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61.
Targeted Resequencing of 29 Candidate Genes and Mouse Expression Studies Implicate ZIC3 and FOXF1 in Human VATER/VACTERL Association
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Alina C. Hilger Jan Halbritter Tracie Pennimpede Amelie van der Ven Georgia Sarma Daniela A. Braun Jonathan D. Porath Stefan Kohl Daw‐Yang Hwang Gabriel C. Dworschak Bernhard G. Hermann Anna Pavlova Osman El‐Maarri Markus M. Nöthen Michael Ludwig Heiko Reutter Friedhelm Hildebrandt 《Human mutation》2015,36(12):1150-1154
The VATER/VACTERL association describes the combination of congenital anomalies including vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects. As mutations in ciliary genes were observed in diseases related to VATER/VACTERL, we performed targeted resequencing of 25 ciliary candidate genes as well as disease‐associated genes (FOXF1, HOXD13, PTEN, ZIC3) in 123 patients with VATER/VACTERL or VATER/VACTERL‐like phenotype. We detected no biallelic mutation in any of the 25 ciliary candidate genes; however, identified an identical, probably disease‐causing ZIC3 missense mutation (p.Gly17Cys) in four patients and a FOXF1 de novo mutation (p.Gly220Cys) in a further patient. In situ hybridization analyses in mouse embryos between E9.5 and E14.5 revealed Zic3 expression in limb and prevertebral structures, and Foxf1 expression in esophageal, tracheal, vertebral, anal, and genital tubercle tissues, hence VATER/VACTERL organ systems. These data provide strong evidence that mutations in ZIC3 or FOXF1 contribute to VATER/VACTERL. 相似文献
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63.
Harilaos Papachristou Evi Aresti Marios Theodorou Georgia Panayiotou 《Cognitive therapy and research》2018,42(3):289-301
College alcohol drinking is a public health concern worldwide. A line of research indicates that higher social anxiety is associated with more severe college drinking. However, other studies reveal a protective role of social anxiety against alcohol drinking in college students. Attempting to reconcile contradictory findings, we examined the hypothesis that there are multiple antagonistic pathways that could explain the social anxiety-college drinking relationship. In addition, there may be individual difference variables that moderate these processes. Furthermore, it was expected that the processes could vary as a function of the alcohol drinking outcomes examined. Expectancy theory emphasizes the role of alcohol outcome expectancies in alcohol drinking. Thus, in the present study we tested whether global positive and negative alcohol outcome expectancies partially mediate the relationship between social anxiety, alcohol consumption, and alcohol-related problems in a sample of 245 university students. We also examined the moderating role of gender in these mediating processes. Results revealed parallel but oppositional processes. Higher social anxiety was associated with heavier alcohol drinking and more serious alcohol-related problems via stronger positive alcohol outcome expectancies. However, the mediating role of positive alcohol outcome expectancies varied as a function of gender. It appears that in female students the mediating effect of positive alcohol outcome expectancies was stronger than in male students. On the other hand, higher social anxiety had a protective role against alcohol consumption but not against alcohol-related problems via stronger negative alcohol outcome expectancies. Finally, there was an inverse direct relationship between social anxiety and alcohol consumption. 相似文献
64.
Several Australian obesity management guidelines have been developed for general practice but, to date, implementation of these guidelines has been shown to be inadequate. In this review, we explore the barriers to obesity treatment and propose a four-stage plan to manage individuals with obesity in general practice using a framework of a multidisciplinary team.Funding: Novo Nordisk. 相似文献
65.
