Recent topics on bone remodeling

The Wnt signaling pathway has recently been demonstrated to play an important role in regulation of bone formation. LRP5 is thought to signal through the canonical Wnt pathway. In humans, LRP5 loss-of-function mutations lead to low bone mass with fractures, while LRP5 gain-of-function mutations lead to high bone mass, thus identifying LRP5 as an important regulator of bone mass. Patients with sclerosteosis have a severe skeletal disorder with progressive bone overgrowth due to a loss of function of the SOST gene, which implicates its role as a suppressor of bone formation. Recent study revealed that SOST is a BMP antagonist with unique ligand specificity, negatively regulating bone formation by repressing BMP-induced osteoblast differentiation or function or both.     

Patterns of anismus and the relation to biofeedback therapy

PURPOSE: A study was undertaken to assess physiologic characteristics and clinical significance of anismus. Specifically, we sought to assess patterns of anismus and the relation of these findings to the success of therapy. METHODS: Sixty-eight patients were found to have anismus based on history and diagnostic criteria including anismus by defecography and at least one of three additional tests: anorectal manometry, electromyography, or colonic transit time study. Interpretation of defecography was based on the consensus of at least three of four observers. Anal canal hypertonia (n=32) was defined when mean and maximum resting pressures were at least 1 standard deviation higher than those in 63 controls. There were two distinct defecographic patterns of anismus: Type A (n=26), a flattened anorectal angle without definitive puborectalis indentation but a closed anal canal; Type B (n=42), a clear puborectalis indentation, narrow anorectal angle, and closed anal canal. Outcomes of 57 patients who had electromyographybased biofeedback therapy were reported as either improved or unimproved at a mean follow-up of 23.7 (range, 6–62) months. These two types of anismus were compared with biofeedback outcome to assess clinical relevance. RESULTS: Patients with Type A anismus showed greater perineal descent at rest (mean, 5.1 vs. 3.5 cm;P < 0.01), greater dynamic descent between rest and evacuation (mean, 2.7 vs. 1.4 cm;P <0.01), greater difference of anorectal angle between rest and evacuation (mean, 14.6 vs. ?3.1°;P <0.001), higher mean resting pressure (mean, 77.1 vs. 62.8 mmHg;P <0.05), lower mean squeeze pressure (58.8 vs. 80.7 mmHg;P <0.05), and a higher incidence of anal canal hypertonia (69.2 vs. 33.3 percent;P <0.01) than did patients with Type B anismus. Only 25 percent of patients who had Type A anismus with anal canal hypertonia were improved by biofeedback therapy. Conversely, 86 percent of patients with Type B anismus without anal canal hypertonia were successfully treated with biofeedback (P <0.001; Fisher's exact test). CONCLUSIONS: These two distinct physiologic patterns of anismus correlate with the success of biofeedback treatment. Therefore, knowledge of these patterns may help direct therapy.     

Comparative effectiveness of statins in secondary prevention among the older people aged 75 years and over

International Journal of Clinical Pharmacy - Background While there is clear evidence for the benefit of statins in the secondary prevention of cardiovascular and cerebrovascular events, there is a...     

A comparison between central blood pressure values obtained by the Gaon system and the SphygmoCor system

Central pulse pressure is correlated with carotid atherosclerosis and the incidence of cardiovascular events more significantly than brachial pulse pressure. Augmentation index (Aix) has been shown to be an independent predictor of cardiovascular morbidity and mortality. Pulse wave analysis using the Gaon system allows for the estimation of central blood pressure (CBP), corrected augmentation index (Aix@HR75), ejection duration (ED) and subendocardial viability ratio (SEVR), and is widely used in clinical research in Korea. However, the accuracy of this system is controversial. From February 2008 to March 2011, 99 patients were recruited for this study. Measurements were taken both by the Gaon system and the SphygmoCor system on the same day for all study participants. The estimated values of CBP, Aix@HR75, ED and SEVR for the two systems were compared using paired t-tests, simple correlation analyses and Bland-Altman plots. Systolic blood pressure (SBP) estimated by the two systems was significantly (P<0.001) correlated; the coefficient was 0.982. The two s.d. of the difference in SBP between these systems was quite small--<7?mm?Hg. Aix@HR75, ED and SEVR as estimated by the two systems were also significantly correlated, although they, especially SEVR, showed much weaker correlations than were observed in SBP: coefficients for Aix@HR75, ED and SEVR were 0.727, 0.648 and 0.230, respectively. We assessed the CBP of Korean patients estimated by the two systems and observed that the correlations of Aix, ED and SEVR were weaker than that of CBP. Such variations may be due to the difference in measuring methods between the devices. As even a slight change in pulse waveforms may result in a large difference in estimations, parameters, including Aix@HR75, ED and SEVR, should be carefully interpreted by experienced clinicians.     

