Control of bone resorption in mice by Schnurri-3

Mice lacking the large zinc finger protein Schnurri-3 (Shn3) display increased bone mass, in part, attributable to augmented osteoblastic bone formation. Here, we show that in addition to regulating bone formation, Shn3 indirectly controls bone resorption by osteoclasts in vivo. Although Shn3 plays no cell-intrinsic role in osteoclasts, Shn3-deficient animals show decreased serum markers of bone turnover. Mesenchymal cells lacking Shn3 are defective in promoting osteoclastogenesis in response to selective stimuli, likely attributable to reduced expression of the key osteoclastogenic factor receptor activator of nuclear factor-κB ligand. The bone phenotype of Shn3-deficient mice becomes more pronounced with age, and mice lacking Shn3 are completely resistant to disuse osteopenia, a process that requires functional osteoclasts. Finally, selective deletion of Shn3 in the mesenchymal lineage recapitulates the high bone mass phenotype of global Shn3 KO mice, including reduced osteoclastic bone catabolism in vivo, indicating that Shn3 expression in mesenchymal cells directly controls osteoblastic bone formation and indirectly regulates osteoclastic bone resorption.     

Change of coronary flow velocity during the cold pressor test is related to endothelial markers in subjects with chest pain and a normal coronary angiogram

Background:

Several studies demonstrated that endothelial or atherosclerotic biomarkers, including plasma free insulin‐like growth factor‐I(IGF‐I), soluble CD40 ligand (sCD40L), adiponectin, and leptin have an influence on coronary endothelial function.

Hypothesis:

The aim of the present study was to investigate whether change of coronary flow velocity of the distal left anterior descending artery (LAD) during the cold pressor test (CPT) with transthoracic Doppler echocardiography (TTE) was associated with these biomarkers in subjects with chest pain and a normal coronary angiogram.

Methods:

In 190 subjects (mean age, 54±11 years; male:female, 113:77) with chest pain and a normal coronary angiogram, peak diastolic velocity (PDV) of the distal LAD during the CPT with TTE was assessed. Acetylcholine provocation test was performed in 58 subjects (mean age, 51±10 years) who were clinically suspected of vasospasm. CPT%PDV was defined as the percent change in PDV during the CPT. Associations between CPT%PDV and clinical parameters were analyzed.

Results:

According to multiple regression analysis, CPT%PDV was associated with plasma free IGF‐I in the entire study population (β=0.295, P<0.001 in all subjects; β=0.341, P=0.001 in males; β=0.243, P=0.037 in females; β=0.303, P=0.002 in nonsmokers; and β=0.256, P=0.047 in smokers), and sCD40L in males (β=?0.269, P=0.008)and smokers (β=?0.261, P=0.046). Subjects with vasospasm to intracoronary acetylcholine had lower plasma free IGF‐I(6.9±3.3 vs 8.9±3.4, P=0.026) and CPT%PDV (8.8±24.9 vs 52.7±26.0, P<0.001) than the others. Plasma adiponectin and leptin were not associated with CPT%PDV.

Conclusions:

Change of coronary flow velocity assessed using the CPT with TTE may be related to endothelial markers, especially plasma free IGF‐I. © 2011 Wiley Periodicals, Inc. Additional Supporting Information may be found in the online version of this article. The authors have no funding, financial relationships, or conflicts of interest to disclose.

     

The Relationship Between Arterial Stiffness and Nonalcoholic Fatty Liver Disease

Aim  

Nonalcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease and some studies have documented its link with cardiovascular risk factors. This study aimed to investigate the association between arterial stiffness and NAFLD.     

Mean platelet volume (MPV) is associated with leukoaraiosis in the apparently healthy elderly

Leukoaraiosis refers to diffuse white matter abnormalities on MR brain scans, which have been suggested to be associated with cerebral microangiopathy and geriatric syndromes such as cognitive impairment, depressive mood and gait disturbance. MPV is a simple indicator of platelet size and has been known to be a marker of platelet activity. MPV is now considered a link between inflammation and thrombosis in multiple cardiovascular and cerebrovascular disorders including hypertension, peripheral artery disease, and stroke. This cross-sectional study aims to evaluate the association between MPV and leukoaraiosis for 223 healthy elderly subjects (142 men, 81 women; mean age 66.0±5.2 years) in a health examination program including brain magnetic resonance imaging (MRI) scans. The overall prevalence rate of leukoaraiosis was 15.3%. The mean MPV was significantly higher in the leukoaraiosis group than control group: 8.4±0.8 and 8.1±1.0, respectively (p=0.036). A higher value of MPV was independently associated with an increased risk of leukoaraiosis. In the multivariate logistic analysis, the odds ratio (OR) (95% confidence interval (CI)) for leukoaraiosis was 1.61 (1.02-2.53) with 1 fL of MPV increment after adjusting for confounding variables. In conclusion, MPV was found to be independently and positively associated with leukoaraiosis. This finding indicates that MPV values may be a useful additional measure in assessing the risk of leukoaraiosis in the clinical setting.     

Which symptoms can distinguish between subjective cognitive impairment (SCI) and mild cognitive impairment (MCI)?

