Hyperostosis in siblings

Infantile cortical hyperostosis – Caffey-Silverman disease – is a familial disorder manifesting in the late fetal period or infancy with excessive periosteal bone formation. Signs and symptoms regress spontaneously within months and result in expanded, deformed bones. The paucity of clinical symptoms may lead to delayed investigation and confusion of the remaining bone changes with those in other conditions. This problem is exemplified by two siblings misdiagnosed as osteogenesis imperfecta. The diagnosis of Caffey-Silverman disease was confirmed by molecular analysis showing the specific COL1A1 mutation in the patients and their clinically unaffected mother. Reduced penetrance rather than autosomal recessive inheritance explains multiple affected siblings born to healthy parents.

Global assessment of nitrogen deposition effects on terrestrial plant diversity : a synthesis

Atmospheric nitrogen (N) deposition is it recognized threat to plant diversity ill temperate and northern parts of Europe and North America. This paper assesses evidence from field experiments for N deposition effects and thresholds for terrestrial plant diversity protection across a latitudinal range of main categories of ecosystems. from arctic and boreal systems to tropical forests. Current thinking on the mechanisms of N deposition effects on plant diversity, the global distribution of G200 ecoregions, and current and future (2030) estimates of atmospheric N-deposition rates are then used to identify the risks to plant diversity in all major ecosystem types now and in the future. This synthesis paper clearly shows that N accumulation is the main driver of changes to species composition across the whole range of different ecosystem types by driving the competitive interactions that lead to composition change and/or making conditions unfavorable for some species. Other effects such its direct toxicity of nitrogen gases and aerosols long-term negative effects of increased ammonium and ammonia availability, soil-mediated effects of acidification, and secondary stress and disturbance are more ecosystem, and site-specific and often play a supporting role. N deposition effects in mediterranean ecosystems have now been identified, leading to a first estimate of an effect threshold. Importantly, ecosystems thought of as not N limited, such as tropical and subtropical systems, may be more vulnerable in the regeneration phase. in situations where heterogeneity in N availability is reduced by atmospheric N deposition, on sandy soils, or in montane areas. Critical loads are effect thresholds for N deposition. and the critical load concept has helped European governments make progress toward reducing N loads on sensitive ecosystems. More needs to be done in Europe and North America. especially for the more sensitive ecosystem types. including several ecosystems of high conservation importance. The results of this assessment Show that the Vulnerable regions outside Europe and North America which have not received enough attention are ecoregions in eastern and Southern Asia (China, India), an important part of the mediterranean ecoregion (California, southern Europe). and in the coming decades several subtropical and tropical parts of Latin America and Africa. Reductions in plant diversity by increased atmospheric N deposition may be more widespread than first thought, and more targeted Studies are required in low background areas, especially in the G200 ecoregions

Nuclear factor κB-inducing kinase activation as a mechanism of pancreatic β cell failure in obesity

The nuclear factor κB (NF-κB) pathway is a master regulator of inflammatory processes and is implicated in insulin resistance and pancreatic β cell dysfunction in the metabolic syndrome. Whereas canonical NF-κB signaling is well studied, there is little information on the divergent noncanonical NF-κB pathway in the context of pancreatic islet dysfunction. Here, we demonstrate that pharmacological activation of the noncanonical NF-κB-inducing kinase (NIK) disrupts glucose homeostasis in zebrafish in vivo. We identify NIK as a critical negative regulator of β cell function, as pharmacological NIK activation results in impaired glucose-stimulated insulin secretion in mouse and human islets. NIK levels are elevated in pancreatic islets isolated from diet-induced obese (DIO) mice, which exhibit increased processing of noncanonical NF-κB components p100 to p52, and accumulation of RelB. TNF and receptor activator of NF-κB ligand (RANKL), two ligands associated with diabetes, induce NIK in islets. Mice with constitutive β cell-intrinsic NIK activation present impaired insulin secretion with DIO. NIK activation triggers the noncanonical NF-κB transcriptional network to induce genes identified in human type 2 diabetes genome-wide association studies linked to β cell failure. These studies reveal that NIK contributes a central mechanism for β cell failure in diet-induced obesity

