Protective effect of low-dose risedronate against osteocyte apoptosis and bone loss in ovariectomized rats

Osteocyte apoptosis is the first reaction to estrogen depletion, thereby stimulating osteoclastic bone resorption resulting in bone loss. We investigated the effects of two different risedronate (RIS) doses (high and low) on osteocyte apoptosis, osteoclast activity and bone loss in ovariectomized rats. Forty rats with ovariectomy (OVX) and sham ovariectomy (SHAM) were divided into 4 groups: 1) SHAM rats treated with saline (SHAM); 2) OVX rats treated with saline (OVX); 3) OVX rats treated with low-dose RIS (OVX-LR, 0.08 μg/kg/day); 4) OVX rats treated with high-dose RIS (OVX-HR, 0.8 μg/kg/day). All animals were sacrificed 90 days after surgery for the examinations of osteocyte apoptosis by caspase-3 staining, osteoclast activity by TRAP staining and bone volume by micro-CT scanning in lumbar vertebral cancellous bone. Both low and high dose RIS significantly reduced caspase-3 positive osteocytes, empty lacunae and TRAP positive osteoclasts in OVX rats. Although the difference in caspase-3 positive osteocytes was not significant between the OVX-LR and OVX-HR groups, numerically these cells were significantly more prevalent in OVX-HR (not OVX-LR) group than in SHAM group. TRAP positive osteoclasts were significantly higher in OVX-LR group than in SHAM or OVX-HR group. There was no significant difference in bone volume among the OVX-LR, OVX-HR and SHAM groups, but lower in OVX group alone. However, significant increase in trabecular thickness only occurred in OVX-LR group. We conclude that both low and high dose RIS significantly inhibit osteocyte apoptosis and osteoclast activity in OVX rats, but the low-dose RIS has weaker effect on osteoclast activity. However, low-dose RIS preserves cancellous bone mass and microarchitecture as well as high-dose RIS after estrogen depletion

Outer-inner Dual Reinforced Micro/Nano Hierarchical Scaffolds for Promoting Osteogenesis

Biomimetic scaffolds have been extensively studied for guiding osteogenesis through structural cues. Inspired by the natural bone growth process, we have employed a hierarchical outer-inner dual reinforcing strategy, which relies on the interfacial ionic bond interaction between amine/calcium and carboxyl group, to build a nanofiber/particle dual strengthened hierarchical silk fibroin scaffold. The scaffold can provide applicable form of osteogenic structural cue and mimic the natural bone forming process. Owing to the active interaction between compositions located in the outer pore space and the inner pore wall, the scaffold has over 4 times improvement on mechanical property, followed by significant alteration on cell-scaffold interaction pattern, demonstrated by over 2 times’ elevation on the spreading area and enhanced osteogenic activity potentially involving activities of integrin, Vinculin and Yes-associated protein (YAP). In vivo performance of the scaffold identified the inherent osteogenic effect of structural cue, which promotes rapid and uniform regeneration. Overall, the hierarchical scaffold is promising in promoting uniform bone regeneration through its specific structural cue endowed by its micro-nano construction.Peer reviewe

The Arctic freshwater system : changes and impacts

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 112 (2007): G04S54, doi:10.1029/2006JG000353.Dramatic changes have been observed in the Arctic over the last century. Many of these involve the storage and cycling of fresh water. On land, precipitation and river discharge, lake abundance and size, glacier area and volume, soil moisture, and a variety of permafrost characteristics have changed. In the ocean, sea ice thickness and areal coverage have decreased and water mass circulation patterns have shifted, changing freshwater pathways and sea ice cover dynamics. Precipitation onto the ocean surface has also changed. Such changes are expected to continue, and perhaps accelerate, in the coming century, enhanced by complex feedbacks between the oceanic, atmospheric, and terrestrial freshwater systems. Change to the arctic freshwater system heralds changes for our global physical and ecological environment as well as human activities in the Arctic. In this paper we review observed changes in the arctic freshwater system over the last century in terrestrial, atmospheric, and oceanic systems.The authors gratefully acknowledge the National Science Foundation (NSF) for funding this synthesis work. This paper is principally the work of authors funded under the NSF-funded Freshwater Integration (FWI) study

Relationship between lactate dehydrogenase and albuminuria in Chinese hypertensive patients

