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1.
Josephine Prener Holtan Knut Teigen Ingvild Aukrust Ragnheiður Bragadóttir Gunnar Houge 《Ophthalmic genetics》2019,40(2):124-128
Purpose: To clinically and genetically characterise a second family with dominant ARL3-related retinitis pigmentosa due to a specific ARL3 missense variant, p.(Tyr90Cys).Methods: Clinical examination included optical coherence tomography, electroretinography, and ultra-wide field retinal imaging with autofluorescence. Retrospective data were collected from the registry of inherited retinal diseases at Oslo university hospital. DNA was analysed by whole-exome sequencing and Sanger sequencing. The ARL3 missense variant was visualized in a 3D-protein structure.Results: The phenotype was non-syndromic retinitis pigmentosa with cataract associated with early onset of decreased central vision and central retinal thinning. Sanger sequencing confirmed the presence of a de novo ARL3 missense variant p.(Tyr90Cys) in the index patient and his affected son. We did not find any other cases with rare ARL3 variants in a cohort of 431 patients with retinitis pigmentosa-like disease. By visualizing Tyr90 in the 3D protein structure, it seems to play an important role in packing of the α/β structure of ADP-ribosylation factor-like 3 (ARL3). When changing Tyr90 to cysteine, we observe a loss of interactions in the core of the α/β structure that is likely to affect folding and stability of ARL3.Conclusion: Our study confirms that the ARL3 missense variant p.(Tyr90Cys) causes retinitis pigmentosa. In 2016, Strom et al. reported the exact same variant in a mother and two children with RP, labelled ?RP83 in the OMIM database. Now the questionmark can be removed, and ARL3 should be added to the list of genes that may cause non-syndromic dominant retinitis pigmentosa. 相似文献
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Hui Xing Lau Sarah El-Heis Qai Ven Yap Yiong Huak Chan Cheryl Pei Ting Tan Neerja Karnani Karen Mei Ling Tan Elizabeth Huiwen Tham Anne Eng Neo Goh Oon Hoe Teoh Kok Hian Tan Johan Gunnar Eriksson Yap Seng Chong Mary Foong-Fong Chong Hugo Van Bever Bee Wah Lee Lynette P. Shek Keith M. Godfrey Evelyn Xiu Ling Loo 《Clinical and experimental allergy》2021,51(10):1346-1360
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Stefano Cascinu György Bodoky Kei Muro Eric Van Cutsem Sang Cheul Oh Gunnar Folprecht Sumitra Ananda Gustavo Girotto Zev A. Wainberg Maria Luisa Limon Miron Jaffer Ajani Ran Wei Astra M. Liepa Roberto Carlesi Michael Emig Atsushi Ohtsu 《The oncologist》2021,26(3):e414-e424
BackgroundIn the intent‐to‐treat (ITT) population of the RAINBOW study, objective response rate (ORR) was 28% and 16% in the ramucirumab and control arms, respectively. To further characterize tumor response, we present details on timing and extent of tumor shrinkage, as well as associations with symptom palliation.Materials and MethodsTumor response was assessed with RECIST v1.1, and quality of life (QoL) was assessed with the European Organization for Research and Treatment of Cancer Quality‐of‐Life Questionnaire‐Core 30 (EORTC QLQ‐C30) v3.0. Prespecified and post hoc analyses were conducted in the ITT population, patients with measurable disease, or responders, and included best overall response (BOR), ORR, disease control rate (DCR), duration of response, time to response (TtR), change in tumor size, and associations of QoL with tumor shrinkage and BOR.ResultsIn both treatment arms, median TtR was 1.5 months. Responses were more durable in the ramucirumab versus control arm (median 4.4 vs. 2.8 months). In patients with measurable disease (78% of ITT), ORR was 36% versus 20%; DCR was 81% versus 61% in the ramucirumab versus control arms. Waterfall plots demonstrated more tumor shrinkage in the ramucirumab versus control arm. Regardless of treatment, tumor response and stable disease were associated with improved or stable QoL, with more tumor shrinkage associated with greater symptom palliation.ConclusionTreatment with ramucirumab plus paclitaxel yielded the highest ORR reported to date for patients with previously treated advanced gastric or gastroesophageal junction adenocarcinoma. Additional details demonstrate robustness of tumor response results. The extent of tumor shrinkage is directly associated with symptom palliation and should be considered