Independent Factors Contributing to Daytime and Nighttime Asthmatic Cough Refractory to Inhaled Corticosteroids.

Background: Cough is a common feature of asthma, which is often resistant to inhaled corticosteroids (ICSs). The pathophysiology of this refractoriness may differ between daytime and nighttime asthmatic cough. We sought to identify factors contributing to ICS-refractory daytime and nighttime asthmatic cough.

The BioGIT System: a Valuable In Vitro Tool to Assess the Impact of Dose and Formulation on Early Exposure to Low Solubility Drugs After Oral Administration.

The purpose of this study was to evaluate the usefulness of the in vitro biorelevant gastrointestinal transfer (BioGIT) system in assessing the impact of dose and formulation on early exposure by comparing in vitro data with previously collected human plasma data of low solubility active pharmaceutical ingredients. Eight model active pharmaceutical ingredients were tested; Lu 35-138C (salt of weak base in a HP-beta-CD solution, three doses), fenofibrate (solid dispersion, tablet, two doses), AZD2207 EQ (salt of weak base, capsule, three doses), posaconazole (Noxafil® suspension, two doses), SB705498 (weak base, tablets vs. capsules), cyclosporine A (Sandimmun® vs.

Free‑floating cancer cells in lymph node sinuses of hilar lymph node‑positive patients with non‑small cell lung cancer.

Previous studies demonstrated that free‑floating cancer cells (FFCCs) in the lymph node sinuses were of prognostic significance for colorectal and gastric cancer. The present study investigated the clinical significance of detecting FFCCs using Fast Red staining for cytokeratin in stage I/II non‑small cell lung cancer (NSCLC) patients and hilar lymph node positive NSCLC patients who underwent curative resection. Between 2002 and 2011, a total of 164 patients (including 22 hilar lymph node positive patients) were investigated.

Single-center analysis of appendiceal neoplasms.

The purpose of the present study was to evaluate the recent trend of diagnosing appendiceal diseases through the analysis of appendectomy materials, stressing the importance of their pathological examination. A clinicopathological assessment of patients undergoing an appendectomy was conducted, based on the pathological examination of resected appendiceal lesions. Using a pathological database of surgical specimens from patients who underwent an appendectomy between March 2002 and September 2014, a retrospective, single-center analysis was performed.

Results of a phase II trial for high-risk neuroblastoma treatment protocol JN-H-07: a report from the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG).

Background: The Japanese Children's Cancer Group (JCCG) Neuroblastoma Committee (JNBSG) conducted a phase II clinical trial for high-risk neuroblastoma treatment. We report the result of the protocol treatment and associated genomic aberration studies.

Methods: JN-H-07 was a single-arm, late phase II trial for high-risk neuroblastoma treatment with open enrollment from June 2007 to February 2009.

High-grade PanIN presenting with localised stricture of the main pancreatic duct: A clinicopathological and molecular study of 10 cases suggests a clue for the early detection of pancreatic cancer.

Aims: This study aimed to identify the pathological features of high-grade PanIN that presents with imaging-detectable abnormalities.

Methods And Results: Ten cases of isolated, main-duct, high-grade PanIN as the primary clinical presentation were identified. All patients presented with stenosis of the main pancreatic duct, with two being associated with extensive upstream duct dilatation (>5 mm in diameter).

Vessel Morphologies of the Brain in Cytological Squash Preparations Are Useful for Intraoperative Diagnosis of High-Grade Astrocytomas.

Objective: The aim of this study was to determine whether intraoperative cytological evaluation of squash preparations is of benefit for differentiating high-grade from low-grade astrocytomas.

Methods: Squash preparations of 42 astrocytomas were classified histologically according to the World Health Organization (WHO) 2007 classification system as grade II (n = 12), grade III (n = 11), and grade IV (n = 19) and were divided into 2 groups, namely a low-grade group (grade II) and a high-grade group (grades III and IV). The focus was on morphological cell and vessel characteristics, namely nuclear atypia, chromatin pattern, nuclear enlargement, variation in nuclear size, the presence of nucleoli, mitosis, tumor necrosis, cell density, multibranched vessels, and vascular dilatation, and these characteristics were compared between the low- and high-grade groups.

