Renal failure following insulin purging in atypical anorexia nervosa and type 1 diabetes mellitus

ObjectiveAnorexia nervosa (AN) and atypical anorexia nervosa (AAN) are severe and complex eating disorders that can be prevalent among individuals with type 1 diabetes mellitus (T1DM). Insulin purging, characterized by the intentional underuse / omission of insulin to control weight, is under-recognized in medicine and is a purging strategy of patients with AN or AAN and comorbid T1DM. Often, this can lead to renal failure, necessitating a (pancreas-) kidney transplantation. This article presents a comprehensive overview of the interplay between AN/AAN and T1DM and summarizes the evidence in literature.MethodsA narrative review is presented on basis of a detailed case study of a 32-year-old female with end-stage renal failure seeking (pancreas-) kidney transplantation displaying etiology, diagnosis, comorbidities, complications, and treatment of AN and AAN with emphasis on those patients with T1DM.ResultsInsulin purging in patients with AN/AAN and coexisting T1DM can exacerbate T1DM complications, including accelerating the onset of end-stage renal failure. A multidisciplinary approach including nutrition treatment and psychotherapeutic techniques was considered necessary for treatment, focusing on psychosomatic in-patient care before and after organ transplantation.ConclusionInsulin purging in patients with AAN and T1DM poses severe health risks, including accelerated renal complications. For those considering transplantation, insulin purging has explicitly to be diagnosed and a holistic treatment addressing both the renal condition and psychosomatic symptoms/disorders is crucial for successful post-transplant outcomes

Mental disorders are no predictors to determine the duration of cannabis-based treatment for chronic pain

BackgroundChronic pain (CP), a complex biopsychosocial disorder with a global prevalence of up to 33%, can be treated by following multidisciplinary approaches that may include cannabis-based medicine (CBM). However, because CBM continues to be a new treatment, questions remain regarding the ideal duration for CBM and its psychosocial determinants, including mental comorbidities.MethodsIn a retrospective cross-sectional study involving 46 patients with CP (ICD-10 code F45.4-), three validated instruments—the German Pain Questionnaire, the Depression Anxiety Stress Scale (DASS), and the Marburg Questionnaire of Habitual WellBeing—were used to identify pain-specific psychosocial determinants and mental disorders. Descriptive analyses, a group differences analysis, and a logistic regression analysis were performed using SPSS.ResultsThe patients most frequently reported low back pain as the primary location of their CP, and in attributing the condition to tissue damage, most had largely adopted a somatic orientation in conceptualizing their illness. Most had experienced CP for more than 5 years (M = 5.13 years, SD = 1.41) and, as a consequence, faced significant restrictions in their everyday life and exhibited low subjective wellbeing (MFHW median = 4.00, N = 43, Q1: 2.00, Q3: 9.00, range: 0–20). Comorbidities among the patients included depression, (DASS-Depression, median: 11.50, Q1: 7.00, Q3: 16.25), anxiety (DASS-Anxiety, median: 4.50, Q1: 2.75, Q3: 8.00), and stress (DASS-Stress, median: 11.00, Q1: 7.00, Q3: 15.00). Between the two cannabis-based treatments with a course lasting either less or more than a year, the duration of treatment showed no between-group differences in terms of sociodemographic factors, pain-specific factors, conceptualizations of the illness, or mental disorders. Psychosocial determinants such as subjective wellbeing and mental comorbidities were not significant predictors of the duration of cannabis-based treatment.ConclusionWe found no evidence indicating that the benefits of short-term vs. long-term cannabis-based treatment can be predicted by mental comorbidities or psychosocial factors. However, because CBM may be included in approaches to treat CP, questions about the ideal duration of such treatment remain to be answered

Cloud property datasets retrieved from AVHRR, MODIS, AATSR and MERIS in the framework of the Cloud_cci project

New cloud property datasets based on measurements from the passive imaging satellite sensors AVHRR, MODIS, ATSR2, AATSR and MERIS are presented. Two retrieval systems were developed that include components for cloud detection and cloud typing followed by cloud property retrievals based on the optimal estimation (OE) technique. The OE-based retrievals are applied to simultaneously retrieve cloud-top pressure, cloud particle effective radius and cloud optical thickness using measurements at visible, near-infrared and thermal infrared wavelengths, which ensures spectral consistency. The retrieved cloud properties are further processed to derive cloud-top height, cloud-top temperature, cloud liquid water path, cloud ice water path and spectral cloud albedo. The Cloud_cci products are pixel-based retrievals, daily composites of those on a global equal-angle latitude–longitude grid, and monthly cloud properties such as averages, standard deviations and histograms, also on a global grid. All products include rigorous propagation of the retrieval and sampling uncertainties. Grouping the orbital properties of the sensor families, six datasets have been defined, which are named AVHRR-AM, AVHRR-PM, MODIS-Terra, MODIS-Aqua, ATSR2-AATSR and MERIS+AATSR, each comprising a specific subset of all available sensors. The individual characteristics of the datasets are presented together with a summary of the retrieval systems and measurement records on which the dataset generation were based. Example validation results are given, based on comparisons to well- established reference observations, which demonstrate the good quality of the data. In particular the ensured spectral consistency and the rigorous uncertainty propagation through all processing levels can be considered as new features of the Cloud_cci datasets compared to existing datasets. In addition, the consistency among the individual datasets allows for a potential combination of them as well as facilitates studies on the impact of temporal sampling and spatial resolution on cloud climatologies

