Acute effects of doorway stretch on the glenohumeral rotational range of motion and scapular position in high-school baseball players.

BACKGROUND: Pectoralis minor tightness has been thought to affect the scapular position. Despite the wide implementation of doorway stretch in clinical practice owing to its apparent effectiveness in stretching the pectoralis minor, limited studies have investigated its influence on the glenohumeral rotational range of motion (ROM). This study aimed to examine the acute effects of doorway stretch on the glenohumeral rotational ROM and the correlation between the scapular position and ROM. MATERIALS AND METHODS: In total, 34 male high-school baseball players participated in this study. Outcomes included the pectoralis minor muscle length, glenohumeral rotational ROM, and scapular position. The distance between the sternocostal joint of rib 4 and the coracoid process was measured as the pectoralis minor length. Internal and external rotation ROM with the shoulder abducted at 90° were measured. The scapular position was defined by the following two measurements: the distance between the surface and the posterolateral corner of the acromion as well as the scapular index. The participants performed doorway stretch by abducting and externally rotating the shoulder at 90° and flexing the elbow at 90°. The outcomes were compared before and after stretching. Furthermore, the correlation between these changes was investigated. RESULTS: Pectoralis minor muscle length and glenohumeral internal rotation ROM was significantly higher after stretching than before, and the scapular position also significantly changed (P < .01 for both). A moderate correlation was found between the degree of change in the glenohumeral internal rotational ROM and scapular position (r = 0.44, P < .01). DISCUSSION: Our results indicated that doorway stretch significantly increased the pectoralis minor muscle length and glenohumeral internal rotation ROM and significantly altered the scapular position. Furthermore, a significant correlation between the degree of change in the scapular position and glenohumeral internal rotation ROM was observed. These results suggest that doorway stretch could be beneficial for improving the scapular position and glenohumeral internal rotation ROM, which are considered the cause of throwing injuries. Furthermore, the glenohumeral ROM may be affected by the scapular position.

Antibody to CD137 Activated by Extracellular Adenosine Triphosphate Is Tumor Selective and Broadly Effective In Vivo without Systemic Immune Activation.

Agonistic antibodies targeting CD137 have been clinically unsuccessful due to systemic toxicity. Because conferring tumor selectivity through tumor-associated antigen limits its clinical use to cancers that highly express such antigens, we exploited extracellular adenosine triphosphate (exATP), which is a hallmark of the tumor microenvironment and highly elevated in solid tumors, as a broadly tumor-selective switch. We generated a novel anti-CD137 switch antibody, STA551, which exerts agonistic activity only in the presence of exATP. STA551 demonstrated potent and broad antitumor efficacy against all mouse and human tumors tested and a wide therapeutic window without systemic immune activation in mice. STA551 was well tolerated even at 150 mg/kg/week in cynomolgus monkeys. These results provide a strong rationale for the clinical testing of STA551 against a broad variety of cancers regardless of antigen expression, and for the further application of this novel platform to other targets in cancer therapy. SIGNIFICANCE: Reported CD137 agonists suffer from either systemic toxicity or limited efficacy against antigen-specific cancers. STA551, an antibody designed to agonize CD137 only in the presence of extracellular ATP, inhibited tumor growth in a broad variety of cancer models without any systemic toxicity or dependence on antigen expression.See related commentary by Keenan and Fong, p. 20.This article is highlighted in the In This Issue feature, p. 1.

Blueberry Prevents the Bladder Dysfunction in Bladder Outlet Obstruction Rats by Attenuating Oxidative Stress and Suppressing Bladder Remodeling.

Various berries demonstrate antioxidant activity, and this effect is expected to prevent chronic diseases. We examined whether a diet containing blueberry powder could prevent the development of bladder dysfunction secondary to bladder outlet obstruction (BOO). Eighteen 8-week-old male Sprague-Dawley rats were randomly divided into three groups: Sham (sham operated + normal diet), N-BOO (BOO operated + normal diet) and B-BOO (BOO operated + blueberry diet). Four weeks after BOO surgery, the N-BOO group developed bladder dysfunction with detrusor overactivity. The B-BOO group showed significantly improved micturition volume and micturition interval. The urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) were measured as oxidative stress markers. In the N-BOO group, 8-OHdG increased 1.6-fold and MDA increased 1.3-fold at 4 weeks after surgery, whereas the increase in 8-OHdG was significantly reduced by 1.1-fold, despite a similar increase in MDA, in the B-BOO group. Bladder remodeling was confirmed due to bladder hypertrophy, fibrosis and increased connexin43 expression in the N-BOO group, but these histological changes were reduced in the B-BOO group. The intake of blueberries prevented the development of bladder dysfunction secondary to BOO. This effect seems to be related to antioxidation and the inhibition of bladder remodeling.

A New Conditionally Immortalized Human Fetal Brain Pericyte Cell Line: Establishment and Functional Characterization as a Promising Tool for Human Brain Pericyte Studies.

While pericytes wrap around microvascular endothelial cells throughout the human body, their highest coverage rate is found in the brain. Brain pericytes actively contribute to various brain functions, including the development and stabilization of the blood-brain barrier (BBB), tissue regeneration, and brain inflammation. Accordingly, detailed characterization of the functional nature of brain pericytes is important for understanding the mechanistic basis of brain physiology and pathophysiology. Herein, we report on the development of a new human brain pericyte cell line, hereafter referred to as the human brain pericyte/conditionally immortalized clone 37 (HBPC/ci37). Developed via the cell conditionally immortalization method, these cells exhibited excellent proliferative ability at 33 °C. However, when cultured at 37 °C, HBPC/ci37 cells showed a differentiated phenotype that was marked by morphological alterations and increases in several pericyte-enriched marker mRNA levels, such as platelet-derived growth factor receptor ß. It was also found that HBPC/ci37 cells possessed the facilitative ability of in vitro BBB formation and differentiation into a neuronal lineage. Furthermore, HBPC/ci37 cells exhibited the typical "reactive" features of brain pericytes in response to pro-inflammatory cytokines. To summarize, our results clearly demonstrate that HBPC/ci37 cells possess the ability to perform several key brain pericyte functions while also showing the capacity for extensive and continuous proliferation. Based on these findings, it can be expected that, as a unique human brain pericyte model, HBPC/ci37 cells have the potential to contribute to significant advances in the understanding of human brain pericyte physiology and pathophysiology.

