Effects of insulin resistance and insulin secretion on the efficacy of interventions to retard development of type 2 diabetes mellitus: the DA Qing IGT and Diabetes Study

OBJECTIVE: To investigate the effects of insulin resistance (IR) and insulin secretion (IS) on the development of diabetes mellitus in individuals with impaired glucose tolerance (IGT) who underwent lifestyle interventions. METHODS: 284 out of 577 individuals with IGT identified by population-based screening in Da Qing, China, who were randomized to undergo diet change and/or increased physical activity had baseline fasting and 2 h post-load insulin determinations. They were followed for 6 years for the development of diabetes. IR and IS were assessed using calculated indices based on fasting plasma insulin and glucose. The interactions of IR, IS, obesity and plasma glucose and the effects of the lifestyle interventions were evaluated using Cox Proportional Hazards analysis. RESULTS: Both IR and IS were significantly associated with the development of diabetes. Lifestyle interventions were more effective in those with lower IT and higher IS at baseline. Diet plus exercise interventions resulted in significantly lower incidence of diabetes, even after controlling for IR, IS, BMI and 2hrPG. CONCLUSION: Both IR and beta-cell function were predictors of diabetes in Chinese with IGT. Lifestyle intervention reduced the incidence of DM and these interventions were more effective in those with less IR.     

Interleukin-11 stimulates multilineage progenitors, but not stem cells, in murine and human long-term marrow cultures

Interleukin-11 (IL-11) is a bone marrow microenvironment-derived growth factor with pleiotropic effects on a variety of hematopoietic cells. To more accurately assess the effects of IL-11 on stem and progenitor compartments within the hematopoietic microenvironment (HM), we added recombinant human (rh) IL-11 to human and murine long-term bone marrow cultures (LTMC) and analyzed primitive (high proliferative potential- colony forming cells [HPP-CFC], long-term culture-initiating cells [LTC- IC], and long-term reconstituting stem cells) and progenitor (day 12 colony forming unit-spleen [CFU-S12], colony forming unit-megakaryocyte [CFU-Mk] and colony forming unit-granulocyte/macrophage [CFU-GM]) compartments throughout the duration of the cultures. rhIL-11 (100 ng/mL) added twice weekly resulted in significantly increased nonadherent (NA) cellularity, CFU-GM, and CFU-Mk production in human LTMC. Addition of rhIL-11 to murine LTMC was associated with a 5- to 40- fold increase in CFU-GM and a four- to 20-fold increase in day 12 CFU-S in NA cells. However, IL-11 had no significant effect on total HPP-CFC concentration and decreased the size of the more primitive stem/progenitor compartment as evidenced by both decreased LTC-IC frequency in human LTMC and decreased frequency of long-term reconstituting stem cells in murine LTMC. These data suggest that IL-11 may increase commitment of stem cells into a multipotential progenitor compartment.     

Cross-sectional analysis of the implant-abutment interface

The purpose of this study was to develop a technique to evaluate the implant-abutment gap of an external hexagon implant system as a function of radius. Six implants of 3.75 mm in diameter (Conexao Sistema de Protese Ltda, Sao Paulo, Brazil) and their respective abutments were screw connected and torqued to 20 N cm(-1). The implants were mounted in epoxy assuring an implant long-axis position perpendicular to the vertical axis. Each implant was grounded through its thickness parallel to implant long-axis at six different distance interval. Implant-abutment gap distances were recorded along the implant-abutment region for each section. Individual measurements were related to their radial position through trigonometric inferences. A sixth degree polynomial line fit approach determined radial adaptation patterns for each implant. Micrographs along implant sections showed a approximately 300 mum length implant-abutment engagement region. All implants presented communication between external and internal regions through connection gaps and inaccurate implant-abutment alignment. Average gap distances were not significantly different between implants (P > 0.086). Polynomial lines showed implant-abutment gap values below 10 mum from 0 mum to approximately 250 mum of the implant-abutment engagement region. Gap distances significantly increased from approximately 250 mum to the outer radius of the implant-abutment engagement region. The technique described provided a broader scenario of the implant-abutment gap adaptation compared with previous work concerning implant-abutment gap determination, and should be considered for better understanding mechanical aspects or biological effects of implant-abutment adaptation on peri-implant tissues.     

Analysis of autonomic outcomes in APOLLO,a phase III trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (n = 148) or placebo (n = 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo [COMPASS-31, least squares (LS) mean difference, − 7.5; 95% CI: − 11.9, − 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, − 1.1; − 1.8, − 0.5], nutritional status (modified body mass index, LS mean difference, 115.7; − 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, − 0.3; − 0.5, − 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, − 5.3; 95% CI: − 7.9, − 2.7) and individual domains, orthostatic intolerance (− 4.6; − 6.3, − 2.9) and gastrointestinal symptoms (− 0.8; − 1.5, − 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.

     

肢带型肌营养不良的MRI表现

目的 观察肢带型肌营养不良的MRI表现。方法 回顾性分析7例经临床及病理检查确诊为肢带型肌营养不良患者的MRI资料,观察双侧大腿肌群脂肪沉积与炎性水肿情况,采用4分法进行评价。并进行统计学分析。结果 肢带型肌营养不良患者大腿肌群MRI均可见脂质沉积和炎性水肿性改变。不同肌肉间脂肪沉积(χ²=75.596,P<0.01)与炎性水肿差异均有统计学意义(χ²=41.368,P<0.01),双侧大腿肌群间脂肪沉积与炎性水肿差异均无统计学意义(P均>0.05)。结论 肢带型肌营养不良患者大腿肌群MRI信号特点及分布具有一定特征,MR检查有助于疾病的诊断。     

Prevalence of Candida spp., xerostomia,and hyposalivation in oral lichen planus – A controlled study

Objective

To determine the frequency of Candida spp., xerostomia, and salivary flow rate (SFR) in three different groups: patients with OLP (OLP group), patients with oral mucosal lesions other than OLP (non‐OLP group), and subjects without oral mucosal lesions (control group).

Material and methods

Xerostomia as well as SFR was investigated in the three groups. Samples for isolation of Candida spp. were collected from OLP lesions (38 patients), non‐OLP lesions (28 patients), and healthy subjects (32 subjects).

Results

There was no statistically significant difference regarding the frequency of xerostomia and hyposalivation among the three groups (P > 0.05). A higher prevalence for colonization by Candida spp. was found in the healthy subject as compared to that of patients with OLP (P = 0.03) and non‐OLP (P = 0.02) groups. Low SFR was not a factor for colonization by Candida spp.

Conclusions

Xerostomia and hyposalivation occur with similar frequency in subjects with and without oral lesions; also, the presence of oral lesions does not increase the susceptibility to colonization by Candida spp. It seems that any study implicating Candida spp. in the malignant transformation of oral lesions should be carried out mostly on a biochemical basis, that is, by testing the capability of Candida spp. to produce carcinogenic enzyme.