Factors associated with father involvement in infant care

OBJECTIVE: To identify factors associated with the lack of active father involvement in infant care at four months of age. METHODS: Cross-sectional study involving families of 153 infants at four months of age, interviewed in their homes by two family therapists. In addition to father involvement in infant care, sociodemographic, parental mental health (using the Self Report Questionnaire-20 scale and Diagnostic and Statistical Manual of Mental Disorders-IV criteria assessment) and quality of couple relationship characteristics (using the Assessment of Relational Functioning from Diagnostic and Statistical Manual of Mental Disorders-IV) were analyzed. Poisson regression was employed to assess the association between lack of father involvement in child care and the variables selected. Prevalence ratio was used to estimate the magnitude of associations. RESULTS: Fathers of 13% of infants had no contact with their children. Among families whose parents lived together (78% of all), 33% of the fathers reported not actively participating in their children's care. Problematic couple relationship and mother as a housewife were associated with lack of father involvement in infant care. CONCLUSIONS: High prevalence of families whose father is not actively involved with infant care, especially when couple relationship is problematic and the mother does not have a paid job.OBJETIVO: Identificar factores asociados a la falta del envolvimiento activo del papá en los cuidados de niños a los cuatro meses. MÉTODOS: Se realizó estudio transversal involucrando familias de 153 niños de cuatro meses de edad, y se entrevistaron en sus casas por dos terapeutas de familias en Porto Alegre (Sureste de Brasil), 1998-2000. Además de involucrar al padre en los cuidados del lactante se examinaron características sociodemográficas, salud mental de los papás (utilizando la escala Self Report Questionnaire-20 y evaluación con los criterios del Diagnostic and Statistical Manual of Mental Disorders-IV) y calidad de la relación de pareja (usando la escala GlobalAssesment of Relational Functioning del Diagnostic and Statistical Manual of Mental Disorders-IV). Se utilizó la regresión de Poisson para evaluar la asociación entre falta de envolvimiento del papá en los cuidados del hijo y variables seleccionadas. La magnitud de las asociaciones fue estimada por la razón de prevalencia. RESULTADOS: Los papás de 13% de los lactantes no tenían contacto alguno con sus hijos. Entre las familias en que los papás cohabitaban (78% del total), 33% de ellos expresaron no participar activamente en los cuidados de sus hijos. La relación de pareja problemática y la mamá ser "del hogar" se mostraron asociados a la falta de envolvimiento de los papás en los cuidados del hijo. CONCLUSIONES: Es alta la prevalencia de familias en las cuales el papá no se involucra de manera activa en el cuidado de su hijo, ocurriendo en especial cuando la relación de pareja es problemática y la mamá no tiene trabajo remunerado.OBJETIVO: Identificar fatores associados à falta de envolvimento ativo do pai nos cuidados de crianças aos quatro meses. MÉTODOS: Estudo transversal envolvendo famílias de 153 crianças aos quatro meses de vida, entrevistadas em suas casas por dois terapeutas de famílias. Além do envolvimento do pai nos cuidados do lactente foram examinadas características sociodemográficas, saúde mental dos pais (utilizando a escala Self Report Questionnaire-20 e avaliação com os critérios do Diagnostic and Statistical Manual of Mental Disorders-IV) e qualidade do relacionamento conjugal (usando a escala Global Assessment of Relational Functioning do Diagnostic and Statistical Manual of Mental Disorders-IV). Utilizou-se regressão de Poisson para avaliar a associação entre falta de envolvimento do pai nos cuidados do filho e variáveis selecionadas. A magnitude das associações foi estimada pela razão de prevalências. RESULTADOS: Os pais de 13% dos lactentes não tinham qualquer contato com seus filhos. Entre as famílias em que os pais coabitavam (78% do total), 33% dos pais relataram não participar ativamente nos cuidados de seus filhos. Relação conjugal problemática e mãe ser "do lar" mostraram-se associadas à falta de envolvimento dos pais nos cuidados do filho. CONCLUSÕES: É alta a prevalência de famílias nas quais o pai não tem envolvimento ativo no cuidado de seu filho, ocorrendo em especial quando a relação conjugal é problemática e a mãe não tem trabalho remunerad

treatment of brain disease in the mucopolysaccharidoses

Abstract The mucopolysaccharidosis (MPS) disorders are a group of lysosomal storage diseases caused by lysosomal enzyme deficits that lead to glycosaminoglycan accumulation, affecting various tissues throughout the body based on the specific enzyme deficiency. These disorders are characterized by their progressive nature and a variety of somatic manifestations and neurological symptoms. There are established treatments for some MPS disorders, but these mostly alleviate somatic and non-neurological symptoms and do not cure the disease. Patients with MPS I, II, III, and VII can present with neurological manifestations such as neurocognitive decline and behavioral problems. Treatment of these neurological manifestations remains challenging due to the blood-brain barrier (BBB) that limits delivery of therapeutic agents to the central nervous system (CNS). New therapies that circumvent this barrier and target brain disease in MPS are currently under development. They primarily focus on facilitating penetration of drugs through the BBB, delivery of recombinant enzyme to the brain by gene therapy, or direct CNS administration. This review summarizes existing and potential future treatment approaches that target brain disease in MPS. The information in this review is based on current literature and presentations and discussions during a closed meeting by an international group of experts with extensive experience in managing and treating MPS

