Anisotropic Mechanical Properties of Collagen Hydrogels Induced by Uniaxial-Flow for Ocular Applications

Engineering of well-organized tissue constructs is active in the field of material science for biomedical applications. Here, we propose a method for orienting collagen in transparent high-density collagen hydrogels using a simple rolling method. Structural organization and mechanical function were adjusted by regulating the thickness of the construct and the cross-linking reagent. Directionality of collagen alignment on the microscopic scale was achieved parallel to the extensional flow. The preferential alignment of collagen significantly affected the mechanical properties of the construct, with strong tensile strength in the direction parallel to the collagen, and high elastic strain in the perpendicular direction. The tensile strength in the parallel direction was effectively increased by 67% by increasing the cross-linking reagents by 33%, without affecting transparency which remained at 70–80% to visible light. The constructs exhibit good biocompatibility for as a substrate for the expansion of corneal epithelial cells isolated from human donor cornea, indicating the potential for tissue engineering and biomedical applications, particularly for ocular treatments.     

Sclerostin antibody stimulates bone regeneration after experimental periodontitis

The reconstruction of large osseous defects due to periodontitis is a challenge in regenerative therapy. Sclerostin, secreted by osteocytes, is a key physiological inhibitor of osteogenesis. Pharmacologic inhibition of sclerostin using sclerostin‐neutralizing monoclonal antibody (Scl‐Ab) thus increases bone formation, bone mass and bone strength in models of osteopenia and fracture repair. This study assessed the therapeutic potential of Scl‐Ab to stimulate alveolar bone regeneration following experimental periodontitis (EP). Ligature‐induced EP was induced in rats to generate localized alveolar bone defects. Following 4 weeks of disease induction, Scl‐Ab (+EP) or vehicle (+/? EP) were systemically delivered, twice weekly for up to 6 wks to determine the ability of Scl‐Ab to regenerate bone around tooth‐supporting osseous defects. 3 and 6 wks after the initiation of Scl‐Ab or vehicle treatment, femur and maxillary jawbones were harvested for histology, histomorphometry, and micro‐computed tomography (micro‐CT) of linear alveolar bone loss (ABL) and volumetric measures of bone support, including bone volume fraction (BVF) and tissue mineral density (TMD). Serum was analyzed to examine bone turnover markers during disease and regenerative therapy. Vehicle + EP animals exhibited maxillary bone loss (BVF, TMD and ABL) at ligature removal and thereafter. 6 weeks of Scl‐Ab significantly improved maxillary bone healing, as measured by BVF, TMD and ABL, when compared to vehicle + EP. After 6 weeks of treatment, BVF and TMD values in the Scl‐Ab + EP group were similar to those of healthy controls. Serum analysis demonstrated higher levels of bone formation markers osteocalcin and PINP in Scl‐Ab treatment groups. Scl‐Ab restored alveolar bone mass following experimental periodontitis. These findings warrant further exploration of Scl‐Ab therapy in this and other oral bone defect disease scenarios. © 2013 American Society for Bone and Mineral Research.     

Adiponectin Is a Candidate Biomarker of Lower Extremity Bone Density in Men With Chronic Spinal Cord Injury

Adipose tissue is a major regulator of bone metabolism and in the general population obesity is associated with greater bone mineral density (BMD). However, bone‐fat interactions are multifactorial, and may involve pathways that influence both bone formation and resorption with competing effects on the skeleton. One such pathway involves adipocyte production of adipokines that regulate bone metabolism. In this study we determined the association between BMD, walking status, and circulating adipokines (adiponectin and leptin) in 149 men with chronic spinal cord injury (SCI). Although adipokine levels did not vary significantly based on walking status, there was a significant inverse association between adiponectin and BMD in wheelchair users independent of body composition. We found no association between adiponectin and BMD in the walkers and no association between leptin and BMD in either group. These findings suggest that for subjects with chronic SCI, walking may mitigate the effect of adiponectin mediated bone loss. For wheelchair users, adipose‐derived adiponectin may contribute to SCI‐induced osteoporosis because the osteoprotective benefits of obesity appear to require mechanical loading during ambulation. © 2014 American Society for Bone and Mineral Research.     

