , Atrofias Ópticas Hereditárias , Receptores de Superfície Celular
11.
BMC Pediatr ; 21(1): 293, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193099

RESUMO

BACKGROUND: The spondylodysplastic Ehlers-Danlos subtype (OMIM #130070) is a rare connective tissue disorder characterized by a combination of connective tissue symptoms, skeletal features and short stature. It is caused by variants in genes encoding for enzymes involved in the proteoglycan biosynthesis or for a zinc transporter. PRESENTATION OF CASES: We report two brothers with a similar phenotype of short stature, joint hypermobility, distinct craniofacial features, developmental delay and severe hypermetropia indicative for a spondylodysplastic Ehlers-Danlos subtype. One also suffered from a recurrent pneumothorax. Gene panel analysis identified two compound heterozygous variants in the B4GALT7 gene: c.641G > A and c.723 + 4A > G. B4GALT7 encodes for galactosyltransferase I, which is required for the initiation of glycosaminoglycan side chain synthesis of proteoglycans. CONCLUSIONS: This is a first full report on two cases with spondylodysplastic Ehlers-Danlos syndrome and the c.723 + 4A > G variant of B4GALT7. The recurrent pneumothoraces observed in one case expand the variable phenotype of the syndrome.


Assuntos
Nanismo , Síndrome de Ehlers-Danlos , Instabilidade Articular , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/genética , Humanos , Instabilidade Articular/genética , Masculino , Fenótipo , Irmãos
12.
BMJ Open ; 11(7): e053184, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234002

RESUMO

INTRODUCTION: Siblings share a lifelong bond in their relationship, and they may choose to provide support to their brother or sister with a neurodisability. Previous reviews summarised programmes that only focused on the behavioural, emotional and psychological outcomes of the siblings. There is a need to synthesise existing evidence and enhance our understanding about programmes for siblings to acquire knowledge, develop skills and become empowered that can help them to provide support to their brother or sister with a neurodisability. The objective of this review is to identify and map the characteristics and outcomes of programmes designed to prepare siblings in their future roles to support their brother or sister with a neurodisability. METHODS AND ANALYSIS: This review will be conducted using the Joanna Briggs Institute methodology for scoping reviews. An integrated knowledge translation approach will be used by partnering with the Sibling Youth Advisory Council comprised of siblings of individuals with a disability throughout all review phases. Databases to be searched include PsycINFO, Cumulative Index of Nursing and Allied Health Literature, Sociological Abstracts, Education Resources Information Center, EMBASE, Web of Science, MEDLINE (Ovid) and SPORTDiscus, from date of inception to November 2020. Studies of programmes designed for siblings of individuals with neurodisabilities, with no exclusion on the age of siblings or context, and published in English will be included. Extracted data will include details of programme structure and content, eligibility criteria and participants, context, study methods and outcomes. A summary of the results will be presented in a tabular form to provide an overview of the programmes with an accompanying narrative summary to address the research questions of this review. DISSEMINATION: Findings from this review will be shared using dissemination strategies in partnership with the Sibling Youth Advisory Council. We will share the findings with key stakeholders such as healthcare providers, researchers, and patient and family advocacy groups.


Assuntos
Pessoas com Deficiência , Irmãos , Adolescente , Pessoal de Saúde , Humanos , Masculino , Literatura de Revisão como Assunto
13.
Health Aff (Millwood) ; 40(7): 1084-1089, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34228524

RESUMO

Immigrant children in the US have very limited health insurance coverage and health care access. Immigration status is not static: Census data show that the majority of census respondents who enter as noncitizen children eventually become citizens. Eligibility restrictions that prevent noncitizen children from being publicly insured can contribute to their experiencing poorer health and higher medical costs in their adult lives. We isolate the impact of lack of citizenship from socioeconomic factors by comparing citizen and noncitizen siblings living in mixed-status families, using fixed-effects models to net out socioeconomic factors shared within families. Lacking citizenship increased a child's risk of being uninsured and lowered by 26 percentage points the chances that they would have Medicaid or Children's Health Insurance Program coverage. Noncitizen children had significantly more delays in needed medical care because of cost, primarily mediated by the lack of insurance coverage. The US should reexamine policies that exclude noncitizen children from public health insurance programs.


Assuntos
Seguro Saúde , Irmãos , Adulto , Criança , Acesso aos Serviços de Saúde , Humanos , Cobertura do Seguro , Medicaid , Pessoas sem Cobertura de Seguro de Saúde , Estados Unidos
14.
Am J Case Rep ; 22: e932374, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34283821

