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Introduction Patients with rheumatoid arthritis (RA) treated with abatacept (ABT) are at increased risk for vaccine-preventable infections. The aim of the present study is to evaluate the humoral response to 23-valent pneumococcal polysaccharide (PPSV23) vaccination in RA patients receiving ABT. Methods The immunogenicity study was nested within a randomized, double-blind placebo-controlled study, designed to evaluate the efficacy of the PPSV23. PPSV23 was given to 111 RA patients, who were classified into three groups: RA control (n = 35), methotrexate (MTX) alone (n = 55), and ABT (n = 21). Before and 4–6 weeks after vaccination, we measured the patients’ concentrations of antibodies against pneumococcal serotypes 6B and 23F using an enzyme-linked immunosorbent assay and determined their antibody functionality using a multiplexed opsonophagocytic killing assay, reported as the opsonization index (OI). Results The pneumococcal serotype-specific IgG concentrations and OIs were both significantly increased in all treatment groups in response to PPSV23 vaccination. In the ABT group, the IgG responses for the 6B serotype were lower compared with those in the MTX alone or control groups, whereas the OI responses were similar to those in the other two groups. In a subgroup analysis, the pneumococcal serotype-specific IgG responses were significantly lower in both serotypes (6B and 23F) in the ABT/MTX group; however, the OI responses in the ABT group were not different from the control group. There was no association between the pneumococcal serotype-specific IgG and OI responses for the 6B serotype in patients receiving ABT in contrast to the control or MTX alone patients. No severe adverse effects were observed in any of the treatment groups. Conclusions OI responses indicate antibody functionality rather than simply their amount, so the similarity of these measurements between all three groups suggests that RA patients receiving ABT still benefit from receiving the PPSV23 vaccination, even though they produce less IgG in response to it. The results suggest an influence of ABT on the humoral response to PPSV23 vaccination under MTX treatment; however, preserved opsonin responses are expected in RA patients treated with ABT plus MTX. Trial registration University Hospital Medical Information Network Clinical Trials Registry: UMIN000009566. Registered 12 December 2012.

Glutathione S-transferase (GST) A1 catalyses the activated heterocyclic aromatic a mine carcinogenN-acetoxy-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OAc-PhIP). This case-control study was carried out to examine whether the genetic polymorphism of GSTA1 is associated with the risk oforal squamous cell carcinoma among Japanese people in relation to their smoking status. In this study, 97 Japanese oral squamous cell carcinoma patients and 457 healthy controls were compared for the frequencies of theGSTA1 genotypes ((*) A:-567T,-69C,-52G,(*) B:-567G,-69T,-52A). The frequencies ofGSTA1 (*)A/(*)B+(*)B/(*) B genotypes were 32.3% in male cancer patients and 11.4% in female cancer patients, compared with 20.1% in the male control group (Odds ratio (OR)=1.86; 95% confidence interval (CI) 0.99-3.46) and 23.1% in the female control group (OR=0.58; 95% CI 0.18-1.81). TheGSTA1 (*)A/(*)B+(*)B/(*) B genotypes were associated with an 86% increased risk of oral squamous cell carcinoma among males, albeit without statistical significance. Also, among male smokers, the frequency ofGSTA1 (*)A/(*)B+(*)B/(*) B genotypes was significantly higher among the oral squamous cell carcinoma patients (33.3%) than among the controls (19.6%). The OR of the male smokers with theGSTA1 (*)A/(*)B+(*)B/(*) B genotypes for oral squamous cell carcinoma was 1.97 (95% CI 1.02-3.79). We present the first evidence of an association betweenGSTA1 (*) B and oral squamous cell carcinoma among smokers. This study suggests that the GSTA1 polymorphism and tobacco smoke-derived PhIP are associated with oral squamous cell carcinoma susceptibility among male smokers.

