Influence of methylphenidate on brain development – an update of recent animal experiments

Methylphenidate (MPH) is the most commonly used drug to treat attention deficit/hyperactivity disorder (ADHD) in children effectively and safely. In spite of its widespread application throughout one of the most plastic and sensitive phases of brain development, very little is known to date about its long-term effects on brain structure and function. Hence, this short review updates the influence of MPH on brain development, since recent human and animal studies suggest that MPH alters the dopaminergic system with long-term effects beyond the termination of treatment. Animal studies imply that the effects of MPH may depend on the neural responder system: Whereas structural and functional parameters are improved by MPH in animals with psychomotor impairments, they remain unaltered or get worse in healthy controls. While recent behavioural studies do not fully support such a differential effect of MPH in ADHD, the animal studies certainly prompt for further investigation of this issue. Furthermore, the abuse of MPH, when (rarely) intravenously applied, may even impair the maturation of dopaminergic fibres in subcortical brain areas. This argues for careful clinical assessment and diagnostics of ADHD symptomatology not only in conjunction with the prescription of MPH. Hence, one should be assured that MPH is only given to children with clear ADHD symptomatology leading to psychosocial impairment. The animal data suggest that under these conditions MPH is supportive for brain development and the related behaviour in children with ADHD

Optimizing an Organized Modularity Measure for Topographic Graph Clustering: a Deterministic Annealing Approach

This paper proposes an organized generalization of Newman and Girvan's modularity measure for graph clustering. Optimized via a deterministic annealing scheme, this measure produces topologically ordered graph clusterings that lead to faithful and readable graph representations based on clustering induced graphs. Topographic graph clustering provides an alternative to more classical solutions in which a standard graph clustering method is applied to build a simpler graph that is then represented with a graph layout algorithm. A comparative study on four real world graphs ranging from 34 to 1 133 vertices shows the interest of the proposed approach with respect to classical solutions and to self-organizing maps for graphs

Altered serum thyrotropin concentrations in dogs with primary hypoadrenocorticism before and during treatment

BACKGROUND: Thyrotropin (TSH) can be increased in humans with primary hypoadrenocorticism (HA) before glucocorticoid treatment. Increase in TSH is a typical finding of primary hypothyroidism and both diseases can occur concurrently (Schmidt's syndrome); therefore, care must be taken in assessing thyroid function in untreated human patients with HA. OBJECTIVE: Evaluate whether alterations in cTSH can be observed in dogs with HA in absence of primary hypothyroidism. ANIMALS: Thirty dogs with newly diagnosed HA, and 30 dogs in which HA was suspected but excluded based on a normal ACTH stimulation test (controls) were prospectively enrolled. METHODS: cTSH and T4 concentrations were determined in all dogs and at selected time points during treatment (prednisolone, fludrocortisone, or DOCP) in dogs with HA. RESULTS: cTSH concentrations ranged from 0.01 to 2.6 ng/mL (median 0.29) and were increased in 11/30 dogs with HA; values in controls were all within the reference interval (range: 0.01-0.2 ng/dL; median 0.06). There was no difference in T4 between dogs with increased cTSH (T4 range 1.0-2.1; median 1.3 μg/dL) compared to those with normal cTSH (T4 range 0.5-3.4, median 1.4 μg/dL; P=0.69) and controls (T4 range 0.3-3.8, median 1.8 μg/dL; P=0.35). After starting treatment, cTSH normalized after 2-4 weeks in 9 dogs and after 3 and 4 months in 2 without thyroxine supplementation. CONCLUSIONS AND CLINICAL RELEVANCE: Evaluation of thyroid function in untreated dogs with HA can lead to misdiagnosis of hypothyroidism; treatment with glucocorticoids for up to 4 months can be necessary to normalize cTSH

Quantification of hydrogen in nanostructured hydrogenated passivating contacts for silicon photovoltaics combining SIMS-APT-TEM : A multiscale correlative approach

