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HLA-A, -C, -B, and -DRB1 genotypes were analyzed in 178 Japanese COVID-19 patients to investigate the association of HLA with severe COVID-19. Analysis of 32 common HLA alleles at four loci revealed a significant association between HLA-DRB1*09:01 and severe COVID-19 (odds ratio [OR], 3.62; 95% CI, 1.57-8.35; p = 0.00251 [permutation p value = 0.0418]) when age, sex, and other common HLA alleles at the DRB1 locus were adjusted. The DRB1*09:01 allele was more significantly associated with risk for severe COVID-19 compared to preexisting medical conditions such as hypertension, diabetes, and cardiovascular diseases. These results indicate a potential role for HLA in predisposition to severe COVID-19.

The purpose of this study was to clarify the effects of fabrication method of restorative resin-based composites on its wear using enamel as antagonist teeth. Wear evaluation was performed via two-body wear test using hemispherical samples of restorative resin-based composite (abrader specimen) fabricated through direct restoration method, indirect restoration method, and CAD/CAM, and bovine enamel (substrate specimen). As a result, there was a difference in wear volume between resin-based composite and bovine enamel depending on the fabrication method. Resin composite used for indirect restoration method showed more wear in both the abrader and substrate specimens. Resin composite used for CAD/CAM crowns showed greater wear volume in the abrader specimen. In conclusion, results clarified that fabrication method of restorative resin-based composite has an influence on the wear of the resin composite itself and enamel as antagonist teeth.

Interleukin (IL)-38 was discovered in 2001 and is a member of the IL-1 family of cytokines. IL-38 shows anti-inflammatory activity in several inflammatory diseases. In lung adenocarcinoma, we previously demonstrated that high IL-38 expression in tumor cells was associated with poor prognosis. However, the role of IL-38 in the tumor microenvironment has not been clarified. IL-38-plasmid-transfected Lewis lung carcinoma cells (LLC-IL38) and empty vector-transfected LLC cells (LLC-vector) were established. Cell proliferation in vitro and tumor growth in vivo were examined, and immunohistochemical staining was used to assess tumor-infiltrating lymphocytes (TILs). A CD8+ lymphocyte depletion model was established to show the association between IL-38 and CD8+ lymphocytes. Moreover, we examined the association between IL-38 expression and CD8+ TILs in human samples, analyzing immunohistochemical staining in 226 patients with radically resected lung adenocarcinoma. Tumor growth of LLC-IL38 in vivo was significantly increased compared with that of LLC-vector, although cell proliferation of LLC-IL38 in vitro was lower than that of LLC-vector. CD8+ TILs were significantly decreased in LLC-IL38 tumor compared with LLC-vector tumor. The difference in tumor growth between LLC-IL38 and LLC-vector became insignificant after depletion of CD8+ lymphocytes. In immunohistochemical staining in tissues from patients with lung adenocarcinoma, multivariate analysis showed high IL-38 expression was an independent negative predicter of high density of CD8+ TILs. We demonstrated that high IL-38 expression in tumor cells was significantly associated with reduction of CD8+ TILs and tumor progression. These results suggest that IL-38 could be a therapeutic target for lung cancer.