The SCI, the MCI, and the Alzheimer's disease (AD) are on a spectrum of disease progression; therefore, identification of the earliest signs of cognitive deterioration is becoming a crucial issue. The goal of this study was to examine symptom characteristics and distinguish predictive symptoms in patients with MCI compared with SCI, using caregiver questionnaires. We assessed the Korean Dementia Screening Questionnaire (KDSQ) and Seoul Instrumental activities of Daily Living (S-IADL) of 344 subjects with SCI and 697 with MCI. Multivariate logistic regression analyses were conducted after adjusting for age, sex, and educational status. Common and rare symptoms were similar between the SCI and MCI groups. The most distinguishing features of KDSQ were 'Finds it hard to go somewhere on his/her own using public transportation' (odds ratio=OR=4.56, p<0.0001), 'Has difficulty in operating appliances' (OR=2.47, p=0.001), and 'Keeps repeating the same question' (OR=2.03, p<0.0001). In S-IADL, the most outstanding features were 'using household appliances' (OR=3.99, p<0.0001), 'taking medication' (OR=2.38, p=0.01), and 'using public transportation' (OR=1.94, p=0.04). The dysfunction in 'using household appliance' and 'using public transportation' reflect the possibility of MCI rather than SCI. Therefore, it is suggested that these symptoms also have a discriminative and predictive power in identifying SCI.     

The association between the triglyceride to high-density lipoprotein cholesterol ratio with insulin resistance (HOMA-IR) in the general Korean population: based on the National Health and Nutrition Examination Survey in 2007-2009

Aim

To investigate circulating visfatin and vaspin levels in first-degree relatives of subjects with type 2 diabetes mellitus (FDRs) who frequently have higher value of HOMA-IR and beta cell dysfunction.

Methods

Serum visfatin and vaspin concentrations were measured in 179 Iranian subjects (90 normoglycemic FDRs and 89 age- and sex-matched healthy controls) using enzyme-linked immunosorbent assay (ELISA) methods.

Result

Serum visfatin levels were significantly lower in the FDRs when compared to the controls (1.71 ± 0.93 ng/ml versus 2.69 ± 2.02 ng/ml, p = 0.0001). However, no significant difference was found in serum vaspin concentrations between the FDRs and the controls (0.452 ± 0.254 ng/ml versus 0.409 ± 0.275 ng/ml, p > 0.05). In multiple logistic regression analysis, the FDRs showed a significant association with lower visfatin levels after adjustments for age, sex, Body Mass Index, systolic and diastolic blood pressures, lipid profile, blood glucose levels and HOMA-IR [odds ratios (OR) = 1.71, 95% confidence interval (1.30-2.25); p < 0.0001].

Conclusion

The FDRs showed a significant association with lower visfatin levels. The observed lower circulating visfatin levels in FDRs may suggest a pathophysiological role for visfatin in beta cell dysfunction in this group.     

The Impact of Personality Traits on Ratings of Obsessive-Compulsive Symptoms

Objective

The goal of this study was to evaluate consistencies and discrepancies between clinician-administered and self-report versions of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and to examine relationships between these scales and personality traits.

Methods

A total of 106 patients with obsessive-compulsive disorder (OCD) participated in this study. All participants were assessed with both clinician-administered and self-report versions of the Y-BOCS. The Structured Clinical Interview for DSM-IV Axis II Disorders Personality Questionnaire (SCID-II-PQ) was used to evaluate relationships between personality traits and scores on the Y-BOCS.

Results

Scores on the clinician-administered Y-BOCS and its obsession subscale were significantly higher than were those on the self-report version. However, we found no significant differences in compulsion subscale scores. We also found that the discrepancies in the scores on the two versions of the Y-BOCS and its compulsion subscale were significantly positively correlated with scores for narcissistic personality traits on the SCID-II-PQ. Additionally, narcissistic personality traits had a significant effect on the discrepancy in the scores on the two versions of the Y-BOCS and its compulsion subscale in the multiple linear regression analysis.

Conclusion

This is the first study to elucidate relationships between personality traits and discrepancies between scores on the two versions of the Y-BOCS. Although clinicians tend to rate obsessive symptoms as being more severe than do patients, clinicians may underestimate the degree to which individuals with narcissistic personality traits suffer more from subjective discomfort due to compulsive symptoms. Therefore, the effect of personality traits on symptom severity should be considered in the treatment of OCD.     

Construction of a Tissue‐Engineered Annulus Fibrosus

The intervertebral disc is composed of load‐bearing fibrocartilage that may be subjected to compressive forces up to 10 times the body weight. The multilaminated outer layer, the annulus fibrosus (AF), is vulnerable to damage and its regenerative potential is limited, sometimes leading to nuclear herniation. Scaffold‐based tissue engineering of AF using stem cell technology has enabled the development of bi‐laminate constructs after 10 weeks of culture. It is difficult to know if these constructs are limited by the differentiation state of the stem cells or the culture system. In this study, we have characterized an expandable scaffold‐free neoconstruct using autologous AF cells. The construct was prepared from pellet cultures derived from monolayer cultures of AF cells from mature pigs that became embedded in their own extracellular matrix. The pellet cultures were incubated for 24 h in a standardized conical tube and then carefully transferred intact to a culture flask and incubated for 21 days to allow continued matrix synthesis. Cell viability was maintained above 90% throughout the culture period. The engineered scaffold‐free construct was compared with the native AF tissue by characterization of gene expression of representative markers, histological architecture, and biochemical composition. The morphological and biochemical characteristics of the cultured disc construct are very similar to that of native AF. The cell number per gram of construct was equal to that of native AF. Expression of aggrecan was elevated in the engineered construct compared with RNA extracted from the AF. The glycosaminoglycan content in the engineered construct showed no significant difference to that from native construct. These data indicate that scaffold‐free tissue constructs prepared from AF cells using a pellet‐culture format may be useful for in vitro expansion for transplantation into damaged discs.