Administering xCT Inhibitors Based on Circadian Clock Improves Antitumor Effects.

Clock genes encoding transcription factors that regulate circadian rhythms may inform chronomodulated chemotherapy, where time-dependent dose alterations might affect drug efficacy and reduce side effects. For example, inhibiting the essential cystine transporter xCT with sulfasalazine induces growth arrest in cancer cells. Although the anticancer effects of sulfasalazine have been studied extensively, its effects on transcriptional control of xCT expression have not been studied.

Discovery of 3,5-Diphenyl-4-methyl-1,3-oxazolidin-2-ones as Novel, Potent, and Orally Available Δ-5 Desaturase (D5D) Inhibitors.

The discovery and optimization of Δ-5 desaturase (D5D) inhibitors are described. Investigation of the 1,3-oxazolidin-2-one scaffold was inspired by a pharmacophore model constructed from the common features of several hit compounds, resulting in the identification of 3,5-diphenyl-1,3-oxazolidin-2-one 5h as a novel lead showing potent in vitro activity. Subsequent optimization focused on the modification of two metabolic sites, which provided (4S,5S)-5i, a derivative with improved metabolic stability.

The influence of foot position on lower leg muscle activity during a heel raise exercise measured with fine-wire and surface EMG.

Objective: Exercises for lower leg muscles are important to improve function. To examine the influence of foot position on lower leg muscle activity during heel raises.

Design: Cross-sectional laboratory study.

Dysfunction of the circadian transcriptional factor CLOCK in mice resists chemical carcinogen-induced tumorigenesis.

The chronic disruption of circadian rhythms has been implicated in the risk of cancer development in humans and laboratory animals. The gene product CLOCK is a core molecular component of the circadian oscillator, so that mice with a mutated Clock gene (Clk/Clk) exhibit abnormal rhythms in various physiological processes. However, we demonstrated here that Clk/Clk mice resisted chemical carcinogen-induced tumorigenesis by suppressing epidermal growth factor (EGF) receptor-mediated proliferation signals.

Dietary supplementation with essence of chicken enhances daily oscillations in plasma glucocorticoid levels and behavioral adaptation to the phase-shifted environmental light-dark cycle in mice.

Maintenance of circadian rhythms is essential to many aspects of human health, including metabolism and neurological and psychiatric well-being. Chronic disruption of circadian clock function is implicated in increasing the risk of metabolic syndrome, cardiovascular events and development of cancers. However, there are little approaches to reinforce the function of circadian clock for prevention of these diseases.

Comparison of muscle synergies before and after 10 minutes of running.

[Purpose] The purpose of this study was to investigate the modular control of locomotor tasks and compared the modules before and after a running intervention. [Subjects and Methods] Electromyographic measurements were performed on eight young, healthy males engaged in a 60s run on a treadmill at 2.8 m/s before and immediately after the 600s of running intervention.

Physical activity and asthma control level in children and adolescents.

Background And Objective: Physical activity is defined as any bodily movement produced by a muscle contraction with increased energy expenditure. The aim of this study was to assess the physical activity, asthma control level, spirometric measurements and quality of life in children and adolescents with asthma.

Methods: We included all children and adolescents aged 7-17 years who had a diagnosis of atopic asthma and who attended the Pediatric Pulmonology Outpatient Clinic of the State University of Campinas, Brazil.

Updated comprehensive epidemiology, microbiology, and outcomes among patients with acute cholangitis.

Background: The international practice guidelines for patients with acute cholangitis and cholecystitis were released in 2007 (TG07) and revised in 2013 (TG13). This study investigated updated epidemiology and outcomes among patients with acute cholangitis on a larger scale for the first time.

Methods: This is an international multi-center retrospective observational study in Japan and Taiwan.

Vancomycin induces reactive oxygen species-dependent apoptosis via mitochondrial cardiolipin peroxidation in renal tubular epithelial cells.

Vancomycin (VCM) is a first-line antibiotic for serious infections caused by methicillin-resistant Staphylococcus aureus. However, nephrotoxicity is one of the most complaint in VCM therapy. We previously reported that VCM induced apoptosis in a porcine proximal tubular epithelial cell line (LLC-PK1), in which mitochondrial complex I may generate superoxide, leading to cell death.

