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Various biomarkers of oxidative stress and redox status have been used in a number of clinical and epidemiological studies related to diseases and conditions that involve disturbances of the redox balance. However, a comprehensive study of diurnal variations of a set of biomarkers has not been conducted so far. Adenine sulfate Therefore, the aim of this study is to investigate circadian rhythm and time-of-day-effects of a set of frequently used biomarkers of oxidative stress, redox and antioxidant status in serum/plasma. These biomarkers include Reactive Oxygen Metabolites (ROM), Biological Antioxidant Potency (BAP), Total Thiols in Proteins (TTP), high-sensitive C-Reactive Protein (CRP) and Uric Acid (UA). During a 24-hr study, blood sampling was conducted 6 times at 4-hr intervals. The presence of circadian rhythm was analyzed with CircWave analysis, whereas the effect of time was analyzed with Repeated Measures ANOVA (RM-ANOVA). Thereby, the main focus was on the time points in working hours (8, 12 and 16 hr), which are used frequently in practice. Of all investigated biomarkers, only TTP in males demonstrated statistically significant circadian rhythm (p = 0.040). A statistically significant effect between all six time points with RM-ANOVA was observed for ROM, TTP and UA in both genders, and for BAP in females only. No statistically significant differences were observed between the time points 8 hr and 12 hr for any of the biomarkers that were assessed in our study. In conclusion, diurnal variations in some of the studied biomarkers that we demonstrate here should be taken into account when designing and conducting clinical and epidemiological studies. It is advised to standardize the time of sampling with a preference in the morning hours.
Blau syndrome (BS) is a rare dominantly-inherited autoinflammatory disorder characterized by the triad of arthritis, uveitis and dermatitis that is consequence of gain-of-function
mutations. We describe the clinical features and genetic basis of a family with two affected members in consecutive generations affected with childhood onset arthritis and uveitis.
Clinical features were retrospectively collected from clinical records. Genetic studies were performed using the Sanger method of DNA sequencing.
The proband is a 44 years-old female, who was diagnosed with juvenile onset arthritis at the age of 9 years. She subsequently developed uveitis at age 12 and since then she was managed between the uveitis and rheumatology services. The proband's daughter developed episcleritis at the age of 7 years, and arthritis with bilateral intermediate uveitis two years later.
analyses revealed in both patients the heterozygous c.1494A>C transversion, predicted to lead the novel, missense p.E498D variant in tions in the treatment of BS and other inflammatory granulomatous diseases.ATG16L1 is a critical mediator of macroautophagy/autophagy required for LC3 lipidation and autophagosome formation. However, ATG16L1 has a C-terminal domain including 7 WD40-type repetitions (WD40 domain, WDD) that is unnecessary for the conventional autophagic pathway. Instead, this domain mediates unconventional activities where LC3 is lipidated in atypical subcellular localizations unrelated to canonical double-membrane autophagosomes. The WDD provides a docking surface for molecules including a specific amino acid motif, thus engaging the LC3 lipidation capabilities of ATG16L1 in single-membrane structures. The physiological implications of such atypical activities are poorly characterized. In a recent report we described the improvement of the WDD-binding motif and the identification of transmembrane molecules that harbor this element in their intracellular region. One of them, IL10RB (interleukin 10 receptor subunit beta), binds the WDD after IL10 activation to facilitate endocytosis, early trafficking and signaling of IL10-IL10R complexes without influencing their degradation rate. These results reveal a novel unconventional role of ATG16L1 in cytokine signaling that does not entail a degradative purpose, thus contributing to catalog the physiological roles played by unconventional activities of the autophagic machinery.
To explore the processes of community reintegration of children and families at least one year following a paediatric brain injury from the perspective of caregivers and outpatient/community service providers.
A qualitative analysis of semi-structured interviews from outpatient or community service providers (
= 14; occupational, physical, and speech and language therapists, neuropsychologists, school counsellors, recreational providers) and caregivers of six children (
= 8) at least one year after their injury. Interviews were transcribed and thematically coded using deductive (employing Bronfenbrenner's ecological systems theory) and inductive approaches.
Themes from both providers and caregivers indicated additional supports needed at all levels of Bronfenbrenner's ecological systems theory (i.e., individual, microsystem, mesosystem/exosystem, macrosystem, chronosystem). Participants felt that several characteristics would be needed in an ideal service system following paediatric brain injury inc suggest that children and families have substantial community reintegration needs following paediatric brain injury. Multi-system interventions are needed to support long-term community reintegration, especially those that increase communication and support transitions. There is also a strong need for alternative funding to support these efforts.Implications for RehabilitationFamilies with a child with a moderate to severe brain injury face challenges with community reintegration a year or more after their child's injury.Effort should be put into helping families navigate the complex medical, insurance, and school systems with a navigator service and step-down care to ensure a continuum of care and to support community reintegration.Special support should be provided during transitions, such as transitions from hospital care to outpatient care, and across school transitions.
In patients with stage 0-A (as per Milan criteria) hepatocellular carcinoma (HCC) image-guided ablation is less invasive and requires shorter hospitalization than resection, but long-term prognosis is poorer. This meta-analysis was conducted to investigate whether liver stiffness measurement (LSM) could be used to predict prognosis in HCC patients after tumor ablation.
A literature search was conducted for all studies published till July 2020 in PubMed, Web of Science, Cochrane Library and EMBASE. Studies were included if they investigated the association between pretreatment LSM and prognosis in HCC patients treated with ablation. Subgroup analysis, meta-regression, publication bias assessment and sensitivity were conducted.
Eight studies (with a total of 1276 HCC patients) were included in this meta-analysis. All patients were treated with radiofrequency ablation. Pooled results showed that high pretreatment LSM were associated with poor overall survival (OS) (hazard ratio [HR] = 4.31, 95% confidence interval [CI] 2.
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