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91.
Hermine A van Duyvenvoorde Julian C Lui Sarina G Kant Wilma Oostdijk Antoinet CJ Gijsbers Mari?tte JV Hoffer Marcel Karperien Marie JE Walenkamp Cees Noordam Paul G Voorhoeve Verónica Mericq Alberto M Pereira Hedi L Claahsen-van de Grinten Sandy A van Gool Martijn H Breuning Monique Losekoot Jeffrey Baron Claudia AL Ruivenkamp Jan M Wit 《European journal of human genetics : EJHG》2014,22(5):602-609
Height is a highly heritable and classic polygenic trait. Recent genome-wide association studies (GWAS) have revealed that at least 180 genetic variants influence adult height. However, these variants explain only about 10% of the phenotypic variation in height. Genetic analysis of short individuals can lead to the discovery of novel rare gene defects with a large effect on growth. In an effort to identify novel genes associated with short stature, genome-wide analysis for copy number variants (CNVs), using single-nucleotide polymorphism arrays, in 162 patients (149 families) with short stature was performed. Segregation analysis was performed if possible, and genes in CNVs were compared with information from GWAS, gene expression in rodents'' growth plates and published information. CNVs were detected in 40 families. In six families, a known cause of short stature was found (SHOX deletion or duplication, IGF1R deletion), in two combined with a de novo potentially pathogenic CNV. Thirty-three families had one or more potentially pathogenic CNVs (n=40). In 24 of these families, segregation analysis could be performed, identifying three de novo CNVs and nine CNVs segregating with short stature. Four were located near loci associated with height in GWAS (ADAMTS17, TULP4, PRKG2/BMP3 and PAPPA). Besides six CNVs known to be causative for short stature, 40 CNVs with possible pathogenicity were identified. Segregation studies and bioinformatics analysis suggested various potential candidate genes. 相似文献
92.
The incidence of obesity, increased weight gain and the popularity of high-fat / high-sugar diets are seriously impacting upon the global population. Billions of individuals are affected, and although diet and lifestyle are of paramount importance to the development of adult obesity, compelling evidence is emerging which suggests that maternal obesity and related disorders may be passed on to the next generation by non-genetic means. The processes acting within the uteri of obese mothers may permanently predispose offspring to a diverse plethora of diseases ranging from obesity and diabetes to psychiatric disorders. This review aims to summarise some of the molecular mechanisms and active processes currently known about maternal obesity and its effect on foetal and neonatal physiology and metabolism. Complex and multifactorial networks of molecules are intertwined and culminate in a pathologically synergistic manner to cause disruption and disorganisation of foetal physiology. This altered phenotype may potentiate the cycle of intergenerational transmission of obesity and related disorders.Key Words: Maternal obesity, Epigenetics, Reactive oxygen species 相似文献
93.
Adam H. Dowling Angus Burns Donal Macauley Thérèse M. Garvey Garry J.P. Fleming 《Journal of dentistry》2013
Objectives
To compare contact point displacement measurements, used to determine the Little's Irregularity Index (LII) score on study casts and digital models of study casts by an independent examiner.Methods
The contact point displacement measurements of the six maxillary anterior labial teeth were measured on ten study casts using digital callipers and their associated digital models using Creo Parametric software on five occasions following scanning using a LAVA Chairside Oral Scanner (LCOS) three-dimensional (3D) intra oral scanner. Means, standard deviations and coefficients of variation (CoV) were determined, data analyses (Pearson's correlation coefficients (PCCs) and Intraclass correlation coefficients (ICCs)) and statistical analyses (three and two-way analyses of variance (ANOVAs) and Independent Sample Student's t-tests) were carried out (p < 0.05).Results
Significant positive correlations for the contact point displacement measurements were evident between all measurement time points for the study casts (r > 0.978; p < 0.0001 and ICC > 0.910; p < 0.0001) and the digital models (r > 0.963; p < 0.0001 and ICC > 0.986; p < 0.0001). The CoV results showed that the contact point displacement measurement data from the digital models was more reproducible than the study casts. Of the 50 Independent Sample Student's t-tests, 21 significant increases (p < 0.042) were reported in contact point displacement measurements <2.9 mm for the digital models compared with the study casts.Conclusion
The use of 3D digital models can improve the reliability of LII measurements by reducing the subjectivity associated with choosing the anatomic tooth contact points and the awkwardness of measuring the contact point displacements on study casts using a cumbersome calliper technique.Clinical significance
Intra-examiner variability in the measurement of LII is still evident with digital models suggesting that either improved software specifically aimed at the orthodontic community be identified or a new method for measuring anterior incisor crowding be sought. 相似文献94.
95.
The anti-diabetic drug metformin is rapidly emerging as a potential anti-cancer agent. Metformin, effective in treating type 2 diabetes and the insulin resistance syndromes, improves insulin resistance by reducing hepatic gluconeogenesis and by enhancing glucose uptake by skeletal muscle. Epidemiological studies have consistently associated metformin use with decreased cancer incidence and cancer-related mortality. Furthermore, numerous preclinical and clinical studies have demonstrated anti-cancer effects of metformin, leading to an explosion of interest in evaluating this agent in human cancer. The effects of metformin on circulating insulin levels indicate a potential efficacy towards cancers associated with hyperinsulinaemia; however, metformin may also directly inhibit tumour growth. In this review, we describe the mechanism of action of metformin and summarise the epidemiological, clinical and preclinical evidence supporting a role for metformin in the treatment of cancer. In addition, the challenges associated with translating preclinical results into therapeutic benefit in the clinical setting will be discussed. 相似文献
96.