Calf muscle activity alteration with foot orthoses insertion during walking measured by fine-wire electromyography.

[Purpose] The purpose of the study was to assess the muscle activity change of the tibialis posterior, flexor digitorum longus, and peroneus longus during gait with orthoses. [Subjects and Methods] Sixteen healthy males participated in this study. Activity of each muscle was measured by using fine-wire and surface electromyography.

Evaluation of a proper cutoff value on quantitative dual-energy perfusion CT for the assessment of acute pulmonary thromboembolism.

Background The cutoff value for assessing the severity of acute pulmonary thromboembolism (PTE) using relative volumetric evaluations of dual-energy perfusion computed tomography (DEpCT) is unclear. Purpose To determine the proper cutoff value for determining the severity of PTE using DEpCT volumetry. Material and Methods A total of 185 patients with venous thromboembolism were included in this study, of whom 61 were diagnosed with acute PTE.

Methanol-Triggered Vapochromism Coupled with Solid-State Spin Switching in a Nickel(II)-Quinonoid Complex.

A highly methanol-selective vapochromic response has been realized in a Ni -quinonoid complex, [Ni(HL ) ] (H L =4-methylamino-6-methyliminio-3-oxocyclohexa-1,4-dien-1-olate) which exhibits a reversible structural transformation including a coordination geometrical change between the square-planar and octahedral structure by the selective uptake of methanol vapor. This was accompanied by a remarkable color change between purple and orange, as well as temperature-robust spin-state switching in the solid state under ambient conditions. It is remarkable that the properties are derived by the fine structural modification of the quinonoid ligand such as methyl or ethyl analogues.

Distinct and Shared Endophenotypes of Neural Substrates in Bipolar and Major Depressive Disorders.

Little is known about disorder-specific biomarkers of bipolar disorder (BD) and major depressive disorder (MDD). Our aim was to determine a neural substrate that could be used to distinguish BD from MDD. Our study included a BD group (10 patients with BD, 10 first-degree relatives (FDRs) of individuals with BD), MDD group (17 patients with MDD, 17 FDRs of individuals with MDD), and 27 healthy individuals.

Numerical Estimation of the Pseudo-Jahn-Teller Effect Using Nonadiabatic Coupling Integrals in Monocyclic and Bicyclic Conjugated Molecules.

The pseudo-Jahn-Teller (pJT) effect in monocyclic and bicyclic conjugated molecules was investigated by using the state-averaged multiconfiguration self-consistent field (MCSCF) method, together with the 6-31G(d,p) basis sets. Following the perturbation theory, the force constant along a normal mode Q is given by the sum of the classical force constant and the vibronic contribution (VC) resulting from the interaction of the ground state with excited states. The latter is given as the sum of individual contributions arising from vibronic interactions between the ground state and excited states.

Methicillin-Resistant Staphylococcus epidermidis Is Part of the Skin Flora on the Hands of Both Healthy Individuals and Hospital Workers.

Staphylococcus epidermidis, a major skin flora on hands, acts as a reservoir of various antimicrobial resistance determinants including staphylococcal cassette chromosome mec (SCCmec) and contributes to multidrug resistance for S. aureus. The aim of this study was understanding the characteristics of commensal S.

[Multidrug-Resistant Acinetobacter baumannii].

Teikyo University Hospital reported an outbreak of multidrug-resistant Acinetobacter baumannii (MDRAB) to the local public health department in 2010. The number of inpatients with MDRAB including asympto- matic carriers was 58 between August 2009 and September 2010. The way to tackle infection control issues has been comprehensively revised since this event in our hospital.

Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a global health problem, and novel therapies to treat CKD are urgently needed. Here, we show that inhibition of G/G switch 2 (G0s2) ameliorates renal inflammation in a mouse model of CKD. Renal expression of chemokine (C-C motif) ligand 2 (Ccl2) was increased in response to p65 activation in the kidneys of wild-type 5/6 nephrectomy (5/6Nx) mice.

Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia.

