4.5SH RNA counteracts deleterious exonization of SINE B1 in mice.

4.5SH RNA is a highly abundant, small rodent-specific noncoding RNA that localizes to nuclear speckles enriched in pre-mRNA-splicing regulators. To investigate the physiological functions of 4.5SH RNA, we have created mutant mice that lack the expression of 4.5SH RNA. The mutant mice exhibited embryonic lethality, suggesting that 4.5SH RNA is an essential species-specific noncoding RNA in mice. RNA-sequencing analyses revealed that 4.5SH RNA protects the transcriptome from abnormal exonizations of the antisense insertions of the retrotransposon SINE B1 (asB1), which would otherwise introduce deleterious premature stop codons or frameshift mutations. Mechanistically, 4.5SH RNA base pairs with complementary asB1-containing exons via the target recognition region and recruits effector proteins including Hnrnpm via its 5' stem loop region. The modular organization of 4.5SH RNA allows us to engineer a programmable splicing regulator to induce the skipping of target exons of interest. Our results also suggest the general existence of splicing regulatory noncoding RNAs.

Intravenously engrafted human multilineage-differentiating stress-enduring (Muse) cells rescue erectile function after rat cavernous nerve injury.

OBJECTIVE: To evaluate the effect of intravenous administration of human multilineage-differentiating stress-enduring (Muse) cells on rat postoperative erectile dysfunction (ED) with cavernous nerve (CN) injury without an immunosuppressant. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomised into three groups after CN crush injury. Either human-Muse cells, non-Muse mesenchymal stem cells (MSCs) (both 1.0 × 105 cells), or vehicle was infused intravenously at 3 h after CN injury without immunosuppressant. Erectile function was assessed by measuring intracavernous pressure (ICP) and arterial pressure (AP) during pelvic nerve electrostimulation 28 days after surgery. At 48 h and 28 days after intravenous infusion of Muse cells, the homing of Muse cells and non-Muse MSCs was evaluated in the major pelvic ganglion (MPG) after CN injury. In addition, expressions of C-X-C motif chemokine ligand (Cxcl12) and glial cell line-derived neurotrophic factor (Gdnf) in the MPG were examined by real-time polymerase chain reaction. Statistical analyses and comparisons among groups were performed using one-way analysis of variance followed by the Tukey test for parametric data and Kruskal-Wallis test followed by the Dunn-Bonferroni test for non-parametric data. RESULTS: The mean (SEM) ICP/AP values at 28 days were 0.51 (0.02) in the Muse cell group, 0.37 (0.03) in the non-Muse MSC group, and 0.36 (0.04) in the vehicle group, showing a significant positive response in the Muse cell group compared with the non-Muse and vehicle groups (P = 0.013 and P = 0.010, respectively). In the MPG, Muse cells were observed to be engrafted at 48 h and expressed Schwann cell markers S100 (~46%) and glial fibrillary acidic protein (~24%) at 28 days, while non-Muse MSCs were basically not engrafted at 48 h. Higher gene expression of Cxcl12 (P = 0.048) and Gdnf (P = 0.040) was found in the MPG of the Muse group than in the vehicle group 48 h after infusion. CONCLUSION: Intravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf.

Real-Time Monitoring of the Structural Transition of Bombyx mori Liquid Silk under Pressure by Solid-State NMR.

Silk fibroin is stored in the silk glands of Bombyx mori silkworms as a condensed aqueous solution called liquid silk. It is converted into silk fibers at the silkworm's spinnerets under mechanical forces including shear stress and pressure. However, the detailed mechanism of the structural transition of liquid silk to silk fibers under pressure is not well understood. Magic angle spinning (MAS) in solid-state nuclear magnetic resonance (NMR) can exert pressure on liquid samples in a quantitative manner. In this study, solid-state NMR was used to quantitatively analyze the impact of pressure on the structural transition of liquid silk. A combination of 13C DD-MAS and CP-MAS NMR measurements enabled the conformation and dynamics of the crystalline region of the silk fibroin (both before (Silk Ip) and after (Silk IIp) the structural transition) to be detected in real time with atomic resolution. Spectral analyses proposed that the pressure-induced structural transition from Silk Ip to Silk IIp proceeds by a two-step autocatalytic reaction mechanism. The first reaction step is a nucleation step in which Silk Ip transforms to single lamellar Silk IIp, and the second is a growth step in which the single lamellar Silk IIp acts as a catalyst that reacts with Silk Ip molecules to further form Silk IIp molecules, resulting in stacked lamellar Silk IIp. Furthermore, the rate constant in the second step shows a significant pressure dependence, with an increase in pressure accelerating the formation of large stacked lamellar Silk IIp.