Impacts of Increased Atmospheric CO2 on Ocean Chemistry and Ecosystems

Lead Partner: National University of Ireland Galway. Project Partner: Marine InstituteOcean pH is a function of the seawater carbonate system, which is a function of both the influx of CO2 from the atmosphere and the resulting concentration of CO2 in the water (i.e. pCO2). Uptake of anthropogenic carbon dioxide from the atmosphere is reducing ocean pH; a phenomenon referred to as ocean acidification. It is estimated that there has been a decrease of 0.1 pH units in the surface waters of the world’s oceans since the start of the industrial revolution with a reduction of 0.3 – 0.5 forecast by 2100. There is growing concern over the potential consequences of ocean acidification for marine ecosystems and the services they provide for mankind. This project was aimed at enabling the capability and developing the expertise within Ireland to measure and quantify the flux of CO2 into (or out of) the ocean; to monitor seasonal trends in pCO2 and CO2 fluxes; to determine the current baseline state and variability of the carbonate system; and to evaluate the potential impact of future changes on ecosystems with the ultimate aim of contributing to more informed policy development.This project (Grant-Aid Agreement No. SS/CC/07/001(01)) was carried out under the Sea Change strategy with the support of the Marine Institute and the Marine Research Sub-Programme of the National Development Plan 2007–2013. Support was also provided by NUI Galway College Fellowship and by the EPA Fellowship 2006-PhD-AQ-2.Funder: Marine Institut

Retardation of arsenic transport through a Pleistocene aquifer

Groundwater drawn daily from shallow alluvial sands by millions of wells over large areas of south and southeast Asia exposes an estimated population of over a hundred million people to toxic levels of arsenic. Holocene aquifers are the source of widespread arsenic poisoning across the region. In contrast, Pleistocene sands deposited in this region more than 12,000 years ago mostly do not host groundwater with high levels of arsenic. Pleistocene aquifers are increasingly used as a safe source of drinking water and it is therefore important to understand under what conditions low levels of arsenic can be maintained. Here we reconstruct the initial phase of contamination of a Pleistocene aquifer near Hanoi, Vietnam. We demonstrate that changes in groundwater flow conditions and the redox state of the aquifer sands induced by groundwater pumping caused the lateral intrusion of arsenic contamination more than 120 metres from a Holocene aquifer into a previously uncontaminated Pleistocene aquifer. We also find that arsenic adsorbs onto the aquifer sands and that there is a 16–20-fold retardation in the extent of the contamination relative to the reconstructed lateral movement of groundwater over the same period. Our findings suggest that arsenic contamination of Pleistocene aquifers in south and southeast Asia as a consequence of increasing levels of groundwater pumping may have been delayed by the retardation of arsenic transport

Retardation of arsenic transport through a Pleistocene aquifer

Groundwater drawn daily from shallow alluvial sands by millions of wells over large areas of south and southeast Asia exposes an estimated population of over a hundred million people to toxic levels of arsenic1. Holocene aquifers are the source of widespread arsenic poisoning across the region2, 3. In contrast, Pleistocene sands deposited in this region more than 12,000 years ago mostly do not host groundwater with high levels of arsenic. Pleistocene aquifers are increasingly used as a safe source of drinking water4 and it is therefore important to understand under what conditions low levels of arsenic can be maintained. Here we reconstruct the initial phase of contamination of a Pleistocene aquifer near Hanoi, Vietnam. We demonstrate that changes in groundwater flow conditions and the redox state of the aquifer sands induced by groundwater pumping caused the lateral intrusion of arsenic contamination more than 120 metres from a Holocene aquifer into a previously uncontaminated Pleistocene aquifer. We also find that arsenic adsorbs onto the aquifer sands and that there is a 16–20-fold retardation in the extent of the contamination relative to the reconstructed lateral movement of groundwater over the same period. Our findings suggest that arsenic contamination of Pleistocene aquifers in south and southeast Asia as a consequence of increasing levels of groundwater pumping may have been delayed by the retardation of arsenic transport.National Science Foundation (U.S.) (NSF grant EAR09-11557)Swiss Agency for Development and Cooperation (Grant NAFOSTED 105-09-59-09 to CETASD, the Centre for Environmental Technology and Sustainable Development (Vietnam))National Institute of Environmental Health Sciences (NIEHS grant P42 ES010349)National Institute of Environmental Health Sciences (NIEHS grant P42 ES016454

Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function

In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P = 5.6 × 10−9) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 × 10−4-2.2 × 10−7. Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in genera

1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function

HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10(-8) previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples

First Community-Wide, Comparative Cross-Linking Mass Spectrometry Study

The number of publications in the field of chemical cross-linking combined with mass spectrometry (XL-MS) to derive constraints for protein three-dimensional structure modeling and to probe protein-protein interactions has increased during the last years. As the technique is now becoming routine for in vitro and in vivo applications in proteomics and structural biology there is a pressing need to define protocols as well as data analysis and reporting formats. Such consensus formats should become accepted in the field and be shown to lead to reproducible results. This first, community-based harmonization study on XL-MS is based on the results of 32 groups participating worldwide. The aim of this paper is to summarize the status quo of XL-MS and to compare and evaluate existing cross-linking strategies. Our study therefore builds the framework for establishing best practice guidelines to conduct cross-linking experiments, perform data analysis, and define reporting formats with the ultimate goal of assisting scientists to generate accurate and reproducible XL-MS results

1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function

HapMap imputed genome-wide association studies (GWAS) have revealed > 50 loci at which common variants with minor allele frequency > 5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 x 10(-8) previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until wholegenome sequencing becomes feasible in large samples