热针配合中药熏洗联合药物治疗类风湿关节炎128例疗效观察

【目的】观察热针配合中药熏洗对药物治疗类风湿关节炎(RA)疗效的影响。【方法】将128例RA患者随机分为治疗组(N=64例)和对照组(N=64例)。治疗组采用热针治疗仪配合中药熏洗联合西药美洛昔康、柳氮磺胺吡啶、甲氨喋呤方案治疗;对照组采用纯西药治疗。两组疗程均为1个月。观察两组治疗前后晨僵时间、握力、压痛关节数、压痛指数、关节休息痛、肿胀关节数、肿胀指数以及病人和医生评价,并观察两组患者治疗前后类风湿因子(RF)、C-反应蛋白(CRP)、血沉(ESR)、白细胞计数(WBC)和血小板计数(PLT)等指标的变化情况。【结果】总有效率治疗组为78.1%,对照组为53.1%,治疗组疗效优于对照组(P<0.05)。治疗1个月后,两组患者的晨僵时间、双手平均握力、关节压痛和关节肿胀均有明显改善(与治疗前比较,P<0.01),且治疗组优于对照组(P<0.01)。两组治疗后血中RF、CRP、ESR、WBC和PLT等指标均有下降(与治疗前比较,P<0.01),且治疗组血中CRP、ESR、PLT的下降较对照组明显(P<0.01)。【结论】热针配合中药熏洗联合西药治疗类风湿关节炎疗效优于单纯西药治疗。     

Quality of Life after Obesity Surgery, an Evidence-Based Medicine Literature Review: How to Improve Systematic Searches for Enhanced Decision-Making and Clinical Outcomes

Background: Research attests to the exponential sweep of clinical obesity in America. Obesity has become one of the most profound public health concerns, closely linked to increased morbidity, mortality, and social, occupational, and psychological discrimination. It is incumbent for specialists to design treatment and outcome analysis based accurately upon systematic research. Regulators, payors, and most notably, patients, need reliable and effective treatment to determine practical standards, manage cost of care, and protocols. Methods: A comprehensive evidence-based medicine (EBM) review was done of relevant research on quality-of-life (QoL) outcomes after obesity surgery. The Cochrane Collaboration was the EBM searching resource utilized for this project, accessed via the Internet. A systematic EBM search design was implemented. Results: In the search, QoL reported 3,234 hits, "obesity surgery" reported 33 hits, QoL and obesity surgery" reported 6 hits, and QoL and hypertension reported 288 hits. Conclusion: We found that a thorough EBM search can be achieved using the Cochrane Collaboration, which provides an efficient, effective and ethical means to enhance evidence-based clinical decision-making in treating severely obese surgery patients.     

中药贴脐治疗肝郁气滞型经前期综合征的研究

[目的]探讨中药贴脐对肝郁气滞型经前期综合征患者的疗效.[方法]将符合诊断标准的42例试验对象随机分成治疗组和对照组,分别进行3个疗程的中药贴脐和口服中药治疗.中药贴脐剂药物及口服中药药物均以柴胡疏肝散加减组成.通过治疗前后的经前期症状问卷和SCL-90量表数据对比及两组之间的疗效对比,分析该疗法对肝郁气滞型经前期综合...     

Patients with Alcohol Problems in the Emergency Department, Part 2: Intervention and Referral

Abstract. Early intervention and appropriate referral of patients with alcohol problems have the potential to reduce alcohol-related morbidity and mortality. Part 1 of this series introduced screening tools that can be applied in the ED to allow early detection of at-risk drinkers. This article was developed by members of the SAEM Substance Abuse Task Force and describes assessment and intervention techniques once the at-risk or dependent drinkers has been identified. Appropriate aftercare and referral of patients found to have alcohol problems are also discussed.     