Multiscale characterization of the hydrogenation process of silicon solar cell contacts based on c-Si/SiOx/nc-SiCx(p) has been performed by combining dynamic secondary ion mass-spectrometry (D-SIMS), atom probe tomography (APT), and transmission electron microscopy (TEM). These contacts are formed by high-temperature firing, which triggers the crystallization of SiCx, followed by a hydrogenation process to passivate remaining interfacial defects. Due to the difficulty of characterizing hydrogen at the nm-scale, the exact hydrogenation mechanisms have remained elusive. Using a correlative TEM-SIMS-APT analysis, we are able to locate hydrogen trap sites and quantify the hydrogen content. Deuterium (D), a heavier isotope of hydrogen, is used to distinguish hydrogen introduced during hydrogenation from its background signal. D-SIMS is used, due to its high sensitivity, to get an accurate deuterium-to-hydrogen ratio, which is then used to correct deuterium profiles extracted from APT reconstructions. This new methodology to quantify the concentration of trapped hydrogen in nm-scale structures sheds new insights on hydrogen distribution in technologically important photovoltaic materials

Determination of Angptl4 mRNA as a Diagnostic Marker of Primary and Metastatic Clear Cell Renal-Cell Carcinoma

International audienceBACKGROUND: We have previously shown that angiopoietin-like 4 (angptl4) mRNA, a hypoxia-inducible gene, is highly expressed in clear cell renal-cell carcinoma (ccRCC), the most common subtype of RCC for which no specific marker is available. We here investigated whether angptl4 mRNA 1) could be a useful diagnostic and/or prognostic marker of ccRCC in a large and comprehensive retrospective series, 2) induction is dependent on the VHL status of tumors. METHODOLOGY/PRINCIPAL FINDINGS: Using in situ hybridization, we report that angptl4 mRNA is expressed in 100% of both sporadic (n = 102) and inherited (n = 6) primary ccRCCs, without any statistical association with nuclear grade (p = 0.39), tumor size (p = 0.09), stage grouping (p = 0.17), progression-free survival (p = 0.94), and overall survival (p = 0.80). Angptl4 mRNA was also expressed in 26 (87%) of 30 secondary ccRCCs but neither in any other secondary RCCs (n = 7). In contrast, angptl4 mRNA was neither expressed in 94% non-ccRCC renal tumors (papillary RCCs (n = 46), chromophobe RCCs (n = 28), and oncocytomas (n = 9)), nor in non-renal clear cell carcinomas (n = 39). Angptl4 expression was also examined in tumors associated (n = 23) or not associated (n = 66) with VHL disease. 40 (98%) hemangioblastomas expressed angptl4 whereas all pheochromocytomas (n = 23) and pancreatic tumors (n = 25) were angptl4-negative, whatever their VHL status. CONCLUSIONS/SIGNIFICANCE: Angptl4 mRNA expression was highly associated with ccRCC (p = 1.5 10(-49), Chi square test) allowing to define its expression as a diagnosis marker for primary ccRCC. Moreover, angptl4 mRNA allows to discriminate the renal origin of metastases of clear-cell carcinomas arising from various organs. Finally, inactivation of VHL gene is neither necessary nor sufficient for angptl4 mRNA induction

The Montreal model: an integrative biomedical-psychedelic approach to ketamine for severe treatment-resistant depression