Abstract Lactate dehydrogenase (LDH) has been reported to be positively correlated with albuminuria assessed by urinary albumin‐to‐creatinine ratio (UACR) in patients with sickle cell disease; both LDH and albuminuria are positively associated with the severity of hypertension (HTN). Here, a cross‐sectional study was performed to investigate the association between LDH and albuminuria in Chinese hypertensives. A total of 1169 Chinese individuals (aged 58.0 ± 11.5 years, 60.4% male), who were admitted to our hospital, were included in this study. Based on the level of LDH, all hypertensives (n = 802) were divided into three groups: HTN1 (lowest tertile of LDH, n = 264), HTN2 (mediate tertile of LDH, n = 268), and HTN3 (highest tertile of LDH, n = 270). Hypertensives with hyperhomocysteinemia were defined as hypertensives with homocysteine ≥15μmol/L. Meanwhile, 367 normotensives served as controls. Compared with normotensives, the levels of LDH and UACR were significantly higher in hypertensives (p < .05). There was an increasing trend of albuminuria (UACR ≥30 mg/g) from control, HTN1, HTN2 to HTN3 group (4% vs. 12.1% vs. 14.9% vs. 19.6%, χ2 = 38.886, p < .001). Stepwise multiple regression analysis showed an independent association between LDH and UACR in patients with HTN (β = 0.085, p < .05), but not in normotensives. After further stratification in hypertensive patients, this correlation remained in the male (β = 0.161, p < .001), elderly (age ≥65 years, β = 0.174, p < .001) and especially hypertensives with hyperhomocysteinemia (β = 0.402, p < .001). LDH combined with white blood cell (WBC) counts was observed to have better discrimination for albuminuria than creatinine united with cystatin C in hypertensives according to receiver operation characteristic curves (area under curve: 0.637 vs. 0.535, z = 2.563, p = .0104). In conclusion, the level of LDH was associated with albuminuria in Chinese patients with HTN, particularly in hypertensives with hyperhomocysteinemia. LDH combined with WBC provided better prediction of albuminuria than routine renal function assessment in hypertensives. Further studies are needed to confirm LDH as an early marker for the risk of kidney involvement among hypertensives

The necessity of strength evaluation in assessment of clinical outcome after shoulder surgery: follow-up data from patients with complex proximal humerus fractures treated by locking plate fixation

In order to minimize the bias of Constant score, we modified the allocation of strength subscore. One hundred and two patients with 3- and 4-part proximal humerus fractures were treated using locking plate fixation and followed up for &gt;1 year. The clinical outcomes were assessed by DASH score, abbreviated Constant score (Abb.CS, strength item excluded), modified Constant score (Mod.CS, with 12-pound strength), and original Constant score (CS, with 25-pound strength). The satisfaction rate was determined for each scoring instrument. Compared to CS, the satisfaction rate was significantly higher in DASH score, Abb.CS and Mod.CS (all p &lt; 0.001), but the latter 3 groups did not show significant difference. ROC analysis showed that a &gt;7-pound shoulder strength was present in patients with satisfied outcome assessed by DASH score. In conclusion, strength evaluation is necessary for the assessment of shoulder function, but the over-allocated strength should be modified in Constant score

Development and validation of a nomogram for arterial stiffness

Abstract Even though as a gold standard for noninvasive measurement of arterial stiffness, carotid‐femoral pulse wave velocity (cfPWV) is not widely used in primary healthcare institutions due to time‐consuming and unavailable equipment. The aim of this study was to develop a convenient and low‐cost nomogram model for arterial stiffness screening. A cross‐sectional study was undertaken in the department of general practice, the First Affiliated Hospital of Fujian Medical University. Arterial stiffness was defined as cfPWV ≥ 10 m/s. A total of 2717 participants were recruited to construct the nomogram using the least absolute shrinkage and selection operator and logistic regressions. Receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis, clinical impact curve were used to evaluate the performance of the model. The model was validated internally and externally (399 participants) by bootstrap method. Arterial stiffness was identified in 913 participants (33.60%). Age, sex, waist to hip ratio, systolic blood pressure, duration of diabetes, heart rate were selected to construct the nomogram model. Good discrimination and accuracy were exhibited with area under curve of 0.820 (95% CI 0.803–0.837) in ROC curve and mean absolute error = 0.005 in calibration curve. A positive net benefit was shown in decision curve analysis and clinical impact curve. A satisfactory agreement was displayed in internal validation and external validation. The low cost and user‐friendly nomogram is suitable for arterial stiffness screening in primary healthcare institutions