Clinical impact of multimodal treatment including chemoradiotherapy, conversion surgery and postoperative chemotherapy for borderline resectable and unresectable locally advanced pancreatic cancer without disease progression after gemcitabine plus nab-paclitaxel.

BACKGROUND: The purpose of this study was to investigate treatment outcomes of chemoradiotherapy (CRT) using S-1 with or without conversion surgery after gemcitabine plus nab-paclitaxel (GnP) for borderline resectable (BR) and unresectable locally advanced (UR-LA) pancreatic cancer. METHODS: From 2016 to 2020, patients without disease progression after GnP for BR or UR-LA pancreatic cancer underwent CRT with S-1. If distant metastasis was not detected after CRT, conversion surgery and oral administration of S-1 as postoperative adjuvant chemotherapy for at least 6 months was performed. RESULTS: Forty patients were included in the present study. The median number of cycles of GnP was 6. Surgery was performed after CRT in 25 patients. The median progression-free survival (PFS) and overall survival (OS) periods from the start of radiotherapy were 24.6 and 27.4 months, respectively. The OS periods from the start of radiotherapy in patients who underwent conversion surgery and those who did not undergo conversion surgery were 41.3 and 16.8 months, respectively. The PFS periods from the start of radiotherapy in patients who underwent surgery and those who did not undergo surgery were 28.3 and 8.6 months, respectively. Patients who were able to receive S-1 after conversion surgery for more than 6 months had better OS than those who were not (p = 0.039), although there was no significant difference of PFS (p = 0.365). CONCLUSIONS: In BR/UR-LA pancreatic cancer without disease progression after GnP, multimodal treatment including CRT, conversion surgery and the scheduled postoperative chemotherapy may be effective.

Development and validation of an [18F]FDG-PET/CT radiomic model for predicting progression-free survival for patients with stage II - III thoracic esophageal squamous cell carcinoma who are treated with definitive chemoradiotherapy.

BACKGROUND: Radiomics is a method for extracting a large amount of information from images and used to predict treatment outcomes, side effects and diagnosis. In this study, we developed and validated a radiomic model of [18F]FDG-PET/CT for predicting progression-free survival (PFS) of definitive chemoradiotherapy (dCRT) for patients with esophageal cancer. MATERIAL AND METHODS: Patients with stage II - III esophageal cancer who underwent [18F]FDG-PET/CT within 45 days before dCRT between 2005 and 2017 were included. Patients were randomly assigned to a training set (85 patients) and a validation set (45 patients). Radiomic parameters inside the area of standard uptake value ≥ 3 were calculated. The open-source software 3D slicer and Pyradiomics were used for segmentation and calculating radiomic parameters, respectively. Eight hundred sixty radiomic parameters and general information were investigated.In the training set, a radiomic model for PFS was made from the LASSO Cox regression model and Rad-score was calculated. In the validation set, the model was applied to Kaplan-Meier curves. The median value of Rad-score in the training set was used as a cutoff value in the validation set. JMP was used for statistical analysis. RStudio was used for the LASSO Cox regression model. p < 0.05 was defined as significant. RESULTS: The median follow-up periods were 21.9 months for all patients and 63.4 months for survivors. The 5-year PFS rate was 24.0%. In the training set, the LASSO Cox regression model selects 6 parameters and made a model. The low Rad-score group had significantly better PFS than that the high Rad-score group (p = 0.019). In the validation set, the low Rad-score group had significantly better PFS than that the high Rad-score group (p = 0.040). CONCLUSIONS: The [18F]FDG-PET/CT radiomic model could predict PFS for patients with esophageal cancer who received dCRT.

Survival prediction nomogram for patients with vertebral bone metastases treated with palliative radiotherapy.