Long-term outcomes with agalsidase alfa enzyme replacement therapy: Analysis using deconstructed composite events

This is a retrospective analysis of Fabry Outcome Survey data from children/adults (n = 677) receiving agalsidase alfa enzyme replacement therapy for a median of 3 years, examining cerebrovascular, cardiac, and renal morbidity endpoints separately. Cardiac events occurred at younger ages than cerebrovascular or renal events, cerebrovascular events were more frequent in females than males, and males were more likely to experience cardiac and renal events at a younger age than females

Long-term outcomes with agalsidase alfa enzyme replacement therapy : analysis using deconstructed composite events

Altres ajuts: This work was supported by Shire International GmbH.This is a retrospective analysis of Fabry Outcome Survey data from children/adults (n = 677) receiving agalsidase alfa enzyme replacement therapy for a median of 3 years, examining cerebrovascular, cardiac, and renal morbidity endpoints separately. Cardiac events occurred at younger ages than cerebrovascular or renal events, cerebrovascular events were more frequent in females than males, and males were more likely to experience cardiac and renal events at a younger age than females

Evidence that oxidative stress is increased in patients with X-linked adrenoleukodystrophy

AbstractX-linked adrenoleukodystrophy (X-ALD) is a hereditary disorder of peroxisomal metabolism biochemically characterized by the accumulation of very long chain fatty acids (VLCFA), particularly hexacosanoic acid (C26:0) and tetracosanoic acid (C24:0) in different tissues and in biological fluids. The disease is clinically characterized by central and peripheral demyelination and adrenal insufficiency, which is closely related to the increased concentrations of these fatty acids. However, the mechanisms underlying the brain damage in X-ALD are poorly known. Considering that free radical generation is involved in various neurodegererative disorders, like Parkinson disease, multiple sclerosis and Alzheimer's disease, in the present study we evaluated various oxidative stress parameters, namely chemiluminescence, thiobarbituric acid reactive species (TBA-RS), total radical-trapping antioxidant potential (TRAP), and total antioxidant reactivity (TAR) in plasma of X-ALD patients, as well as the activities of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) in erythrocytes and fibroblasts from these patients. It was verified a significant increase of plasma chemiluminescence and TBA-RS, reflecting induction of lipid peroxidation, as well as a decrease of plasma TAR, indicating a deficient capacity to rapidly handle an increase of reactive species. We also observed a significant increase of erythrocytes GPx activity and of catalase and SOD activities in fibroblasts from the patients studied. It is therefore proposed that oxidative stress may be involved in pathophysiology of X-ALD

Characterization of glycan substrates accumulating in GM1 Gangliosidosis

Introduction: GM1 gangliosidosis is a rare autosomal recessive genetic disorder caused by the disruption of the GLB1 gene that encodes β-galactosidase, a lysosomal hydrolase that removes β-linked galactose from the non-reducing end of glycans. Deficiency of this catabolic enzyme leads to the lysosomal accumulation of GM1 and its asialo derivative GA1 in β-galactosidase deficient patients and animal models. In addition to GM1 and GA1, there are other glycoconjugates that contain β-linked galactose whose metabolites are substrates for β-galactosidase. For example, a number of N-linked glycan structures that have galactose at their non-reducing end have been shown to accumulate in GM1 gangliosidosis patient tissues and biological fluids. Objective: In this study, we attempt to fully characterize the broad array of GLB1 substrates that require GLB1 for their lysosomal turnover. Results: Using tandem mass spectrometry and glycan reductive isotope labeling with data-dependent mass spectrometry, we have confirmed the accumulation of glycolipids (GM1 and GA1) and N-linked glycans with terminal beta-linked galactose. We have also discovered a novel set of core 1 and 2 O-linked glycan metabolites, many of which are part of structurally-related isobaric series that accumulate in disease. In the brain of GLB1 null mice, the levels of these glycan metabolites increased along with those of both GM1 and GA1 as a function of age. In addition to brain tissue, we found elevated levels of both N-linked and O-linked glycan metabolites in a number of peripheral tissues and in urine. Both brain and urine samples from human GM1 gangliosidosis patients exhibited large increases in steady state levels for the same glycan metabolites, demonstrating their correlation with this disease in humans as well. Conclusions: Our studies illustrate that GLB1 deficiency is not purely a ganglioside accumulation disorder, but instead a broad oligosaccharidosis that include representatives of many β-linked galactose containing glycans and glycoconjugates including glycolipids, N-linked glycans, and various O-linked glycans. Accounting for all β-galactosidase substrates that accumulate when this enzyme is deficient increases our understanding of this severe disorder by identifying metabolites that may drive certain aspects of the disease and may also serve as informative disease biomarkers to fully evaluate the efficacy of future therapies