Immunotherapy has become a standard treatment option for non-small cell lung cancer (NSCLC), with the tumor microenvironment attracting significant attention. CD8 + and forkhead box protein P3 + (FoxP3 +) tumor-infiltrating lymphocytes (TILs) influence the tumor microenvironment, but the clinical significance of CD8 + and FoxP3 + TILs in stage IA lung adenocarcinoma (LAD) is poorly understood. We analyzed 203 patients with stage IA primary LAD who had undergone surgery at Kyushu University from January 2003 to December 2012. We evaluated CD8 + and FoxP3 + TILs by immunohistochemistry. We set the cutoff values at 50 cells/0.04 mm2 for CD8 + TILs and 20 cells/0.04 mm2 for FoxP3 + TILs, respectively. We divided the patients into four groups: CD8-Low/FoxP3-Low; CD8-High/FoxP3-Low; CD8-Low/FoxP3-High; and CD8-High/FoxP3-High. We compared clinical outcomes among them. Programmed cell death ligand-1 (PD-L1) expression by tumor cells was also evaluated as previously reported. Respectively, 104 (51.2%), 46 (22.7%), 22 (10.8%), and 31 (15.3%) patients were classified as CD8-Low/FoxP3-Low, CD8-High/FoxP3-Low, CD8-Low/FoxP3-High, and CD8-High/FoxP3-High. Both disease-free survival (DFS) and overall survival (OS) were significantly worse in the CD8-Low/FoxP3-High group than the other groups (5-year DFS: 66.3% vs. 90.5%; P = 0.0007, 5-year OS: 90.9% vs. 97.0%; P = 0.0077). In the multivariate analysis, CD8-Low/FoxP3-High and PD-L1 expression were independent prognostic factors of DFS, and lymphatic invasion, surgical procedure, and PD-L1 expression were independent prognostic factors of OS. CD8-Low/FoxP3-High was an independent prognostic factor of DFS (hazard ratio: 3.22; 95% confidence interval: 1.321–7.179; P = 0.0121) in stage IA LAD. Immunosuppressive conditions were associated with poor prognosis in stage IA LAD.

Predicting future economic trends appropriately is essential to economic policy making. Currently, the DSGE model approach is a benchmark economic forecasting technique widely employed. However, large external shocks, such as large-scale natural disasters and COVID-19, challenge current approaches to economic forecasting. Multiple approaches will be needed in this situation, including reduced-form model and indicator-based approaches. This paper discusses different forecasting approaches, by comparing forecasts during normal times and crisis periods. The Medium-term Projection Framework (MPF), used in the Economic Outlook for Southeast Asia, China and India series, receives particular attention. The paper also examines challenges unique to developing Asia and large external shock periods. The measurement of potential output, difficulties in modelling the credit channel, and the incorporation of Big Data pose challenges regarding developing Asian countries, and large external shocks may force deviation from assumptions of traditional frameworks such as rational expectations. Finally, this paper points out that natural disasters will be a useful proxy for large shocks in Developing Asia.

Background There is limited evidence for pulmonary arterial hypertension (PAH)-targeted therapy in patients with pulmonary hypertension associated with respiratory disease (R-PH). Therefore, we conducted a multicenter prospective study of patients with R-PH to examine real-world characteristics of responders by evaluating demographics, treatment backgrounds, and prognosis.Methods and Results:Among the 281 patients with R-PH included in this study, there was a treatment-naive cohort of 183 patients with normal pulmonary arterial wedge pressure and 1 of 4 major diseases (chronic obstructive pulmonary diseases, interstitial pneumonia [IP], IP with connective tissue disease, or combined pulmonary fibrosis with emphysema); 43% of patients had mild ventilatory impairment (MVI), whereas 52% had a severe form of PH. 68% received PAH-targeted therapies (mainly phosphodiesterase-5 inhibitors). Among patients with MVI, those treated initially (i.e., within 2 months of the first right heart catheterization) had better survival than patients not treated initially (3-year survival 70.6% vs. 34.2%; P=0.01); there was no significant difference in survival in the group with severe ventilatory impairment (49.6% vs. 32.1%; P=0.38). Responders to PAH-targeted therapy were more prevalent in the group with MVI. Conclusions This first Japanese registry of R-PH showed that a high proportion of patients with MVI (PAH phenotype) had better survival if they received initial treatment with PAH-targeted therapies. Responders were predominant in the group with MVI.

No imaging modality can be used to evaluate Fontan-associated liver disease (FALD). We retrospectively reviewed hepatic gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) characteristics of patients within 1 year post-Fontan procedure, and we evaluated the association between hepatic imaging abnormalities and clinical parameters, including follow-up cardiac catheterization and laboratory test findings. The EOB-MR images were graded, based on the extent of the decreased enhancement, as “normal” (Grade 1), “segmental” (Grade 2), “regional” (Grade 3), and “diffuse” (Grade 4). We enrolled 37 patients (mean age, 3.5 ± 1.0 years): 9 patients had Grade 1 or 2; 14 patients, Grade 3; and 14 patients, Grade 4. EOB-MRI revealed characteristic reticular or mosaic patterns of diminished enhancement (i.e. “frog spawn” appearance). Ultrasonography did not detect diminished enhancement or “frog spawn” appearance. A trend existed toward increased grade severity in imaging with increased central venous pressure, pulmonary vascular resistance, and gamma-glutamyltransferase levels. Noninvasive EOB-MRI revealed the characteristic pattern of diminished enhancement, which was correlated with certain clinical parameters indicative of Fontan physiology and liver dysfunction. Early-stage FALD may occur soon after the Fontan procedure and is associated with increased pressure in the inferior vena cava and hepatic veins.

