The possibilities and prospects of obtaining high-resolution information (below 30 Å) on biological material using the electron microscope: Some comments and reports inspired by an EMBO workshop held at Gais, Switzerland, October 1973

Commercially available electron microscopes routinely provide resolution of some 2-4 Å, as determined on the spacing of crystalline lattices of certain stable, small-molecular substances. On biological material either macromolecules or macromolecular assemblies— ‘biologically significant' details below some 20 Å have hitherto not been observed.we consider as ‘biologically significant' those structural details observed or contained in electronmicrographs which are consistent with, or confirmed by, other data obtained from biochemical or functional experiments or by other physical methods (optical, magnetic, electric

Management of Orofacial Manifestations of Juvenile Idiopathic Arthritis: Interdisciplinary Consensus-Based Recommendations

Involvement of the temporomandibular joint (TMJ) is common in juvenile idiopathic arthritis (JIA). TMJ arthritis can lead to orofacial symptoms, orofacial dysfunction, and dentofacial deformity with negative impact on quality of life. Management involves interdisciplinary collaboration. No current recommendations exist to guide clinical management. We undertook this study to develop consensus-based interdisciplinary recommendations for management of orofacial manifestations of JIA, and to create a future research agenda related to management of TMJ arthritis in children with JIA. Recommendations were developed using online surveying of relevant stakeholders, systematic literature review, evidence-informed generation of recommendations during 2 consensus meetings, and Delphi study iterations involving external experts. The process included disciplines involved in the care of orofacial manifestations of JIA: pediatric rheumatology, radiology, orthodontics, oral and maxillofacial surgery, orofacial pain specialists, and pediatric dentistry. Recommendations were accepted if agreement was >80% during a final Delphi study. Three overarching management principles and 12 recommendations for interdisciplinary management of orofacial manifestations of JIA were outlined. The 12 recommendations pertained to diagnosis (n = 4), treatment of TMJ arthritis (active TMJ inflammation) (n = 2), treatment of TMJ dysfunction and symptoms (n = 3), treatment of arthritis-related dentofacial deformity (n = 2), and other aspects related to JIA (n = 1). Additionally, a future interdisciplinary research agenda was developed. These are the first interdisciplinary recommendations to guide clinical management of TMJ JIA. The 3 overarching principles and 12 recommendations fill an important gap in current clinical practice. They emphasize the importance of an interdisciplinary approach to diagnosis and management of orofacial manifestations of JIA

The Role of Dysregulated Glucose Metabolism in Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer and also one of the most poorly understood. Other health issues that are affecting women with increasing frequency are obesity and diabetes, which are associated with dysglycemia and increased blood glucose. The Warburg Effect describes the ability of fast-growing cancer cells to preferentially metabolize glucose via anaerobic glycolysis rather than oxidative phosphorylation. Recent epidemiological studies have suggested a role for hyperglycemia in the pathogenesis of a number of cancers. If hyperglycemia contributes to tumour growth and progression, then it is intuitive that antihyperglycemic drugs may also have an important antitumour role. Preliminary reports suggest that these drugs not only reduce available plasma glucose, but also have direct effects on cancer cell viability through modification of molecular energy-sensing pathways. This review investigates the effect that hyperglycemia may have on EOC and the potential of antihyperglycemic drugs as therapeutic adjuncts

Effect of different quantities of a sugared clear fluid on gastric emptying and residual volume in children: a crossover study using magnetic resonance imaging