Diurnal variations in pain hypersensitivity are common in chronic pain disorders, but the underlying mechanisms are enigmatic. Here, we report that mechanical pain hypersensitivity in sciatic nerve-injured mice shows pronounced diurnal alterations, which critically depend on diurnal variations in glucocorticoids from the adrenal glands. Diurnal enhancement of pain hypersensitivity is mediated by glucocorticoid-induced enhancement of the extracellular release of ATP in the spinal cord, which stimulates purinergic receptors on microglia in the dorsal horn.

Treatment with infliximab for pediatric Crohn's disease: Nationwide survey of Japan.

Background And Aim: Childhood-onset inflammatory bowel disease (IBD) is characterized by extensive intestinal involvement and rapid early progression. Infliximab (IFX), cyclosporin (CYA), and tacrolimus (FK506) are increasingly used to treat pediatric IBD; however, their long-term effects and adverse events have not been properly investigated in pediatric patients. The aim of this study was to characterize the effects of these biologics and immunomodulators on pediatric IBD patients in Japan.

A Preanalytic Validation Study of Automated Bone Scan Index: Effect on Accuracy and Reproducibility Due to the Procedural Variabilities in Bone Scan Image Acquisition.

Unlabelled: The effect of the procedural variability in image acquisition on the quantitative assessment of bone scan is unknown. Here, we have developed and performed preanalytical studies to assess the impact of the variability in scanning speed and in vendor-specific γ-camera on reproducibility and accuracy of the automated bone scan index (BSI).

Methods: Two separate preanalytical studies were performed: a patient study and a simulation study.

High-resolution CT findings of idiopathic pneumonia syndrome after haematopoietic stem cell transplantation: based on the updated concept of idiopathic pneumonia syndrome by the American Thoracic Society in 2011.

Idiopathic pneumonia syndrome (IPS) is an acute lung dysfunction of non-infectious aetiology and a severe complication following haematopoietic stem cell transplantation (HSCT). Recently, the American Thoracic Society (ATS) updated the concept of IPS and extended the concept to a wider range; it defined IPS as "an idiopathic syndrome of pneumopathy after HSCT, with evidence of widespread alveolar injury and in which infectious aetiologies and cardiac dysfunction, acute renal failure, or iatrogenic fluid overload have been excluded." The ATS also categorised the presumed site of primary tissue injury into three patterns (pulmonary parenchyma, vascular endothelium, and airway epithelium), each of which has several entities.

High-resolution CT findings of primary lung cancer with cavitation: a comparison between adenocarcinoma and squamous cell carcinoma.

Aim: To evaluate the high-resolution computed tomography (CT) findings of primary lung cancer with cavitation and compare the findings in adenocarcinoma and squamous cell carcinoma.

Materials And Methods: The high-resolution CT findings of tumours with cavitation were retrospectively evaluated in 60 patients. Forty-seven of the lesions were diagnosed as adenocarcinomas; 13 were diagnosed as squamous cell carcinomas.

Relationship between diverse patient body size- and image acquisition-related factors, and quantitative and qualitative image quality in coronary computed tomography angiography: a multicenter observational study.

Purpose: We investigated the effects of patient- and image acquisition-related factors on the image quality in coronary CT angiography (CCTA).

Materials And Methods: We enrolled 1197 patients (728 men; 65 ± 12 years). All underwent CCTA under the routine scan protocol in 23 participating hospitals.

Mitochondrial DNA 5178 C/A polymorphism modulates the effects of coffee consumption on elevated levels of serum liver enzymes in male Japanese health check-up examinees: an exploratory cross-sectional study.

Background: Longevity-associated mitochondrial DNA 5178 cytosine/adenine (Mt5178 C/A) polymorphism modulates the effects of coffee consumption on the risk of hypertension, dyslipidemia, and abnormal glucose tolerance. The objective of this study was to investigate whether Mt5178 C/A polymorphism modifies the effects of coffee consumption on abnormally elevated levels of serum liver enzymes in male Japanese health check-up examinees.

Methods: A total of 421 male subjects (mean age ± SD, 54.

MRI of giant cell tumour of larynx: marked hypointensity due to abundant haemosiderin deposition.

Giant cell tumours (GCTs) are benign tumours commonly found in the long bones. Rarely, they may occur in the larynx, often resulting in hoarseness and anterior neck swelling. Since Wessely reported the first case of laryngeal GCT in 1940, 35 cases have been identified.