The incidence of prostate cancer is increasing in low-risk populations such as Japanese. One of the causes of this increase is considered to be associated with the Western diet, especially the high intake of red meat and fat. Glutathione S-transferase (GST) A1, T1, M1, and P1 are phase II enzymes that are important for activation and detoxification of chemical carcinogens. In this study, 190 Japanese male patients with prostate cancer and 294 healthy controls, frequency-matched for age, were compared for frequencies of GSTA1, GSTT1, GSTM1, and GSTP1 genotypes. Among smokers, the frequency of the GSTA1*A/*B or *B/*B genotype in patients with prostate cancer (27.8%) showed a statistically significant increase compared with the control group frequency (18.2%; odds ratio [OR] =1.72; 95% CI, 1.01-2.94). In addition, the frequency of GSTT1 nondeletion genotype was associated with prostate cancer among smokers (OR =1.68; 95% CI, 1.06-2.68). The OR of carrying the combined genotyping of GSTA1*A/*B or *B/*B and GSTT1 nondeletion was 2.08 (95% CI, 1.14-3.80) with the combined genotyping of GSTA1*A/*A and GSTT1 null as a reference. On the other hand, no significant associations were observed for genotypes of GSTM1 and GSTP1 I105V. These findings suggest that the GSTA1 and GSTT1 polymorphisms are associated with prostate cancer susceptibility, especially among smokers.

Objectives：Glutathione S-transferase (GST) A1 catalyses the activated heterocyclic aromatic amine carcinogen N-acetoxy-2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (N-OAc-PhIP). This case-control study was carried out to examine whether the genetic polymorphism of GSTA1 is associated with the risk of oral squamous cell carcinoma among Japanese people in relation to their smoking status. Methods：In this study, 97 Japanese oral squamous cell carcinoma patients and 457 healthy controls were compared for the frequencies of the GSTA1 genotypes (*A：-567T, -69C, -52G, *B：-567G, -69T, -52A). Results：The frequencies of GSTA1 *A/*B+*B/*B genotypes were 32.3% in male cancer patients and 11.4% in female cancer patients, compared with 20.1% in the male control group (Odds ratio (OR)=1.86；95% confidence interval (CI) 0.99-3.46) and 23.1% in the female control group (OR=0.58；95% CI 0.18-1.81). The GSTA1 *A/*B+*B/*B genotypes were associated with an 86% increased risk of oral squamous cell carcinoma among males, albeit without statistical significance. Also, among male smokers, the frequency of GSTA1 *A/*B+*B/*B genotypes was significantly higher among the oral squamous cell carcinoma patients (33.3%) than among the controls (19.6%). The OR of the male smokers with the GSTA1 *A/*B+*B/*B genotypes for oral squamous cell carcinoma was 1.97 (95% CI 1.02-3.79). Conclusions：We present the first evidence of an association between GSTA1 *B and oral squamous cell carcinoma among smokers. This study suggests that the GSTA1 polymorphism and tobacco smoke-derived PhIP are associated with oral squamous cell carcinoma susceptibility among male smokers.

Carbonate, the major carbon reservoir on Earth’s surface, can enter into the mantle by subduction. However, evidence for recycled surficial carbonates in the deep mantle is still scarce. Ocean island basalts from Cook-Austral islands and St. Helena Island, widely called HIMU basalts because of their high μ =  238 U/ 204 Pb sources, are thought to be fed by mantle plumes originating in the lower mantle. Here we report exceptionally high δ 66 Zn values (δ 66 Zn = 0.38 ± 0.03‰) of these HIMU lavas relative to most published data for oceanic basalts (δ 66 Zn = 0.31 ± 0.10‰), which requires a source contributed by isotopically heavy recycled surficial carbonates. During subduction of the oceanic lithosphere, melting of mixed surficial carbonates and basaltic crust in the deep mantle generates carbonatite melts, which metasomatizes the nearby mantle and the resultant carbonated mantle ultimately evolves into a high-δ 66 Zn HIMU source. High-δ 66 Zn signatures of HIMU basalts, therefore, demonstrate that carbonates can be transported into Earth’s deep mantle. Zhang et al. perform high-precision zinc (Zn) isotopic analysis on lavas from St. Helena Island in the Atlantic, and Cook-Austral Islands in the Pacific, and confirm that ancient superficial carbonates were transported into the deep mantle billions of years ago.