RESUMO

BACKGROUND Current treatment options for progressive intrahepatic familial cholestasis type 1 (PFIC-1) comprise ursodeoxycholic acid (UDCA), partial external biliary diversion (PEBD), and liver transplantation (LTx). The role and timing of LTx in PFIC-1 remains debated. We present 2 case reports of male siblings with PFIC-1 who benefited from different treatments. CASE REPORT Both siblings harbored a homozygous truncating mutation in ATP8B1 characteristic for PFIC-1 and both underwent PEBD after unsuccessful UDCA treatment at the age of 7 and 5 months, respectively. The older brother, after initial improvement of symptoms, developed severe pruritus, cholestasis, and diarrhea 9 months after PEBD and underwent LTx at the age of 16 months. Chronic diarrhea and abnormal transaminases activity appeared soon after transplantation. A liver biopsy was performed 3 months after LTx and showed severe macrovesicular steatosis (95%). Sixteen months after LTx, total biliary diversion was performed, with rapid relief from diarrhea and significant regression of graft steatosis by <30%. In his brother we observed persistent severe pruritus and cholestasis after PEBD, but we decided to postpone LTx due to lack of a living related donor and risk of graft steatosis. Eight months after PEBD, bilirubin and bile acids significantly decreased and pruritus disappeared completely. Currently, in 5-year follow-up, liver function is stable and he has no pruritus. CONCLUSIONS The good effect of PEBD may be delayed in PFIC-1, even in severe mutation; thus, the decision to perform LTx should be made cautiously. Total biliary diversion is an efficient procedure in case of persistent symptoms after LTx and can reverse graft steatosis in children with PFIC-1.


Assuntos
Colestase Intra-Hepática , Colestase , Transplante de Fígado , Adenosina Trifosfatases , Criança , Colestase Intra-Hepática/genética , Colestase Intra-Hepática/cirurgia , Humanos , Lactente , Masculino , Mutação , Irmãos , Resultado do Tratamento
15.
BMJ Case Rep ; 14(7)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301685

RESUMO

This is a case report of 'familial giant cell arteritis' in three siblings from northwest India. This is the first case report of 'familial giant cell arteritis' in a non-Caucasian family.


Assuntos
Arterite de Células Gigantes , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/genética , Humanos , Índia , Irmãos
16.
Vasc Health Risk Manag ; 17: 415-419, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34321884

RESUMO

The "Lebanese allele" {LDLR c.2043 C>A (p.cys681X)} is a nonsense mutation in the low-density lipoprotein receptor (LDLR) gene that results in a truncated non-functioning LDLR protein. We report two sisters of Lebanese descent who presented with familial hypercholesterolemia (FH) and were both heterozygous for the Lebanese allele, but had very distinct LDL-C levels and clinical phenotypes. Whereas one of the sisters had LDL-C in the expected range of Heterozygous FH (HeFH) with the Lebanese allele (LDL-C of 292 mg/dl), the other sister had a more severe LDL-C phenotype in the Homozygous FH (HoFH) range (LDL-C of 520 mg/dl) along with manifest atherosclerosis. Surprisingly, she did not demonstrate a compound heterozygote or double heterozygote status. We discuss different mechanisms that are purported to play a role in modifying the phenotype of FH, including different variants and polygenic modifiers. HeFH patients with the Lebanese allele can have a wide spectrum of LDL-C levels that range from the typical heterozygous to homozygous phenotypes.


Assuntos
LDL-Colesterol/sangue , Códon sem Sentido , Hiperlipoproteinemia Tipo II/genética , Receptores de LDL/genética , Irmãos , Feminino , Predisposição Genética para Doença , Hereditariedade , Heterozigoto , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Pessoa de Meia-Idade , Linhagem , Fenótipo , Índice de Gravidade de Doença
17.
Nat Genet ; 53(8): 1125-1134, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34312540

RESUMO

Autism is a highly heritable complex disorder in which de novo mutation (DNM) variation contributes significantly to risk. Using whole-genome sequencing data from 3,474 families, we investigate another source of large-effect risk variation, ultra-rare variants. We report and replicate a transmission disequilibrium of private, likely gene-disruptive (LGD) variants in probands but find that 95% of this burden resides outside of known DNM-enriched genes. This variant class more strongly affects multiplex family probands and supports a multi-hit model for autism. Candidate genes with private LGD variants preferentially transmitted to probands converge on the E3 ubiquitin-protein ligase complex, intracellular transport and Erb signaling protein networks. We estimate that these variants are approximately 2.5 generations old and significantly younger than other variants of similar type and frequency in siblings. Overall, private LGD variants are under strong purifying selection and appear to act on a distinct set of genes not yet associated with autism.


Assuntos
Transtorno do Espectro Autista/genética , Predisposição Genética para Doença , Proteínas/genética , Transtorno Autístico/genética , Evolução Molecular , Dosagem de Genes , Haplótipos , Humanos , Desequilíbrio de Ligação , Modelos Genéticos , Mutação , Linhagem , Polimorfismo de Nucleotídeo Único , Mapas de Interação de Proteínas/genética , Irmãos , Sequenciamento Completo do Genoma
18.
Rinsho Ketsueki ; 62(6): 593-601, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34219086