Hypoadiponectinemia in Extremely Low Gestational Age Newborns with Severe Hyperglycemia – A Matched-Paired Analysis

BACKGROUND: Hyperglycemia is commonly observed in extremely low gestational age newborns (ELGANs) and is associated with both increased morbidity and mortality. The objective of this study was to examine the relationship between neonatal hyperglycemia and adiponectin levels in ELGANs. METHODOLOGY/PRINCIPAL FINDINGS: Ten preterm infants between 22+6/7 and 27+3/7 weeks' gestation with neonatal hyperglycemia (defined as pre-feeding blood glucose levels above 200mg/dl on two consecutive measurements with a maximum parenteral glucose infusion of 4 mg/kg*min(-1)) formed the case cohort of this study. To every single patient of this case cohort a patient with normal fasting ( = pre-feeding) blood glucose levels was matched in terms of gestational age and gender. Adiponectin ELISAs were performed both at onset of hyperglycemia and at term-equivalent age. In the case cohort 9/10 patients had to be treated with insulin for 1-26 days (range 0.01-0.4 IU/kg*h(-1)). Compared to matched-paired controls, significant hypoadiponectinemia was observed at onset of hyperglycemia in these affected patients (6.9 µg/ml versus 15.1 µg/ml, p = 0.009). At term equivalent age, normoglycemia without any insulin treatment was found in both groups. Moreover, adiponectin levels at that time were no longer significantly different (12.3 µg/ml versus 20.0 µg/ml; p = 0.051) possibly indicating a mechanistic relevance of this adipokine in regulating insulin sensitivity in ELGANs. CONCLUSIONS/SIGNIFICANCE: Decreased circulating adiponectin levels are correlated with hyperglycemia in ELGANs and may contribute to the pathogenesis of impaired glucose homeostasis in these infants. These findings suggest that adiponectin might be a potential future drug target for the potentially save treatment of hyperglycemia in pre-term infants

Mapping research activity on mental health disorders in Europe: Study protocol for the Mapping_NCD project

© 2016 The Author(s). Background: Mental health disorders (MHDs) constitute a large and growing disease burden in Europe, although they typically receive less attention and research funding than other non-communicable diseases (NCDs). This study protocol describes a methodology for the mapping of MHD research in Europe as part of Mapping_NCD, a 2-year project funded by the European Commission which seeks to map European research funding and impact for five NCDs in order to identify potential gaps, overlaps, synergies and opportunities, and to develop evidence-based policies for future research. Methods: The project aims to develop a multi-focal view of the MHD research landscape across the 28 European Union Member States, plus Iceland, Norway and Switzerland, through a survey of European funding entities, analysis of research initiatives undertaken in the public, voluntary/not-for-profit and commercial sectors, and expert interviews to contextualize the gathered data. The impact of MHD research will be explored using bibliometric analyses of scientific publications, clinical guidelines and newspaper stories reporting on research initiatives. Finally, these research inputs and outputs will be considered in light of various metrics that have been proposed to inform priorities for the allocation of research funds, including burden of disease, treatment gaps and cost of illness. Discussion: Given the growing burden of MHDs, a clear and broad view of the current state of MHD research is needed to ensure that limited resources are directed to evidence-based priority areas. MHDs pose a particular challenge in mapping the research landscape due to their complex nature, high co-morbidity and varying diagnostic criteria. Undertaking such an effort across 31 countries is further challenged by differences in data collection, healthcare systems, reimbursement rates and clinical practices, as well as cultural and socioeconomic diversity. Using multiple methods to explore the spectrum of MHD research funding activity across Europe, this project aims to develop a broad, high-level perspective to inform priority setting for future research