110 research outputs found
Psychological health and inflammation in adolescents with juvenile idiopathic arthritis: describing the relationships between psychological health, laboratory measures of inflammation and disease activity for adolescents with juvenile idiopathic arthritis
Patients with inflammatory arthritis often report flares of disease during times of psychological distress. This is particularly pertinent during adolescence, a time when mental health problems often become apparent. Increasing scientific evidence supports the concept that psychological stress and depression can promote increased systemic pro-inflammatory cytokine production driven by reduced cortisol sensitivity. For patients with inflammatory arthritis, it is possible that psychological distress reduces cortisol sensitivity, increasing proinflammatory cytokine production, which leads to worsened disease activity. This association has never been explored in detail for patients with juvenile idiopathic arthritis (JIA) or in a purely adolescent population. In this thesis I profile the psychological health of 136 adolescent JIA patients and 88 healthy adolescent controls. I also investigate the associations between psychological health, disease activity and inflammatory measures. I demonstrate that depressive symptoms are highly prevalent for all adolescents (both adolescent JIA patients and healthy adolescents). There were no differences in anxiety, depression, mental wellbeing or resilience questionnaire scores between adolescent JIA patients and adolescent healthy controls. However, JIA patients reported significantly lower controllable life event scores than healthy adolescents, which is likely indicative of the lifestyle limitations that they experience. Depression and anxiety strongly associated with worsened disability and pain. When longitudinal associations between depression and disease activity were explored using data from the Childhood Arthritis Prospective Study, depression at diagnosis was found to predict future disability and pain. Disability, pain and active joint count at diagnosis were found to predict future depressive symptoms. Inflammatory mechanisms were also explored. For adolescent healthy controls, increased anxiety and depression associated with an increased pro-inflammatory profile (increased lipopolysaccharide (LPS) induced IL-6 production from peripheral blood mononuclear cells). This was consistent with previous studies. However, for JIA patients, anxiety and depression associated with an antiinflammatory profile (increased sensitivity to glucocorticoid inhibition of the LPS-induced IL-6 response). The association between anxiety, depression and increased cortisol sensitivity for JIA patients does not explain the association between anxiety, depression, disability and pain. Rather, the association between psychological health and disability and pain may be explained by subtle behavioural and cognitive changes. The increased cortisol sensitivity seen with higher anxiety and depression scores appears to be unrelated to disease activity. Overall, this thesis suggests that increased psychological support for adolescent JIA patients, especially at diagnosis, may improve their mental health and could impact on current and future pain and disability. This thesis therefore supports the notion for routine assessment of mental wellbeing and psychological distress during adolescent rheumatology appointments
Binge eating disorders and psychotherapy: is it possible to systematize a psychodynamic formulation case?
The Core Conflictual Relationship Theme (CCRT) method establishes psychotherapeutic guidelines for a patient's relational patterns. The CCRT was used in the analysis of narratives coming from psychodynamic psychotherapy sessions (taped and transcribed) from a patient suffering from Binge Eating Episodes. The CCRT method made it possible to systematize the connection between psychological conflicts and symptoms, not always an easy task for psychiatrists and psychologists in training.O método Tema Central de Conflito nos Relacionamentos - CCRT sistematiza as inferências feitas por psicoterapeutas dos padrões de relacionamento de pacientes submetidos à psicoterapia. O CCRT foi utilizado na análise das narrativas de uma paciente com Compulsão Alimentar Periódica, submetida a sessões de psicoterapia (gravadas e transcritas). Com o método CCRT foi possível sistematizar a relação entre os conflitos psíquicos e o aparecimento de sintomas, uma tarefa nem sempre fácil para psiquiatras e psicólogos em formação.Universidade Federal de São Paulo (UNIFESP)Universidade de São Paulo Instituto de PsicologiaUniversidade de São Paulo Faculdade de Filosofia, Ciência e Letras de Ribeirão PretoUniversidade de São Paulo Faculdade de Medicina Hospital das ClínicasUNIFESPSciEL
Fomitiporia mediterranea M. Fisch., the historical Esca agent: a comprehensive review on the main grapevine wood rot agent in Europe
International audienceFomitiporia mediterranea M. Fisch. (Fmed) is a basidiomycete first described in 2002, and was considered up to then as part of Fomitiporia punctata (P. Karst) Murrill. This fungus can degrade lignocellulosic biomass, causing white rot and leaving bleached fibrous host residues. In Europe Fmed is considered the main grapevine wood rot (Esca) agent within the Esca disease complex, which includes some of the most economically important Grapevine Trunk Diseases (GTDs). This review summarises and evaluates published research on Fmed, on white rot elimination by curettage or management by treatments with specific products applied to diseased grapevines, and on the relationship between wood symptoms and Grapevine Leaf Stripe Disease (GLSD) in the Esca disease complex. Information is also reviewed on the fungus biology, mechanisms of pathogenicity, and their possible relationships with external foliar symptoms of the Esca disease complex. Information on Fmed control strategies is also reviewed
Multifocal demyelinating motor neuropathy and hamartoma syndrome associated with a de novo PTEN mutation.