Background: In the treatment of vertebral bone metastases, estimating patient prognosis is important to select the optimal treatment strategy. The purpose of this study was to identify prognostic factors for vertebral bone metastases treated with palliative radiotherapy and to establish a nomogram for predicting patient survival. Materials and methods: We analyzed patients who underwent palliative radiotherapy for vertebral bone metastasis between January 2010 and December 2020 at a single institution. Exclusion criteria were as follows: (1) primary bone malignancy, (2) stereotactic body radiotherapy, (3) concurrent radiotherapy to sites other than the vertebral bone, (4) radiotherapy to other sites within 12 weeks before or after the current radiotherapy, and (5) lack of more than half of blood test data before radiotherapy. Results: A total of 487 patients met the inclusion criteria. Clinical and hematologic data were collected from the patient record system. Patients were divided into training and test groups in a 7:3 ratio. Multivariate Cox regression analysis in the training cohort revealed six significant factors, including a history of chemotherapy, primary site (breast cancer, prostate cancer, or hematologic malignancy), use of analgesics, neutrophil-lymphocyte ratio, serum albumin, and lactate dehydrogenase. A prognostic nomogram was developed and validated in the test cohort. The area under the curve (AUC) values in predicting survival at 6, 24, and 60 months were 0.83, 0.88, and 0.88 in the training cohort and 0.85, 0.81, and 0.79 in the test cohort, respectively. Conclusions: This nomogram may help to select the treatment strategy for vertebral bone metastases.

Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice.

BACKGROUND: In clinical practice, the effect of durvalumab and radiation pneumonitis (RP) on survival after intensity-modulated radiotherapy (IMRT) is not fully understood. The purpose of this retrospective study was to investigate factors related to distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) after IMRT for locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: All patients who were treated with conventional fractionated IMRT for LA-NSCLC between April 2016 and March 2021 were eligible. Time-to-event data were assessed by using the Kaplan-Meier estimator, and the Cox proportional hazards model was used for prognostic factor analyses. Factors that emerged after the start of IMRT, such as durvalumab administration or the development of RP, were analysed as time-dependent covariates. RESULTS: A total of 68 consecutive patients treated with conventional fractionated IMRT for LA-NSCLC were analysed. Sixty-six patients completed radiotherapy, 50 patients received concurrent chemotherapy, and 36 patients received adjuvant durvalumab. During the median follow-up period of 14.3 months, 23 patients died, and tumour progression occurred in 37 patients, including 28 patients with distant metastases. The 1-year DMFS rate, PFS rate and OS rate were 59.9%, 48.7% and 84.2%, respectively. Grade 2 RP occurred in 16 patients, grade 3 in 6 patients and grade 5 in 1 patient. The 1-year cumulative incidences of grade 2 or higher RP and grade 3 or higher RP were 33.8% and 10.3%, respectively. The results of multivariate analyses showed that durvalumab had a significantly lower hazard ratio (HR) for DMFS, PFS and OS (HR 0.31, p < 0.01; HR 0.33, p < 0.01 and HR 0.32, p = 0.02), respectively. Grade 2 or higher RP showed significance for DMFS and a nonsignificant trend for OS (HR 2.28, p = 0.04 and HR 2.12, p = 0.13), respectively, whereas a higher percentage of lung volume receiving 20 Gy or higher was significant for PFS (HR 2.25, p = 0.01). CONCLUSIONS: In clinical practice, durvalumab administration following IMRT with concomitant chemotherapy showed a significant survival benefit. Reducing the risk of grade 2 or higher RP would also be beneficial.

Palliative radiotherapy for gastric cancer bleeding: a multi-institutional retrospective study.

