What is the absolute risk of developing diabetes mellitus in patients with glucocorticoid-treated polymyalgia rheumatica and giant cell arteritis? a systematic review and meta-analysis

Background: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are treated with glucocorticoids (GCs) but long-term GC use is associated with diabetes mellitus (DM). The absolute incidence of this serious complication in this patient group remains unclear. Objectives: To quantify the absolute risk of GC-induced DM in PMR and GCA in published literature. Methods: We identified literature from inception to February 2016 reporting diabetes following exposure to oral GC in patients with PMR and/or GCA without preexisting diabetes. A random-effects meta-analysis was performed to summarise the literature. Risk of bias was assessed using the Cochrane Collaboration tool. Results: 21 eligible publications were identified. In studies of patients with GCA, mean cumulative GC dose was almost two times higher than in studies of PMR (8.9g vs 5.0g), with slightly longer treatment duration but much longer duration of follow-up (8.8years vs 4.4years). The incidence proportion (cumulative incidence) of patients who developed new-onset DM was 6% (95% CI: 3–9%) for PMR and 12% (95% CI: 8–17%) for GCA. Heterogeneity between studies was high (I2=78.2%), as there were differences in study designs, patient population, geographical locations and treatment strategies. Based on UK data on incidence rate of DM in the general population1, the expected background incidence rate of DM over 4.4 years in PMR patients and 8.8 years in GCA patients (the duration of follow-up) would be 4.8% and 9.7%, respectively. Very little information on predictors of DM in PMR or GCA patients was found. The overall risk of bias was high for many of the observational studies, especially relating to definition and recording of outcome and prognostic variables. Conclusions: Physicians should screen patients treated for PMR/GCA for DM but it remains unclear what is the time-period of greatest risk and the influence of risk factors. Our meta-analysis produced plausible estimates of DM incidence in patients with PMR and GCA but there is insufficient published data to allow precise quantification of the DM risk or, crucially, which patients are at greatest ris

Red cell function at extreme altitudes on Mount Everest

As part of the American Medical Research Expedition to Everest in 1981, we measured hemoglobin concentration, red cell 2,3-diphosphoglycerate (2,3-DPG), Po2 at which hemoglobin is 50% saturated (P50), and acid-base status in expedition members at various altitudes. All measurements were made in expedition laboratories and, with the exception of samples from the South Col of Mt. Everest (8,050 m), within 2 h of blood collection. In vivo conditions were estimated from direct measurements of arterial blood gases and pH or inferred from base excess and alveolar PCO2. As expected, increased 2,3-DPG was associated with slightly increased P50, when expressed at pH 7.4. Because of respiratory alkalosis, however, the subjects' in vivo P50 at 6,300 m (27.6 Torr) was slightly less than at sea level (28.1 Torr). The estimated in vivo P50 was progressively lower at 8,050 m (24.9 Torr) and on the summit at 8,848 m (19.4 Torr in one subject). Our data suggest that, at extreme altitude, the blood O2 equilibrium curve shifts progressively leftward because of respiratory alkalosis. This left shift protects arterial O2 saturation at extreme altitude

Queen Dominance May Reduce Worker Mushroom Body Size in a Social Bee

The mushroom body (MB) is an area of the insect brain involved in learning, memory, and sensory integration. Here, we used the sweat bee Megalopta genalis (Halictidae) to test for differences between queens and workers in the volume of the MB calyces. We used confocal microscopy to measure the volume of the whole brain, MB calyces, optic lobes, and antennal lobes of queens and workers. Queens had larger brains, larger MB calyces, and a larger MB calyces:whole brain ratio than workers, suggesting an effect of social dominance in brain development. This could result from social interactions leading to smaller worker MBs, or larger queen MBs. It could also result from other factors, such as differences in age or sensory experience. To test these explanations, we next compared queens and workers to other groups. We compared newly emerged bees, bees reared in isolation for 10 days, bees initiating new observation nests, and bees initiating new natural nests collected from the field to queens and workers. Queens did not differ from these other groups. We suggest that the effects of queen dominance over workers, rather than differences in age, experience, or reproductive status, are responsible for the queen–worker differences we observed. Worker MB development may be affected by queen aggression directly and/or manipulation of larval nutrition, which is provisioned by the queen. We found no consistent differences in the size of antennal lobes or optic lobes associated with differences in age, experience, reproductive status, or social caste.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150573/1/dneu22705_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150573/2/dneu22705.pd

Demographic and clinical characteristics associated with advanced stage colorectal cancer: a registry-based cohort study in Saudi Arabia