RESUMO

A human leukocyte antigen (HLA)-matched related donor is considered as the first donor candidate in case of allogenic hematopoietic stem cell transplantation (allo-HSCT). Given the declining birthrate and aging population in Japan, the number of sibling donors is also decreasing. Hence, candidates other than HLA-matched siblings, named "alternative donors," have attracted increasing attention. Improved graft-versus-host disease (GvHD) prophylaxis with posttransplant cyclophosphamide or pretransplant antithymocyte globulin represented a major breakthrough in allo-HSCT with alternative donors by overcoming the barriers of HLA mismatch. In addition, there have been improved outcomes of unrelated cord blood transplantation, owing to better unit selection along with improved GvHD prophylaxis and supporting strategies. These changes have expanded the range of donor options and consequently, increased donor availability at the critical moment for allo-HSCT. The next challenge that warrants further investigation is the development of personalized strategies to select the best donor from the available multiple options according to the status of each patient.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Idoso , Soro Antilinfocitário , Humanos , Japão , Irmãos , Doadores de Tecidos
19.
Dev Psychol ; 57(5): 771-782, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34166020

RESUMO

Most U.S. children grow up with siblings. Theory and prior work suggest that older siblings are important sources of gender-related information and socialization. However, few studies have investigated the patterns of these associations longitudinally across early childhood. The present study examines the influence of sibling presence and gender composition on the trajectory of early gender-typed behavior and appearance in children from age 2 through 6 in a diverse sample of Dominican American (36%), African American (33%), and Mexican American (31%) mother-child dyads (N = 232; 112 girls, 120 boys) from low-income households in New York City (M = $20,459, SD = 14,632). Results found that children without older siblings spent more time playing with counterstereotypical toys and their mothers' reports indicated similar behavior over the past month (e.g., a girl playing with toy vehicles and balls; a boy playing with toy kitchen sets and dolls) than children with older siblings. Further, children with at least one other-gender sibling (e.g., a girl with an older brother) played more frequently with counterstereotypical toys compared with children with only same-gender siblings (e.g., a girl with only older sisters). Results on the relation between siblings and gender appearance were mixed. Older siblings may thus influence early trajectories of important gender domains (e.g., toy play), which can have various long-term implications for developing skills and interests. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Identidade de Gênero , Irmãos , Pré-Escolar , Feminino , Humanos , Masculino , Americanos Mexicanos , Jogos e Brinquedos , Socialização
20.
Neuroimage Clin ; 31: 102717, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34119903

RESUMO

Mild cognitive impairment (MCI) can be an early manifestation of Alzheimer's disease (AD) pathology, other pathologic entities [e.g., cerebrovascular disease, Lewy body disease, LATE (limbic-predominant age-related TDP-43 encephalopathy)], or mixed pathologies, with concomitant AD- and non-AD pathology being particularly common, albeit difficult to identify, in living MCI patients. The National Institute on Aging and Alzheimer's Association (NIA-AA) A/T/(N) [ß-Amyloid/Tau/(Neurodegeneration)] AD research framework, which classifies research participants according to three binary biomarkers [ß-amyloid (A+/A-), tau (T+/T-), and neurodegeneration (N+/N-)], provides an indirect means of identifying such cases. Individuals with A+T-(N+) MCI are thought to have both AD pathologic change, given the presence of ß-amyloid, and non-AD pathophysiology, given neurodegeneration without tau, because in typical AD it is tau accumulation that is most tightly linked to neuronal injury and cognitive decline. Thus, in A+T-(N+) MCI (hereafter referred to as "mismatch MCI" for the tau-neurodegeneration mismatch), non-AD pathology is hypothesized to drive neurodegeneration and symptoms, because ß-amyloid, in the absence of tau, likely reflects a preclinical stage of AD. We compared a group of individuals with mismatch MCI to groups with A+T+(N+) MCI (or "prodromal AD") and A-T-(N+) MCI (or "neurodegeneration-only MCI") on cross-sectional and longitudinal cognition and neuroimaging characteristics. ß-amyloid and tau status were determined by CSF assays, while neurodegeneration status was based on hippocampal volume on MRI. Overall, mismatch MCI was less "AD-like" than prodromal AD and generally, with some exceptions, more closely resembled the neurodegeneration-only group. At baseline, mismatch MCI had less episodic memory loss compared to prodromal AD. Longitudinally, mismatch MCI declined more slowly than prodromal AD across all included cognitive domains, while mismatch MCI and neurodegeneration-only MCI declined at comparable rates. Prodromal AD had smaller baseline posterior hippocampal volume than mismatch MCI, and whole brain analyses demonstrated cortical thinning that was widespread in prodromal AD but largely restricted to the medial temporal lobes (MTLs) for the mismatch and neurodegeneration-only MCI groups. Longitudinally, mismatch MCI had slower rates of volume loss than prodromal AD throughout the MTLs. Differences in cross-sectional and longitudinal cognitive and neuroimaging measures between mismatch MCI and prodromal AD may reflect disparate underlying pathologic processes, with the mismatch group potentially being driven by non-AD pathologies on a background of largely preclinical AD. These findings suggest that ß-amyloid status alone in MCI may not reveal the underlying driver of symptoms with important implications for enrollment in clinical trials and prognosis.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Peptídeos beta-Amiloides , Biomarcadores , Estudos Transversais , Progressão da Doença , Humanos , Masculino , Irmãos , Proteínas tau
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