BACKGROUND: Palliative radiotherapy for gastric cancer bleeding has been reported to be a safe and effective treatment, but predictive factors for achievement of hemostasis and overall survival have not been established. METHODS: In this retrospective study, 120 courses of palliative radiotherapy for gastric cancer bleeding in 117 patients in 4 institutes in Japan were reviewed with approval of the ethical committee in each institute. The rate of achieving hemostasis was evaluated by 50% or more reduction of red blood cell transfusion before and after the start of radiotherapy, elevation of blood hemoglobin concentration in a period of 4 weeks from the start of radiotherapy or improvement of subjective or objective clinical symptoms in a period of 4 weeks from the start of radiotherapy. Predictive factors for overall survival and achieving hemostasis were investigated with the Cox hazards model. RESULTS: The median overall survival period was 3.7 months. Multivariate analysis showed that absence of metastatic disease, higher biological effective dose, higher serum albumin level, lower blood urea nitrogen level and lower neutrophil-to-lymphocyte ratio (NLR) were associated with longer overall survival. Elevation of hemoglobin concentration in a period of 4 weeks from the start of radiotherapy (mean concentration: 8.2 g/dL vs. 8.9 g/dL, p = 0.006) and decrease in the amount of red cell transfusion from a 4-week period before to a 4-week period after the start of radiotherapy (mean amount: 716 mL vs. 230 mL, p < 0.0001) were observed. The overall rate of achievement of hemostasis was 59.6%. In multivariate analysis, higher biological effective dose was associated with achievement of hemostasis. Grade 2 or higher acute adverse effects related to radiotherapy were observed in 17.5% of cases in 120 treatment courses. Six cases (5.0%) had grade 3 or 4 adverse effects including gastric penetration in 1 patient and anorexia requiring total parental nutrition in 3 patients. No grade 5 adverse effects were observed. CONCLUSIONS: Palliative radiotherapy for gastric cancer bleeding seems to be an effective and safe treatment strategy. Higher treatment dose was associated with longer overall survival and a hemostatic effect. Some hematological parameters may predict overall survival, and they would be helpful for deciding the treatment strategy.

Presence of ß-Turn Structure in Recombinant Spider Silk Dissolved in Formic Acid Revealed with NMR.

Spider dragline silk is a biopolymer with excellent mechanical properties. The development of recombinant spider silk protein (RSP)-based materials with these properties is desirable. Formic acid (FA) is a spinning solvent for regenerated Bombyx mori silk fiber with excellent mechanical properties. To use FA as a spinning solvent for RSP with the sequence of major ampullate spider silk protein from Araneus diadematus, we determined the conformation of RSP in FA using solution NMR to determine the role of FA as a spinning solvent. We assigned 1H, 13C, and 15N chemical shifts to 32-residue repetitive sequences, including polyAla and Gly-rich regions of RSP. Chemical shift evaluation revealed that RSP is in mainly random coil conformation with partially type II ß-turn structure in the Gly-Pro-Gly-X motifs of the Gly-rich region in FA, which was confirmed by the 15N NOE data. In addition, formylation at the Ser OH groups occurred in FA. Furthermore, we evaluated the conformation of the as-cast film of RSP dissolved in FA using solid-state NMR and found that ß-sheet structure was predominantly formed.

Recombinant Spider Silk Fiber with High Dimensional Stability in Water and Its NMR Characterization.

Spider dragline silk has unique characteristics of strength and extensibility, including supercontraction. When we use it as a biomaterial or material for textiles, it is important to suppress the effect of water on the fiber by as much as possible in order to maintain dimensional stability. In order to produce spider silk with a highly hydrophobic character, based on the sequence of ADF-3 silk, we produced recombinant silk (RSSP(VLI)) where all QQ sequences were replaced by VL, while single Q was replaced by I. The artificial RSSP(VLI) fiber was prepared using formic acid as the spinning solvent and methanol as the coagulant solvent. The dimensional stability and water absorption experiments of the fiber were performed for eight kinds of silk fiber. RSSP(VLI) fiber showed high dimensional stability, which is suitable for textiles. A remarkable decrease in the motion of the fiber in water was made evident by 13C solid-state NMR. This study using 13C solid-state NMR is the first trial to put spider silk to practical use and provide information regarding the molecular design of new recombinant spider silk materials with high dimensional stability in water, allowing recombinant spider silk proteins to be used in next-generation biomaterials and materials for textiles.

Patterns of failure after salvage chemoradiotherapy for postoperative loco-regional recurrent esophageal cancer: 20-year experience in a single institution in Japan.