Background and purpose: To compare chemoradiotherapy (CRT) with low-dose continuous 5-fluorouracil (5FU) to CRT with 5FU+cisplatin (CDDP) for esophageal squamous cell carcinoma (ESCC) in a retrospective cohort study. Methods and materials: We reviewed the cases of Stage I–IV ESCC patients who underwent definitive CRT in 2000–2014. Concomitant chemotherapy was one of the three regimens: (1) high-dose intermittent 5FU and CDDP (standard-dose FP: SDFP), (2) low-dose continuous 5FU and CDDP (LDFP), or (3) low-dose continuous 5FU (LD5FU). The general selection criteria for chemotherapy were: SDFP for patients aged

Contra-rotating small-sized fans are used as cooling fans for electric equipment. The internal flow condition between the front and rear rotors of the contra-rotating small-sized fan is not known well especially at the low flow rate. Furthermore, the blade row distance between the front and rear rotors is an important parameter for the contra-rotating small-sized fan and its influence on the internal flow condition is not clarified at the low flow rate. Therefore, the internal flow condition of the contra-rotating small-sized fan at the low flow rate is investigated by the numerical analysis in this research. The numerical analysis results are validated by comparing the fan static pressure curves of the numerical results to the experimental results. The internal flow condition at the low flow rate is clarified using the numerical models of the different blade row distance L = 10 mm and 30 mm. In the present paper, pressure fluctuations phase locked each front and rear rotor’s rotation are shown and the influences of the wake and the potential interference are discussed by the unsteady numerical analysis results at the low flow rate.

Smart cities represent the future of urban development in Emerging Asia as more and more cities and countries resort to smart technologies to build more efficient and liveable urban environments, boost economic growth, foster well-being and facilitate citizen engagement. Policy makers in the region have adopted plans to develop and promote the use of technology to organise and run urban areas. Governments have also provided significant financial backing to smart city projects, acknowledging the importance of public support in this field. The development of smart cities offers significant prospects to tackle enduring issues faced by Emerging Asian cities in policy areas such as transport, the provision of public services, education, healthcare and utilities.

The purpose of this study was to clarify the effects of fabrication method of restorative resin-based composites on its wear using enamel as antagonist teeth. Wear evaluation was performed via two-body wear test using hemispherical samples of restorative resin-based composite (abrader specimen) fabricated through direct restoration method, indirect restoration method, and CAD/CAM, and bovine enamel (substrate specimen). As a result, there was a difference in wear volume between resin-based composite and bovine enamel depending on the fabrication method. Resin composite used for indirect restoration method showed more wear in both the abrader and substrate specimens. Resin composite used for CAD/CAM crowns showed greater wear volume in the abrader specimen. In conclusion, results clarified that fabrication method of restorative resin-based composite has an influence on the wear of the resin composite itself and enamel as antagonist teeth.

Polyarteritis nodosa (PAN) is a rare form of vasculitis that occurs in childhood and affects small- and medium-sized arteries. Large aneurysms due to PAN can induce fatal complications like rupturing or occlusion of the affected arteries. Here, we report a case of a 4-month-old girl with PAN complicated by a large superior mesenteric artery aneurysm and ileal obstruction. We controlled her blood pressure to prevent the artery from rupturing. A combination of prednisolone, intravenous cyclophosphamide, and plasma exchange reduced the inflammation. She developed mechanical ileus due to ileum stricture and underwent bowel resection. Histopathological examinations revealed reparative arteritis around the healed ulcer. Her postoperative course was uneventful without further dilatation of the aneurysm. This case highlights the importance of intensive immunosuppressive therapy and appropriate blood pressure control in pediatric patients with PAN complicated by large aneurysms. Mechanical ileus can develop and may require surgical management even after remission of vasculitis.

