Load-bearing capacity of all-ceramic posterior four-unit fixed partial dentures with different zirconia frameworks

The aim of this in vitro study was to compare the load-bearing capacity of posterior four-unit fixed partial dentures (FPDs) produced with two different yttria-stabilized polycrystalline tetragonal zirconia (Y-TZP) ceramics, one being a presintered material, the other a fully sintered, hot isostatically pressed material. Additionally, as a novel approach, the influence of preliminary mechanical damage upon the fracture force of an FPD has been investigated. A total of 20 frameworks each were milled from presintered zirconia and from fully sintered zirconia. Prior to veneering, 10 frameworks of each material were 'damaged' by a defined saw cut similar to an accidental flaw generated during shape cutting. Before fracture testing, all FPDs were subjected to thermal and mechanical cycling. Additionally, scanning electron microscopy was used to investigate fracture surfaces. Statistical analysis showed that FPDs milled from fully sintered zirconia had a significantly higher fracture resistance compared with specimens made from presintered material, whereas preliminary damage did not have a significant effect. After aging, FPDs made from both materials were capable of withstanding occlusal forces reported in the literature. Therefore, both types of Y-TZP may be suitable for posterior four-unit all-ceramic FPDs, although further prolonged aging experiments and prospective clinical trials are required to prove their fitness for clinical use.     

Neuropeptide Y Attenuates Stress‐Induced Bone Loss Through Suppression of Noradrenaline Circuits

Chronic stress and depression have adverse consequences on many organ systems, including the skeleton, but the mechanisms underlying stress‐induced bone loss remain unclear. Here we demonstrate that neuropeptide Y (NPY), centrally and peripherally, plays a critical role in protecting against stress‐induced bone loss. Mice lacking the anxiolytic factor NPY exhibit more anxious behavior and elevated corticosterone levels. Additionally, following a 6‐week restraint, or cold‐stress protocol, Npy‐null mice exhibit three‐fold greater bone loss compared to wild‐type mice, owing to suppression of osteoblast activity. This stress‐protective NPY pathway acts specifically through Y2 receptors. Centrally, Y2 receptors suppress corticotropin‐releasing factor expression and inhibit activation of noradrenergic neurons in the paraventricular nucleus. In the periphery, they act to control noradrenaline release from sympathetic neurons. Specific deletion of arcuate Y2 receptors recapitulates the Npy‐null stress response, coincident with elevated serum noradrenaline. Importantly, specific reintroduction of NPY solely in noradrenergic neurons of otherwise Npy‐null mice blocks the increase in circulating noradrenaline and the stress‐induced bone loss. Thus, NPY protects against excessive stress‐induced bone loss, through Y2 receptor‐mediated modulation of central and peripheral noradrenergic neurons. © 2014 American Society for Bone and Mineral Research.     

Interreader and intermodality reliability of standard anteroposterior radiograph and magnetic resonance imaging in detection and classification of lumbosacral transitional vertebra

Background contextDifferent types of lumbosacral transitional vertebra (LSTV) are classified based on the relationship of the transverse process of the last lumbar vertebra to the sacrum. The Ferguson view (30° angled anteroposterior [AP] radiograph) is supposed to have a sufficient interreader reliability in classification of LSTV, but is not routinely available. Standard AP radiographs and magnetic resonance imaging (MRI) are often available, but their reliability in detection and classification of LSTV is unknown.PurposeThe purpose of this study was to evaluate the interreader reliability of detection and classification of LSTV with standard AP radiographs and report its accuracy by use of intermodality statistics compared with MRI as the gold standard.Study design/settingRetrospective case control study.Patient sampleA total of 155 subjects (93 cases: LSTV type 2 or higher; 62 controls).Outcome measuresInterreader reliability in detection and classification of LSTV using standard AP radiographs and coronal MRI as well as accuracy of radiographs compared with MRI.MethodsAfter institutional review board approval, coronal MRI scans and conventional AP radiographs of 155 subjects (93 LSTV type 2 or higher and 62 controls) were retrospectively reviewed by two independent, blinded readers and classified according to the Castellvi classification. Interreader reliability was assessed using kappa statistics for detection of an LSTV and identification of all subtypes (six variants; 1: no LSTV or type I, 2: LSTV type 2a, 3: LSTV type 2b, 4: LSTV type 3a, 5: LSTV type 3b, 6: LSTV type 4) for MRI scans and standard AP radiographs. Further, accuracy and positive and negative predictive values were calculated for standard AP radiographs to detect and classify LSTV using MRI as the gold standard.ResultsThe interreader reliability was at most moderate for the detection (k=0.53) and fair for classification (wk=0.39) of LSTV in standard AP radiograph. However, the interreader reliability was very good for detection (k=0.93) and classification (wk=0.83) of LSTV in MRI. The accuracy and positive and negative predictive values of standard AP radiograph were 76% to 84%, 72% to 86%, and 79% to 81% for the detection and 53% to 58%, 51% to 76%, and 49% to 55% for the classification of LSTV, respectively.ConclusionStandard AP radiographs are insufficient to detect or classify LSTV. Coronal MRI scans, however, are highly reliable for classification of LSTV.     

