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81.
P?ivi E Korhonen Hannu Kautiainen Pekka M?ntyselk? 《The British journal of general practice》2014,64(627):e611-e615
Background
Self-rated health is an independent predictor of mortality. However, general health checks in populations unselected for disease or risk factors have not been shown to reduce mortality or morbidity.Aim
To describe new comorbidities and cardiovascular risk factors in apparently healthy people and to relate this to their self-rated health.Design and setting
A targeted screening programme identified 462 middle-aged people with cardiovascular risk factors without previously diagnosed chronic disease in a Finnish community in 2005–2006.Method
Home blood pressure monitoring, oral glucose tolerance test, estimated glomerular filtration rate, and ankle brachial index were used to detect previously undiagnosed conditions. The Short-Form Health Survey and Beck’s Depression Inventory were completed by participants before the diagnostic tests were performed.Results
The prevalence of previously undiagnosed disease was: hypertension 113/462 (24% [95% confidence interval {CI} = 21% to 29%]), diabetes 19/462 (4% [95% CI = 2% to 6%]), renal insufficiency 23/462 (5% [95% CI = 3% to 7%]), and peripheral arterial disease 17/462 (4% [95% CI = 2% to 5%]). Of the 139 participants who regarded their health as ‘fair–poor’, 60 (43%) had a previously undetected condition affecting their vasculature.Conclusion
Out of the screen-detected apparently healthy cardiovascular risk subjects, one in three had undiagnosed hypertension, diabetes, peripheral arterial disease, or renal insufficiency. Those individuals experiencing ill health tended to be at high risk of cardiovascular problems. 相似文献82.
Copy number alterations and neoplasia‐specific mutations in MELK,PDCD1LG2, TLN1, and PAX5 at 9p in different neoplasias 下载免费PDF全文
Virinder Kaur Sarhadi Leo Lahti Ilari Scheinin Pekka Ellonen Eeva Kettunen Massimo Serra Katia Scotlandi Piero Picci Sakari Knuutila 《Genes, chromosomes & cancer》2014,53(7):579-588
Genetic alterations affecting 9p are commonly present in many cancer types and many cancer‐related genes are located in this chromosomal region. We sequenced all of the genes located in a 32Mb region of 9p by targeted next generation sequencing (NGS) in 96 patients with different cancer types, including acute lymphoblastic leukemia, bone malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma, fibrosarcoma, Ewing's sarcoma, and lung carcinoma. Copy number alterations (CNA), and mutations were studied from the NGS data. We detected a deletion at the CDKN2A locus as being the most frequent genetic alteration in all cancer types. In addition to this locus, NGS also identified other small regions of copy number loss and gain. However, different cancer types did not reveal any statistically significant differences with regard to CNA frequency or type. Of the 191 genes within the target region, two novel recurrent mutations were found in the MELK and PDCD1LG2 genes. The most commonly mutated gene in sarcomas was TLN1 (8%) and PAX5 in ALL (9%). Mutations in PAX5, and RUSC2, were seen exclusively in ALL patients and those in KIAA1432, CA9, TLN1, and MELK only in sarcomas (MFH, FS, EFT). Thus using targeted NGS of the 9p region, in addition to commonly deleted CDKN2A locus, we were able to identify a number of small deletions and gains, as well as novel recurrent mutations in different cancer types. © 2014 Wiley Periodicals, Inc. 相似文献
83.
84.
Elmeri M. Jokinen Pekka A. Postila Mira Ahinko Sanna Niinivehmas Olli T. Pentikinen 《Chemical biology & drug design》2019,94(4):1799-1812
A novel virtual screening methodology called fragment‐ and negative image‐based (F‐NiB) screening is introduced and tested experimentally using phosphodiesterase 10A (PDE10A) as a case study. Potent PDE10A‐specific small‐molecule inhibitors are actively sought after for their antipsychotic and neuroprotective effects. The F‐NiB combines features from both fragment‐based drug discovery and negative image‐based (NIB) screening methodologies to facilitate rational drug discovery. The selected structural parts of protein‐bound ligand(s) are seamlessly combined with the negative image of the target's ligand‐binding cavity. This cavity‐ and fragment‐based hybrid model, namely its shape and electrostatics, is used directly in the rigid docking of ab initio generated ligand 3D conformers. In total, 14 compounds were acquired using the F‐NiB methodology, 3D quantitative structure–activity relationship modeling, and pharmacophore modeling. Three of the small molecules inhibited PDE10A at ~27 to ~67 μM range in a radiometric assay. In a larger context, the study shows that the F‐NiB provides a flexible way to incorporate small‐molecule fragments into the drug discovery. 相似文献
85.