LOX Fails to Substitute for RANKL in Osteoclastogenesis.

Osteoclasts are the exclusive bone-resorbing cells that have a central role in bone homeostasis as well as bone destruction in cancer and autoimmune disease. Both mouse and human genetic studies have clearly proven that receptor activator of NF-κB ligand (RANKL; encoded by the Tnfsf11 gene) and its receptor RANK are essential for osteoclastogenesis. Although there have been several reports on RANKL-independent osteoclastogenesis, previous studies have never provided in vivo evidence showing RANKL can be substituted by other molecules using RANKL- or RANK-deficient genetic backgrounds. Thus, to date, there is no clear evidence of RANKL-independent osteoclastogenesis and no molecule has ever been proven capable of inducing osteoclast differentiation more efficiently than RANKL. Recently, lysyl oxidase (LOX), the enzyme that mediates collagen cross-linking, has been shown to induce human osteoclasts in the absence of RANKL and has a stronger osteoclastogenic activity than RANKL. Here, we investigated the effect of LOX on osteoclast differentiation using RANKL- and RANK-deficient cells to strictly explore RANKL-independent osteoclastogenesis. CD14+ human peripheral blood cells as well as osteoclast precursor cells derived from wild-type, RANKL- and RANK-deficient mice were treated with RANKL and/or LOX in short-term (3 days) or long-term (3 weeks) experimental settings. LOX treatment alone did not result in the formation of tartrate-resistant acid phosphatase (TRAP)+ cells or resorption pits in either short-term or long-term culture. In combination with RANKL, long-term treatment with LOX synergistically promoted osteoclastogenesis in cells derived from wild-type mice; however, this was abrogated in RANKL-deficient cells. Long-term treatment with LOX stimulated RANKL expression in mouse bone marrow stromal cells via the production of reactive oxygen species (ROS). Furthermore, LOX injection failed to rescue the phenotype of RANKL-deficient mice. These results suggest that LOX has the ability to induce RANKL expression on stromal cells; however, it fails to substitute for RANKL in osteoclastogenesis. © 2016 American Society for Bone and Mineral Research.

Evaluation of Secure Computation in a Distributed Healthcare Setting.

Issues related to ensuring patient privacy and data ownership in clinical repositories prevent the growth of translational research. Previous studies have used an aggregator agent to obscure clinical repositories from the data user, and to ensure the privacy of output using statistical disclosure control. However, there remain several issues that must be considered. One such issue is that a data breach may occur when multiple nodes conspire. Another is that the agent may eavesdrop on or leak a user's queries and their results. We have implemented a secure computing method so that the data used by each party can be kept confidential even if all of the other parties conspire to crack the data. We deployed our implementation at three geographically distributed nodes connected to a high-speed layer two network. The performance of our method, with respect to processing times, suggests suitability for practical use.

Implementation and evaluation of an efficient secure computation system using 'R' for healthcare statistics.

BACKGROUND AND OBJECTIVE: While the secondary use of medical data has gained attention, its adoption has been constrained due to protection of patient privacy. Making medical data secure by de-identification can be problematic, especially when the data concerns rare diseases. We require rigorous security management measures. MATERIALS AND METHODS: Using secure computation, an approach from cryptography, our system can compute various statistics over encrypted medical records without decrypting them. An issue of secure computation is that the amount of processing time required is immense. We implemented a system that securely computes healthcare statistics from the statistical computing software 'R' by effectively combining secret-sharing-based secure computation with original computation. RESULTS: Testing confirmed that our system could correctly complete computation of average and unbiased variance of approximately 50,000 records of dummy insurance claim data in a little over a second. Computation including conditional expressions and/or comparison of values, for example, t test and median, could also be correctly completed in several tens of seconds to a few minutes. DISCUSSION: If medical records are simply encrypted, the risk of leaks exists because decryption is usually required during statistical analysis. Our system possesses high-level security because medical records remain in encrypted state even during statistical analysis. Also, our system can securely compute some basic statistics with conditional expressions using 'R' that works interactively while secure computation protocols generally require a significant amount of processing time. CONCLUSIONS: We propose a secure statistical analysis system using 'R' for medical data that effectively integrates secret-sharing-based secure computation and original computation.

Statistical disclosure limitation of health data based on Pk-anonymity.

The Act for the Protection of Personal Information in Japan considers as personal information any quasi-identifier that may be used to obtain information that identifies individuals through comparisons with datasets. Studies using health records are not widely conducted because of the concern regarding the safety of anonymized health records. To increase the safety of such records, we used the Pk-anonymity method. In this method, attributes are probabilistically randomized and then reconstructions are performed on the basis of statistical information from perturbed data. Hence, it is expected to provide more precise statistics and more reliably preserve privacy than the traditional "k-anonymity" method. We anonymized health records, performed cross tabulation, and assessed the error rate using original data. This study shows that the Pk-anonymity method can be used to perform safety statistical disclosures with low error rates, even in small cases.