Hormonal determinants of regional body composition in adolescent girls with anorexia nervosa and controls

We have previously demonstrated that girls with anorexia nervosa (AN) have higher levels of GH and cortisol and lower levels of estradiol than healthy adolescents. The effects of endocrine alterations on regional body composition in AN, however, have not been reported. We, therefore, enrolled 23 adolescent girls with AN and 20 healthy girls of comparable maturity in a study examining regional body composition. Levels of estradiol and IGF-I, as well as measures of GH and cortisol concentration (using cluster analysis of data obtained from frequent sampling q30' for 12 h overnight) were examined to determine hormonal determinants of regional body composition in adolescent girls with AN and controls. Girls with AN were followed for 1 yr and examined again at weight recovery (10% increase in body mass index) (n = 11). Percent trunk fat and trunk to extremity fat ratio (T/E fat) were significantly reduced in girls with AN compared with healthy adolescents (P = 0.001 and 0.01, respectively). Percent trunk lean mass and trunk to extremity lean mass ratio (T/E lean) were higher in AN than in controls (P = 0.01 and 0.009); percent extremity lean mass was lower in AN (P = 0.009). In healthy controls, total area under the curve (AUC) for GH correlated inversely with percent trunk fat and T/E fat (r = -0.66, P = 0.002 and r = -0.62, P = 0.003). Similar correlations were observed between other measures of GH concentration (mean and nadir) and percent trunk fat and T/E fat. No relationship was observed between GH concentration and regional lean mass or between cortisol concentration and regional body composition. In contrast, GH concentration did not predict regional body composition in adolescents with AN on regression analysis. However, nadir cortisol concentration correlated inversely with percent extremity lean mass (r = -0.49; P = 0.02) and positively with percent trunk lean mass and T/E lean (r = 0.48, P = 0.03; and r = 0.49, P = 0.02) in girls with AN. A similar trend was observed between other measures of cortisol concentration (mean cortisol and AUC) and percent trunk lean mass and T/E lean in AN. Trunk fat was lowest in girls with AN who had high GH but low cortisol levels (based on median values), whereas some preservation of trunk fat was observed in girls with low GH and high cortisol levels. Weight recovery occurred in seven of 11 girls with low GH and high cortisol values; however, only two of the nine girls with high GH and low cortisol recovered weight. High GH with lower cortisol levels may thus be a marker of greater severity of AN. Our results suggest that in healthy controls, GH concentration predicts regional body composition and favors a redistribution of body fat such that T/E fat ratio decreases. In AN, however, high levels of GH and cortisol have contrasting associations with fat mass. High cortisol levels in AN predict a redistribution of lean body mass such that extremity lean mass decreases. Further studies are necessary to better understand the implications of these data.     

Quantifying a Rare Disease in Administrative Data: The Example of Calciphylaxis

BACKGROUND

Calciphylaxis, a rare disease seen in chronic dialysis patients, is associated with significant morbidity and mortality. As is the case with other rare diseases, the precise epidemiology of calciphylaxis remains unknown. Absence of a unique International Classification of Diseases (ICD) code impedes its identification in large administrative databases such as the United States Renal Data System (USRDS) and hinders patient-oriented research. This study was designed to develop an algorithm to accurately identify cases of calciphylaxis and to examine its incidence and mortality.

DESIGN, PARTICIPANTS, AND MAIN MEASURES

Along with many other diagnoses, calciphylaxis is included in ICD-9 code 275.49, Other Disorders of Calcium Metabolism. Since calciphylaxis is the only disorder listed under this code that requires a skin biopsy for diagnosis, we theorized that simultaneous application of code 275.49 and skin biopsy procedure codes would accurately identify calciphylaxis cases. This novel algorithm was developed using the Partners Research Patient Data Registry (RPDR) (n?=?11,451 chronic hemodialysis patients over study period January 2002 to December 2011) using natural language processing and review of medical and pathology records (the gold-standard strategy). We then applied this algorithm to the USRDS to investigate calciphylaxis incidence and mortality.

