The Biomedical Research Hub: a federated platform for patient research data

ObjectiveThe objective was to develop and operate a cloud-based federated system for managing, analyzing, and sharing patient data for research purposes, while allowing each resource sharing patient data to operate their component based upon their own governance rules. The federated system is called the Biomedical Research Hub (BRH).Materials and MethodsThe BRH is a cloud-based federated system built over a core set of software services called framework services. BRH framework services include authentication and authorization, services for generating and assessing findable, accessible, interoperable, and reusable (FAIR) data, and services for importing and exporting bulk clinical data. The BRH includes data resources providing data operated by different entities and workspaces that can access and analyze data from one or more of the data resources in the BRH.ResultsThe BRH contains multiple data commons that in aggregate provide access to over 6 PB of research data from over 400 000 research participants.Discussion and conclusionWith the growing acceptance of using public cloud computing platforms for biomedical research, and the growing use of opaque persistent digital identifiers for datasets, data objects, and other entities, there is now a foundation for systems that federate data from multiple independently operated data resources that expose FAIR application programming interfaces, each using a separate data model. Applications can be built that access data from one or more of the data resources.     

Restricted Arp3 expression in the testis prevents blood–testis barrier disruption during junction restructuring at spermatogenesis

In epithelia, a primary damage of tight junctions (TJ) always leads to a secondary disruption of adherens junction (AJ), and vice versa. This response, if occurring in the testis, would disrupt spermatogenesis because the blood–testis barrier (BTB) must remain intact during the transit of spermatids in the seminiferous epithelium, which is associated with extensive apical ectoplasmic specialization (apical ES, a testis-specific AJ type) restructuring. As such, apical ES restructuring accompanied with the transit of developing spermatids during spermiogenesis must be segregated from the BTB to avoid an immunological barrier breakdown in all stages of the seminiferous epithelial cycle, except at stage VIII when spermiation and BTB restructuring take place concurrently. We report herein a mechanism involving restricted spatial and temporal expression of Arp2/3 complex and N-WASP, whose actin branching activity associated with apical ES and BTB restructuring in the seminiferous epithelium. High expression of Arp3 at the apical ES was shown to correlate with spermatid movement and proper spermatid orientation. Likewise, high Arp3 level at the BTB associated with its restructuring to accommodate the transit of preleptotene spermatocytes at stage VIII of the epithelial cycle. These findings were validated by in vitro and in vivo studies using wiskostatin, an inhibitor that blocks N-WASP from activating Arp2/3 complex to elicit actin branching. Inhibition of actin branching caused a failure of spermatid transit plus a loss of proper orientation in the epithelium, and a “tightened” Sertoli cell TJ permeability barrier, supporting the role of Arp2/3 complex in segregating the events of AJ and BTB restructuring.     

The phosphoinositide-specific phospholipase C inhibitor U73122 (1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione) spontaneously forms conjugates with common components of cell culture medium.

Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in the regulation of Ca(2+) release from inositol 1,4,5-triphosphate-sensitive stores. U73122 (1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione) has been extensively used as a pharmacological inhibitor of PLC to elucidate the importance of this enzyme family in signal transduction pathways. U73122 has an electrophilic maleimide group, which readily reacts with nucleophiles such as thiols and amines. In the current study the conjugation of U73122 to common components of cell culture medium, namely l-glutamine, glutathione, and bovine serum albumin (BSA), was demonstrated. The half-life of U73122 on incubation with phosphate-buffered saline (PBS), Hanks' buffered saline solution (with 2 mM glutamine), optimized basal nutrient medium (MCDB131, without BSA), complete medium, Dulbecco's modified Eagle's medium (with 2 mM l-glutamine) was approximately 150, 60, 32, 30, and 18 min, respectively. However, U73122 was not recoverable from medium supplemented with 0.5% BSA. U73122 underwent hydrolysis of the maleimide group when incubated with PBS. Glutamine conjugates of U73122 were identified in cell culture medium. Furthermore, the inhibition of epidermal growth factor-stimulated Ca(2+) release in a human epidermoid carcinoma cell line (A431) by U73122 was substantially reduced by the presence of BSA in a time-dependent manner. In complex cellular assays, the availability of U73122 to inhibit PLC may be limited by its chemical reactivity and lead to the misinterpretation of results in pharmacological assays.     