Cluster of differentiation 69 (CD69), known as an early activation marker of lymphocytes, has been demonstrated to regulate inflammatory events in various disease models. Although the increased number of CD69-expressed T lymphocytes in the lungs of patients with chronic obstructive pulmonary disease (COPD) has been reported, a functional role of CD69 in the pathogenesis of COPD remains unknown. To address to this question, CD69-deficient (CD69KO) mice and wild-type (WT) mice were subjected to a mouse model of porcine pancreatic elastase (PPE)-induced pulmonary inflammation and emphysema. In the two genotypes, PPE increased counts of macrophages, neutrophils and lymphocytes in bronchoalveolar lavage fluid (BALF) and induced emphysematous changes in the lung, whereas those two pathological signs were significantly enhanced in CD69KO mice compared to WT mice. Moreover, the PPE-induced levels of IL-17 and IL-6 in BALF were significantly higher in CD69KO mice than in WT mice at the acute inflammatory phase. Immunofluorescent studies showed that IL-17 and IL-6 were predominantly expressed in CD4+ and γδ T cells and macrophages, respectively. Concomitant administration of IL-17- and IL-6-neutralizing antibodies significantly attenuated the PPE-induced emphysematous changes in the two genotypes. These findings suggest that CD69 negatively regulates the development of PPE-induced emphysema in part at least through modulating function of IL-17-producing T cells., Highlights • CD69 negatively modulated elastase-induced pulmonary inflammation and emphysema. • Disruption of the CD69 gene enhanced the elastase-induced IL-6 and IL-17 expression. • Th17 and γδ T cells affected the elastase-induced emphysema via producing IL-17. • Neutralization of IL-6&17 signals attenuated the elastase-induced emphysema.

We investigated the outcomes of treatment for patients with localized prostate cancer (PCa) treated with 3D conformal radiation therapy (3D-CRT) followed by two-fraction high-dose-rate brachytherapy within a single day (2-fr.-HDR-BT/day) at a single institution. A total of 156 consecutive Asian males (median age, 67 years) were enrolled. To compare our findings with those of other studies, we analyzed our results using the D'Amico classification, assigning the patients to low- ( n = 5; 3.2%), intermediate- ( n = 36; 23.1%) and high-risk ( n = 115; 73.7%) groups (Stage T3 PCa patients were classified as high-risk). One patient in the D'Amico low-risk group (20%), 13 intermediate-risk patients (36.1%) and 99 high-risk patients (86.1%) underwent androgen deprivation therapy. We administered a prescription dose of 39 Gy in 13 fractions of 3D-CRT combined with 18 Gy of HDR-BT in two 9-Gy fractions delivered within a single day. We did not distinguish between risk groups in determining the prescription dose. The median follow-up period was 38 months. Of the 156 patients, one died from primary disease and five died from other diseases. The 3-year overall survival (OS) rates were 100%, 100% and 93.7%, and the 3-year ‘biochemical no evidence of disease (bNED)’ rates were 100%, 100% and 96.9% for the D'Amico low-, intermediate- and high-risk groups, respectively. No patient developed ≥ Grade 3 early toxicity. The Grade 3 late genitourinary toxicity rate was 2.6%, and no ≥ Grade 3 late gastrointestinal toxicity occurred. The efficacy and safety of this study were satisfactory, and longer-term follow-up is necessary.