Background Gastric emptying in the first 2 h after 7 ml kg−1 of sugared clear fluid has recently been investigated in healthy children using magnetic resonance imaging (MRI). This study aims to compare gastric volume and emptying half-life during 1 h after 3 or 7 ml kg−1 sugared clear fluid intake. Methods Fourteen healthy volunteer children aged 11.1 (8.2-12.5) yr were investigated prospectively after administration of 3 and 7 ml kg−1 diluted raspberry syrup in a randomized order, after overnight fasting (baseline). Gastric content volume (GCVw) was assessed with a 1.5 Tesla MRI scanner in a blinded fashion. Data are presented as median (range) and compared using the Wilcoxon test. Results Baseline GCVw was 0.39 (0.04-1.00) and 0.34 (0.07-0.75) before intake of 3 and 7 ml kg−1 syrup, respectively (P=0.93). GCVw was 0.45 (0.04-1.55)/1.33 (0.30-2.60) ml kg−1 60 min after ingestion of 3/7 ml kg−1 syrup (P=0.002). Thus GCVw had declined to baseline after 3 ml kg−1 (P=0.39) but not after 7 ml kg−1 (P=0.001) within 60 min. T1/2 was 20 (10-62)/27 (13-43) min (P=0.73) after 3/7 ml kg−1. Conclusion In healthy volunteer children, residual GCVw 1 h after intake of 3 ml kg−1 syrup is significantly smaller than that after 7 ml kg−1 and within the range of baselin

Remodelling of the right ventricle after early pulmonary valve replacement in children with repaired tetralogy of Fallot: assessment by cardiovascular magnetic resonance

Aims Correct timing of pulmonary valve replacement (PVR) is crucial for preventing complications of pulmonary regurgitation and right ventricular (RV) dilatation after repair of tetralogy of Fallot. We sought to assess the remodelling of the RV after early PVR in children, using cardiovascular magnetic resonance (CMR). Methods and results Twenty children with severe pulmonary regurgitation and RV dilatation and mean age 13.9±3 years underwent CMR evaluation 5.6±1.8 months before and 5.9±0.6 months after PVR. PVR was performed when the RV end-diastolic volume exceeded 150 mL/m2, as measured by CMR. The time interval between primary repair and PVR was 12±3 years. Post-operative CMR demonstrated a significant reduction of the RV end-diastolic volume from 189.8±33.4 to 108.7±25.8 mL/m2 (P<0.0001), of the RV end-systolic volume from 102.4±27.3 to 58.2±16.3 mL/m2 (P<0.0001), and of the RV mass from 48.7±12.3 to 35.8±7.7 g/m2 (P<0.0001). The RV ejection fraction did not change significantly. Conclusion Prompt RV remodelling, with reduction of RV volume and mass, is observed after performing PVR if the RV end-diastolic volume exceeds 150 mL/m2. Early PVR may prevent the detrimental complications of severe pulmonary regurgitatio

Early diagnosis of temporomandibular joint involvement in juvenile idiopathic arthritis: a pilot study comparing clinical examination and ultrasound to magnetic resonance imaging

Objectives. To study the validity of both rheumatological and orthodontic examinations and ultrasound (US) as screening methods for early diagnosis of TMJ arthritis against the gold standard MRI. Methods. Thirty consecutive juvenile idiopathic arthritis (JIA) patients were included in this pilot study. Rheumatological and orthodontic examinations as well as US were performed within 1 month of the MRI in a blinded fashion. Joint effusion and/or increased contrast enhancement of synovium or bone were considered signs of active arthritis on MRI. Results. A total of 19/30 (63%) patients and 33/60 (55%) joints had signs of TMJ involvement on MRI. This was associated with condylar deformity in 9/19 (47%) patients and 15/33 (45%) joints. Rheumatological, orthodontic and US examinations correctly diagnosed 11 (58%), 9 (47%) and 6 (33%) patients, respectively, with active TMJ arthritis, but misdiagnosed 8 (42%), 10 (53%) and 12 (67%) patients, respectively, as having no signs of inflammation. The best predictor for active arthritis on MRI was a reduced maximum mouth opening. Conclusion. None of the methods tested was able to reliably predict the presence or absence of MRI-proven inflammation in the TMJ in our cohort of JIA patients. US was the least useful of all methods tested to exclude active TMJ arthriti