Ana Gvozdenovic Matthias JE Arlt Carmen Campanile Patrick Brennecke Knut Husmann Yufei Li Walter Born Roman Muff Bruno Fuchs 《Journal of bone and mineral research》2013,28(4):838-847
Formation of metastases in the lungs is the major cause of death in patients suffering from osteosarcoma (OS). Metastases at presentation and poor response to preoperative chemotherapy are strong predictors for poor patient outcome. The elucidation of molecular markers that promote metastasis formation and/or chemoresistance is therefore of importance. CD44 is a plasma membrane glycoprotein that binds to the extracellular matrix component hyaluronan (HA) and has been shown to be involved in metastasis formation in a variety of other tumors. Here we investigated the role of CD44 expression on OS tumor formation and metastasis. High CD44 expression, evaluated with a tissue microarray including samples from 53 OS patients and stained with a pan‐CD44 antibody (Hermes3), showed a tendency (p < 0.08) to shortened overall survival. However, nonresponders and patients with lung metastases and high CD44 expression had significantly poorer prognosis than patients with low CD44 expression. Overexpression of the standard CD44 isoform (CD44s) and its HA‐binding defective mutant R41A in osteoblastic SaOS‐2 cells resulted in HA‐independent higher migration rates and increased chemoresistance, partially dependent on HA. In an orthotopic mouse model of OS, overexpression of CD44s in SaOS‐2 cells resulted in an HA‐dependent increased primary tumor formation and increased numbers of micrometastases and macrometastases in the lungs. In conclusion, although CD44 failed to be an independent predictor for patient outcome in this limited cohort of OS patients, increased CD44 expression was associated with even worse survival in patients with chemoresistance and with lung metastases. CD44‐associated chemoresistance was also observed in vitro, and increased formation of lung metastases was found in vivo in SCID mice. © 2013 American Society for Bone and Mineral Research. 相似文献
97.
Dowling C 《Journal of the Irish Dental Association》2012,58(2):88
There are several government agencies that may inspect your dental practice. The majority of inspections are carried out by the National Employment Rights Authority, the Health and Safety Authority, the Revenue Commissioners and the Radiological Protection Institute of Ireland. Below is a summary of the minimum requirements that should be in place to ensure compliance with the relevant legislation. You should always seek appropriate advice for your own particular circumstances. 相似文献
98.
Niklas Sandström Bernard Yan Richard Dowling John Laidlaw Peter Mitchell 《Journal of clinical neuroscience》2013,20(9):1213-1218
Poor-grade (World Federation of Neurological Surgeons [WFNS] clinical grading scale grades IV and V) subarachnoid hemorrhage (SAH) is associated with significant morbidity and mortality. However, the correlation between the timing, modality of intervention (clipping or coiling) and the clinical outcome is not clear. This study aims to examine this correlation. Patients presenting with WFNS grades IV and V aneurysmal SAH between 1997 and 2008 to a single centre were studied. An aggressive policy of early intervention was followed, and the selection of endovascular versus microsurgical intervention was made according to angiographic rather than clinical features. Clinical outcomes were graded using the modified Rankin scale (mRS) at 6 month follow-up. One hundred and forty-three poor-grade patients (23.9% of all 598 aneurysmal SAH patients) were studied. Treatment was microsurgical in 83 (58.0%) and endovascular in 60 (42%) patients. Twenty patients (14.0%) were lost to follow-up. Good outcome (mRS 0-2) at 6 months was found in 45 microsurgical patients (63.3%) and 24 endovascular patients (46.1%). This trend towards better clinical outcomes in the microsurgical group was not statistically significant. With an aggressive early treatment policy more than half of the poor-grade SAH patients demonstrated a good clinical outcome. Microsurgery and endovascular treatment, when selected primarily according to angiographic features, were equally likely to achieve good outcome. 相似文献
99.
R. McConkey S. Dowling D. Hassan S. Menke 《Journal of intellectual disability research : JIDR》2013,57(10):923-935
Background Although the promotion of social inclusion through sports has received increased attention with other disadvantaged groups, this is not the case for children and adults with intellectual disability who experience marked social isolation. The study evaluated the outcomes from one sports programme with particular reference to the processes that were perceived to enhance social inclusion. Method The Youth Unified Sports programme of Special Olympics combines players with intellectual disabilities (called athletes) and those without intellectual disabilities (called partners) of similar skill level in the same sports teams for training and competition. Alongside the development of sporting skills, the programme offers athletes a platform to socialise with peers and to take part in the life of their community. Unified football and basketball teams from five countries – Germany, Hungary, Poland, Serbia and Ukraine – participated. Individual and group interviews were held with athletes, partners, coaches, parents and community leaders: totalling around 40 informants per country. Results Qualitative data analysis identified four thematic processes that were perceived by informants across all countries and the two sports to facilitate social inclusion of athletes. These were: (1) the personal development of athletes and partners; (2) the creation of inclusive and equal bonds; (3) the promotion of positive perceptions of athletes; and (4) building alliances within local communities. Conclusions Unified Sports does provide a vehicle for promoting the social inclusion of people with intellectual disabilities that is theoretically credible in terms of social capital scholarship and which contains lessons for advancing social inclusion in other contexts. Nonetheless, certain limitations are identified that require further consideration to enhance athletes' social inclusion in the wider community. 相似文献
100.