Early parental death and psychosocial risk factors for dementia: A case-control study in Europe

Objectives: To assess the association between early parental death and the risk of dementia in adult life, and to examine the risk factors associated with early parental death in people with and without dementia. Methods / Design: A population-based case-control study of a sample of 65,997 participants from the Survey of Health, Ageing and Retirement in Europe study. Early parental death was operationalized as parental death at the age of ≤ 16 years. Main analyses were conducted using bivariate and multivariate logistic regression analyses. Results: The odds ratio (OR) for dementia in individuals who experienced early parental death (father or mother) at the age of ≤ 16 years was 1.83 (95%CI 1.61-2.09) and 1.54 (95%CI 1.35-1.76) adjusted for age, gender, and education. In the multivariate logistic regression analysis carried out with the whole sample, early parental death increased the risk of dementia (OR = 1.50, 95%CI 1.31-1.72), along with older age (OR = 5.92, 95%CI 4.86-7.17), neuroticism (OR = 2.94,95%CI 2.61-3.31), low education level (OR = 1.84, 95%CI 1.64- 2.05) and low income (OR = 1.49, 95%CI 1.34-1.67). Discussion: Early parental death (< 16 years) was associated with an increased risk of dementia. We discuss the neurobiological markers associated with adverse childhood experiences (ACEs) and dementia as well as interventions to counteract the negative health effects on adults

Field Emission from Self-Assembled Arrays of Lanthanum Monosulfide Nanoprotrusions

The field emission properties of LaS nanoprotrusions called nanodomes, formed by pulsed laser deposition on porous anodic alumina films, have been analyzed with scanning anode field emission microscopy. The voltage necessary to produce a given field emission current is 3.5 times less for nanodomes than for thin films. Assuming the same work function for LaS thin films and nanoprotrusions, that is, 1 eV, a field enhancement factor of 5.8 is extracted for the nanodome emitters from Fowler-Nordheim plots of the field emission data. This correlates well with the aspect ratio of the tallest nanodomes observed in atomic force micrograph measurements

Drp1 overexpression induces desmin disassembling and drives kinesin-1 activation promoting mitochondrial trafficking in skeletal muscle

Mitochondria change distribution across cells following a variety of pathophysiological stimuli. The mechanisms presiding over this redistribution are yet undefined. In a murine model overexpressing Drp1 specifically in skeletal muscle, we find marked mitochondria repositioning in muscle fibres and we demonstrate that Drp1 is involved in this process. Drp1 binds KLC1 and enhances microtubule-dependent transport of mitochondria. Drp1-KLC1 coupling triggers the displacement of KIF5B from kinesin-1 complex increasing its binding to microtubule tracks and mitochondrial transport. High levels of Drp1 exacerbate this mechanism leading to the repositioning of mitochondria closer to nuclei. The reduction of Drp1 levels decreases kinesin-1 activation and induces the partial recovery of mitochondrial distribution. Drp1 overexpression is also associated with higher cyclin-dependent kinase-1 (Cdk-1) activation that promotes the persistent phosphorylation of desmin at Ser-31 and its disassembling. Fission inhibition has a positive effect on desmin Ser-31 phosphorylation, regardless of Cdk-1 activation, suggesting that induction of both fission and Cdk-1 are required for desmin collapse. This altered desmin architecture impairs mechanotransduction and compromises mitochondrial network stability priming mitochondria transport through microtubule-dependent trafficking with a mechanism that involves the Drp1-dependent regulation of kinesin-1 complex

Accuracy and limitations of the growth hormone (GH) releasing hormone-arginine retesting in young adults with childhood-onset GH deficiency