PURPOSE: The purpose of the present study was to evaluate patterns of recurrence after salvage chemoradiotherapy (SCRT) for postoperative loco-regional recurrent esophageal cancer. METHODS: We reviewed records for 114 patients with postoperative loco-regional recurrent esophageal cancer treated by platinum-based chemoradiotherapy between 2000 and 2020, and we evaluated the patterns of failure in patients who had recurrence again or who had been observed for 2 years or more after SCRT at the last observation date. RESULTS: One hundred and three patients were enrolled in this study. The median observation period for survivors was 60 months. Fifty-three patients died of esophageal cancer and nine patients died of other diseases. The 5-year overall survival rate, cause-specific survival rate and disease-control rate were 43.7%, 45.3% and 37.0%, respectively. Sixty-five patients had failure after SCRT. In those patients, 26 patients had only distant organ or non-regional lymph node metastases, 26 patients had only loco-regional failure, and 13 patients had both. Of those 65 patients, 64 patients showed failure within 42 months after SCRT. Of 39 patients with loco-regional failure, failure in the irradiated field was observed in 28 patients. Of those 28 patients, 27 patients showed failure within 24 months and the other patient showed failure at 26.5 months. CONCLUSIONS: The patterns of failure after SCRT for patients with postoperative loco-regional recurrent esophageal cancer were shown. The patterns of failure suggest that follow-up for at least 4 years after SCRT should be performed for those patients.

The benefit of concurrent chemotherapy with radiotherapy for esophageal cancer is limited in Asian patients aged 80 years or older: a SEER database analysis.

PURPOSE: To evaluate the benefit of concurrent chemotherapy with radiotherapy (RT) for esophageal cancer in Asian patients aged ≥ 80 years using the Surveillance, Epidemiology, and End Results (SEER) database. MATERIALS AND METHODS: Among more than 7000 patients with squamous cell carcinoma or adenocarcinoma who were treated by RT without surgery for esophageal cancer in the SEER database, 2047 patients aged ≥ 80 years were analyzed. Patients who received chemoradiotherapy (CRT group) and patients who received RT alone (RT alone group) were matched with a propensity score. RESULTS: The median observation period for survivors was 57 months. The 3-year and 5-year overall survival rates in all patients were 15.2% and 8.5%, respectively. The 3-year and 5-year cause-specific survival rates in all patients were 20.8% and 14.5%, respectively. After propensity score matching, the overall survival rate in the CRT group was significantly higher than that in the RT alone group (5-year overall survival rates: 11.9% and 3.2%, respectively, p < 0.001). In 108 Asian or Pacific Islander patients, there was no significant difference (5-year overall survival rates: 13.5% and 0%, respectively, p = 0.291), although the overall survival rate in the CRT group was significantly higher than that in the RT alone group in any other race. CONCLUSIONS: It is controversial whether CRT is beneficial for Asian or Pacific Islander patients aged 80 years or older with esophageal cancer based on Analysis of data in SEER database.

Clinical outcomes and prognostic factors for esophageal cancer in patients aged 80 years or older who were treated with definitive radiotherapy and chemoradiotherapy.

OBJECTIVE: Aging of populations has been rapidly increasing worldwide. The aim of this study was to identify prognostic factors of overall survival (OS) and progression-free survival (PFS) in patients aged 80 years or older who had esophageal cancer and received radiotherapy. METHODS: Patients aged 80 years or older who received radiotherapy between 2004 and 2015 were retrospectively reviewed. Pretreatment age, gender, performance status, Charlson comorbidity index score, tumor location, histology, clinical stage, results of blood tests and treatment methods were obtained to determine prognostic factors of OS and PFS. Survival curves were drawn using the Kaplan-Meier method and prognostic factors were analyzed using Cox's hazards model. RESULTS: Ninety-two patients were included. Thirty-five patients were treated with chemo-radiotherapy. The median follow-up period was 19.0 months. The 3-year OS and PFS rates were 44.7% and 28.4%, respectively. In multivariate analysis, clinical stage (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.40-3.73, p = 0.001) and the geriatric nutritional risk index (GNRI, HR 0.95, 95% CI 0.92-0.97, p < 0.001) were significant prognostic factors of OS. Clinical stage (HR 2.06, 95% CI 1.34-3.18, p = 0.001), tumor location (HR 2.04, 95% CI 1.39-3.01, p < 0.001) and GNRI (HR 0.96, 95% CI 0.94-0.99, p = 0.003) were significant prognostic factors of PFS. CONCLUSION: Clinical stage and GNRI were significant prognostic factors of OS and PFS. Tumor location was a significant prognostic factor of PFS. These prognostic factors might be useful for decision-making for elderly patients with esophageal cancer.

IMRT improves local control in patients with nasopharyngeal carcinoma compared with conventional radiotherapy: propensity score-matched analysis.