Inflammatory biomarkers have been associated with clinical outcomes in non-small cell lung cancer (NSCLC). However, the best prognostic marker(s) has not been identified, and the association between inflammatory markers and clinical characteristics is poorly understood. We selected 1,237 patients with resected NSCLC from Kyushu University (2003-2015) and Kyushu Cancer Center (2009-2015) in Japan. Pearson product-moment correlation coefficient among inflammatory markers and area under curve (AUC) of receiver operating characteristic (ROC) curve analyses for overall survival (OS) were calculated. We analyzed the associations between inflammatory markers and clinical factors using Student's t-test. Univariate and multivariate analyses with Cox proportional hazards regression analyses were performed to evaluate the relationship between survival and clinical factors. The cut-off values for neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio, and derived NLR (dNLR) were determined by ROC curve analyses for OS. We found a strong positive correlation between NLR and dNLR (r = 0.9629). The AUC of LMR was the highest amongst the measured metrics, and the AUC of NLR was higher than dNLR. Levels of some inflammatory markers were associated with sex, smoking, squamous cell carcinoma, and pathological stage. LMR ≥ 5.11 and lactate dehydrogenase (LDH) concentration ≥ 222 (U/L) were independent predictors of both disease-free survival (DFS) and OS (LMR; P = 0.0009 and 0.0008, LDH; P = 0.0195 and 0.0187, respectively). Certain inflammatory markers, potentially linked to smoking, were associated with an advanced pathological stage in NSCLC. LMR and LDH were independent predictors of both DFS and OS.

Growing teratoma syndrome (GTS) of the lung is extremely rare, and there are very few reports on this condition. This is a case report of GTS of the lung that was successfully treated by resection. A 19-year-old man, who had been diagnosed with a testicular tumor, lung metastases and left hilar lymph node metastasis, underwent surgical resection for left testicular cancer. After orchiectomy and chemotherapy, the patient was successfully treated with wedge resection of the right upper lobe and left upper lobectomy. In conclusion, the current case suggests that some patients with GTS might be successfully treated by surgical resection.

Objectives: Even with advanced image guidance, biopsies occasionally fail to diagnose small lung lesions, which are highly suggestive of primary lung cancer by radiological examination. The aim of this study was to evaluate the outcome of stereotactic body radiotherapy (SBRT) to treat small lung lesions clinically diagnosed as primary lung cancer., Materials and methods: This is a prospective, multi-institutional observation study. Strict inclusion and exclusion criteria were determined in a nation-wide consensus meeting and used to include patients who were clinically diagnosed with primary lung cancer using precise imaging modalities, for whom further surgical intervention was not feasible, who refused watchful waiting, and who were highly tolerable of SBRT with informed consent. SBRT was performed with 48 Gy in 4 fractions at the tumor isocenter., Results: From August 2009 to August 2014, 62 patients from 11 institutions were enrolled. Their median age was 80 years. The tumors ranged in size from 9 to 30 mm in diameter (median, 18 mm). The median follow-up interval was 55 months. The 3-year overall survival rate was 83.3% (95% confidence interval (CI) 71.1–90.7%) for all the patients and 94.7% (95% CI 68.1–99.2%) for the patients younger than 75 years. Local failure, regional lymph node metastases and distant metastases occurred in 4 (6.4%), 3 (4.8%) and 11 (17.7%) patients, respectively. Grades 3 and 4 toxicities were observed in 8 (12.9%) patients and 1 (1.6%) patient, respectively. No grade 5 toxicities were observed., Conclusions: SBRT is safe and effective for patients with small lung lesions clinically diagnosed as primary lung cancer that satisfied the proposed strict indication criteria as previously reported. A prospective interventional study is required to ascertain if SBRT is an alternative strategy for these patients.

In this study, we conducted experimental measurements and computational analysis to investigate the aerodynamics of a shuttlecock, especially the effects of the camber of the shuttle’s skirt. The static aerodynamic coefficient from the experiment showed that the camber of the skirt was able to modify the aerodynamic characteristics. A positive camber, which indicates bending the blade toward the outside, causes a slight increase in lift and a decrease in drag. On the other hand, a negative camber causes an increase in drag, and an insensitive region in the lift and a pitching coefficient of approximately 0° was observed. This result leads to instability in the flight of the shuttlecock. The pressure distribution calculated using computational fluid dynamics revealed that each blade functions as a two-dimensional airfoil. However, in most cases, the blade is in stall condition due to an initial divergence angle of the skirt.