Anne‐Maree Kelly Oene Van Meer Gerben Keijzers Justina Motiejunaite Peter Jones Richard Body Simon Craig Mehmet Karamercan Sharon Klim Veli‐Pekka Harjola Franck Verschuren Anna Holdgate Michael Christ Adela Golea Colin A. Graham Jean Capsec Cinzia Barletta Luis Garcia‐Castrillo Win S. Kuan Said Laribi 《Internal medicine journal》2020,50(2):200-208
86.
Kim Fejgin Jacob Nielsen Michelle R. Birknow Jesper F. Bastlund Vibeke Nielsen Jes B. Lauridsen Hreinn Stefansson Stacy Steinberg Helge B.D. Sorensen Troels E. Mortensen Peter H. Larsen Ib V. Klewe Søren V. Rasmussen Kari Stefansson Thomas M. Werge Pekka Kallunki Kenneth V. Christensen Michael Didriksen 《Neuropsychopharmacology》2014
87.
Objective : To resolve if TBX22 mutations cause isolated tongue-tie in the Finnish population. Design : Mutation analysis of the coding region of the TBX22 gene in 50 Finnish isolated tongue-tie patients and 61 control samples. Results : One putative sequence variation was identified from two male patients, but whether this represents a polymorphism or causative mutation remains unknown. Conclusions : Mutations in the coding region of the TBX22 gene are not a major cause of ankyloglossia in the Finnish population and do not explain the sex difference or inheritance of tongue-tie. 相似文献
88.
Missing a canine is of serious concern in social life of a patient in most of societies. While conventional fixed partial dentures and implant-supported restorations may often be the treatment of choice, fiber-reinforced composite (FRC) resins offer a conservative, fast and cost-effective alternative for single and multiple teeth replacement. This clinical report presents two cases where FRC technology was successfully used to restore canine edentulous area in terms of esthetic-cosmetic values and functionality. 相似文献
89.
Diamond-Blackfan anemia (DBA) is a congenital erythroid hypoplasia caused by a functional haploinsufficiency of genes encoding for ribosomal proteins. Recently, a case study reported a patient who became transfusion-independent in response to treatment with the amino acid L-leucine. Therefore, we have validated the therapeutic effect of L-leucine using our recently generated mouse model for RPS19-deficient DBA. Administration of L-leucine significantly improved the anemia in Rps19-deficient mice (19% improvement in hemoglobin concentration; 18% increase in the number of erythrocytes), increased the bone marrow cellularity, and alleviated stress hematopoiesis. Furthermore, the therapeutic response to L-leucine appeared specific for Rps19-deficient hematopoiesis and was associated with down-regulation of p53 activity. Our study supports the rationale for clinical trials of L-leucine as a therapeutic agent for DBA. 相似文献
90.
Ukkola A Mäki M Kurppa K Collin P Huhtala H Kekkonen L Kaukinen K 《European Journal of Internal Medicine》2012,23(4):384-388
ObjectiveThe clinical presentation of coeliac disease has changed and patients are often overweight at diagnosis. There is concern that patients might gain further weight while on a gluten-free diet (GFD). The aim of the study was to evaluate the impact of a GFD on the body mass index (BMI) in a nationwide cohort of coeliac patients and to determine variables predictive of favourable or unfavourable BMI changes.MethodsWe prospectively investigated weight and disease-related issues in 698 newly detected adults diagnosed due to classical or extraintestinal symptoms or by screening. BMI at diagnosis and after one year on a GFD were assessed and compared with that in the general population.ResultsAt diagnosis, 4% of subjects were underweight, 57% normal, 28% overweight and 11% obese. On a GFD, 69% of underweight patients gained and 18% of overweight and 42% of obese lost weight; in the rest BMI remained stable. Changes were similar in both symptom- and screen-detected patients. The coeliac group had a more favourable BMI pattern than the general population. Favourable BMI changes were associated with subjects' self-rated expertise on GFD and young age at diagnosis, but not dietary counselling received.ConclusionsBMI improved similarly in screen- and symptom-detected coeliac disease patients on a GFD. 相似文献