OBJECTIVE: To describe a patient with a multifocal demyelinating motor neuropathy with onset in childhood and a mutation in phosphatase and tensin homolog (PTEN), a tumor suppressor gene associated with inherited tumor susceptibility conditions, macrocephaly, autism, ataxia, tremor, and epilepsy. Functional implications of this protein have been investigated in Parkinson and Alzheimer diseases. METHODS: We performed whole-exome sequencing in the patient's genomic DNA validated by Sanger sequencing. Immunoblotting, in vitro enzymatic assay, and label-free shotgun proteomic profiling were performed in the patient's fibroblasts. RESULTS: The predominant clinical presentation of the patient was a childhood onset, asymmetric progressive multifocal motor neuropathy. In addition, he presented with macrocephaly, autism spectrum disorder, and skin hamartomas, considered as clinical criteria for PTEN-related hamartoma tumor syndrome. Extensive tumor screening did not detect any malignancies. We detected a novel de novo heterozygous c.269T>C, p.(Phe90Ser) PTEN variant, which was absent in both parents. The pathogenicity of the variant is supported by altered expression of several PTEN-associated proteins involved in tumorigenesis. Moreover, fibroblasts showed a defect in catalytic activity of PTEN against the secondary substrate, phosphatidylinositol 3,4-trisphosphate. In support of our findings, focal hypermyelination leading to peripheral neuropathy has been reported in PTEN-deficient mice. CONCLUSION: We describe a novel phenotype, PTEN-associated multifocal demyelinating motor neuropathy with a skin hamartoma syndrome. A similar mechanism may potentially underlie other forms of Charcot-Marie-Tooth disease with involvement of the phosphatidylinositol pathway
EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia.
The exosome is a multi-protein complex, required for the degradation of AU-rich element (ARE) containing messenger RNAs (mRNAs). EXOSC8 is an essential protein of the exosome core, as its depletion causes a severe growth defect in yeast. Here we show that homozygous missense mutations in EXOSC8 cause progressive and lethal neurological disease in 22 infants from three independent pedigrees. Affected individuals have cerebellar and corpus callosum hypoplasia, abnormal myelination of the central nervous system or spinal motor neuron disease. Experimental downregulation of EXOSC8 in human oligodendroglia cells and in zebrafish induce a specific increase in ARE mRNAs encoding myelin proteins, showing that the imbalanced supply of myelin proteins causes the disruption of myelin, and explaining the clinical presentation. These findings show the central role of the exosomal pathway in neurodegenerative disease
Trends of Exposure to Acrylamide as Measured by Urinary Biomarkers Levels within the HBM4EU Biomonitoring Aligned Studies (2000–2021)
This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?Acrylamide, a substance potentially carcinogenic in humans, represents a very prevalent contaminant in food and is also contained in tobacco smoke. Occupational exposure to higher concentrations of acrylamide was shown to induce neurotoxicity in humans. To minimize related risks for public health, it is vital to obtain data on the actual level of exposure in differently affected segments of the population. To achieve this aim, acrylamide has been added to the list of substances of concern to be investigated in the HBM4EU project, a European initiative to obtain biomonitoring data for a number of pollutants highly relevant for public health. This report summarizes the results obtained for acrylamide, with a focus on time-trends and recent exposure levels, obtained by HBM4EU as well as by associated studies in a total of seven European countries. Mean biomarker levels were compared by sampling year and time-trends were analyzed using linear regression models and an adequate statistical test. An increasing trend of acrylamide biomarker concentrations was found in children for the years 2014–2017, while in adults an overall increase in exposure was found to be not significant for the time period of observation (2000–2021). For smokers, represented by two studies and sampling for, over a total three years, no clear tendency was observed. In conclusion, samples from European countries indicate that average acrylamide exposure still exceeds suggested benchmark levels and may be of specific concern in children. More research is required to confirm trends of declining values observed in most recent years.This work received external funding from the European Union’s Horizon 2020 research and
innovation program under grant agreement No. 733032 and received co-funding from the author’s
organizations. The Norwegian Institute of Public Health (NIPH) contributed to the funding of the
Norwegian Environmental Biobank (NEB). The laboratory measurements were partly funded by the
Research Council of Norway through research projects (275903 and 268465).info:eu-repo/semantics/publishedVersio
