Plasma Renin Activity and Its Association With Ischemic Heart Disease,Congestive Heart Failure,and Cerebrovascular Disease in a Large Hypertensive Cohort

Plasma renin activity (PRA) may be a surrogate for vascular damage. The authors hypothesize that PRA is associated with cardiovascular and cerebrovascular disease (CED). A cross‐sectional study (January 1, 1998, to December 31, 2009) was performed on hypertensive individuals 18 years and older using multivariable logistic regression models to estimate odds ratios (ORs) for ischemic heart disease (IHD), congestive heart failure (CHF), and CED based on PRA quartiles controlling for age, sex, race, diabetes mellitus (DM), and medication use. Among 7887 individuals (60% women; 34% whites, 23% blacks, and 19% Hispanics; and 29% with DM), the adjusted ORs (95% CI) for IHD were 0.94 (0.80–1.10), 1.09 (0.92–1.29), and 1.18 (1.00–1.39); for CHF were 1.23 (0.99–1.53), 1.27 (1.01–1.61), and 1.41 (1.13–1.77); and for CED were 0.95 (0.78–1.17), 0.77 (0.61–0.97), and 0.97 (0.78–1.20) for the second, third, and fourth quartiles compared with the first quartile. Higher PRA was associated with greater likelihood for prevalent IHD and CHF but not CED in this large ethnically diverse population of hypertensive individuals.     

Atomic layout of an orthodontic titanium mini-implant in human tissue: Insights into the possible mechanisms during osseointegration

Objectives:To evaluate nanoscale molecular interactions in the interface between human bone and orthodontic titanium implants.Materials and Methods:An orthodontic implant (sandblasted with large grit and with an acid-etched surface treated with Ti6A14V alloy) retrieved from the mandible of human after 2 months of healing was used to analyze the molecular interactive mechanism between the implant and the surrounding bone tissue. To preserve the natural state of the sample as much as possible, cryofixation and scanning electron microscope/focused ion beam milling without any chemical treatment were used during sample preparation. Atom probe tomography was used to investigate the chemical composition and structure at the interface between the implant and human bone tissue.Results:Three-dimensional (3D) reconstruction of the whole sample revealed a 20 × 50-nm² plate-like bony element diffusion layer in the sample. The iso concentration analysis of the diffusion layer indicated that the bony element, calcium, and the implant element, titanium oxide, were interspersed with each other. Detailed ionic distribution was illustrated by 3D reconstruction with partial region of interest and one-dimensional concentration profiles of the implant-bone interface.Conclusions:The study results advance nanoscale understanding of osseointegration and suggest a potential nanostructure for increasing bond strength of biomaterials to bone.     

Timing of Return to Dialysis in Patients with Failing Kidney Transplants

In the last decade, the number of patients starting dialysis after a failed kidney transplant has increased substantially. These patients appear to be different from their transplant‐naïve counterparts, and so may be the timing of dialysis therapy initiation. An increasing number of studies suggest that in transplant‐naïve patients, later dialysis initiation is associated with better outcomes. Very few data are available on timing of dialysis reinitiation in failed transplant recipients, and they suggest that an earlier return to dialysis therapy tended to be associated with worse survival, especially among healthier and younger patients and women. Failed transplant patients may also have unique issues such as continuation of immunosuppression versus withdrawal or the need for remnant allograft nephrectomy with regard to dialysis reinitiation. These patients may have a different predialysis preparation work‐up, worse blood pressure control, higher or lower serum phosphorus levels, lower serum bicarbonate concentration, and worse anemia management. The choice of dialysis modality may also represent an important question for these patients, even though there appears to be no difference in mortality between patients starting peritoneal versus hemodialysis. Finally, failed transplant patients returning to dialysis appear to have a higher mortality rate compared with transplant‐naïve incident dialysis patients, especially in the first several months of dialysis therapy. In this review, we will summarize the available data related to the timing of dialysis initiation and outcomes in failed kidney transplant patients after returning to dialysis.     

Loss of p53 cooperates with K‐ras activation to induce glioma formation in a region‐independent manner

Gliomas are recognized as a heterogeneous group of neoplasms differing in their location and morphological features. These differences, between and within varying grades of gliomas, have not been explained solely on the grounds of an oncogenic stimulus. Interactions with the tumor microenvironment as well as inherent characteristics of the cell of origin are likely a source of this heterogeneity. There is an ongoing debate over the cell of origin of gliomas, where some suggest a progenitor, while others argue for a stem cell origin. Thus, it is presumed that neurogenic regions of the brain such as the subventricular zone (SVZ) containing large numbers of neural stem and progenitor populations are more susceptible to transformation. Our studies demonstrate that K‐ras^G12D cooperates with the loss of p53 to induce gliomas from both the SVZ and cortical region, suggesting that cells in the SVZ are not uniquely gliomagenic. Using combinations of doxycycline‐inducible K‐ras^G12D and p53 loss, we show that tumors induced by the cooperative actions of these genes remain dependent on active K‐ras expression, as deinduction of K‐ras^G12D leads to complete tumor regression despite absence of p53. These results suggest that the interplay between specific combinations of genetic alterations and susceptible cell types, rather than the site of origin, are important determinates of gliomagenesis. Additionally, this model supports the view that, although several genetic events may be necessary to confer traits associated with oncogenic transformation, inactivation of a single oncogenic partner can undermine tumor maintenance, leading to regression and disease remission. GLIA 2013;61:1862–1872     