Metzgeroth G Adelberger V Dorn-Beineke A Kuhn C Schatz M Maywald O Bertsch T Wisser H Hehlmann R Hastka J 《European journal of haematology》2005,75(4):309-317
OBJECTIVES: Soluble transferrin receptor (sTfR) and zinc protoporphyrin (ZPP) are both parameters of iron deficient erythropoiesis (IDE), the sTfR measurement is commonly regarded to be the more sensitive test. sTfR also reflects erythropoietic activity, it is increased in enhanced erythropoiesis. METHODS: We investigated the diagnostic accuracy of sTfR in assessment of iron deficiency (ID) and compared it with ZPP. The study was performed on 174 subjects, in which ID has been precisely staged. RESULTS: Individuals without ID and patients with storage iron depletion only, had normal sTfR values. Patients classified as IDE and patients with iron deficiency anemia had significantly increased sTfR. There was a good correlation between sTfR and hemoglobin (r = -0.86; P < 0.0001) and between sTfR and ZPP (r = 0.86; P < 0.0001). When diagnosing ID, ZPP was the more sensitive test. In mildly developed IDE associated with ZPP-ratios between 40 and 70 micromol/mol heme, the sTfR concentration was elevated in only 25% of the cases. Reliably elevated sTfR values were observed only in more advanced IDE, associated with ZPP > 70 mumol/mol heme. CONCLUSIONS: ZPP is not inferior to sTfR when diagnosing IDE. Given the good correlation between sTfR and ZPP and because ZPP is uninfluenced by the erythropoietic activity, sTfR and ZPP are not competitors, rather efficient partners in diagnosing anemias. By measuring ZPP and sTfR simultaneously, the diagnostic uncertainty inherent in each of them individually can be eliminated. In particular, the simultaneous determination of ZPP and sTfR enhances the diagnostic power of sTfR in assessment of the erythropoietic activity. 相似文献
66.
Sarah J. Holmes Richard W. Whitehouse Ric Swindell Georgia Economou Judith E. Adams Stephen M. Shalet 《Clinical endocrinology》1995,42(6):627-633
OBJECTIVE Previous studies of the effect of GH replacement on bone mass in adults with GH deficiency have produced conflicting results. We have studied the effect of 6 and 12 months of GH replacement on bone mass in adults with adult onset GH deficiency. DESIGN Double blind placebo controlled study of GH replacement (0.125 IU/kg/week for the first month and 0.25 IU/kg/week thereafter) for 6 months and an open study for a further 6 or 12 months. PATIENTS Twenty-two adults (10 men, 12 women), aged 41.5±2.1 years (mean ± SE, range 23.6–59.5), with adult onset GH deficiency. MEASUREMENTS Single-energy quantitative computed tomography was used to measure vertebral trabecular bone mineral density (BMD), single-photon absorptiometry (SPA) was used to measure forearm cortical and integral bone mineral content and BMD and dual-energy X-ray absorptiometry (DXA) was used to measure lumbar spine, femoral neck, trochanteric and Ward's triangle Integral BMD. RESULTS After 6 months of GH replacement (n=21) there was a significant decrease In forearm cortical BMD (SPA: median change ?0.009g/cm2, P=0.01), forearm Integral BMD (SPA: median change ?0.016g/cm2, P=0.03), lumbar spine BMD (DXA: median change ?0.022g/cm2; P=0.003) and femoral neck BMD (DXA: median change ?0.029g/cm2, P=0.006). After 12 months of GH replacement (n=13) there was a significant decrease in lumbar spine BMD (DXA: median change ?0.035 g/cm2, P=0.002) from baseline. There was no significant Increase in bone mass at any site after 6 or 12 months of GH replacement. Change In bone mass was not influenced by sex of the patient or by presence or absence of additional pituitary hormone deficiencies. CONCLUSION The response of bone mass to 6 and 12 months of GH replacement in adults with adult onset GH deficiency is disappointing. Longer-term studies are required to determine whether prolonged GH replacement has a beneficial effect on bone mass. 相似文献
67.
