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Erika Cecon Anna Ivanova Marine Luka Florence Gbahou Anne Friederich Jean‐Luc Guillaume Patrick Keller Klaus Knoch Raise Ahmad Philippe Delagrange Michele Solimena Ralf Jockers 《Journal of pineal research》2019,66(2)
Melatonin receptors play important roles in the regulation of circadian and seasonal rhythms, sleep, retinal functions, the immune system, depression, and type 2 diabetes development. Melatonin receptors are approved drug targets for insomnia, non‐24‐hour sleep‐wake disorders, and major depressive disorders. In mammals, two melatonin receptors (MTRs) exist, MT1 and MT2, belonging to the G protein‐coupled receptor (GPCR) superfamily. Similar to most other GPCRs, reliable antibodies recognizing melatonin receptors proved to be difficult to obtain. Here, we describe the development of the first monoclonal antibodies (mABs) for mouse MT1 and MT2. Purified antibodies were extensively characterized for specific reactivity with mouse, rat, and human MT1 and MT2 by Western blot, immunoprecipitation, immunofluorescence, and proximity ligation assay. Several mABs were specific for either mouse MT1 or MT2. None of the mABs cross‐reacted with rat MTRs, and some were able to react with human MTRs. The specificity of the selected mABs was validated by immunofluorescence microscopy in three established locations (retina, suprachiasmatic nuclei, pituitary gland) for MTR expression in mice using MTR‐KO mice as control. MT2 expression was not detected in mouse insulinoma MIN6 cells or pancreatic beta‐cells. Collectively, we report the first monoclonal antibodies recognizing recombinant and native mouse melatonin receptors that will be valuable tools for future studies. 相似文献
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Harinakshi Sanikini David C. Muller Marisa Sophiea Sabina Rinaldi Antonio Agudo Eric J. Duell Elisabete Weiderpass Kim Overvad Anne Tjønneland Jytte Halkjær Marie-Christine Boutron-Ruault Franck Carbonnel Iris Cervenka Heiner Boeing Rudolf Kaaks Tilman Kühn Antonia Trichopoulou Georgia Martimianaki Anna Karakatsani Valeria Pala Domenico Palli Amalia Mattiello Rosario Tumino Carlotta Sacerdote Guri Skeie Charlotta Rylander María-Dolores Chirlaque López Maria-Jose Sánchez Eva Ardanaz Sara Regnér Tanja Stocks Bas Bueno-de-Mesquita Roel C.H. Vermeulen Dagfinn Aune Tammy Y.N. Tong Nathalie Kliemann Neil Murphy Marc Chadeau-Hyam Marc J. Gunter Amanda J. Cross 《International journal of cancer. Journal international du cancer》2020,146(4):929-942
Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers. 相似文献
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The ban of lead in many electronic products and the expectation that, sooner or later, this ban will include the currently exempt piezoelectric ceramics based on Lead-Zirconate-Titanate has motivated many research groups to look for lead-free substitutes. After a short overview on different classes of lead-free piezoelectric ceramics with large strain, this review will focus on Bismuth-Sodium-Titanate and its solid solutions. These compounds exhibit extraordinarily high strain, due to a field induced phase transition, which makes them attractive for actuator applications. The structural features of these materials and the origin of the field-induced strain will be revised. Technologies for texturing, which increases the useable strain, will be introduced. Finally, the features that are relevant for the application of these materials in a multilayer design will be summarized. 相似文献
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Marie Warrer Petersen Tine Sylvest Meyhoff Marie Helleberg Maj-Brit Nørregaard Kjær Anders Granholm Carl Johan Steensen Hjortsø Thomas Steen Jensen Morten Hylander Møller Peter Buhl Hjortrup Mik Wetterslev Gitte Kingo Vesterlund Lene Russell Vibeke Lind Jørgensen Klaus Tjelle Thomas Benfield Charlotte Suppli Ulrik Anne Sofie Andreasen Thomas Mohr Morten H. Bestle Lone Musaeus Poulsen Mette Friberg Hitz Thomas Hildebrandt Lene Surland Knudsen Anders Møller Christoffer Grant Sølling Anne Craveiro Brøchner Bodil Steen Rasmussen Henrik Nielsen Steffen Christensen Thomas Strøm Maria Cronhjort Rebecka Rubenson Wahlin Stephan Jakob Luca Cioccari Balasubramanian Venkatesh Naomi Hammond Vivekanand Jha Sheila Nainan Myatra Christian Gluud Theis Lange Anders Perner 《Acta anaesthesiologica Scandinavica》2020,64(9):1365-1375
Introduction
Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.Methods
The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.Discussion
The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.8.
