Chronic <Emphasis Type="Italic">Escherichia coli</Emphasis> infection induces muscle wasting without changing acetylcholine receptor numbers

Objective Muscle weakness in septic patients is a serious problem as it complicates and lengthens hospital stays, prolongs rehabilitation and increases costs. We examined the effects of a chronic infection with Escherichia coli on muscle function, muscle mass, and the expression of nicotinic acetylcholine receptors (AChRs). Design and setting Prospective, randomized animal study in an animal laboratory, university hospital. Subjects Sprague-Dawley rats. Interventions A catheter was implanted into the external jugular vein of anesthetized rats, and a dose of 3.2 × 10⁸ CFU of E. coli bacteria was injected; the catheter was then sealed and tunneled subcutaneously. Measurements and results Animals injected with E. coli bacteria showed a significant decrease in body and muscle mass over the 14-day experimental period. Neuromuscular function was tested by mechanomyography on days 3, 7, and 14 following injection. Tetanic tension decreased over the time course of sepsis, without effecting tetanic fade. Serum levels of acute-phase protein, α₁-acid glycoprotein, were increased by day 3, and remained significantly higher until day 14. AChRs were quantitated using ¹²⁵I-labeled bungarotoxin and revealed no differences between groups. Conclusions Central venous injection of E. coli bacteria induces systemic inflammation evidenced as loss of body weight, muscle mass and increased α₁-acid glycoprotein levels. The inflammation-induced muscle weakness is due to muscle atrophy and not to upregulated AChRs. This model may prove useful for studying maneuvers to prevent muscle wasting with inflammation.     

Two-centre evaluation of a resin composite/ self-etching restorative system: three-year findings

PURPOSE: This two-centre study evaluated the clinical performance of Class I and Class II restorations of the giomer material Beautifil, placed using Fluorobond, a self-etching adhesive system, to determine the suitability of the test system as an alternative for the restoration of posterior teeth. MATERIALS AND METHODS: A total of 108 restorations, comprising 72 Class II and 36 Class I restorations, was placed predominantly in molars (82%). Evaulations using modified USPHS/Ryge criteria were conducted at baseline and thereafter at 6 months and 1, 2, and 3 years. Die stone replicas of the restored teeth were examined retrospectively. RESULTS: A total of 5 restorations was found to fail during the study-- 3 in the first year and 2 during the third year of the study. Occlusal marginal adaptation was less than ideal at baseline in 11% of cases, primarily as a consequence of overcontouring, as observed in the die stone replicas. The combined percentage Alpha ratings at 3 years were: colour match, 98%; marginal adaptation (occlusal), 78%; marginal adaptation (proximal), 97%; anatomic form (occlusal), 99%; anatomic form (proximal), 95%; surface roughness (occlusal), 100%; surface roughness (proximal), 100%; marginal staining (occlusal), 90%; marginal staining (proximal) 81%; interfacial staining (occlusal), 99%; interfacial staining (proximal), 100%; contacts (occlusal), 95%; contacts (proximal), 93%; sensitivity, 100%; secondary caries, 100%; lustre of restoration, 100%. CONCLUSION: It is concluded that the 3-year performance of Fluorobond-bonded Beautifil for Class I and II restorations demonstrated some marginal changes, but most of the direct evaluation ratings were > 90% Alpha, with the performance observed being similar in the two centres.     

Lessons learned during the conduct of clinical studies in the dental PBRN

Effectively addressing challenges of conducting research in nonacademic settings is crucial to its success. A dental practice-based research network called The Dental Practice-Based Research Network (DPBRN) is comprised of practitioner- investigators in two health maintenance organizations, several universities, many U.S. states, and three Scandinavian countries. Our objective in this article is to describe lessons learned from conducting studies in this research context; the studies are conducted by clinicians in community settings who may be doing their first research study. To date, twenty-one studies have been completed or are in implementation. These include a broad range of topic areas, enrollment sizes, and study designs. A total of 1,126 practitioner-investigators have participated in at least one study. After excluding one study because it involved electronic records queries only, these studies included more than 70,000 patient/participant units. Because the DPBRN is committed to being both practitioner- and patient-driven, all studies must be approved by its Executive Committee and a formal study section of academic clinical scientists. As a result of interacting with a diverse range of institutional and regulatory entities, funding agencies, practitioners, clinic staff, patients, academic scientists, and geographic areas, twenty-three key lessons have been learned. Patients' acceptance of these studies has been very high, judging from high participation rates and their completion of data forms. Early studies substantially informed later studies with regard to study design, practicality, forms design, informed consent process, and training and monitoring methods. Although time-intensive and complex, these solutions improved acceptability of practice-based research to patients, practitioners, and university researchers.     

The varied spectrum of nephroblastomatosis,nephrogenic rests,and Wilms tumors: Review of current definitions and challenges of the field

The diagnosis of multiple or diffuse renal lesions in a child is challenging by imaging and/or pathology. Optimal management requires distinguishing benign lesions such as nephrogenic rests from cancerous lesions such as Wilms tumor, but this is often difficult or impossible. This difficulty is compounded by the overlapping nature of our current radiologic and pathologic definitions of lesions along the spectrum of nephrogenic rests/nephroblastomatosis. We provide a review of these issues, as a collaborative effort between the Children's Oncology Group Renal Tumor Committee and International Society of Pediatric Oncology Renal Tumor Study Group. Our aim is to discuss current challenges in diagnosis and management of these renal lesions, encouraging future work toward consensus definitions for research and patient care.     

IgG N-glycans are associated with prevalent and incident complications of type 2 diabetes

Aims/Hypothesis

Inflammation is important in the development of type 2 diabetes complications. The N-glycosylation of IgG influences its role in inflammation. To date, the association of plasma IgG N-glycosylation with type 2 diabetes complications has not been extensively investigated. We hypothesised that N-glycosylation of IgG may be related to the development of complications of type 2 diabetes.

Methods

In three independent type 2 diabetes cohorts, plasma IgG N-glycosylation was measured using ultra performance liquid chromatography (DiaGene n = 1815, GenodiabMar n = 640) and mass spectrometry (Hoorn Diabetes Care Study n = 1266). We investigated the associations of IgG N-glycosylation (fucosylation, galactosylation, sialylation and bisection) with incident and prevalent nephropathy, retinopathy and macrovascular disease using Cox- and logistic regression, followed by meta-analyses. The models were adjusted for age and sex and additionally for clinical risk factors.

Results

IgG galactosylation was negatively associated with prevalent and incident nephropathy and macrovascular disease after adjustment for clinical risk factors. Sialylation was negatively associated with incident diabetic nephropathy after adjustment for clinical risk factors. For incident retinopathy, similar associations were found for galactosylation, adjusted for age and sex.

Conclusions

We showed that IgG N-glycosylation, particularly galactosylation and to a lesser extent sialylation, is associated with a higher prevalence and future development of macro- and microvascular complications of diabetes. These findings indicate the predictive potential of IgG N-glycosylation in diabetes complications and should be analysed further in additional large cohorts to obtain the power to solidify these conclusions.