Decreased Prevalence of qacA-Positive Methicillin-Resistant Staphylococcus aureus in Hospitalized Patients in Tokyo, Japan.

Presence of methicillin-resistant Staphylococcus aureus (MRSA) strains carrying plasmid-borne multidrug efflux pump-encoding gene, qacA/B, is a serious issue for infection control in hospitals, because they can survive hand hygiene. The qacA/B genes are divided into five subtypes: qacA, qacBI, qacBII, qacBIII, and qacBIV. The aim of this study was to investigate the prevalence and risk factors of hospitalized patients infected by respective qacA/B-positive MRSA strains between 2010 and 2016 in Tokyo, Japan. Of the 600 total MRSA strains observed, the qacA/B-positive strains constituted 19.8% (199 isolates), of which 56.8% (113 isolates), 28.6% (57 isolates), and 14.6% (29 isolates) were classified as qacA, qacBIII, and qacBII-positive strains, respectively. The prevalence of qacA-positive MRSA strains significantly decreased from July 2010 to June 2011 (34.0%) to July 2015 to May 2016 (5.3%) (p < 0.05). When staphylococcal cassette chromosome (SCC)mec types of the respective qacA/B-positive strains were determined, 81.4% of the qacA-positive strains were classified into SCCmec type II, which has recently been decreasing in hospital-acquired MRSA in Japan. Risk factor analysis showed that there were no specific clinical departments associated with the presence of qacA-positive strains. Our findings suggest that change in the MRSA clonal lineages impact to decrease the prevalence of qacA-positive strains in Japanese hospitals.

Change in genotype of methicillin-resistant Staphylococcus aureus (MRSA) affects the antibiogram of hospital-acquired MRSA.

Recently, the dissemination of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) into hospitals has frequently been reported worldwide. Hospital-acquired MRSA (HA-MRSA) strains exhibit high-level resistance to multiple antimicrobial agents, whereas CA-MRSA strains are usually susceptible to non-ß-lactams. Thus, it is predicted that the antibiogram of the HA-MRSA population would change along with the change in genotype of MRSA. Here, we investigated the changes in the MRSA population along with the MRSA antibiogram in a hospital between 2010 and 2016. Staphylococcal cassette chromosome (SCC) mec typing showed that the predominant HA-MRSA strains in the hospital dramatically changed from SCCmec type II, which is the major type of HA-MRSA, to SCCmec type IV, which is the major type of CA-MRSA. Multilocus sequence typing revealed that the predominant SCCmec type IV strain was a clonal complex (CC) 8 clone, which is mainly found among CA-MRSA. Furthermore, the CC1-SCCmec type IV (CC1-IV) clone significantly increased. Both the CC8-IV and CC1-IV clones exhibited high antimicrobial susceptibility. The antibiogram change of the HA-MRSA population was consistent with the antimicrobial susceptibilities and increased prevalence of the CC8-IV and CC1-IV clones. Our data reveal that the change in the genotypes of MRSA strains could impact the antibiogram of HA-MRSA population.

Efficacy and safety of leuprorelin acetate 6-month depot, TAP-144-SR (6M), in combination with tamoxifen in postoperative, premenopausal patients with hormone receptor-positive breast cancer: a phase III, randomized, open-label, parallel-group comparative study.

BACKGROUND: Leuprorelin acetate, a luteinizing hormone-releasing hormone agonist, is used worldwide in premenopausal women with hormone receptor-positive breast cancer. This study was conducted to assess the non-inferiority of the 6-month depot formulation, TAP-144-SR (6M) 22.5 mg to the 3-month depot formulation, TAP-144-SR (3M) 11.25 mg in postoperative, premenopausal patients with hormone receptor-positive breast cancer. METHODS: This was a 96-week phase III, randomized, open-label, parallel-group comparative study. All patients concomitantly received oral tamoxifen (20 mg daily). The primary endpoint was the suppression rate of serum estradiol (E2) to the menopausal level (≤30 pg/mL) from Week 4 through Week 48. RESULTS: In total, 167 patients were randomized to receive TAP-144-SR (6M) (n = 83) or TAP-144-SR (3M) (n = 84) and the E2 suppression rate was 97.6 and 96.4 %, respectively. The estimated between-group difference was 1.2 % (95 % confidence interval -5.2 to 7.8). The non-inferiority of TAP-144-SR (6M) to TAP-144-SR (3M) for E2 suppression was confirmed. As for safety, common adverse events were hot flush and injection site reactions including induration, pain, and erythema in both treatment groups, which were of ≤Grade 2 in severity and not serious. No significant between-group differences in safety profiles and tolerability were observed. CONCLUSIONS: TAP-144-SR (6M) was not inferior to TAP-144-SR (3M) for its suppressive effect on serum E2. TAP-144-SR (6M) was also as well tolerated as TAP-144-SR (3M).