BACKGROUND: It is still controversial whether intensity-modulated radiotherapy has an obvious advantage over conventional radiotherapy. The purposes of this study were to evaluate prognostic factors in pre-treatment characteristics for nasopharyngeal carcinoma and to compare treatment outcomes in patients who received intensity-modulated radiotherapy and patients who received two-dimensional radiotherapy or three-dimensional radiotherapy. METHODS: We reviewed patients with nasopharyngeal carcinoma who received chemoradiotherapy in our hospital during the period from 2000 to 2017, and we excluded patients who had a history of surgery for nasopharyngeal carcinoma and those who had distant metastases before treatment. A total of 72 patients who were treated by radiotherapy with concurrent chemotherapy were enrolled. All of the patients were irradiated with a total dose of 58-70 Gy. Overall survival, locoregional control and progression-free survival rates were compared in the groups treated by intensity-modulated radiotherapy and two-dimensional/three-dimensional radiotherapy. Propensity score matching was performed to homogenize the two groups. RESULTS: The median follow-up period was 62.5 months. After propensity score matching, in patients treated with intensity-modulated radiotherapy, the 5-year rate of overall survival, locoregional control and progression-free survival were 73.5, 95.2 and 72.7%, respectively. In patients treated with two-dimensional/three-dimensional radiotherapy, the 5-year rate of overall survival, locoregional control and progression-free survival were 69.1, 67.7 and 51.8%, respectively. There was a significant difference between the groups only in locoregional control. Late toxicities of grade 2 or higher were occurred in 38.5 and 24.2% of the patients treated by two-dimensional/three-dimensional radiotherapy and intensity-modulated radiotherapy, respectively. CONCLUSIONS: Our results suggested that intensity-modulated radiotherapy is more effective than two-dimensional/three-dimensional radiotherapy in patients with nasopharyngeal carcinoma, especially in locoregional control.

[A case of meningoencephalitis that developed during nivolumab use].

A 72-year-old woman developed a fever and consciousness disturbance after completing 8 courses of nivolumab for lung adenocarcinoma. A cerebrospinal fluid test showed an increased cell count, but bacterial culture, herpes simplex virus-polymerase chain reaction, acid-fast staining, and cytology were negative; serum paraneoplastic syndrome-related antibody was also negative. Serum and cerebrospinal fluid specimens were positive for anti-glutamate receptor (GluR) antibody, and fluid-attenuated inversion recovery images on head magnetic resonance imaging showed a high signal intensity at the right parietal lobe. The condition was determined to be immune-mediated encephalitis, and pulse steroid therapy was performed. The symptoms promptly improved after treatment. The patient in the present case was anti-GluR antibody-positive but was determined to have nivolumab-related encephalitis based on the clinical course. The use of immune checkpoint inhibitors has become widespread in recent years, although it can occasionally lead to encephalitis. We herein report our experience with immune checkpoint inhibitor-related encephalitis, which is seldom reported in Japan.

Vaginal Ureaplasma species increase chorioamnionitis in very preterm infants with preterm premature rupture of the membranes at < 28 weeks of gestation.

Our aim was to investigate the association between vaginal Ureaplasma species (spp.) and the subsequent occurrence of chorioamnionitis (CAM), perinatal death, neonatal morbidity, and long-term neurodevelopmental impairments (NDIs) at 3 years of age. We analyzed 55 pregnant women with singleton pregnancy who had preterm premature rupture of the membranes (pPROM) at < 28+0 weeks of gestation, and delivered between 22+0 and 31+6 weeks at our tertiary hospital in 2007-2016. NDIs were defined as either cerebral palsy or developmental delay evaluated at 1.5 and/or 3 years old. The presence of Ureaplasma spp. and Mycoplasma hominis were evaluated using urea-arginine broth and Mycoplasma PPLO Agar. The presence of Ureaplasma spp. in the vagina was positive in 41%. Vaginal Ureaplasma spp. was a significant risk factor for CAM; however, it was not significantly associated with the occurrence of perinatal death, pulmonary hypoplasia, respiratory distress syndrome, transient tachypnea of the newborn, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia defined as oxygen required and occasional ventilatory assistance required at week 36 as modified (BPD36), or NDIs. The crude odds ratio (95% confidence interval) of Ureaplasma spp. for the occurrence of CAM was 9.5 (1.10-82) (p = 0.041). In very preterm birth infants with pPROM, CAM, BPD36, and NDIs occurred in 78, 60, and 36%, respectively. Vaginal Ureaplasma spp. was a significant risk factor for CAM in very preterm birth infants with pPROM. The incidences of BPD36 and NDIs in such infants were very high, nearing 3/5 and 1/3, respectively.