Time Trends of Acrylamide Exposure in Europe: Combined Analysis of Published Reports and Current HBM4EU Studies
This article belongs to the Special Issue Analysis of Human Biomonitoring Data and Risk Assessment of Human Exposure to Environmental Chemicals: What Do We Learn for Prevention?More than 20 years ago, acrylamide was added to the list of potential carcinogens found in many common dietary products and tobacco smoke. Consequently, human biomonitoring studies investigating exposure to acrylamide in the form of adducts in blood and metabolites in urine have been performed to obtain data on the actual burden in different populations of the world and in Europe. Recognizing the related health risk, the European Commission responded with measures to curb the acrylamide content in food products. In 2017, a trans-European human biomonitoring project (HBM4EU) was started with the aim to investigate exposure to several chemicals, including acrylamide. Here we set out to provide a combined analysis of previous and current European acrylamide biomonitoring study results by harmonizing and integrating different data sources, including HBM4EU aligned studies, with the aim to resolve overall and current time trends of acrylamide exposure in Europe. Data from 10 European countries were included in the analysis, comprising more than 5500 individual samples (3214 children and teenagers, 2293 adults). We utilized linear models as well as a non-linear fit and breakpoint analysis to investigate trends in temporal acrylamide exposure as well as descriptive statistics and statistical tests to validate findings. Our results indicate an overall increase in acrylamide exposure between the years 2001 and 2017. Studies with samples collected after 2018 focusing on adults do not indicate increasing exposure but show declining values. Regional differences appear to affect absolute values, but not the overall time-trend of exposure. As benchmark levels for acrylamide content in food have been adopted in Europe in 2018, our results may imply the effects of these measures, but only indicated for adults, as corresponding data are still missing for children.This work has received external funding from the European Union’s Horizon 2020 research
and innovation program under grant agreement No. 733032 and received co-funding from the
author’s organizations. The Norwegian Institute of Public Health (NIPH) has contributed to the
funding of the Norwegian Environmental Biobank (NEB). The laboratory measurements have partly been funded by the
Research Council of Norway through research projects (275903 and 268465).info:eu-repo/semantics/publishedVersio
A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy : the TURRIFIC randomised trial
BackgroundSevere early onset (less than 34weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders.Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach.MethodsWe have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300mg bd) with that of UDCA tablets (up to 2000mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool.DiscussionOur study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing "standard" UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial.Trial identifiersAustralian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36.EudraCT number: 2018-004011-44.IRAS: 272398.NHMRC registration: APP1152418 and APP117853.Peer reviewe
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The Clinical Outcome Study for dysferlinopathy: An international multicenter study
Objective: To describe the baseline clinical and functional characteristics of an international cohort of 193 patients with dysferlinopathy.
Methods: The Clinical Outcome Study for dysferlinopathy (COS) is an international multicenter study of this disease, evaluating patients with genetically confirmed dysferlinopathy over 3 years. We present a cross-sectional analysis of 193 patients derived from their baseline clinical and functional assessments.
Results: There is a high degree of variability in disease onset, pattern of weakness, and rate of progression. No factor, such as mutation class, protein expression, or age at onset, accounted for this variability. Among patients with clinical diagnoses of Miyoshi myopathy or limb-girdle muscular dystrophy, clinical presentation and examination was not strikingly different. Respiratory impairment and cardiac dysfunction were observed in a minority of patients. A substantial delay in diagnosis was previously common but has been steadily reducing, suggesting increasing awareness of dysferlinopathies.
Conclusions: These findings highlight crucial issues to be addressed for both optimizing clinical care and planning therapeutic trials in dysferlinopathy. This ongoing longitudinal study will provide an opportunity to further understand patterns and variability in disease progression and form the basis for trial design
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