Background: Re-testing for GH secretion is needed to confirm the diagnosis of GH deficiency (GHD) after adult height achievement in childhood-onset GHD (COGHD). Aim: To define the cut-off of GH peak after retesting with GH-releasing hormone plus arginine (GHRHarg) in the diagnosis of permanent GHD in COGHD of different etiology. Patients and methods: Eighty-eight COGHD (median age 17.2 y), 29 idiopathic GHD (IGHD), 44 cancer survivors (TGHD) and 15 congenital GHD (CGHD) were enrolled in the study; 54 had isolated GHD (iGHD) and 34 had multiple pituitary hormone deficiencies (MPHD). All were tested with insulin tolerance test (ITT) and GHRHarg. IGHD with a GH response to ITT 656\ub5g/L were considered true negatives and served as the control group, and patients with a GH response &lt;6\ub5g/L as true positives. Baseline IGF-I was also measured. The diagnostic accuracy of GHRHarg testing and of IGF-I SDS in patients with GHD of different etiologies was evaluated by ROC analysis. Results: Forty-six subjects with a GH peak to ITT 656\ub5g/L and 42 with GH peak &lt;6 \ub5g/L showed a GH peak after GHRHarg between 8.8\u2013124\ub5g/L and 0.3\u201326.3\ub5g/L, respectively; 29 IGHD were true negatives, 42 were true positives and 17 with a high likelihood GHD showed a GH peak to ITT 656\ub5g/L. ROC analysis based on the etiology indicated the best diagnostic accuracy for peak GH cutoffs after GHRHarg of 25.3 \ub5g/L in CGHD, 15.7 in TGHD, and 13.8 in MPHD, and for IGF-1 SDS at 122.1 in CGHD, 121.5 in TGHD, and 121.9 in MPHD. Conclusions: Our findings indicate that the best cut-off for GH peak after retesting with GHRHarg changes according to the etiology of GHD during the transition age. Based on these results the diagnostic accuracy of GHRHarg remains questionable

Effectiveness and Safety of the Switch from Remicade® to CT-P13 in Patients with Inflammatory Bowel Disease

BACKGROUND AND AIMS: To evaluate the clinical outcomes in patients with IBD after switching from Remicade® to CT-P13 in comparison with patients who maintain Remicade®. METHODS: Patients under Remicade® who were in clinical remission with standard dosage at study entry were included. The ''switch cohort'' [SC] comprised patients who made the switch from Remicade® to CT-P13, and the ''non-switch'' cohort [NC] patients remained under Remicade®. RESULTS: A total of 476 patients were included: 199 [42%] in the SC and 277 [58%] in the NC. The median follow-up was 18 months in the SC and 23 months in the NC [p < 0.01]. Twenty-four out of 277 patients relapsed in the NC; the incidence of relapse was 5% per patient-year. The cumulative incidence of relapse was 2% at 6 months and 10% at 24 months in this group. Thirty-eight out of 199 patients relapsed in the SC; the incidence rate of relapse was 14% per patient-year. The cumulative incidence of relapse was 5% at 6 months and 28% at 24 months. In the multivariate analysis, the switch to CT-P13 was associated with a higher risk of relapse (HR = 3.5, 95% confidence interval [CI] = 2-6). Thirteen percent of patients had adverse events in the NC, compared with 6% in the SC [p < 0.05]. CONCLUSIONS: Switching from Remicade® to CT-P13 might be associated with a higher risk of clinical relapse, although this fact was not supported in our study by an increase in objective markers of inflammation. The nocebo effect might have influenced this result. Switching from Remicade® to CT-P13 was safe

European Registry on Helicobacter pylori management (Hp-EuReg): Patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21 533 patients

Objective The best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care. Design International multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables included demographics, previous eradication attempts, prescribed treatment, adverse events and outcomes. Data monitoring was performed to ensure data quality. Time-trend and geographical analyses were performed. Results 30 394 patients from 27 European countries were evaluated and 21 533 (78%) first-line empirical H. pylori treatments were included for analysis. Pretreatment resistance rates were 23% to clarithromycin, 32% to metronidazole and 13% to both. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (39%), achieving 81.5% modified intention-to-treat eradication rate. Over 90% eradication was obtained only with 10-day bismuth quadruple or 14-day concomitant treatments. Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates. Time-trend analysis showed a region-dependent shift in prescriptions including abandoning triple therapies, using higher acid-inhibition and longer treatments, which was associated with an overall effectiveness increase (84%-90%). Conclusion Management of H. pylori infection by European gastroenterologists is heterogeneous, suboptimal and discrepant with current recommendations. Only quadruple therapies lasting at least 10 days are able to achieve over 90% eradication rates. European recommendations are being slowly and heterogeneously incorporated into routine clinical practice, which was associated with a corresponding increase in effectiveness