Comparison of diameters of ipsilateral and contralateral internal mammary arteries by breast MRI in patients with unilateral breast cancer

Purpose

We compared maximal diameters of ipsilateral (IMA) and contralateral (IMA) internal mammary arteries in patients with unilateral breast cancer and analyze the implications of enlargements of ipsilateral or contralateral IMAs in relation to histopathologic factors.

Materials and methods

Of 568 women who underwent breast magnetic resonance imaging (MRI) examinations from January 2009 to May 2012, 196 had unilateral, histologically proven breast cancer. In 156 women, maximal IMA diameters in the second intercostal space were measured by two blinded radiologists in left and right sides using nonenhanced axial T2-weighted turbo spin-echo sequence images.

Results

In the 156 study patients, mean maximal diameter of ipsilateral IMAs (2.37 ± 0.60 mm) was significantly larger than that of contralateral IMAs (2.03 ± 0.58 mm) (p = 0.00). Ipsilateral IMA enlargement was present in 66.7 % of the patients (104 of 156). Furthermore, ipsilateral IMA enlargement was found to be significantly associated with human epidermal growth factor receptor-2 (HER-2) expression (p = 0.039).

Conclusions

Maximal IMA diameter was significantly greater in ipsilateral sides in breast cancer patients. Findings suggest ipsilateral IMA enlargement detected by MRI might be a useful additional predictor of HER-2 expression in unilateral breast cancer.

     

Computer prediction of allergen proteins from sequence-derived protein structural and physicochemical properties

BACKGROUND: Computational methods have been developed for predicting allergen proteins from sequence segments that show identity, homology, or motif match to a known allergen. These methods achieve good prediction accuracies, but are less effective for novel proteins with no similarity to any known allergen. METHODS: This work tests the feasibility of using a statistical learning method, support vector machines, as such a method. The prediction system is trained and tested by using 1005 allergen proteins from the Allergome database and 22,469 non-allergen proteins from 7871 Pfam families. RESULTS: Testing results by an independent set of 229 allergen and 6717 non-allergen proteins from 7871 Pfam families show that 93.0% and 99.9% of these are correctly predicted, which are comparable to the best results of other methods. Of the 18 novel allergen proteins non-homologous to any other proteins in the Swissprot database, 88.9% is correctly predicted. A further screening of 168,128 proteins in the Swissprot database finds that 2.9% of the proteins are predicted as allergen proteins, which is consistent with the estimated numbers from motif-based methods. CONCLUSIONS: Our study suggests that SVM is a potentially useful method for predicting allergen proteins and it has certain capability for predicting novel allergen proteins. Our software can be accessed at .     

Plasticity in sublesionally located neurons following spinal cord injury

Neuronal plasticity has been traditionally associated with learning and memory processes in the hippocampal regions of the brain. It is now generally accepted that plasticity phenomena are also associated with other kinds of cellular changes and modifications occurring in all areas of the CNS after injury or intense neuronal activity. For instance, spinal cord injuries have been associated with a series of cellular modifications and adaptations taking place distally in sublesional areas. Some of these modifications include changes in the expression of immediate early genes (e.g., c-fos and nor-1), TNF-alpha, preprodynorphin, neurotrophic factors (e.g., BDNF and NT-3), and several subtypes of transmembranal receptors (e.g., 5-HT(1A) and 5-HT(2A)). This review constitutes an update of the current knowledge regarding this broadly defined plasticity phenomenon that occurs spontaneously or can be modulated by training in sublesional segments of the spinal cord. Spinal cord plasticity is an increasingly popular field of research, believed by many as being a complex phenomenon that may contribute to the development of innovative therapeutics and rehabilitative approaches for spinal cord injured patients.