BackgroundSubanesthetic ketamine has accumulated meta-analytic evidence for rapid antidepressant effects in treatment-resistant depression (TRD), resulting in both excitement and debate. Many unanswered questions surround ketamine’s mechanisms of action and its integration into real-world psychiatric care, resulting in diverse utilizations that variously resemble electroconvulsive therapy, conventional antidepressants, or serotonergic psychedelics. There is thus an unmet need for clinical approaches to ketamine that are tailored to its unique therapeutic properties.MethodsThis article presents the Montreal model, a comprehensive biopsychosocial approach to ketamine for severe TRD refined over 6 years in public healthcare settings. To contextualize its development, we review the evidence for ketamine as a biomedical and as a psychedelic treatment of depression, emphasizing each perspectives’ strengths, weaknesses, and distinct methods of utilization. We then describe the key clinical experiences and research findings that shaped the model’s various components, which are presented in detail.ResultsThe Montreal model, as implemented in a recent randomized clinical trial, aims to synergistically pair ketamine infusions with conventional and psychedelic biopsychosocial care. Ketamine is broadly conceptualized as a brief intervention that can produce windows of opportunity for enhanced psychiatric care, as well as powerful occasions for psychological growth. The model combines structured psychiatric care and concomitant psychotherapy with six ketamine infusions, administered with psychedelic-inspired nonpharmacological adjuncts including rolling preparative and integrative psychological support.DiscussionOur integrative model aims to bridge the biomedical-psychedelic divide to offer a feasible, flexible, and standardized approach to ketamine for TRD. Our learnings from developing and implementing this psychedelic-inspired model for severe, real-world patients in two academic hospitals may offer valuable insights for the ongoing roll-out of a range of psychedelic therapies. Further research is needed to assess the Montreal model’s effectiveness and hypothesized psychological mechanisms

A review of nitrogen isotopic alteration in marine sediments

Key Points: Use of sedimentary nitrogen isotopes is examined; On average, sediment 15N/14N increases approx. 2 per mil during early burial; Isotopic alteration scales with water depth Abstract: Nitrogen isotopes are an important tool for evaluating past biogeochemical cycling from the paleoceanographic record. However, bulk sedimentary nitrogen isotope ratios, which can be determined routinely and at minimal cost, may be altered during burial and early sedimentary diagenesis, particularly outside of continental margin settings. The causes and detailed mechanisms of isotopic alteration are still under investigation. Case studies of the Mediterranean and South China Seas underscore the complexities of investigating isotopic alteration. In an effort to evaluate the evidence for alteration of the sedimentary N isotopic signal and try to quantify the net effect, we have compiled and compared data demonstrating alteration from the published literature. A >100 point comparison of sediment trap and surface sedimentary nitrogen isotope values demonstrates that, at sites located off of the continental margins, an increase in sediment 15N/14N occurs during early burial, likely at the seafloor. The extent of isotopic alteration appears to be a function of water depth. Depth-related differences in oxygen exposure time at the seafloor are likely the dominant control on the extent of N isotopic alteration. Moreover, the compiled data suggest that the degree of alteration is likely to be uniform through time at most sites so that bulk sedimentary isotope records likely provide a good means for evaluating relative changes in the global N cycle

Urbanes Bauen: Rückbesinnung und Zukunft im urbanen Bauen mit Holz am Bespiel der Wuppertaler Nordstadt

oai:elpub.bib.uni-wuppertal.de:duepublico_mods_0000069

Detecting and staging podoconiosis cases in North West Cameroon: positive predictive value of clinical screening of patients by community health workers and researchers

Background The suitability of using clinical assessment to identify patients with podoconiosis in endemic communities has previously been demonstrated. In this study, we explored the feasibility and accuracy of using Community Health Implementers (CHIs) for the large scale clinical screening of the population for podoconiosis in North-west Cameroon. Methods Before a regional podoconiosis mapping, 193 CHIs and 50 health personnel selected from 6 health districts were trained in the clinical diagnosis of the disease. After training, CHIs undertook community screening for podoconiosis patients under health personnel supervision. Identified cases were later re-examined by a research team with experience in the clinical identification of podoconiosis. Results Cases were identified by CHIs with an overall positive predictive value (PPV) of 48.5% [34.1–70%]. They were more accurate in detecting advanced stages of the disease compared to early stages; OR 2.07, 95% CI = 1.15–3.73, p = 0.015 for all advanced stages). Accuracy of detecting cases showed statistically significant differences among health districts (χ2 = 25.30, p = 0.0001). Conclusion Podoconiosis being a stigmatized disease, the use of CHIs who are familiar to the community appears appropriate for identifying cases through clinical diagnosis. However, to improve their effectiveness and accuracy, more training, supervision and support are required. More emphasis must be given in identifying early clinical stages and in health districts with relatively lower PPVs