when evaluating patient needs and treatment selection. Clinical trial identification number. .Implications for PracticeRamucirumab plus paclitaxel is a recognized standard of care as it improves survival for patients with advanced gastric or gastroesophageal junction adenocarcinoma who have been previously treated with recommended first‐line therapy. These additional data on tumor response demonstrate a positive association between tumor shrinkage and symptom palliation in a patient population that is often symptomatic. These observations included patients with nonmeasurable disease, a group of patients often underrepresented in clinical trials. This knowledge can inform treatment decisions, which align individual patient characteristics and needs with demonstrated benefits. NCT01170663相似文献
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Lesley A. Inker Morgan E. Grams Andrew S. Levey Josef Coresh Massimo Cirillo John F. Collins Ron T. Gansevoort Orlando M. Gutierrez Takayuki Hamano Gunnar H. Heine Shizukiyo Ishikawa Sun Ha Jee Florian Kronenberg Martin J. Landray Katsuyuki Miura Girish N. Nadkarni Carmen A. Peralta Dietrich Rothenbacher Mark Woodward 《American journal of kidney diseases》2019,73(2):206-217
6.
Background
Children have a statutory right to a smoke-free environment, and tobacco control advocates are now considering regulation of smoking behavior in the private sphere. The Norwegian Institute of Public Health has investigated the support for a ban on smoking in cars with children compared to other possible extensions of the tobacco act among the Norwegian public.Material and methods
A nationwide representative survey (CAWI) of 5543 participants was conducted in 2014–2015. Respondents were asked to consider several possible new tobacco control measures, through selfreported ranking on 5-point scales for each measure. Multiple logistic regression models were applied to control for confounders (i.a. smoking behavior) for the tendency to state full support.Results
A majority (78 % of all respondents, 61.8% of daily smokers) supported a proposal prohibiting smoking in cars when children are present. This proposal received substantially more support than bans on private balconies, in parks and at public transport stops and work entrances. Full support for the latter proposals varied between 39.9% and 58.1% (between 2.7% and 16.8% among smokers). Differences by smoking status were maintained after multiple controls.Interpretation
The strong endorsement of the proposal (also provided by the majority of current smokers) suggests high legitimacy and compliance, which means that an implementation could be introduced without serious enforcement problems. 相似文献7.
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Metformin‐associated risk of acute dialysis in patients with type 2 diabetes: A nationwide cohort study 下载免费PDF全文
Nicholas Carlson MD Kristine Hommel MD PhD Jonas B. Olesen MD PhD Thomas A. Gerds Dr.rer.Nat Anne‐Merete Soja MD PhD Tina Vilsbøll MD DMSc Anne‐Lise Kamper MD DMSc Christian Torp‐Pedersen MD DMSC FACC FESC Gunnar Gislason MD PhD FESC FACC FAHA 《Diabetes, obesity & metabolism》2016,18(12):1283-1287
Recent guidelines governing anti‐diabetic medications increasingly advocate metformin as first‐line therapy in all patients with type 2 diabetes. However, metformin could be associated with increased risk of acute kidney injury (AKI), acute dialysis and lactate acidosis in marginal patients. In a retrospective nationwide cohort study, a total of 168 443 drug‐naïve patients with type 2 diabetes ≥50 years, initiating treatment with either metformin or sulphonyl in Denmark between 2000 and 2012 were included in this study (70.7% initiated treatment with metformin); calculation of 1‐year risk of acute dialysis was based on g‐standardization of cause‐specific Cox regression models for acute dialysis, end‐stage renal disease and death. One‐year risks of acute dialysis were 92.4 per 100 000 (95% CI, 67.1‐121.3) and 142.7 per 100 000 (95% CI, 118.3‐168.0) for sulphonylurea and metformin, respectively. The metformin‐associated 1‐year risk of acute dialysis was increased by 50.3 per 100 000 (95% CI, 7.9‐88.6), corresponding to a risk ratio of 1.53 (95% CI, 1.06‐2.23), and a number needed to harm of 1988, thus providing evidence of potential concerns pertaining to the increasing use of metformin. 相似文献