To determine the current practice of stereotactic irradiation (STI) for brain metastases in Japan by a questionnaire survey. A questionnaire was distributed to 313 institutions performing STI with one of the following machines: Gamma Knife (GK), CyberKnife (CK), Novalis (Nov), or other linear accelerator (LINAC)-based systems (OLS). The participation was voluntary. There were 163 responding institutions. The total number of STI treatments between April 2013 and March 2014 was 10,684. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) were performed in 8624 (80.7%) and 2060 (19.3%) cases, respectively. Whole-brain radiation therapy (WBRT) was performed for a total of 3515 cases. For a case model of a 1.5-cm solitary brain metastasis in a non-eloquent area, the most common GTV-PTV margin was 2 mm (22 of 114 institutions), and an institutional standard fraction was 1 (75 of 114 institutions). The doses for the model case also varied from 13.0 to 26.0 Gy (Median 20 Gy) when converted to SRS (α/β = 10). A prescription point was at the PTV margin the most. The median dose constraints which were converted to SRS (α/β = 3) to organs at risk were 12.2, 12.7, and 13.7 Gy for optic nerves, cavernous sinus, and brainstem, respectively. STI for brain metastases in current practice varied significantly among institutions. These different strategies relied mostly on the type of treatment machine used. It is thus necessary to establish a common guideline to express dose prescriptions and plan qualities for different STI machines.

Left pulmonary artery sling (LPAS) is a rare vascular anomaly. The left pulmonary artery arises distally from the right pulmonary artery on the right side of the trachea and passes between the trachea and esophagus towards the left lung, compressing the lower trachea. LPAS is associated with congenital tracheal stenosis, which frequently requires early surgical intervention and has a poor prognosis due to severe airway obstruction after birth. Therefore, LPAS should be prenatally diagnosed to prepare for surgical intervention for tracheal stenosis. To the best of our knowledge, there are few reports on prenatal echocardiographic findings in LPAS. We report three prenatal cases of LPAS, which resulted in respiratory symptoms. We discuss fetal ultrasound findings and highlight the abnormal rotation of the fetal cardiac axis to the right as a useful sign in the prenatal screening of LPAS.

The purpose of this study was to characterize the non-aqueous nanosuspension of a hydrophilic drug prepared by bead milling for cutaneous application. Riboflavin was used as the model hydrophilic drug. The non-aqueous nanosuspensions were prepared by grinding riboflavin with zirconia beads using eight non-aqueous bases. The mean particle size of riboflavin in the suspensions ranged from 206 to 469 nm, as determined by the dynamic light scattering method. Among the well-dispersed samples, riboflavin nanosuspension prepared in oleic acid was selected for evaluation of the drug permeability through rat skin. The cumulative amount and permeation rate of riboflavin from the nanosuspension were approximately three times higher than those for unprocessed riboflavin in oleic acid. Fluorescence imaging of the riboflavin nanosuspension suggested improved penetration of riboflavin into the stratum corneum. Furthermore, the addition of polysorbate 65 or polyglyceryl-6 polyricinoleate to the nanosuspension prepared in oleic acid markedly improved the riboflavin dispersibility. These results show that the preparation of a nanosuspension in a non-aqueous base by bead milling is one of the simple methods to improve the skin permeability of hydrophilic drugs.

This paper deals with the near-field DOA-Matrix method with SAGE algorithm, which is applied for source localization using a uniform linear array antenna. In this paper, we investigate the effect of spatial smoothing processing (SSP) on the performance of the near-field DOA-Matrix method with SAGE algorithm. The computer simulation using electromagnetic field analysis shows the SSP improves the source localization performance with the help of SAGE algorithm especially when the sources are correlated with each other.