Georgia M. Davis Eileen Faulds Tara Walker Debbie Vigliotti Marina Rabinovich Joi Hester Limin Peng Barbara McLean Patricia Hannon Norma Poindexter Petrena Saunders Citlalli Perez-Guzman Seema S. Tekwani Greg S. Martin Guillermo Umpierrez Shivani Agarwal Kathleen Dungan Francisco J. Pasquel 《Diabetes care》2021,44(4):1055
OBJECTIVEThe use of remote real-time continuous glucose monitoring (CGM) in the hospital has rapidly emerged to preserve personal protective equipment and reduce potential exposures during coronavirus disease 2019 (COVID-19).RESEARCH DESIGN AND METHODSWe linked a hybrid CGM and point-of-care (POC) glucose testing protocol to a computerized decision support system for continuous insulin infusion and integrated a validation system for sensor glucose values into the electronic health record. We report our proof-of-concept experience in a COVID-19 intensive care unit.RESULTSAll nine patients required mechanical ventilation and corticosteroids. During the protocol, 75.7% of sensor values were within 20% of the reference POC glucose with an associated average reduction in POC of 63%. Mean time in range (70–180 mg/dL) was 71.4 ± 13.9%. Sensor accuracy was impacted by mechanical interferences in four patients.CONCLUSIONSA hybrid protocol integrating real-time CGM and POC is helpful for managing critically ill patients with COVID-19 requiring insulin infusion. 相似文献
68.
OBJECTIVEThe impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) on the incidence of new-onset type 2 diabetes and diabetic ketoacidosis (DKA) is unclear. It is unknown whether the coincidence of DKA noted in adult patients with type 2 diabetes is an issue for youth during the coronavirus disease 2019 pandemic.RESEARCH DESIGN AND METHODSA retrospective single-center medical record review was conducted in a large, urban children’s hospital of pediatric subjects presenting with new-onset type 2 diabetes between March and August of 2018 to 2020.RESULTSThe proportion of subjects presenting with new-onset type 2 diabetes in DKA dramatically increased in 2020 (9% in 2018, 3% in 2019, and 20% in 2020, P = 0.029).CONCLUSIONSIn 2020, youth with new-onset type 2 diabetes had a greater incidence of DKA at presentation than previously observed. Future studies should examine the impact of SARS-CoV2 exposure on the presentation of type 2 diabetes in all age-groups to inform better patient care. 相似文献
69.
Theodoros Eleftheriadis Georgios Pissas Efi Yiannaki Dimitra Markala Spyridon Arampatzis Georgia Antoniadi Vassilios Liakopoulos Ioannis Stefanidis 《Human immunology》2013
Indoleamine 2,3-dioxygenase (IDO) suppresses adaptive immunity. T-cell proliferation and differentiation to effector cells require increased glucose consumption, aerobic glycolysis and glutaminolysis. The effect of IDO on the above metabolic pathways was evaluated in alloreactive T-cells. Mixed lymphocyte reaction (MLR) in the presence or not of the IDO inhibitor, 1-methyl-dl-tryptophan (1-MT), was used. In MLRs, 1-MT decreased tryptophan consumption, increased cell proliferation, glucose influx and lactate production, whereas it decreased tricarboxylic acid cycle activity. In T-cells, from the two pathways that could sense tryptophan depletion, i.e. general control nonrepressed 2 (GCN2) kinase and mammalian target of rapamycin complex 1, 1-MT reduced only the activity of the GCN2 kinase. Additionally 1-MT treatment of MLRs altered the expression and/or the phosphorylation state of glucose transporter-1 and of key enzymes involved in glucose metabolism and glutaminolysis in alloreactive T-cells in a way that favors glucose influx, aerobic glycolysis and glutaminolysis. Thus in alloreactive T-cells, IDO through activation of the GCN2 kinase, decreases glucose influx and alters key enzymes involved in metabolism, decreasing aerobic glycolysis and glutaminolysis. Acting in such a way, IDO could be considered as a constraining factor for alloreactive T-cell proliferation and differentiation to effector T-cell subtypes. 相似文献