Julie A. Schmidt Georgina K. Fensom Sabina Rinaldi Augustin Scalbert Paul N. Appleby David Achaintre Audrey Gicquiau Marc J. Gunter Pietro Ferrari Rudolf Kaaks Tilman Kühn Heiner Boeing Antonia Trichopoulou Anna Karakatsani Eleni Peppa Domenico Palli Sabina Sieri Rosario Tumino Bas Bueno-de-Mesquita Antonio Agudo Maria-Jose Sánchez María-Dolores Chirlaque Eva Ardanaz Nerea Larrañaga Aurora Perez-Cornago Nada Assi Elio Riboli Konstantinos K. Tsilidis Timothy J. Key Ruth C. Travis 《International journal of cancer. Journal international du cancer》2020,146(3):720-730
Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer. 相似文献
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A study for evaluating the effect of the deltoid-flap repair in massive rotator cuff defects 总被引:2,自引:1,他引:1
Gunter Spahn Stefan Kirschbaum Hans Michael Klinger 《Knee surgery, sports traumatology, arthroscopy》2006,14(4):365-372
The repair of massive cuff defects by direct suture often is impossible. In these cases, a repair by musculo–tendineous flaps (latissimus-dorsi, pectoralis or deltoideus) is required. It was the goal of this study to evaluate the result of delta-flap repair in case of massive cuff defects with a diameter of 5 cm or more. Between 1998 and 2000 for all patients who were suffering from a massive rotator cuff tear more than 5 cm a deltoid transfer was performed. A total of 20 patients (14 male, 6 female; age: 60.9 ± 8.7 years) were available for a follow-up after 47.2 ± 8.0 (range, 36 to 60) month. The operation included an arthroscopic evaluation, acromioplasty with resection of the lateral clavicular end, and biceps tenodesis. The cuff defect was repaired by transfer a muscular flap from the anterior part of the deltoid (about 2×6 cm) into the defect. The patients subjectively rated their result—10 excellent, 9 good, and 1 poor. Preoperatively, the Constant amounted 26.3 ± 5.1 points. At follow-up, the score significantly increased to 74.5 ± 8.5 points. The acromiohumeral distance increased from 4.9 ± 1.1 to 9.2 ± 1.7 mm. In MRI examination of 11 patients all had an intact flap. Two complications (a wound hematoma and a deep infection) did not influence the result. The repair of massive rotator cuff tears by a deltoid transfer produces acceptable clinical and radiological results. 相似文献
10.
Subdental synchondrosis and anatomy of the axis in aging: a histomorphometric study on 30 autopsy cases 总被引:4,自引:4,他引:0
Matthias Gebauer Christian Lohse Florian Barvencik Pia Pogoda Johannes M. Rueger Klaus Püschel Michael Amling 《European spine journal》2006,15(3):292-298
During skeletal development the two ossification centers of the odontoid process are separated from the corpus of the axis by a subdental synchondrosis. This synchondrosis is thought to close and disappear spontaneously in adolescence although this has never been studied in detail. The basis of the dens is of clinical relevance as type II dens fractures are located here. To characterize the morphological architecture of the axis with particular attention to the subdental synchondrosis, the complete axis was harvested from thirty age-matched and gender-matched patients of the three different age groups at autopsy. The subdental synchondrosis and the bone structure of the dens, the basis of the dens and the body of C2 were analyzed by radiography, histology and quantitative histomorphometry. At the macroscopic level the persistency of the subdental synchondrosis in the adult cervical spine was detected in 87% (26 of 30) of the specimens. Histomorphometry revealed a residual disc blastema with an average size of 25.8% of the sagittal depth of the basis of the dens at this level. Bony integration of the synchondrosis was poor throughout all ages. Histologically a cartilaginous matrix composition of the subdental synchondrosis persisted throughout all groups. The trabecular microarchitecture demonstrated a significant reduction of bone volume and trabecular number as well as an increased trabecular separation within the basis of the dens as compared to the corpus or the dens of C2. This histomorphometric data regarding a poor integration of the synchondrosis into the trabecular network and the reduced bone mass within the basis of the dens might offer a previously underestimated explanation for the occurrence of type II dens fractures and their association with pseudoarthrosis, respectively.Matthias Gebauer and Christian Lohse contributed equally to this study and therefore share first authorship. 相似文献