Does low-intensity pulsed ultrasound accelerate phasic calcium phosphate ceramic-induced bone formation?

Purpose: Low-intensity pulsed ultrasound (LIPUS) has been used to stimulate the healing of the fresh fracture, delayed union, and non-union in both animal and clinical studies. Besides, biphasic calcium phosphate ceramic (BCP) is a promising biomaterial for bone repair as it shows favorable biocompatibility, osteoinduction, and osteoconduction. However, scarcity is known about the combined effect of LIPUS and BCP on bone formation. Methods: The combined effect of LIPUS and BCP was studied in a beagle model. Twelve dogs were used. BCP granules without any additions were implanted into bilateral erector spinae muscles. One side is the BCP group, while the counterlateral side is LIPUS + BCP group. Histological and histomorphometric analyses, and quantitative real-time polymerase chain reaction were evaluated. Results: Compared with BCP alone, the LIPUS + BCP showed no advantages in early bone formation. Furthermore, the Notch signaling pathway-related mRNA has no significant difference between the two groups. Conclusions: The preliminary results showed that the BCP, which has intrinsic osteoinduction nature, was an effective and promising material. However, LIPUS has no enhanced effect in BCP induced ectopic bone formation. Furthermore, LIPUS has no effect on the Notch signaling pathway. Whether costly LIPUS could be used in combination with BCP should be a rethink.

Utilizing benchmarked dataset and gene regulatory network to investigate hub genes in postmenopausal osteoporosis

Objective: The objective of this paper was to investigate hub genes of postmenopausal osteoporosis (PO) utilizing benchmarked dataset and gene regulatory network (GRN). Materials and Methods: To achieve this goal, the first step was to benchmark the dataset downloaded from the ArrayExpress database by adding local noise and global noise. Second, differentially expressed genes (DEGs) between PO and normal controls were identified using the Linear Models for Microarray Data package based on benchmarked dataset. Third, five kinds of GRN inference methods, which comprised Zscore, GeneNet, context likelihood of relatedness (CLR) algorithm, Partial Correlation coefficient with Information Theory (PCIT), and GEne Network Inference with Ensemble of trees (Genie3), were described and evaluated by receiver operating characteristic (ROC) and precision and recall (PR) curves. Finally, GRN constructed according to the method with best performance was implemented to conduct topological centrality (closeness) for the purpose of investigate hub genes of PO. Results:A total of 236 DEGs were obtained based on benchmarked dataset of 20,554 genes. By assessing Zscore, GeneNet, CLR, PCIT, and Genie3 on the basis of ROC and PR curves, Genie3 had a clear advantage than others and was applied to construct the GRN which was composed of 236 nodes and 27,730 edges. Closeness centrality analysis of GRN was carried out, and we identified 14 hub genes (such as TTN, ACTA1, and MYBPC1) for PO. Conclusion: In conclusion, we have identified 14 hub genes (such as TN, ACTA1, and MYBPC1) based on benchmarked dataset and GRN. These genes might be potential biomarkers and give insights for diagnose and treatment of PO

Oral versus intravenous steroid therapy for relapses in patients with multiple sclerosis: an updated meta-analysis of six randomized controlled trials / Terapia oral versus intravenosa para recaídas de pacientes com esclerose múltipla: uma metanálise atualizada de seis ensaios clínicos randomizados

PURPOSE: To systematically evaluate whether oral steroids can be used with the same efficacy and safety in comparison with the intravenous regimen for treatment of multiple sclerosis relapses. METHOD: We searched Medline, Embase and Cochrane Library and systematically reviewed articles comparing outcomes of oral versus intravenous steroids for acute relapses in patients with a clinically definite diagnosis of multiple sclerosis. RESULTS: Six articles with 414 participants in total were analyzed. Five of the included trials reported the proportion of patients experiencing improvement in Expanded Disability Status Scale after receiving either oral or intravenous methylprednisolone treatment at four weeks; the pooled results showed that there was no statistically significant difference (OR 0.96; 95% CI 0.60, 1.54; p=0.86) between treatments. Three trials reported the detailed results of adverse events, indicating the two treatments appear to be equally safe. Two trials revealed that there was no significant difference in gadolinium enhancement activity on magnetic resonance imaging. One trial showed that the mean area under the concentration-time curve (AUC) at 24 and 48 hours did not differ between groups. CONCLUSION: No significant differences were found in terms of clinical (benefits and adverse events), radiological and pharmacological outcomes in multiple sclerosis relapses in patients after oral or intravenous steroids treatment. Our meta-analysis provides evidence that oral steroid therapy is not inferior to intravenous steroid therapy. Thus oral administration may be a favorable substitute for intravenous medication of multiple sclerosis relapses.

PROPÓSITO: Avaliar de forma sistemática se esteroides orais podem ser utilizados com a mesma eficácia e segurança em comparação com o regime intravenoso para o tratamento de recaídas da esclerose múltipla (MS). MÉTODO: Foram pesquisados Medline, Embase e Cochrane Library e sistematicamente revistos artigos comparando resultados de esteroides orais versus intravenosos para recaídas agudas em pacientes com diagnóstico de esclerose múltipla clinicamente definida. RESULTADOS: Seis artigos com 414 participantes no total foram analisados. Cinco dos estudos incluídos relataram a proporção de doentes com melhoria através de "Expanded Disability Status Scale" depois de receber um ou outro tratamento: metilprednisolona oral ou intravenosa por quatro semanas. Os resultados combinados mostraram que não houve diferença estatisticamente significativa (OR 0,96; 95% 101 0,60, 1,54 ; p = 0,86). Três estudos mostraram os resultados detalhados de eventos adversos, indicando que os dois tratamentos parecem ser igualmente seguros. Dois ensaios revelaram que não havia nenhuma diferença significativa no aumento de atividade de gadolínio via imagens por ressonância magnética. Um estudo mostrou que a área média sob as curvas de concentração-tempo (AUC) às 24 horas e 48 horas não diferiram entre os grupos. CONCLUSÃO: Não foram encontradas diferenças significativas em termos de clínicos (benefícios e eventos adversos) ou nos resultados radiológicos e farmacológicos em pacientes pós-esteroides por via oral ou intravenosa no tratamento de várias recaídas de esclerose. Nossa metanálise fornece evidências de que a terapia com esteroides por via oral não é inferior à terapia com esteroides por via intravenosa. Assim, a administração oral pode ser um substituto favorável para medicação intravenosa de recidivas da esclerose múltipla.