Mitochondrial damage-associated molecular patterns released by lung transplants are associated with primary graft dysfunction.

Primary graft dysfunction (PGD) is a major limitation in short- and long-term lung transplant survival. Recent work has shown that mitochondrial damage-associated molecular patterns (mtDAMPs) can promote solid organ injury, but whether they contribute to PGD severity remains unclear. We quantitated circulating plasma mitochondrial DNA (mtDNA) in 62 patients, before lung transplantation and shortly after arrival to the intensive care unit.

Trajectories of brain development in school-age children born preterm with very low birth weight.

Preterm birth (gestational age < 37 weeks) with very low birth weight (VLBW, birth weight ≤ 1500 g) is associated with lifelong cognitive deficits, including in executive function, and persistent alterations in cortical and subcortical structures. However, it remains unclear whether "catch-up" growth is possible in the preterm/VLBW brain. Longitudinal structural MRI was conducted with children born preterm with VLBW (n = 41) and term-born peers participating in the Norwegian Mother and Child Cohort Study (MoBa) (n = 128) at two timepoints in early school age (mean ages 8.

Iron oxide nanoparticles enhance Toll-like receptor-induced cytokines in a particle size- and actin-dependent manner in human blood.

To assess the effects of different-sized iron oxide nanoparticles (IONPs) on inflammatory responses in human whole blood. Human whole blood with and without 10 and 30 nm IONPs was incubated with Toll-like receptor (TLR) ligands. Cytokine levels, complement activation, reactive oxygen species and viability were determined.

Clinical Course and Quality of Life in High-Risk Patients With Hypertrophic Cardiomyopathy and Implantable Cardioverter-Defibrillators.

Background: High-risk patients with hypertrophic cardiomyopathy (HCM) are identified by contemporary risk stratification and effectively treated with implantable cardioverter-defibrillators (ICDs). However, long-term HCM clinical course after ICD therapy for ventricular tachyarrhythmias is incompletely understood.

Methods And Results: Cohort of 486 high-risk HCM patients with ICDs was assembled from 8 international centers.

Childhood epilepsy and ADHD comorbidity in an Indian tertiary medical center outpatient population.

This study aimed to assess the prevalence of Attention Deficit Hyperactivity Disorder (ADHD) and its characteristics and risk factors in children with epilepsy at a tertiary medical center in New Delhi. Children with active epilepsy, aged 6 to 12 years, were assessed for ADHD using DSM-IV-TR criteria. Epilepsy and psychiatric characteristics, sociodemographic indicators, and use of antiepileptic drugs were analyzed for differences between the ADHD and non-ADHD groups.

FL-926-16, a novel bioavailable carnosinase-resistant carnosine derivative, prevents onset and stops progression of diabetic nephropathy in db/db mice.

Background And Purpose: The advanced glycation end products (AGEs) participate in the pathogenesis of diabetic nephropathy (DN) by promoting renal inflammation and injury. L-carnosine acts as a quencher of the AGE precursors reactive carbonyl species (RCS), but is rapidly inactivated by carnosinase. In this study, we evaluated the effect of FL-926-16, a carnosinase-resistant and bioavailable carnosine derivative, on the onset and progression of DN in db/db mice.

Proenkephalin, Neutrophil Gelatinase-Associated Lipocalin, and Estimated Glomerular Filtration Rates in Patients With Sepsis.

Background: Proenkephalin (PENK) has been suggested as a novel biomarker for kidney function. We investigated the diagnostic and prognostic utility of plasma PENK in comparison with neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rates (eGFR) in septic patients.

Methods: A total of 167 septic patients were enrolled: 99 with sepsis, 37 with septic shock, and 31 with suspected sepsis.

Multi-drugs resistant acne rosacea in a child affected by Ataxia-Telangiectasia: successful treatment with Isotretinoin.

Ataxia-Telangiectasia is a rare multisystem autosomal recessive disorder [OMIM 208900], caused by mutations in Ataxia-Telangiectasia Mutated gene. It is characterized by neurological, immunological and cutaneous involvement. Granulomas have been previously reported in Ataxia-Telangiectasia patients, even if acne rosacea has not been described.

Determination of prognostic factors in Japanese patients with advanced gastric cancer using the data from a randomized controlled trial, Japan clinical oncology group 9912.

Background: In advanced gastric cancer (AGC), no globally accepted prognostic scoring system has been developed. Therefore, we explored baseline prognostic factors in Japanese AGC patients using the data from a randomized controlled trial, Japan Clinical Oncology Group (JCOG) 9912, which investigated the efficacy of systemic chemotherapy as a first-line treatment.

Patients And Methods: Prognostic factors and prognostic indices for overall survival were screened and evaluated in patients enrolled in JCOG9912 using the Cox proportional hazard model.

Insulin stimulates the expression of the SHARP-1 gene via multiple signaling pathways.

The rat enhancer of split- and hairy-related protein-1 (SHARP-1) is a basic helix-loop-helix transcription factor. An issue of whether SHARP-1 is an insulin-inducible transcription factor was examined. Insulin rapidly increased the level of SHARP-1 mRNA both in vivo and in vitro.

Activation of NADPH oxidase 4 in the endoplasmic reticulum promotes cardiomyocyte autophagy and survival during energy stress through the protein kinase RNA-activated-like endoplasmic reticulum kinase/eukaryotic initiation factor 2α/activating transcription factor 4 pathway.

Rationale: Autophagy is an essential survival mechanism during energy stress in the heart. Oxidative stress is activated by energy stress, but its role in mediating autophagy is poorly understood. NADPH oxidase (Nox) 4 is an enzyme that generates reactive oxygen species (ROS) at intracellular membranes.