Background In Saudi Arabia, approximately one-third of colorectal cancer (CRC) patients are diagnosed at an advanced stage. Late diagnosis is often associated with a worse prognosis. Understanding the risk factors for late-stage presentation of CRC is crucial for developing targeted interventions enabling earlier detection and improved patient outcomes. Methods We conducted a retrospective cohort study on 17,541 CRC patients from the Saudi Cancer Registry (1997–2017). We defined distant CRCs as late-stage and localized and regional CRCs as early-stage. To assess risk factors for late-stage CRC, we first used multivariable logistic regression, then developed a decision tree to segment regions by late-stage CRC risk, and finally used stratified logistic regression models to examine geographical and sex variations in risk factors. Results Of all cases, 29% had a late-stage diagnosis, and 71% had early-stage CRC. Young (< 50 years) and unmarried women had an increased risk of late-stage CRC, overall and in some regions. Regional risk variations by sex were observed. Sex-related differences in late-stage rectosigmoid cancer risk were observed in specific regions but not in the overall population. Patients diagnosed after 2001 had increased risks of late-stage presentation. Conclusion Our study identified risk factors for late-stage CRC that can guide targeted early detection efforts. Further research is warranted to fully understand these relationships and develop and evaluate effective prevention strategies

A peroxisome proliferator-activated receptor-δ agonist provides neuroprotection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease

Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.Peer reviewedPublisher PD

Généralisation du diagramme de Voronoï et placement de formes géométriques complexes dans un nuage de points.

La géométrie algorithmique est une discipline en pleine expansion dont l'objet est la conception d'algorithmes résolvant des problèmes géométriques. De tels algorithmes sont très utiles notamment dans l'ingénierie, l'industrie et le multimédia. Pour être performant, il est fréquent qu'un algorithme géométrique utilise des structures de données spécialisées.Nous nous sommes intéressés à une telle structure : le diagramme de Voronoï et avons proposé une généralisation de celui-ci. Ladite généralisation résulte d'une extension du prédicat du disque vide (prédicat propre à toute région de Voronoï) à une union de disques. Nous avons analysé les régions basées sur le prédicat étendu et avons proposé des méthodes pour les calculer par ordinateur.Par ailleurs, nous nous sommes intéressés aux problèmes de placement de formes , thème récurrent en géométrie algorithmique. Nous avons introduit un formalisme universel pour de tels problèmes et avons, pour la première fois, proposé une méthode de résolution générique, en ce sens qu'elle est apte à résoudre divers problèmes de placement suivant un même algorithme.Nos travaux présentent, d'une part, l'avantage d'élargir le champ d'application de structures de données basées sur Voronoï. D'autre part, ils facilitent de manière générale l'utilisation de la géométrie algorithmique, en unifiant définitions et algorithmes associés aux problèmes de placement de formes.Computational geometry is an active branch of computer science whose goal is the design of efficient algorithms solving geometric problems. Such algorithms are useful in domains like engineering, industry and multimedia. In order to be efficient, algorithms often use special data structures.In this thesis we focused on such a structure: the Voronoi diagram. We proposed a new generalized diagram. We have proceeded by extending the empty disk predicate (satisfied by every Voronoi region) to an arbitrary union of disks. We have analyzed the new plane regions based on the extended predicate, and we designed algorithms for computing them.Then, we have considered another topic, which is related to the first one: shape placement problems. Such problems have been studied repeatedly by researchers in computational geometry. We introduced new notations along with a global framework for such problems. We proposed, for the first time a generic method, which is able to solve various placement problems using a single algorithm.Thus, our work extend the scope of Voronoi based data structures. It also simplifies the practical usage of placement techniques by unifying the associated definitions and algorithms.MULHOUSE-SCD Sciences (682242102) / SudocSudocFranceF

Methotrexate promotes platelet apoptosis via JNK-mediated mitochondrial damage: Alleviation by N-acetylcysteine and N-acetylcysteine amide

Thrombocytopenia in methotrexate (MTX)-treated cancer and rheumatoid arthritis (RA) patients connotes the interference of MTX with platelets. Hence, it seemed appealing to appraise the effect of MTX on platelets. Thereby, the mechanism of action of MTX on platelets was dissected. MTX (10 μM) induced activation of pro-apoptotic proteins Bid, Bax and Bad through JNK phosphorylation leading to Îm dissipation, cytochrome c release and caspase activation, culminating in apoptosis. The use of specific inhibitor for JNK abrogates the MTX-induced activation of pro-apoptotic proteins and downstream events confirming JNK phosphorylation by MTX as a key event. We also demonstrate that platelet mitochondria as prime sources of ROS which plays a central role in MTX-induced apoptosis. Further, MTX induces oxidative stress by altering the levels of ROS and glutathione cycle. In parallel, the clinically approved thiol antioxidant N-acetylcysteine (NAC) and its derivative N-acetylcysteine amide (NACA) proficiently alleviate MTX-induced platelet apoptosis and oxidative damage. These findings underpin the dearth of research on interference of therapeutic drugs with platelets, despite their importance in human health and disease. Therefore, the use of antioxidants as supplementary therapy seems to be a safe bet in pathologies associated with altered platelet functions. © 2015 Paul et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited