Identification of the key interactions in structural transition pathway of FtsZ from Staphylococcus aureus.

The tubulin-homolog protein FtsZ is essential for bacterial cell division. FtsZ polymerizes to form protofilaments that assemble into a contractile ring-shaped structure in the presence of GTP. Recent studies showed that FtsZ treadmilling coupled with the GTPase activity drives cell wall synthesis and bacterial cell division. The treadmilling caused by assembly and disassembly of FtsZ links to a conformational change of the monomer from a tense (T) to a relaxed (R) state, but considerable controversy still remains concerning the mechanism. In this study, we report crystal structures of FtsZ from Staphylococcus aureus corresponding to the T and R state conformations in the same crystal, indicating the structural equilibrium of the two state. The two structures identified a key residue Arg29, whose importance was also confirmed by our modified MD simulations. Crystal structures of the R29A mutant showed T and R state-like conformations with slight but important structural changes compared to those of wild-type. Collectively, these data provide new insights for understanding how intramolecular interactions are related to the structural transition of FtsZ.

A low psoas muscle volume correlates with a longer hospitalization after radical cystectomy.

BACKGROUND: Recently, sarcopenia has been reported as a new predictor for patient outcomes or likelihood of post-operative complications. The purpose of this study was to evaluate the association of the psoas muscle volume with the length of hospitalization among patients undergoing radical cystectomy. METHODS: A total of 63 (80.8%) male patients and 15 (19.2%) female patients who underwent radical cystectomy for their bladder cancer in our institution from 2000 to 2015 were analyzed. The psoas muscle index (PMI) was calculated by normalizing the psoas muscle area calculated using axial computed tomography at the level of the umbilicus (cm2) by the square of the body height (m2). Longer hospitalization was defined as hospitalization exceeding 30 days after surgery. RESULTS: The median PMIs (mean ± standard deviation) were 391 (394 ± 92.1) and 271 (278 ± 92.6) cm2/m2 in men and women, respectively. Thus, the PMIs of male patients were significantly larger than those of females (p < 0.001). Based on the differences in gender, we analyzed 63 male patients for a further analysis. In male patients, those hospitalized longer showed a significantly smaller PMI than those normally discharged (377 ± 93.1 vs. 425 ± 83.4; p = 0.04). Similarly, male patients with a small PMI (<400) had a significantly worse overall survival (p = 0.02) than those with a large PMI (≥400). CONCLUSIONS: The presence of sarcopenia was found to be associated with significantly longer hospitalization after radical cystectomy in male patients. Furthermore, in men, a PMI <400 may suggest a significantly worse prognosis.

[Severe Hyponatremia after Cisplatin-Based Chemotherapy : Two Case Reports].

Hyponatremia is one of the common electrolyte disorders associated with cisplatin (CDDP) administration. We report here two cases of hyponatremia associated with CDDP. Case 1 : A 75-year-old man with urothelial carcinoma of bladder (cT3N1M0) underwent neoadjuvant chemotherapy with CDDP and gemcitabine. He lost consciousness on the eighth day after the chemotherapy. Blood tests showed severe hyponatremia (Na 113 mEq/l), low plasma osmolality and high level of plasma vasopressin. Urine tests showed low osmolality. These findings were consistent with the syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH). His consciousness level was improved after saline infusion and fluid restriction. Case 2 : A 54-year-old man with penile cancer (cT3N2M0) underwent neoadjuvant chemotherapy with CDDP, paclitaxel and fluorouracil. He lost consciousness on the seventh day after the chemotherapy. Blood tests showed hyponatremia(Na 121 mEq/l) with renal dysfunction. We concluded that the hyponatremia is due to the renal salt wasting syndrome (RSWS) based on renal dysfunction and high urinary sodium excretion. His consciousness level was improved after saline infusion. Although it is difficult to distinguish between SIADH and RSWS, correct evaluation is necessary for appropriate management of hyponatremia after CDDP administration.

Self-assessment of pediatric basic life support among nursery teachers in a rural area of Japan.

•Serious injury and deaths can occur in childcare settings.•School teachers in Japan have low confidence about managing serious injuries.•With appropriate education we can increase confidence of childcare workers.•We evaluate the confidence of nursery teachers in pediatric basic life support.

Structural Flexibility of an Inhibitor Overcomes Drug Resistance Mutations in Staphylococcus aureus FtsZ.