绝经后女性类风湿关节炎患者骨密度变化影响因素分析

目的探讨绝经后女性类风湿关节炎(RA)患者发生骨质疏松(OP)的原因。方法收集63例绝经后女性RA患者一般临床资料、疾病活动相关指标、手足X线资料,并同时测量患者7个部位的骨密度。结果23例患者(36.5%)有至少一处检测部位表现为低骨量。前臂和桡尺骨远端的低骨密度发生率(23.8%)与OP总发生率(28.6%)无显著性差异(P>0.05)。OP的发生与疾病活动指标及糖皮质激素的使用均无相关性。多元回归分析显示绝经的年限和关节腔狭窄为低骨量发生的独立危险因素(P<0.05);而雌激素替代疗法(HRT)为低骨量发生的唯一保护因素(P<0.05),小剂量糖皮质激素对本组患者的骨密度无影响。结论OP是绝经后女性RA患者的常见并发症,绝经年限长和关节破坏严重是低骨量发生的独立危险因素,HRT是防治低骨量的保护因素。     

Breast cancer: better care for less cost. Is it possible?

OBJECTIVES: To estimate the potential for cost reduction in the acute care setting and the required investment in the home care setting of implementing an outpatient/early discharge strategy for operable (stages I and II) breast cancer in Canada. METHODS: Data from a community hospital were augmented by expert knowledge and incorporated into the breast cancer submodel of Statistics Canada's Population Health Model. For the estimated 90% of patients for whom this approach was assumed to be appropriate, the resource utilization for outpatient breast-conserving surgery and 2 days of hospitalization for those women undergoing mastectomy was quantified and costed, as were the appropriate home care services. A 5% readmission rate for complications was assumed. Cost per case, total cost burden, investment in home care, savings in acute care, and net savings were calculated. Sensitivity analyses were performed around readmission rates and home care/surgical follow-up costs. All costs were determined in 1995 Canadian dollars. RESULTS: The cost of initial treatment for the 15,399 women diagnosed with stages I and II breast cancer in 1995 in Canada was estimated to be $127.6 million. Hospitalization made up 53% of these costs. Under the outpatient/early discharge strategy, the acute care cost of initial breast cancer management could be reduced by $47.2 million, with an investment in home care of $14.5 million ($453 per patient), resulting in an overall net saving of $33 million. Under this strategy, hospitalization would contribute only 21% to the total care cost. CONCLUSIONS: If Canadian surgeons and healthcare administrators were to work together to put in place processes to support ambulatory breast cancer surgery and if resources were redirected to the provision of home-based post-operative care, there would be potential for a large net healthcare saving and preservation of high-quality patient care.     

Medical practice mergers

Medical practice mergers provide one of the few remaining "clout-enhancing" strategies for physicians. Mergers can create significant benefits for the physicians involved. Achieving these benefits requires overcoming many obstacles and potential pitfalls. This article addresses the benefits to be gained and the difficulties to avoid, and provides an overview of the merger process.     

Distribution of sunscreens on skin

The effectiveness of sunscreens was originally achieved by incorporation of soluble organic UV absorbers such as cinnamates and others into cosmetic formulations. Determinations of the sun protection factor (SPF) of emulsions containing different organic UV absorbers clearly indicate that the efficacy depends on the absorption characteristics of each single UV filter substance. Nowadays, micronised pigments such as titanium dioxide or zinc oxide have also been found to be protective against harmful UV rays. Our investigations using optical and electron microscopy proved that neither surface characteristics, particle size nor shape of the micronised pigments result in any dermal absorption of this substance. Micronised titanium dioxide is solely deposited on the outermost surface of the stratum corneum and cannot be detected in deeper stratum corneum layers, the human epidermis and dermis.