Local release of gemcitabine via in situ UV-crosslinked lipid-strengthened hydrogel for inhibiting osteosarcoma

Osteosarcoma is among the most common malignant bone tumors in human skeletal system. The conventional treatment of osteosarcoma mainly consists of combining neoadjuvant chemotherapy with surgical approach. However, it is crucial to design an artificial implant that possesses excellent biomechanical properties and is capable of sustaining local release of chemotherapeutics. In this study, we envision that the highly efficient combination of gemcitabine (GEM) hydrochloride loaded liposomes with gelatin methacryloyl (GelMA) of in situ photocrosslinkable hydrogel will lead to a multifunctional implant with unique antitumor, mechanical, and biodegradable properties. A sustained controlled release was observed; more specifically, the release of GEM in vitro lasted for 4 days long. Furthermore, its capability in killing MG63 cells was further explored by using the lixivium of GEM-Lip@Gel and GEM-GelMA hydrogel in vitro (composite hydrogel by GEM loaded liposomes blending with GelMA, short for GEM-Lip@Gel), which agreed with the drug release outcome. In addition, these hydrogel showed excellent ability in inhibiting osteosarcoma in vivo by Balb/c mice bearing MG63 cells. Therefore, GEM-loaded lipo-hydrogel certainly has presented itself as a promising strategy for the development of implant in the field of osteosarcoma treatment

Repair of microdamage in osteonal cortical bone adjacent to bone screw.

Up to date, little is known about the repair mode of microdamage in osteonal cortical bone resulting from bone screw implantation. In this study, self-tapping titanium cortical bone screws were inserted into the tibial diaphyses of 24 adult male rabbits. The animals were sacrificed at 1 day, 2 weeks, 1 month and 2 months after surgery. Histomorphometric measurement and confocal microscopy were performed on basic fuchsin stained bone sections to examine the morphological characteristics of microdamage, bone resorption activity and spatial relationship between microdamage and bone resorption. Diffuse and linear cracks were coexisted in peri-screw bone. Intracortical bone resorption was significantly increased 2 weeks after screw installation and reach to the maximum at 1 month. There was no significant difference in bone resorption between 1-month and 2-months groups. Microdamage was significantly decreased within 1 month after surgery. Bone resorption was predisposed to occur in the region of <100 µm from the bone-screw interface, where had extensive diffuse damage mixed with linear cracks. Different patterns of resorption cavities appeared in peri-screw bone. These data suggest that 1) the complex microdamage composed of diffuse damage and linear cracks is a strong stimulator for initiating targeted bone remodeling; 2) bone resorption activities taking place on the surfaces of differently oriented Haversian and Volkmann canals work in a team for the repair of extensive microdamage; 3) targeted bone remodeling is a short-term reaction to microdamage and thereby it may not be able to remove all microdamage resulting from bone screw insertion

Development of a nomogram for screening the risk of left ventricular hypertrophy in Chinese hypertensive patients

Left ventricular hypertrophy (LVH) is an important risk factor for cardiovascular morbidity and mortality in hypertensives. Therefore, early identification of at‐risk patients is necessary. The objective of this study was to estimate the risk of LVH among Chinese hypertensives by designing a nomogram. 832 hypertensives were divided into two groups based on the presence of LVH. The least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression were successively applied for optimal variable selection and nomogram construction. Discrimination power, calibration, and clinical usefulness were evaluated using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis. Internal validation was performed using the bootstrap method. The nomogram included five predictors, namely gender, duration of hypertension, age, body mass index (BMI), and systolic blood pressure. The area under the ROC curve (AUC) was 0.724 (95% CI: 0.687‐0.761), indicating moderate discrimination. The calibration curve showed an excellent agreement between the predicted LVH and the actual LVH probability. The risk threshold between 5% and 72% according to the decision curve analysis, and the nomogram is clinically beneficial. Internal validation by bootstrapping with 1000 samples showed a good C‐index of 0.715, which suggested that the predictive abilities for the training set and testing set were in consistency. Our study proposed a nomogram that can be utilized to assess the LVH risk rapidly for Chinese hypertensives. This tool could be useful in identifying patients at high risk for LVH. Further studies are required to ascertain the stability and applicability of this nomogram