Twenty years of the Fabry Outcome Survey (FOS) : insights, achievements, and lessons learned from a global patient registry

Background: Patient registries provide long-term, real-world evidence that aids the understanding of the natural history and progression of disease, and the efects of treatment on large patient populations with rare diseases. The year 2021 marks the 20th anniversary of the Fabry Outcome Survey (FOS), an international, multicenter, observational registry (NCT03289065). The primary aims of FOS are to broaden the understanding of Fabry disease (FD), an X-linked lysosomal storage disorder, and to improve the clinical management of afected patients. Here, we review the history of FOS and the analyses and publications disseminated from the registry, and we discuss the contributions FOS stud‑ ies have made in understanding FD. Results: FOS was initiated in April 2001 and, as of January 2021, 4484 patients with a confrmed diagnosis and patient informed consent have been enrolled from 144 centers across 26 countries. Data from FOS have been pub‑ lished in nearly 60 manuscripts on a wide variety of topics relevant to FD. Analyses of FOS data have investigated the long-term efectiveness and safety of enzyme replacement therapy (ERT) with agalsidase alfa and its efects on morbidity and mortality, as well as the benefts of prompt and early treatment with agalsidase alfa on the progression of cardiomyopathy and the decline in renal function associated with FD. Based on analyses of FOS data, ERT with agal‑ sidase alfa has also been shown to improve additional signs and symptoms of FD experienced by patients. FOS data analyses have provided a better understanding of the natural history of FD and the specifc populations of women, children, and the elderly, and have provided practical tools for the study of FD. FOS has also provided methodology and criteria for assessing disease severity which contributed to the continuous development of medical practice in FD and has largely improved our understanding of the challenges and needs of long-term data collection in rare diseases, aiding in future rare disease real-world evidence studies. Conclusion: FOS over the last 20 years has substantially increased the scientifc knowledge around improved patient management of FD and continues to expand our understanding of this rare disease

Diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): Expert recommendations for early detection and laboratory diagnosis

Neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of lysosomal storage disorders. NCLs include the rare autosomal recessive neurodegenerative disorder neuronal ceroid lipofuscinosis type 2 (CLN2) disease, caused by mutations in the tripeptidyl peptidase 1 (TPP1)/CLN2 gene and the resulting TPP1 enzyme deficiency. CLN2 disease most commonly presents with seizures and/or ataxia in the late-infantile period (ages 2-4), often in combination with a history of language delay, followed by progressive childhood dementia, motor and visual deterioration, and early death. Atypical phenotypes are characterized by later onset and, in some instances, longer life expectancies. Early diagnosis is important to optimize clinical care and improve outcomes; however, currently, delays in diagnosis are common due to low disease awareness, nonspecific clinical presentation, and limited access to diagnostic testing in some regions. In May 2015, international experts met to recommend best laboratory practices for early diagnosis of CLN2 disease. When clinical signs suggest an NCL, TPP1 enzyme activity should be among the first tests performed (together with the palmitoyl-protein thioesterase enzyme activity assay to rule out CLN1 disease). However, reaching an initial suspicion of an NCL or CLN2 disease can be challenging; thus, use of an epilepsy gene panel for investigation of unexplained seizures in the late-infantile/childhood ages is encouraged. To confirm clinical suspicion of CLN2 disease, the recommended gold standard for laboratory diagnosis is demonstration of deficient TPP1 enzyme activity (in leukocytes, fibroblasts, or dried blood spots) and the identification of causative mutations in each allele of the TPP1/CLN2 gene. When it is not possible to perform both analyses, either demonstration of a) deficient TPP1 enzyme activity in leukocytes or fibroblasts, or b) detection of two pathogenic mutations in trans is diagnostic for CLN2 disease

Cognitive endpoints for therapy development for neuronopathic mucopolysaccharidoses: Results of a consensus procedure

AbstractThe design and conduct of clinical studies to evaluate the effects of novel therapies on central nervous system manifestations in children with neuronopathic mucopolysaccharidoses is challenging. Owing to the rarity of these disorders, multinational studies are often needed to recruit enough patients to provide meaningful data and statistical power. This can make the consistent collection of reliable data across study sites difficult. To address these challenges, an International MPS Consensus Conference for Cognitive Endpoints was convened to discuss approaches for evaluating cognitive and adaptive function in patients with mucopolysaccharidoses. The goal was to develop a consensus on best practice for the design and conduct of clinical studies investigating novel therapies for these conditions, with particular focus on the most appropriate outcome measures for cognitive function and adaptive behavior. The outcomes from the consensus panel discussion are reported here