84 research outputs found

    Grain Surface Models and Data for Astrochemistry

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    AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of ∌25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions

    Endocrine disorders are prominent clinical features in patients with primary antibody deficiencies

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    Background: Primary antibody deficiencies (PADs) and anterior pituitary dysfunction are both rare conditions. However, recent studies have remarkably reported the occurrence of anterior pituitary dysfunction in PAD patients. Methods: In this cross-sectional, single-center study we evaluated the prevalence of endocrine disorders in adult PAD patients. Our study focused on common variable immunodeficiency (CVID), immunoglobulin G (IgG) subclass deficiency (IgGSD), and specific anti-polysaccharide antibody deficiency (SPAD). We assessed hormone levels, performed provocative tests and genetic testing in a subset of patients by direct sequencing of the nuclear factor kappa beta subunit 2 (NFKB2) gene and primary immunodeficiency (PID) gene panel testing by whole exome sequencing (WES). Results: Our results demonstrated that one out of 24 IgGSD/SPAD patients had secondary hypothyroidism and three out of 9 men with IgGSD/SPAD had secondary hypogonadism. Premature ovarian failure was observed in four out of 9 women with CVID and primary testicular failure in one out of 15 men with CVID. In two out of 26 CVID patients we found partial adrenal insufficiency (AI) and in one out of 18 patients with IgGSD/SPAD secondary AI was found. Moreover, in one out of 23 patients with CVID and in two out of 17 patients with IgGSD/SPAD severe growth hormone deficiency (GHD) was found, while one patient with IgGSD/SPAD showed mild GHD. Combined endocrine disorders were detected in two women with CVID (either partial secondary AI or autoimmune thyroiditis with primary hypogonadism) and in three men with IgGSD/SPAD (two with either mild GHD or secondary hypothyroidism combined with secondary hypogonadism, and one man with secondary AI and severe GHD). Genetic testing in a subset of patients did not reveal pathogenic variants in NFKB2 or other known PID-associated genes. Conclusion: This is the first study to describe a high prevalence of both anterior pituitary and end-organ endocrine dysfunction in adult PAD patients. As these endocrine disorders may cause considerable health burden, assessment of endocrine axes should be considered in PAD patients

    Influence of Conversion and Anastomotic Leakage on Survival in Rectal Cancer Surgery; Retrospective Cross-sectional Study

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    Different melatonin rhythms and sleep-wake rhythms in patients on peritoneal dialysis, daytime hemodialysis and nocturnal hemodialysis

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    Background: Little comparative data on sleep-wake rhythms in different dialysis groups exist. The aim of this study was to investigate sleep-wake parameters measured with actigraphy and sleep questionnaires as well as melatonin rhythms in automated peritoneal dialysis, conventional daytime hemodialysis and nocturnal hemodialysis patients. Methods: Conventional daytime dialysis (n = 20), nocturnal hemodialysis (n = 13) and automated peritoneal dialysis patients (n = 6) were included in the study. Melatonin in saliva was sampled at 5 time points (21:00, 23:00, 1:00, 7:00 and 9:00 h). Furthermore, actigraphy measurements and sleep questionnaires were performed. All parameters were tested by Kruskall-Wallis test (followed by post hoc Dunn test) to find significant differences (p < 0.05). Results: Although most sleep parameters were impaired in all three groups, conventional daytime dialysis patients had the worst sleep. In nocturnal hemodialysis patients a normal nocturnal melatonin rise was found. In daytime hemodialysis and automated peritoneal dialysis patients this rise was absent. Conclusions: The study showed impaired sleep parameters in all dialysis patient groups. As automated peritoneal dialysis is also performed during night time, the same effect on normalized melatonin was anticipated as was found in nocturnal hemodialysis. Melatonin seems to play a subordinate role in the sleep-wake rhythm of automated peritoneal dialysis patients

    Effects of nocturnal hemodialysis on melatonin rhythm and sleep-wake behavior: an uncontrolled trial