In the effort to combat antibiotic resistance, inhibitors of the essential bacterial protein FtsZ have emerged as a promising new class of compounds with clinical potential. One such FtsZ inhibitor (TXA707) is associated with potent activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) that are resistant to current standard-of-care antibiotics. However, mutations in S. aureus FtsZ (SaFtsZ) that confer resistance to TXA707 have been observed, with mutations in the Gly196 and Gly193 residues being among the most prevalent. Here, we describe structural studies of an FtsZ inhibitor, TXA6101, which retains activity against MRSA isolates that express either G196S or G193D mutant FtsZ. We present the crystal structures of TXA6101 in complex with both wild-type SaFtsZ and G196S mutant SaFtsZ, as well the crystal structure of TXA707 in complex with wild-type SaFtsZ. Comparison of the three structures reveals a molecular basis for the differential targeting abilities of TXA6101 and TXA707. The greater structural flexibility of TXA6101 relative to TXA707 enables TXA6101 to avoid steric clashes with Ser196 and Asp193. Our structures also demonstrate that the binding of TXA6101 induces previously unobserved conformational rearrangements of SaFtsZ residues in the binding pocket. In aggregate, the structures reported in this work reveal key factors for overcoming drug resistance mutations in SaFtsZ and offer a structural basis for the design of FtsZ inhibitors with enhanced antibacterial potency and reduced susceptibility to mutational resistance.

A case of tubulocystic carcinoma of the kidney with aggressive features.

Tubulocystic carcinoma of the kidney is rare and typically indolent. Our case involved an aggressive tubulocystic carcinoma as well as the radiological confirmation of its relation to papillary renal cell carcinoma. A 46-year-old male presented with renal multiloculated cysts with a solid part. On computed tomography and magnetic resonance imaging, the solid part showed the characteristics of papillary renal cell carcinoma. Contrast enhancement of the solid part was fluffy and sparse because of the coexistence of cysts. Perirenal fat invasion resulted in exophytic cysts, and renal-hilar cystic lymph node metastasis existed. The histopathological diagnosis was tubulocystic carcinoma associated with areas of papillary renal cell carcinoma and poorly differentiated carcinoma with metastasis. Our case suggests that the solid part enhancement of tubulocystic carcinoma tends to be fluffy and sparse, and exophytic cysts and cystic lymph nodes may show radiologically aggressive findings.

Lack of an Association between Neutrophil-to-Lymphocyte Ratio and PSA Failure of Prostate Cancer Patients Who Underwent Radical Prostatectomy.

Introduction. The neutrophil-to-lymphocyte ratio (NLR), which can be easily calculated from routine complete blood counts of the peripheral blood, has been suggested to serve as a prognostic factor for some solid malignancies. In the present study, we aimed to determine the relationship between NLR in prostate cancer patients undergoing radical prostatectomy (RP) and their prognosis. Materials and Methods. We assessed NLR in 73 men (patients) who received RP for their prostate cancer. We also performed immunohistochemistry for CD8 and CD66b in a separate set of RP specimens. Results. The median NLR in the 73 patients was 1.85. There were no significant correlations of NLR with tumor grade (p = 0.834), pathological T stage (p = 0.082), lymph node metastasis (p = 0.062), or resection margin status (p = 0.772). Based on the area under the receiver operator characteristic curve (AUROC) to predict biochemical recurrence after RP, potential NLR cut-off point was determined to be 2.88 or 3.88. However, both of these cut-off points did not precisely predict the prognosis. There were no statistically significant differences in the number of CD66b-positive neutrophils or CD8-positive lymphocytes between stromal tissues adjacent to cancer glands and stromal tissues away from cancer glands and between different grades or stages of tumors. Conclusions. There was no association between NLR and biochemical failure after prostatectomy.

Invasive urothelial carcinoma, lymphoma-like/plasmacytoid variant, successfully treated by radical cystectomy with adjuvant chemotherapy: a case report.

BACKGROUND: Invasive urothelial carcinoma, lymphoma-like/plasmacytoid variant, is a rare histological type of bladder cancer similar to plasma cells and is an aggressive variant of urothelial carcinoma associated with a poor prognosis. CASE PRESENTATION: A 41-year-old Asian man was referred to our hospital due to macroscopic hematuria. Cystoscopy detected a non-papillary tumor, and a transurethral resection of the bladder tumor revealed pT1N0M0 bladder cancer. A pathological examination showed high-grade invasive urothelial carcinoma and a component of signet ring cell carcinoma. A follow-up of the transurethral resection with radical cystectomy was carried out, and a pathological examination showed infiltrating urothelial carcinoma, with partial features of the plasmacytoid variant. We added chemotherapy treatment with gemcitabine and cisplatin for two cycles. Our patient has been free from recurrence for 2 years. CONCLUSIONS: We herein report the case of a patient with a plasmacytoid variant of urothelial carcinoma controlled with radial cystectomy and subsequent chemotherapy.

Epidermal Cyst in the Scrotum Successfully Treated while Preserving the Testis: A Case Report.

A 66-year-old male was referred to our hospital for further examination of a scrotal mass. Because of the risk of testicular cancer, we first clamped the vessels as a course of higher orchiectomy. Then, we approached the tumor through the scrotum and successfully resected it while preserving the testis. A histopathological diagnosis revealed an epidermal cyst. We herein report a rare case of an intrascrotal epidermal cyst successfully treated while preserving the testis.