Prediction of fracture risk in men: a cohort study

FRAX is a tool that identifies individuals with high fracture risk who will benefit from pharmacological treatment of osteoporosis. However, a majority of fractures among elderly occur in people without osteoporosis and most occur after a fall. Our aim was to accurately identify men with a high future risk of fracture, independent of cause. In the population‐based Uppsala Longitudinal Study of Adult Men (ULSAM) and using survival analysis we studied different models' prognostic values (R²) for any fracture and hip fracture within 10 years from age 50 (n = 2322), 60 (n = 1852), 71 (n = 1221), and 82 (n = 526) years. During the total follow‐up period from age 50 years, 897 fractures occurred in 585 individuals. Of these, 281 were hip fractures occurring in 189 individuals. The rates of any fracture were 5.7/1000 person‐years at risk from age 50 years and 25.9/1000 person‐years at risk from age 82 years. Corresponding hip fractures rates were 2.9 and 11.7/1000 person‐years at risk. The FRAX model included all variables in FRAX except bone mineral density. The full model combining FRAX variables, comorbidity, medications, and behavioral factors explained 25% to 45% of all fractures and 80% to 92% of hip fractures, depending on age. The corresponding prognostic values of the FRAX model were 7% to 17% for all fractures and 41% to 60% for hip fractures. Net reclassification improvement (NRI) comparing the full model with the FRAX model ranged between 40% and 53% for any fracture and between 40% and 87% for hip fracture. Within the highest quintile of predicted fracture risk with the full model, one‐third of the men will have a fracture within 10 years after age 71 years and two‐thirds after age 82 years. We conclude that the addition of comorbidity, medication, and behavioral factors to the clinical components of FRAX can substantially improve the ability to identify men at high risk of fracture, especially hip fracture. © 2012 American Society for Bone and Mineral Research.     

Vitamin D–Dependent Rickets Type 1B (25‐Hydroxylase Deficiency): A Rare Condition or a Misdiagnosed Condition?

Vitamin D requires a two‐step activation by hydroxylation: The first step is catalyzed by hepatic 25‐hydroxylase (CYP2R1, 11p15.2) and the second one is catalyzed by renal 1α‐hydroxylase (CYP27B1, 12q13.1), which produces the active hormonal form of 1,25‐(OH)₂D. Mutations of CYP2R1 have been associated with vitamin D–dependent rickets type 1B (VDDR1B), a very rare condition that has only been reported to affect 4 families to date. We describe 7 patients from 2 unrelated families who presented with homozygous loss‐of‐function mutations of CYP2R1. Heterozygous mutations were present in their normal parents. We identified a new c.124_138delinsCGG (p.Gly42_Leu46delinsArg) variation and the previously published c.296T>C (p.Leu99Pro) mutation. Functional in vitro studies confirmed loss‐of‐function enzymatic activity in both cases. We discuss the difficulties in establishing the correct diagnosis and the specific biochemical pattern, namely, very low 25‐OH‐D suggestive of classical vitamin D deficiency, in the face of normal/high concentrations of 1,25‐(OH)₂D. Siblings exhibited the three stages of rickets based on biochemical and radiographic findings. Interestingly, adult patients were able to maintain normal mineral metabolism without vitamin D supplementation. One index case presented with a partial improvement with 1alfa‐hydroxyvitamin D₃ or alfacalcidol (1α‐OH‐D₃) treatment, and we observed a dramatic increase in the 1,25‐(OH)₂D serum concentration, which indicated the role of accessory 25‐hydroxylase enzymes. Lastly, in patients who received calcifediol (25‐OH‐D₃), we documented normal 24‐hydroxylase activity (CYP24A1). For the first time, and according to the concept of personalized medicine, we demonstrate dramatic improvements in patients who were given 25‐OH‐D therapy (clinical symptoms, biochemical data, and bone densitometry). In conclusion, the current study further expands the CYP2R1 mutation spectrum. We note that VDDR1B could be easily mistaken for classical vitamin D deficiency. © 2017 American Society for Bone and Mineral Research.     

清开灵注射液治疗急性中风的Meta分析

背景：中医药学几千年来各界了许多治疗中风有产的疗法和方药,如清开灵注射液（）简称清开灵）等,但因临床研究对方法学的重视仍不够,影响了研究结论的推广和国外医学界的承认。循证医学及系统分析的方法和结果日益得到了国际医学界和卫生决策部门的认可与重视,利用循证医学,系统分析的方法,拿出Ｍｅｔａ分析等数据,将极寺地促进中医药走向世界。目的：在严格的质量评价的基础上,对清开灵的临床疗与安全性进行系统评价。