Evaluation of the effects of a combination of Japanese honey and hydrocolloid dressing on cutaneous wound healing in male mice.

The aim of this study was to evaluate the effect of the combined use of Japanese honey and hydrocolloid dressing (HCD) on cutaneous wound healing. Mice were divided into four groups: the Acacia (Japan) + HCD, Manuka (New Zealand) + HCD, Chinese milk vetch (Japan) + HCD, and HCD (control) groups. The mice received two full-thickness wounds. The wounds of the HCD group were covered with HCD, whereas those of the other groups were treated with 0.1 mL of the relevant type of honey, before being covered with HCD. Wound area was significantly smaller in the HCD group than in the Acacia + HCD and Manuka + HCD groups on day 13 and days 8-14, respectively. Moreover, compared with the HCD group, reepithelialization was delayed in the Acacia + HCD group and reepithelialization and collagen deposition were delayed in the Chinese milk vetch + HCD and Manuka + HCD groups. These results indicate that the combined use of Japanese honey and HCD does not promote cutaneous wound healing compared with the use of HCD alone. Thus, this method is probably not useful for promoting healing.

Stathmin Regulates Hypoxia-Inducible Factor-1α Expression through the Mammalian Target of Rapamycin Pathway in Ovarian Clear Cell Adenocarcinoma.

Stathmin, a microtubule-destabilizing phosphoprotein, is highly expressed in ovarian cancer, but the pathophysiological significance of this protein in ovarian carcinoma cells remains poorly understood. This study reports the involvement of stathmin in the mTOR/HIF-1 α /VEGF pathway in ovarian clear cell adenocarcinoma (CCA) during hypoxia. HIF-1 α protein and VEGF mRNA levels were markedly elevated in RMG-1 cells, a CCA cell line, cultured under hypoxic conditions. Rapamycin, an inhibitor of mTOR complex 1, reduced the level of HIF-1 α and blocked phosphorylation of ribosomal protein S6 kinase 1 (S6K), a transcriptional regulator of mTOR, demonstrating that hypoxia activates mTOR/S6K/HIF-1 α signaling in CCA. Furthermore, stathmin knockdown inhibited hypoxia-induced HIF-1 α and VEGF expression and S6K phosphorylation. The silencing of stathmin expression also reduced Akt phosphorylation, a critical event in the mTOR/HIF-1 α /VEGF signaling pathway. By contrast, stathmin overexpression upregulated hypoxia-induced HIF-1 α and VEGF expression in OVCAR-3 cells, another CCA cell line. In addition, suppression of Akt activation by wortmannin, a phosphoinositide 3-kinase (PI3K) inhibitor, decreased HIF-1 α and VEGF expression. These results illustrate that regulation of HIF-1 α through the PI3K/Akt/mTOR pathway is controlled by stathmin in CCA. Our findings point to a new mechanism of stathmin regulation during ovarian cancer.

Stathmin, a microtubule regulatory protein, is associated with hypoxia-inducible factor-1alpha levels in human endometrial and endothelial cells.

Local hypoxia that occurs during menstruation triggers angiogenesis that is crucial for cyclical remodeling of the endometrium during the menstrual cycle. Hypoxia is thought to be important for the expression of vascular endothelial growth factor (VEGF) via its transcriptional factor, hypoxia inducible factor (HIF)-1alpha, in the endometrium. The activation of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway may modulate HIF-1alpha protein levels. Stathmin, a microtubule regulatory protein, was expressed in the stroma, glandular epithelium, and vascular endothelium in human endometrium. In this study, we examined a possible role of stathmin in hypoxia-induced HIF-1alpha and VEGF expression in primary isolated and immortalized human endometrial stromal cells, glandular epithelial cells, and human umbilical venous endothelial cells (HUVEC). Knocking down stathmin expression using small interfering RNA caused microtubule stabilization and inhibited hypoxia-induced VEGF mRNA expression via the reduction of HIF-1alpha protein levels in endometrial cells and HUVEC. Treatment of the cells with a PI3K inhibitor, wortmannin, inhibited the expression of VEGF mRNA and the accumulation of HIF-1alpha protein. Silencing of stathmin expression repressed the activation (phosphorylation) of Akt in endometrial cells and HUVEC. These results suggest that endometrial stathmin is linked to HIF-1alpha protein accumulation and VEGF expression through the PI3K/Akt signaling pathway and may be involved in regeneration of the endometrium during the menstrual cycle in human uterine cells.