Inhibition of Epidermal Growth Factor Receptor and PI3K/Akt Signaling Suppresses Cell Proliferation and Survival through Regulation of Stat3 Activation in Human Cutaneous Squamous Cell Carcinoma.

Recent studies have emphasized the important role of Stat3 activation in a number of human tumors from the viewpoint of its oncogenic and antiapoptotic activity. In this study, we examined the role and related signaling molecules of Stat3 in the carcinogenesis of human cutaneous squamous cell carcinoma (SCC). In 35 human cutaneous SCC samples, 86% showed overexpression of phosphorylated (p)-Stat3, and most of those simultaneously overexpressed p-EGFR or p-Akt.

Ultraviolet light induces Stat3 activation in human keratinocytes and fibroblasts through reactive oxygen species and DNA damage.

Stat3 is activated by the outer stressors, such as ultraviolet (UV) exposure. In this study, we investigated the Stat3 response to UV irradiation in human epidermal keratinocytes and dermal fibroblasts. Results indicated that UVB and UVC differentially activate Stat3 in these cells.

Muscle-specific overexpression of heparin-binding epidermal growth factor-like growth factor increases peripheral glucose disposal and insulin sensitivity.

Physical exercise ameliorates metabolic disorders such as type 2 diabetes mellitus and obesity, but the molecular basis of these effects remains elusive. In the present study, we found that exercise up-regulates heparin-binding epidermal growth factor-like growth factor (HB-EGF) in skeletal muscle. To address the metabolic consequences of such gain of HB-EGF function, we generated mice that overexpress this protein specifically in muscle.

Cows milk-dependent exercise-induced anaphylaxis under the condition of a premenstrual or ovulatory phase following skin sensitization.

Background: A 24 year-old woman with atopic dermatitis occasionally developed symptoms, including dyspnea and generalized urticaria, following ingestion of food containing cows milk. Similar episodes had continued, and had been treated empirically since the age of 16 years.

Case Summary: Although a skin test and IgE RAST showed positive reactions to cows milk, a provocation test with cows milk alone did not induce any symptoms.

Acquired unilateral melanocytic nevi in otherwise normal skin.

We describe a case with numerous melanocytic nevi in otherwise normal skin. A 5-year-old girl presented with more than 100 small pigment lesions on her left arm, shoulder and upper back without underlying light brown macule. The pigment lesions were first found on her left forearm at 3 months old and gradually increased along with her growth.

Safety and efficacy of growth hormone (GH) during extended treatment of adult Japanese patients with GH deficiency (GHD).

Objectives: To assess the effects of a growth hormone (GH) replacement therapy using a GH dose regimen based on serum insulin-like growth factor (IGF-I) concentrations in Japanese adults with GH deficiency (GHD).

Design: In this multicentre, uncontrolled, open-label study, Japanese adults with GHD who had received either GH replacement therapy (GH-GH group, n=35) or placebo (Placebo-GH group, n=36) in a previous randomised, double-blind, placebo-controlled trial were treated with GH replacement therapy for 48 weeks. GH treatment was started at a dose of 0.

Low serum IGF-I/GH ratio is associated with abnormal glucose tolerance in acromegaly.

Background/aims: Acromegaly is frequently accompanied with impaired glucose tolerance (IGT) and diabetes mellitus (DM). It remains unclear which factors determine the abnormal glucose tolerance status in acromegaly. In addition, diverse actions of GH and IGF-I in regulating glucose metabolism in acromegaly have not yet been well elucidated.

Decreased expression of Toll-like receptor 2 and 4 on macrophages in experimental severe acute pancreatitis.

In severe acute pancreatitis (SAP), immunologic impairment in the early phase may be linked to subsequent infectious complications that are main contributor to the high mortality. Toll-like receptors (TLRs) recognize microorganisms as the innate immune system, and are involved in host defense mechanism. TLR2 recognizes lipoteichoic acid (LTA) of gram-positive bacteria, and TLR4 recognizes lipopolysaccharide (LPS) of gram-negative bacilli.

Forkhead transcription factor FoxO1 in adipose tissue regulates energy storage and expenditure.

Objective: Adipose tissue serves as an integrator of various physiological pathways, energy balance, and glucose homeostasis. Forkhead box-containing protein O subfamily (FoxO) 1 mediates insulin action at the transcriptional level. However, physiological roles of FoxO1 in adipose tissue remain unclear.

Case of superficial mucocele of the lower lip.

Superficial mucocele is a relatively rare bullous disease that develops in the oral mucosa. Although the number of reported cases is limited, it seems that the superficial mucocele has been recognized as an independent disease belonging to a single entity. We report a 48-year-old woman who repeatedly developed superficial mucocele in the oral mucosa.

Relationship of BRAF mutation, morphology, and apoptosis in early colorectal cancer.

Background And Aims: Many investigators have reported flat and depressed lesions as a new type of precursor of colorectal cancer. In our previous study, we determined that mutations in the BRAF gene may contribute to colorectal carcinogenesis by inhibiting apoptosis. However, the relationship among BRAF mutations, morphology and apoptosis in early colorectal cancer has not been clear.

Family history of cancer in Japanese gastric cancer patients.

The aim of this study was to evaluate the family history of cancer in Japanese gastric cancer patients and to investigate the clinicopathological features of gastric cancer patients with and without a family history of cancer. Four hundred and forty gastric cancer patients were enrolled in this study. The family history (first- and second-degree relatives) was investigated.