KEY RESULTS

Comparison of our novel research strategy against the gold standard yielded: sensitivity 89.2 %, specificity 99.9 %, positive likelihood ratio 3,382.3, negative likelihood ratio 0.11, and area under the curve 0.96. Application of the algorithm to the USRDS identified 649 incident calciphylaxis cases over the study period. Although calciphylaxis is rare, its incidence has been increasing, with a major inflection point during 2006–2007, which corresponded with specific addition of calciphylaxis under code 275.49 in October 2006. Calciphylaxis incidence continued to rise even after limiting the study period to 2007 onwards (from 3.7 to 5.7 per 10,000 chronic hemodialysis patients; r?=?0.91, p?=?0.02). Mortality rates among calciphylaxis patients were noted to be 2.5–3 times higher than average mortality rates for chronic hemodialysis patients.

CONCLUSIONS

By developing and successfully applying a novel algorithm, we observed a significant increase in calciphylaxis incidence. Because calciphylaxis is associated with extremely high mortality, our study provides valuable information for future patient-oriented calciphylaxis research, and also serves as a template for investigating other rare diseases.

     

Sealed primary molars are less likely to develop caries

BackgroundThe authors examined the association between light-polymerized resin-based fluoride-releasing sealants and the development of pit-and-fissure caries on primary molars.MethodsIn this 3-year retrospective study, the authors reviewed the dental records of 297 children (1,352 teeth) younger than 6 years who were at high caries risk. Sealant placement or nonplacement on primary molars in the outpatient clinic and operating room setting was recorded, and random-effects logistic regression analysis accounting for the effect of data clustering was performed to measure caries incidence over time.ResultsThe odds of developing pit-and-fissure carious lesions on sealed primary molars were 0.055 times (95% confidence interval [CI], 0.011 to 0.285; P = .001) and 0.013 times (95% CI, 0.001 to 0.159; P = .001) the odds of that on nonsealed primary molars in the outpatient clinic and in the operating room, respectively. In molars that became carious, those sealed were associated with longer time to caries development in both the outpatient clinic (2.69 years, 95% CI, 2.08 to 3.29) and operating room (1.97 years, 95% CI, 1.45 to 2.48).ConclusionsSealed primary molars were less likely to develop pit-and-fissure caries when placed in both the clinic and operating room settings.Practical ImplicationsDental sealants on primary molars should be considered for children at high caries risk.     

Double deletion of orexigenic neuropeptide Y and dynorphin results in paradoxical obesity in mice

Objective

Orexigenic neuropeptide Y (NPY) and dynorphin (DYN) regulate energy homeostasis. Single NPY or dynorphin deletion reduces food intake or increases fat loss. Future developments of obesity therapeutics involve targeting multiple pathways. We hypothesised that NPY and dynorphin regulate energy homeostasis independently, thus double NPY and dynorphin ablation would result in greater weight and/or fat loss than the absence of NPY or dynorphin alone.

Design and methods

We generated single and double NPY and dynorphin knockout mice (NPYΔ, DYNΔ, NPYDYNΔ) and compared body weight, adiposity, feeding behaviour, glucose homeostasis and brown adipose tissue uncoupling protein-1 (UCP-1) expression to wildtype counterparts.

Results

Body weight and adiposity were significantly increased in NPYDYNΔ, but not in NPYΔ or DYNΔ. This was not due to increased food intake or altered UCP-1 expression, which were not significantly altered in double knockouts. NPYDYNΔ mice demonstrated increased body weight loss after a 24-h fast, with no effect on serum glucose levels after glucose injection.

Conclusions

Contrary to the predicted phenotype delineated from single knockouts, double NPY and dynorphin deletion resulted in heavier mice, with increased adiposity, despite no significant changes in food intake or UCP-1 activity. This indicates that combining long-term opioid antagonism with blockade of NPY-ergic systems may not produce anti-obesity effects.     

Trajectories of the cortisol awakening responses during weight gain in anorexia nervosa patients with severe and less severe symptoms

The aim of this study was to examine the features and changes of the cortisol awakening response (CAR) in patients with anorexia nervosa (AN) with severe and less severe symptoms over the course of inpatient treatment.     

Dissociation,childhood trauma,and the response to fluoxetine in bulimic patients

Histories of childhood trauma have been reported previously in bulimic subjects but no study to date has assessed how these experiences may affect response to fluoxetine. Thirty outpatient subjects in a placebo-controlled trial of 60 mg of fluoxetine for the treatment of bulimia nervosa completed the Dissociative Experiences Scale and a self-report instrument assessing trauma. Response to treatment was measured with the Hamilton Depression Scale-17 (HAMD-17), the CGI, the PGI, and the change in number of binges per day. Subjects taking fluoxetine with histories of physical abuse showed a significantly greater drop in HAMD-17 scores than those without such histories. No relationship between a reported history of abuse and the response of binging to fluoxetine was found. A history of abuse does not appear to predict the response of hinging to fluoxetine but may predict a greater response of nonspecific symptoms like depression. © 1994 by John Wiley & Sons, Inc.