A prospective,randomized placebo‐controlled clinical trial on the effects of a fluoride rinse on white spot lesion development and bleeding in orthodontic patients

Demineralizations around orthodontic brackets are a main disadvantage of orthodontic treatment. Several methods have been advocated to prevent their development, such as fluoride rinses or varnishes. In this randomized clinical trial, a fluoride rinse (a combination of sodium fluoride and amine fluoride) was compared with a placebo rinse, to be used every evening after toothbrushing. A total of 81 participants (mean age: 13.3 yr) completed the study (mean treatment period: 24.5 months). Demineralizations, measured using quantitative light‐induced fluorescence and the decayed, missing, and filled surfaces (DMFS) index, were assessed before treatment (baseline) and around 6 wk after debonding (post treatment). Bleeding scores were measured at baseline, and during and post treatment. The incidence rate ratio for demineralizations was 2.6 (95% CI: 1.1–6.3) in the placebo group vs. the fluoride group. In the fluoride group, 31% of participants developed at least one demineralization, compared with 47% in the placebo group. Relative to baseline, gingival bleeding increased significantly in the placebo group 1 yr after the start of treatment and onwards. For the fluoride group, bleeding scores during treatment were not different from those at baseline. In conclusion, using a fluoride rinse helps to maintain better oral health during fixed appliance treatment, resulting in fewer demineralizations.     

Improved GFR and renal plasma perfusion following remote ischaemic conditioning in a porcine kidney transplantation model

Delayed graft function (DGF) complicates approximately 25% of kidney allografts donated after brain death (DBD). Remote ischaemic conditioning (rIC) involves brief, repetitive, ischaemia in a distant tissue in connection with ischaemia/reperfusion in the target organ. rIC has been shown to induce systemic protection against ischaemic injuries. Using a porcine kidney transplantation model with donor (63 kg) recipient (15 kg) size mismatch, we investigated the effects of recipient rIC on early renal plasma perfusion and GFR. Brain death was induced in donor pigs (n = 8) and kidneys were removed and kept in cold storage until transplantation. Nephrectomized recipient pigs were randomized to rIC (n = 8) or non‐rIC (n = 8) with one kidney from the same donor in each group. rIC consisted of 4 × 5 min clamping of the abdominal aorta. GFR was significantly higher in the rIC group compared with non‐rIC (7.2 ml/min vs. 3.4 ml/min; ΔGFR = 3.7 ml/min, 95%‐CI: 0.3–7.2 ml/min, P = 0.038). Renal plasma perfusion in both cortex and medulla measured by dynamic contrast‐enhanced magnetic resonance imaging (MRI) was significantly higher over time in the rIC group compared with non‐rIC. This experimental study demonstrated a positive effect of rIC on early graft perfusion and function in a large animal transplantation model.     

Atorvastatin dose-dependently decreases hepatic lipase activity in type 2 diabetes: effect of sex and the LIPC promoter variant

OBJECTIVE: Hepatic lipase (HL) is involved in the metabolism of several lipoproteins and may contribute to the atherogenic lipid profile in type 2 diabetes. Little is known about the effect of cholesterol synthesis inhibitors on HL activity in relation to sex and the hepatic lipase gene, the LIPC promoter variant in type 2 diabetes. Therefore, we studied the effect of atorvastatin 10 mg (A10) and 80 mg (A80) on HL activity in 198 patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Patients (aged 45-75 years, without manifest coronary artery disease, total cholesterol 4.0-8.0 mmol/l, and fasting triglycerides [TG] 1.5-6.0 mmol/l) were included in a double-blind, randomized, placebo-controlled trial for 30 weeks (Diabetes Atorvastatin Lipid Intervention study). RESULTS: HL activity at baseline was significantly higher in our population compared with an age-matched control group without type 2 diabetes (406 +/- 150 vs. 357 +/- 118 units/l). HL activity in men versus women (443 +/- 158 vs. 358 +/- 127 units/l), in carriers of the LIPC C/C allele versus carriers of the T/T allele (444 +/- 142 vs. 227 +/- 96 units/l), and in Caucasians versus blacks (415 +/- 150 vs. 260 +/- 127 units/l) all differed significantly (P < 0.001). Atorvastatin dose-dependently decreased HL (A10, -11%; A80, -22%; both P < 0.001). Neither sex nor the LIPC C-->T variation influenced the effect of atorvastatin on HL activity. CONCLUSIONS: Sex, LIPC promoter variant, and ethnicity significantly contribute to the baseline variance in HL activity. Atorvastatin treatment in diabetic dyslipidemia results in a significant dose-dependent decrease in HL activity, regardless of sex or the LIPC promoter variant.     

Corpus callosum differences associated with persistent stuttering in adults

Recent studies have implicated anatomical differences in speech-relevant brain regions of adults who stutter (AWS) compared to normally fluent adults (NFA). The present study focused on the region of the corpus callosum (CC) which is involved in interhemispheric processing between the left and right cerebral hemispheres. Two-dimensional segmentation of area and voxel-based morphometry were used to evaluate the corpus callosum. Results revealed that the rostrum and anterior midbody of the CC were larger in AWS than NFA. In addition, the overall callosa area was larger in AWS than NFA. The group comparison of white matter volume showed a cluster of increased white matter volume predominantly encompassing the rostrum across the midline portion in AWS. These results potentially reflect anatomical changes associated with differences in the hemispheric distribution of language processes that have been reported previously in AWS.     

MicroRNAs in Atrial Fibrillation: from Expression Signatures to Functional Implications

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with pronounced morbidity and mortality. Its prevalence, expected to further increase for the forthcoming years, and associated frequent hospitalizations turn AF into a major health problem. Structural and electrical atrial remodelling underlie the substrate for AF, but the exact mechanisms driving this remodelling remain incompletely understood. Recent studies have shown that microRNAs (miRNA), short non-coding RNAs that regulate gene expression, may be involved in the pathophysiology of AF. MiRNAs have been implicated in AF-induced ion channel remodelling and fibrosis. MiRNAs could therefore provide insight into AF pathophysiology or become novel targets for therapy with miRNA mimics or anti-miRNAs. Moreover, circulating miRNAs have been suggested as a new class of diagnostic and prognostic biomarkers of AF. However, the origin and function of miRNAs in tissue and plasma frequently remain unknown and studies investigating the role of miRNAs in AF vary in design and focus and even present contradicting results. Here, we provide a systematic review of the available clinical and functional studies investigating the tissue and plasma miRNAs in AF and will thereafter discuss the potential of miRNAs as biomarkers or novel therapeutic targets in AF.     

An islet-homing NOD CD8+ cytotoxic T cell clone recognizes GAD65 and causes insulitis

T cells play a central role in the development of diabetes both in man and in the non-obese diabetic (NOD) mouse. Both the CD4(+) and CD8(+) subsets of T cells are required for the normal development of IDDM in NOD mice. Islet reactive CD4(+) T cells play a clear pathogenic role as evidenced from the isolation of diabetogenic CD4(+) T cell clones. CD8(+) T cells seem to be involved in the initiation of diabetes as lack of these cells leads to protection from diabetes. We have isolated a GAD(65) reactive, cytotoxic CD8(+) T cell clone R1 that produces large quantities of IFNgamma and accelerates the onset of insulitis. This clone proliferates and produces IFNgamma in response to GAD(65) presenting APCs and kills GAD(65) presenting targets. Furthermore, it expresses TNFalpha, CD25, CD28, CD44, CD45 and LFA1, but not CD95L This is the first example of a GAD(65)specific CD8(+) T cell clone that accelerates the onset of the insulitis, although it does not appear to accelerate the onset of diabetes.