One of the mitogen-activated protein kinases, p38α plays a crucial role in various inflammatory diseases and apoptosis of various types of cells. In this study, we investigated the pathophysiological roles of p38α in spinal cord injury (SCI), using a mouse model. Lateral hemisection at T9 of the SC was performed in wild type (WT) and p38α+/- mice (p38α-/- showed embryonic lethality). p38α+/- mice showed a better functional recovery from SCI-associated paralyzed hindlimbs compared to WT mice at 7 days post-injury (dpi), which remained until 28 dpi (an end time point of monitoring the behavior). In histopathological analysis at 28 dpi, there was more axonal regeneration with remyelination on the caudal side of the lesion epicenter in p38α+/- mice than in WT mice. At 7 dpi, infiltration of inflammatory cells into the lesion and expression of cytokines in the lesion were reduced in p38α+/- mice compared with WT mice. At the same time point, the number of apoptotic oligodendrocytes in the white matter at the caudal boarder of the lesion of p38α+/- mice was lower than that of WT mice. At 14 dpi, more neural and oligodendrocyte precursor cells in the gray matter and white matter, respectively, were observed around the lesion epicenter of p38α+/- mice compared with the case of WT mice. At the same time point, astrocytic scar formation was less apparent in p38α+/- than in WT mice, while compaction of inflammatory immune cells associated with the wound contraction was more apparent in p38α+/- than in WT mice. Furthermore, we verified the effectiveness of oral administration of SB239063, a p38α inhibitor on the hindlimb locomotor recovery after SCI. These results suggest that p38α deeply contributes to the pathogenesis of SCI and that inhibition of p38α is a beneficial strategy to recovery from SCI.

Objectives: We evaluated the efficacy of balloon dilatation after bilateral pulmonary artery banding for the treatment of severe congenital heart disease that depends on patent ductus arteriosus for systemic circulation. Background: Neonatal cardiopulmonary bypass can cause brain injury, which may result in a severely impaired neurodevelopmental outcome. Hence, we perform bilateral pulmonary artery banding combined with postoperative percutaneous trans catheter angioplasty with balloon dilatation as first-stage palliation. Methods: From October 2007 to December 2013, 27 consecutive patients underwent bilateral pulmonary artery banding at our institution. We retrospectively obtained their diagnostic, clinical, and catheter examination data from the medical records. Results: Bilateral pulmonary artery banding was performed at a median of 7 days. Among the 27 patients, 16 underwent expansive angioplasty using a balloon catheter at each banding site to increase pulmonary blood flow. The mean age at dilatation was 53.4 ± 25.9 days, and the mean pulmonary artery index significantly increased from 130.6 mm2/m2 ± 51.1 mm2/m2 before dilatation to 243.6 mm2/ m2 ± 93.5 mm2/m2 after dilatation (p

Our objectives were to (1) investigate the feasibility of the use of the Japanese version of the Hopkins Verbal Learning Test-Revised (HVLT-R); (2) identify the clinical factors influencing the HVLT-R scores of patients undergoing whole-brain radiation therapy (WBRT); and (3) compare the neurocognitive function (NCF) after WBRT in different dose fractionation schedules. We administered the HVLT-R (Japanese version) before (baseline) and at four and eight months after WBRT in 45 patients who received either therapeutic (35Gy-in-14, n = 16; 30Gy-in-10, n = 18) or prophylactic (25Gy-in-10, n = 11) WBRT. Sixteen patients dropped out before the eight-month examination, due mostly to death from cancer. The Karnofsky Performance Status (KPS) 80–100 group had significantly higher baseline total recall (TR) scores (p = 0.0053), delayed recall (DR) scores (p = 0.012), and delayed recognition (DRecog) scores (p = 0.0078). The patients aged ≤65 years also had significantly higher TR scores (p = 0.030) and DRecog scores (p = 0.031). The patients who underwent two examinations (worse-prognosis group) had significantly decreased DR scores four months after WBRT compared to the baseline (p = 0.0073), and they were significantly more likely to have declined individual TR scores (p = 0.0017) and DR scores (p = 0.035) at four months. The eight-month HVLT-R scores did not significantly decline regardless of the WBRT dose fractionation. The baseline NCF was determined by age and KPS, and the early decline in NCF is characteristic of the worse-prognosis group.