Denosumab Reduces Cortical Porosity of the Proximal Femoral Shaft in Postmenopausal Women With Osteoporosis

Hip fractures account for over one‐half the morbidity, mortality, and cost associated with osteoporosis. Fragility of the proximal femur is the result of rapid and unbalanced bone remodeling events that excavate more bone than they deposit, producing a porous, thinned, and fragile cortex. We hypothesized that the slowing of remodeling during treatment with denosumab allows refilling of the many cavities excavated before treatment now opposed by excavation of fewer new resorption cavities. The resulting net effect is a reduction in cortical porosity and an increase in proximal femur strength. Images were acquired at baseline and 36 months using multidetector CT in 28 women receiving denosumab and 22 women receiving placebo in a substudy of FREEDOM, a randomized, double‐blind, placebo‐controlled trial involving women with postmenopausal osteoporosis. Porosity was quantified using StrAx1.0 software. Strength was estimated using finite element analysis. At baseline, the higher the serum resorption marker, CTx, the greater the porosity of the total cortex (r = 0.34, p = 0.02), and the higher the porosity, the lower the hip strength (r = –0.31, p = 0.03). By 36 months, denosumab treatment reduced porosity of the total cortex by 3.6% relative to baseline. Reductions in porosity relative to placebo at 36 months were 5.3% in total cortex, 7.9% in compact‐appearing cortex, 5.6% in outer transitional zone, and 1.8% in inner transitional zone (all p < 0.01). The improvement in estimated hip integral strength of 7.9% from baseline (p < 0.0001) was associated with the reduction in total porosity (r = –0.41, p = 0.03). In summary, denosumab reduced cortical porosity of the proximal femoral shaft, resulting in increased mineralized matrix volume and improved strength, changes that may contribute to the reduction in hip and nonvertebral fractures reported with denosumab therapy. © 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).     

Triad of bilateral duplicated permanent teeth, persistent open apex, and tooth malformation: a case report

AIM: The aim of this article is to report a case of bilateral multiple impacted supernumerary teeth. A discussion of possible mechanisms of development is also presented along with a concise review of the literature. BACKGROUND: Supernumerary teeth occur in the context of various scenarios in the primary and the permanent dentition. Multiple supernumerary teeth are a rare finding especially in the absence of associated syndrome or disease. REPORT: A case of bilateral multiple impacted supernumerary teeth localized to the mandibular premolar region is reported. Some of the supernumerary teeth as well as the erupted premolars had persistent open apices. Coronal malformation of the right maxillary first premolar was another interesting finding. There was an absence of any concomitant disease. SUMMARY: The aforementioned combination of findings has not been reported previously. The anatomical, geometrical, and spatial relationships of supernumerary teeth with their erupted equivalents may shed light on some controversial aspects of the etiology.     

Synthesis of thioether derivatives of quinazoline-4-one-2-thione and evaluation of their antiplatelet aggregation activity

A series of 2-(arylmethylthio)-3-phenylquinazolin-4-one derivatives have been synthesized and their antiplatelet aggregation activities were assessed against ADP and arachidonic acid-induced platelet aggregation in human plasma. Among the tested thioethers, derivative 2, 3, 5 and 16 were the most potent compounds with satisfactory IC₅₀ for inhibition of platelet aggregation induced by ADP. Analysis of global physicochemical parameters shows some correlations between activities and molecular volume and also surface area of the studied derivatives.     

Cortical Porosity Identifies Women With Osteopenia at Increased Risk for Forearm Fractures

Most fragility fractures arise among the many women with osteopenia, not the smaller number with osteoporosis at high risk for fracture. Thus, most women at risk for fracture assessed only by measuring areal bone mineral density (aBMD) will remain untreated. We measured cortical porosity and trabecular bone volume/total volume (BV/TV) of the ultradistal radius (UDR) using high‐resolution peripheral quantitative computed tomography, aBMD using densitometry, and 10‐year fracture probability using the country‐specific fracture risk assessment tool (FRAX) in 68 postmenopausal women with forearm fractures and 70 age‐matched community controls in Olmsted County, MN, USA. Women with forearm fractures had 0.4 standard deviations (SD) higher cortical porosity and 0.6 SD lower trabecular BV/TV. Compact‐appearing cortical porosity predicted fracture independent of aBMD; odds ratio (OR) = 1.92 (95% confidence interval [CI] 1.10–3.33). In women with osteoporosis at the UDR, cortical porosity did not distinguish those with fractures from those without because high porosity was present in 92% and 86% of each group, respectively. By contrast, in women with osteopenia at the UDR, high porosity of the compact‐appearing cortex conferred an OR for fracture of 4.00 (95% CI 1.15–13.90). In women with osteoporosis, porosity is captured by aBMD, so measuring UDR cortical porosity does not improve diagnostic sensitivity. However, in women with osteopenia, cortical porosity was associated with forearm fractures. © 2014 American Society for Bone and Mineral Research.