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    Background: End-stage renal disease and its treatment are associated with sleep disturbances such as deterioration of the circadian sleep-wake pattern. Melatonin rhythm, which has an important role in this pattern, is disturbed. The nocturnal melatonin surge is absent in this population. Whether nocturnal in-center hemodialysis changes melatonin and sleep-wake rhythms is unknown. Study Design: A nonrandomized uncontrolled trial. Patients served as their own controls. Setting & Participants: Thirteen daytime hemodialysis patients (median age, 58 years; 5 women) from our hospital receiving conventional daytime hemodialysis 3 times weekly for 3 to 4 hours each session. Interventions: Six months of treatment with nocturnal in-center dialysis 4 nights/wk with 8-hour sessions. Outcomes & Measurements: At baseline, while still on conventional hemodialysis therapy, polysomnography was performed, sleep questionnaires were filled out, and melatonin concentration in saliva was obtained. After 6 months of in-center nocturnal hemodialysis, all measurements were repeated. Results : After 6 months of in-center nocturnal hemodialysis, polysomnography showed significant improvements in sleep efficiency (P = 0.05) and stage 3/4 sleep (P = 0.03) in comparison to t = 0. Trends in improvement of rapid-eye-movement sleep, awake time, and oxygen saturation were seen after 6 months of in-center nocturnal hemodialysis therapy. Sleep questionnaires showed a trend in improved sleep quality and daytime function. Patients were less exhausted during the daytime. The nocturnal melatonin surge was partially restored. Limitations: Small sample size and a nonrandomized uncontrolled study design. Conclusions: Patients after 6 months of in-center nocturnal hemodialysis had significant improvements in subjective and objective sleep parameters and partially restored nocturnal melatonin rhythm

    Interobserver agreement of scoring of histopathological characteristics and classification of lupus nephritis.

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    Contains fulltext : 69663.pdf (publisher's version ) (Open Access)BACKGROUND: Assessing renal biopsies from patients with lupus nephritis (LN) is a difficult task and it is subject to interobserver variability. In this study the interobserver agreement amongst five nephropathologists was analysed. METHODS: Five specialized nephropathologists scored 126 biopsies, comprising 87 first and 39 repeat biopsies from 87 patients with biopsy-proven proliferative LN, included in a randomized controlled trial. The interobserver agreement [expressed as intraclass correlation coefficients (ICC)] of the scored histopathological items was calculated. Also, the WHO1995 and ISN/RPS2003 classification systems for LN were compared, with extra attention being given to the comparison between patients with diffuse proliferative LN with either segmental (IV-S) or global (IV-G) lesions. RESULTS: There was a wide range of agreement. A good interobserver agreement (ICC>0.6) was present in 15%, and a moderate interobserver agreement (ICC 0.4-0.6) in 31% of the scored items. The activity index for LN showed a good (ICC 0.716) and the chronicity index a moderate (ICC 0.494) interobserver agreement. Both classification systems showed low agreement, although consensus was easily reached. Patients classified as IV-S (n=15) had more favorable clinical parameters at study entry than those with class IV-G (n=57). Although suggested by others, we found no differences in outcome between these two subclasses. CONCLUSIONS: This study shows that, although definitions were agreed upon beforehand, even specialized on nephropathologists have difficulties with scoring histopathological characteristics of LN, particularly with SLE the classification systems

    Functionally distinct regulatory RNAs generated by bidirectional transcription and processing of microRNA loci.

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    Many microRNA (miRNA) loci exhibit compelling hairpin structures on both sense and antisense strands; however, the possibility that a miRNA gene might produce functional species from its antisense strand has not been examined. We report here that antisense transcription of the Hox miRNA locus mir-iab-4 generates the novel pre-miRNA hairpin mir-iab-8, which is then processed into endogenous mature miRNAs. Sense and antisense iab-4/iab-8 miRNAs are functionally distinguished by their distinct domains of expression and targeting capabilities. We find that miR-iab-8-5p, like miR-iab-4-5p, is also relevant to Hox gene regulation. Ectopic mir-iab-8 can strongly repress the Hox genes Ultrabithorax and abdominal-A via extensive arrays of conserved target sites, and can induce a dramatic homeotic transformation of halteres into wings. We generalize the antisense miRNA principle by showing that several other loci in both invertebrates and vertebrates are endogenously processed on their antisense strands into mature miRNAs with distinct seeds. These findings demonstrate that antisense transcription and processing contributes to the functional diversification of miRNA genes
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