To investigate the effects of a respiratory gating and multifield technique on the dose-volume histogram (DVH) in radiotherapy for esophageal cancer. Twenty patients who underwent four-dimensional computed tomography for esophageal cancer were included. We retrospectively created the four treatment plans for each patient, with or without the respiratory gating and multifield technique: No gating-2-field, No gating-4-field, Gating-2-field, and Gating-4-field plans. We compared the DVH parameters of the lung and heart in the No gating-2-field plan with the other three plans. In the comparison of the parameters in the No gating-2-field plan, there are significant differences in the Lung V5Gy, V20Gy, mean dose with all three plans and the Heart V25Gy–V40Gy with Gating-2-field plan, V35Gy, V40Gy, mean dose with No Gating-4-field plan and V30Gy–V40Gy, and mean dose with Gating-4-field plan. The lung parameters were smaller in the Gating-2-field plan and larger in the No gating-4-field and Gating-4-field plans. The heart parameters were all larger in the No gating-2-field plan. The lung parameters were reduced by the respiratory gating technique and increased by the multifield technique. The heart parameters were reduced by both techniques. It is important to select the optimal technique according to the risk of complications.

A case of a 62-year-old woman with breast cancer who developed an atypical femoral fracture during denosumab therapy for bone metastasis is reported. About 8.5 years before the fracture, she was diagnosed with breast cancer with liver and bone metastases and started receiving chemotherapy. Three and a half years later, zoledronic acid (40 mg every 4 weeks) was added, which was continued for 2 years and 4 months. At around 1.5 years after discontinuation of zoledronic acid, bone metastasis recurred and she began treatment with denosumab at 120 mg every 4 weeks. Fifteen months after starting denosumab, she sustained a left subtrochanteric fracture. Faint hot spots in the bilateral subtrochanteric regions were found on bone scintigraphy 2 months after the start of denosumab, and the tracer accumulation was slightly increased on bone scintigraphy 1 year later. Prior to the fracture, she had been experiencing a dull ache in her left thigh for a few months. Our case suggests that denosumab treatment for bone metastasis is a risk factor for atypical femoral fractures, and that thigh pain and subtrochanteric hot spots on bone scintigraphy could be signs of an impending fracture.

Background Various signals are known to participate in the pathogenesis of lung fibrosis. Our aim was to determine which signal is predominantly mobilized in the early inflammatory phase and thereafter modulates the development of lung fibrosis. Methods Mice received a single dose of 3 mg/kg body weight of bleomycin (BLM) and were sacrificed at designated days post-instillation (dpi). Lung homogenates and sections from mice in the early inflammatory phase were subjected to phospho-protein array analysis and immunofluorescence studies, respectively. Bronchoalveolar lavage fluid (BALF) from mice was subjected to an enzyme-linked immunosorbent assay (EIA) for interleukin (IL)-6 and evaluation of infiltrated cell populations. The effects of endogenous and exogenous IL-6 on the BLM-induced apoptotic signal in A549 cells and type 2 pneumocytes were elucidated. In addition, the effect of IL-6-neutralizing antibody on BLM-induced lung injury was evaluated. Results Phospho-protein array revealed that BLM induced phosphorylation of molecules downstream of the IL-6 receptor such as Stat3 and Akt in the lung at 3 dpi. At 3 dpi, immunofluorescence studies showed that signals of phospho-Stat3 and -Akt were localized in type 2 pneumocytes, and that BLM-induced IL-6-like immunoreactivity was predominantly observed in type 2 pneumocytes. Activation of caspases in BLM-treated A549 cells and type 2 pneumocytes was augmented by application of IL-6-neutralizing antibody, a PI3K inhibitor or a Stat3 inhibitor. EIA revealed that BLM-induced IL-6 in BALF was biphasic, with the first increase from 0.5 to 3 dpi followed by the second increase from 8 to 10 dpi. Blockade of the first increase of IL-6 by IL-6-neutralizing antibody enhanced apoptosis of type 2 pneumocytes and neutrophilic infiltration and markedly accelerated fibrosis in the lung. In contrast, blockade of the second increase of IL-6 by IL-6-neutralizing antibody ameliorated lung fibrosis. Conclusions The present study demonstrated that IL-6 could play a bidirectional role in the pathogenesis of lung fibrosis. In particular, upregulation of IL-6 at the early inflammatory stage of BLM-injured lung has antifibrotic activity through regulating the cell fate of type 2 pneumocytes in an autocrine/paracrine manner. Electronic supplementary material The online version of this article (doi:10.1186/s12931-015-0261-z) contains supplementary material, which is available to authorized users.