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Proguanil Hydrochloride.

Literature data relevant to the decision to waive in vivo bioequivalence testing for the approval of generic immediate release solid oral dosage forms of proguanil hydrochloride are reviewed. To elucidate the Biopharmaceutics Classification System (BCS) classification, experimental solubility and dissolution studies were also carried out. The antimalarial proguanil hydrochloride, effective via the parent compound proguanil and the metabolite cycloguanil, is not considered to be a narrow therapeutic index drug.

Novel application of three-dimensional shear wave elastography in the detection of clinically significant prostate cancer.

The present study evaluated three-dimensional shear wave elastography (3D SWE) in the detection of clinically significant prostate cancer. Clinically significant prostate cancer was defined by a minimum of one biopsy core with a Gleason score of 3+4 or 6 with a maximum cancer core length >4 mm. Patients with serum prostate-specific antigen levels of 4.

Idiopathic multicentric Castleman's disease: a clinicopathologic study in comparison with IgG4-related disease.

The present study aimed to compare clinicopathologic features between idiopathic multicentric Castleman's disease (n=22) and IgG4-related disease (n=26). Histology was analyzed using lymph node and lung biopsies. The expression of IL-6 mRNA in tissue was also examined by hybridization and real-time PCR.

[THE CAUSES OF ACUTE COUGH: A SINGLE-CENTER STUDY IN JAPAN].

Background: Cough is the most frequent presenting complaint in clinics, and is classified into the following three groups: acute, subacute and chronic. The major causes of acute cough are infectious diseases, however, few observations on acute cough have been reported.

Methods: We retrospectively assessed the causes of acute cough among patients who had visited the respiratory clinic of our hospital because of acute cough from September 2014 to August 2015.

Baseline serum CXCL10 and IL-12 levels may predict severe asthmatics' responsiveness to omalizumab.

Background: Omalizumab, a humanized anti-IgE monoclonal antibody, is the first molecularly targeted drug for severe asthmatics. However, responses to omalizumab vary widely among patients.

Objectives: This study aimed to assess the potential of baseline serum cytokine levels as predictors of responsiveness to omalizumab.

Identification of the genetic and clinical characteristics of neuroblastomas using genome-wide analysis.

To provide better insight into the genetic signatures of neuroblastomas, we analyzed 500 neuroblastomas (included specimens from JNBSG) using targeted-deep sequencing for 10 neuroblastoma-related genes and SNP arrays analysis. ALK expression was evaluated using immunohistochemical analysis in 259 samples. Based on genetic alterations, the following 6 subgroups were identified: groups A ( abnormalities), B (other gene mutations), C ( amplification), D (11q loss of heterozygosity [LOH]), E (at least 1 copy number variants), and F (no genetic changes).

[FOCAL THERAPY WITH HIGH-INTENSITY FOCUSED ULTRASOUND FOR THE LOCALIZED PROSTATE CANCER BASED ON THE LOCALIZATION WITH MRI-TRUS FUSION IMAGE-GUIDED BIOPSY: 1-YEAR PROSPECTIVE STUDY].

(Objective) To evaluate the efficacy and invasiveness of focal therapy with transrectal high-intensity focused ultrasound (HIFU) for localized prostate cancer based on spatial location of significant cancer with magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) fusion image-guided biopsy. (Methods) Patients with low- and intermediate-risk significant prostate cancer who were followed-up at least 1 year, were prospectively recruited. The spatial localization of the significant cancer was determined by MRI-TRUS fusion image-guided transperineal prostate biopsy.

Disruption of circadian clockwork in in vivo reprogramming-induced mouse kidney tumors.