Mycobacterium tuberculosis Transmission among Elderly Persons, Yamagata Prefecture, Japan, 2009-2015.

In many countries with low to moderate tuberculosis (TB) incidence, cases have shifted to elderly persons. It is unclear, however, whether these cases are associated with recent Mycobacterium tuberculosis transmission or represent reactivation of past disease. During 2009-2015, we performed a population-based TB investigation in Yamagata Prefecture, Japan, using in-depth contact tracing and 24-loci variable-number tandem-repeat typing optimized for Beijing family M. tuberculosis strains. We analyzed 494 strains, of which 387 (78.3%) were derived from elderly patients. Recent transmission with an epidemiologic link was confirmed in 22 clusters (70 cases). In 17 (77.3%) clusters, the source patient was elderly; 11 (64.7%) of the 17 clusters occurred in a hospital or nursing home. In this setting, the increase in TB cases was associated with M. tuberculosis transmissions from elderly persons. Prevention of transmission in places where elderly persons gather will be an effective strategy for decreasing TB incidence among predominantly elderly populations.

[COMPARISON OF QuantiFERON® TB GOLD TEST RESULTS BEFORE AND AFTER ENDOTOXIN CONTAMINATION].

PURPOSE: In response to a case of endotoxin contamination of tubes used in QuantiFERON® TB Gold (QFT-3G) testing in Japan in 2013, the effect of this contamination on QFT-3G test results was investigated. METHODS: We analyzed QFT-3G results from 4,258 participants in a tuberculosis contact investigation in Yamagata, Japan from September 2010 to April 2015. Of these, 2,488 samples were collected before the endotoxin contamination, while 1,770 samples were collected after the contamination. RESULTS: Negative control values in the group tested after the contamination were significantly lower than those in the group tested before the contamination (P < 0.0005). The proportion of positive controls that exceeded the calculated limit (10IU/ml) in the group tested after the contamination (87.8%) was lower than that in the group tested before the contamination (96.8%; P < 0.0005). The proportion of intermediate results in the group tested after the contamination (3.2%) was markedly lower than that in the group tested before the contamination (6.6%). DISCUSSION: Differences in QFT-3G test results were found to be related to a difference in blood collection before or after endotoxin contamination of blood collection tubes. Values resulting from QFT-3G testing were lower in blood samples that were collected after the contamination relative to those collected before the contamination.

Biological reaction to small-diameter vascular grafts made of silk fibroin implanted in the abdominal aortae of rats.

BACKGROUND: Bombyx mori silk fibroin (SF) is biocompatible and degradable and has been proposed as a new material for small-diameter vascular grafts. We compared biological reactions to vascular grafts made of SF and polyethylene terephthalate (PET) to reveal the potential ability of SF as a base and/or coating materials for vascular prostheses. METHODS: SF was combined with PET or gelatin (G) to make 4 types of vascular grafts (SF/SF, SF/G, PET/SF, and PET/G, shown as "base/coating material," respectively), which are 1.5 mm in diameter and 10 mm in length. The 4 types of grafts (n = 6, respectively) were implanted into rat abdominal aortae and explanted 2 weeks or 3 months later. RESULTS: Two weeks after implantation, there are no significant differences among the 4 kinds of grafts in biological reactions evaluated by histopathologic examination. However, a remarkable difference was observed after 3 months. The area of tissue infiltration into the inside of the graft wall was approximately 2.5 times larger in SF/SF than that in PET/G. The endothelialization was achieved almost 100% in SF/SF, despite only 50% was achieved in PET/G. CONCLUSIONS: Results show that SF has a higher potential as a base of vascular grafts than the commercially available PET/G graft. The larger tissue infiltration area in PET/SF compared with that in PET/G also indicates the potential of SF as a coating material. In the present study, SF delivered promising results as base and coating materials for small-diameter vascular prostheses.