Objective Synovial fibroblasts (SFs) in rheumatoid arthritis (RA) and osteoarthritis (OA) play biphasic roles in joint destruction and regeneration of bone/cartilage as mesenchymal stem cells (MSCs). Although MSCs contribute to joint homeostasis, such function is impaired in arthritic joints. We have identified functionally distinct three SF subsets characterized by the expression of CD34 and THY1 as follows: CD34 + THY1 + , CD34 − THY1 − , and CD34 − THY1 + . The objective of this study was to clarify the differentiation potentials as MSCs in each SF subset since both molecules would be associated with the MSC function. Methods SF subsets were isolated from synovial tissues of 70 patients (RA: 18, OA: 52). Expressions of surface markers associated with MSCs (THY1, CD34, CD73, CD271, CD54, CD44, and CD29) were evaluated in fleshly isolated SF subsets by flow cytometry. The differentiation potentials of osteogenesis, chondrogenesis, and adipogenesis were evaluated with histological staining and a quantitative polymerase chain reaction of differentiation marker genes. Small interfering RNA was examined to deplete THY1 in SFs. Results The expression levels of THY1 + , CD73 + , and CD271 + were highest and those of CD54 + and CD29 + were lowest in CD34 + THY1 + among three subsets. Comparing three subsets, the calcified area, alkaline phosphatase (ALP)-stained area, and cartilage matrix subset were the largest in the CD34 + THY1 + subset. Consistently, the expressions of differentiation markers of the osteoblasts ( RUNX2 , ALPL , and OCN ) or chondrocytes ( ACAN ) were the highest in the CD34 + THY1 + subset, indicating that the CD34 + THY1 + subset possessed the highest osteogenic and chondrogenic potential among three subsets, while the differentiation potentials to adipocytes were comparable among the subsets regarding lipid droplet formations and the expression of LPL and PPARγ . The knockdown of THY1 in bulk SFs resulted in impaired osteoblast differentiation indicating some functional aspects in this stem-cell marker. Conclusion The CD34 + THY1 + SF subset has high osteogenic and chondrogenic potentials. The preferential enhancement of MSC functions in the CD34 + THY1 + subset may provide a new treatment strategy for regenerating damaged bone/cartilage in arthritic joints.

This paper reports an overview and some important results of microgravity experiments called Dynamic Surf, which have been conducted on board the International Space Station from 2013 to 2016. The present project mainly focuses on the relations between the Marangoni instability in a high-Prandtl-number (Pr= 67 and 112) liquid bridge and the dynamic free surface deformation (DSD) as well as the interfacial heat transfer. The dynamic free surface deformations of large-scale liquid bridges (say, for diameters greater than 10 mm) are measured with good accuracy by an optical imaging technique. It is found that there are two causes of the dynamic free surface deformation in the present study: the first is the time-dependent flow behavior inside the liquid bridge due to the Marangoni instability, and the second is the external disturbance due to the residual acceleration of gravity, i.e., g-jitter. The axial distributions of DSD along the free surface are measured for several conditions. The critical parameters for the onset of oscillatory Marangoni convection are also measured for various aspect ratios (i.e., relative height to the diameter) of the liquid bridge and various thermal boundary conditions. The characteristics of DSD and the onset conditions of instability are discussed in this paper.

Purpose This study aimed to identify and compare risk factors for surgical site infection (SSI) and non-surgical site infections (non-SSIs), particularly urinary tract infection (UTI), after spine surgery. Methods We retrospectively reviewed 825 patients (median age 59.0 years (range 33–70 years); 442 males) who underwent spine surgery at Kagoshima University Hospital from January 2009 to December 2014. Patient parameters were compared using the Mann–Whitney U and Fisher’s exact tests. Risk factors associated with SSI and UTI were analyzed via the multiple logistic regression analysis. P  < 0.05 was considered statistically significant. Results SSI occurred in 14 of 825 cases (1.7 %), and non-SSI occurred in 23 of 825 cases (2.8 %). Most non-SSIs were UTIs (20 of 23 cases, 87.0 %). In the 14 patients with SSI, UTI occurred before SSI onset in one patient, and after SSI onset in two patients. UTI onset before SSI was not a risk factor for SSI. Multiple logistic regression analysis indicated that common risk factors for SSI and UTI were operation time ( P  = 0.0019 and 0.0162, respectively) and ASA classification 3 ( P  = 0.0132 and 0.0356, respectively). The 1 week post-operative C-reactive protein (CRP) level was a risk factor for UTI ( P  = 0.0299), but not for SSI ( P  = 0.4996). Conclusions There was no relationship between SSI and symptomatic UTI after spine surgery. Risk factors for post-operative SSI and UTI were operative time and ASA classification 3; 1 week post-operative CRP was a risk factor for UTI only.