The circadian clock, which regulates cellular physiology, such as energy metabolism, resides in each cell level throughout the body. Recently, it has been elucidated that the cellular circadian clock is closely linked with cellular differentiation. Moreover, the misregulation of cellular differentiation in mouse embryonic stem cells (ESCs) induced abnormally differentiated cells with impaired circadian clock oscillation, concomitant with the post-transcriptional suppression of CLOCK proteins.

Laparoscopic intraperitoneal onlay mesh for pediatric incisional hernia-a case report.

Background: The incidence of incisional hernia in pediatric patients is low in comparison with that reported in adults. In the pediatric population, primary closure has generally been favored. However, synthetic or biomedical mesh offers advantages in the repair of larger defects when primary closure is difficult.

Association of interleukin 1 receptor-like 1 gene polymorphisms with eosinophilic phenotype in Japanese adults with asthma.

Background: IL1RL1 (ST2) is involved in Th2 inflammation including eosinophil activation. Single nucleotide polymorphisms (SNPs) of the IL1RL1 gene are associated with asthma development and increased peripheral blood eosinophil counts. However, the association between IL1RL1 SNPs and eosinophilic phenotype among adults with asthma remains unexplored.

Sensitization to Staphylococcus aureus enterotoxins in smokers with asthma.

Background: Sensitization to Staphylococcus aureus enterotoxins (SEs) augments eosinophilic inflammation in asthma. Recent epidemiologic studies demonstrate that sensitization to SEs is increased in healthy smokers; however, there is no evidence on the association between sensitization to SEs and eosinophilic inflammation in smokers with asthma.

Objective: To clarify the role of SEs on clinical indexes, including eosinophilic inflammation and lung function in smokers with asthma.

Sequential actions of immune effector cells induced by viral activation of dendritic cells to eliminate murine neuroblastoma.

Purpose: In preclinical trails, we reported the antitumor effect of dendritic cells activated with Sendai virus (rSeV/DC) combined with γ-irradiation against neuroblastoma. However, what kind of effector cells for the combined therapy were used to show the antitumor effect was unclear. In this study, we performed radiation and rSeV/DC therapy in vivo and examined the effector cells involved.

Genomic analysis-integrated whole-exome sequencing of neuroblastomas identifies genetic mutations in axon guidance pathway.

Neuroblastoma (NB) is a childhood solid malignant tumor originating from precursor cells of the peripheral nervous system. We have previously established a risk classification system based on DNA copy number profiles. To further explore the pathogenesis of NBs in distinct risk groups, we performed whole-exome sequencing analysis of 57 primary and 7 recurrent/metastatic tumors with unique chromosomal aberration profiles as categorized by our genomic sub-grouping system.

Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Folic Acid.

This work presents a review of literature and experimental data relevant to the possibility of waiving pharmacokinetic bioequivalence studies in human volunteers for approval of immediate-release solid oral pharmaceutical forms containing folic acid as the single active pharmaceutical ingredient. For dosage forms containing 5 mg folic acid, the highest dose strength on the World Health Organization Essential Medicines List, the dose/solubility ratio calculated from solubility studies was higher than 250 mL, corresponding to a classification as "not highly soluble." Small, physiological doses of folic acid (≤320 μg) seem to be absorbed completely via active transport, but permeability data for higher doses of 1-5 mg are inconclusive.

Video-assisted segmental resection of an intrapulmonary bronchogenic cyst mimicking a middle mediastinal cystic tumor.

We report a case of an intrapulmonary bronchogenic cyst that radiologically mimicked a cystic tumor of the middle mediastinum. During video-assisted thoracoscopic surgery, the lesion was confirmed to be in the lung parenchyma rather than in the mediastinum. A video-assisted thoracoscopic anterior basal segmentectomy was eventually performed, and an intrapulmonary bronchogenic cyst was the diagnosis based on histology.

A screening echocardiogram to identify diastolic dysfunction leads to better outcomes.

Background: Diastolic dysfunction (DD) can lead to heart failure and higher mortality. Echocardiograms can detect DD but are not indicated for screening in older adults. Our aim was to evaluate the prevalence of DD and the impact of identifying it in seniors.