Inflammatory Cytokines and Chemokines Are Synergistically Induced in a ROS-Dependent Manner by a Co-Culture of Corneal Epithelial Cells and Neutrophil-like Cells in the Presence of Particulate Matter.

Ocular exposure to particulate matter (PM) causes local inflammation; however, the influence of neutrophils on PM-induced ocular inflammation is still not fully understood. In this study, we constructed a system to investigate the role of PM in ocular inflammation using a co-culture of human corneal epithelial cells (HCE-T) and differentiation-induced neutrophils (dHL-60). To investigate whether HCE-T directly endocytosed PM, we performed a holographic analysis, which showed the endocytosis of PM in HCE-T. The cytokines and chemokines produced by HCE-T were measured using an ELISA. HCE-T treated with PM produced IL-6 and IL-8, which were inhibited by N-Acetyl-L-cysteine (NAC), suggesting the involvement of ROS. Their co-culture with dHL-60 enhanced their production of IL-6, IL-8, and MCP-1. This suggests an inflammatory loop involving intraocular corneal epithelial cells and neutrophils. These cytokines and chemokines are mainly regulated by NF-κB. Therefore, this co-culture system was examined in the presence of an IKK inhibitor known to downregulate NF-κB activity. The IKK inhibitor dramatically suppressed the production of these factors in co-culture supernatants. The results suggest that the inflammatory loop observed in the co-culture is mediated through ROS and the transcription factor NF-κB. Thus, the co-culture system is considered a valuable tool for analyzing complex inflammations.

Radiotherapy with or without chemotherapy for locally advanced head and neck cancer in elderly patients: analysis of the Head and Neck Cancer Registry of Japan.

BACKGROUND: Whether concurrent chemotherapy with radiotherapy (CRT) is effective for elderly patients with head and neck cancer is a controversial topic. This study aimed to analyze the effectiveness of CRT vs. radiation therapy (RT) among elderly patients in Japan. METHODS: Data from the Head and Neck Cancer Registry of Japan were extracted and analyzed. Patients with locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, or larynx who received definitive CRT or RT between 2011 and 2014 were included. RESULTS: CRT was administered to 78% of the 1057 patients aged ≥ 70 years and 67% of the 555 patients aged ≥ 75 years. For the patients aged ≥ 75 years, the overall survival (OS) rate was significantly better in the CRT group than in the RT group (P < 0.05), while the progression-free survival (PFS) rate was not significantly different (P > 0.05). The add-on effect of CRT was significantly poor in elderly patients (P < 0.05), and it was not a significant factor in the multivariate analysis for patients aged ≥ 75 years. After propensity score matching, there were no significant differences in the OS and PFS rates between the patients aged ≥ 70 years and those aged ≥ 75 years (all, P > 0.05). CONCLUSION: Although aggressive CRT is administered to elderly patients in Japan, its effectiveness is uncertain. Further prospective randomized trials are needed to verify whether CRT is superior to RT alone for elderly patients.

Psychogenic fever and postural tachycardia syndrome among school-aged children and adolescents with fever of unknown origin.

BACKGROUND: Although fever is a common symptom in pediatric practice, its origin is often unknown in pediatric patients. Psychogenic fever is a stress-related, psychosomatic disease observed especially in young women. This study aimed to estimate the prevalence of psychogenic fever in pediatric patients with fever of unknown origin by surveying the medical records of school-aged children and adolescents. METHODS: The study subjects included 47 patients aged 6-15 years who visited the Department of Pediatrics in Kansai Medical University Medical Center between January 2006 and December 2020 with fever of unknown origin. Data on age, sex, final estimated diagnosis, and comorbid psychosocial issues were collected from the medical records. RESULTS: The study was composed of 47 patients, including 22 male and 25 female patients (male/female ratio, 1:1.36). The mean age was 10.1 (standard deviation, 2.4) years for boys and 11.6 (standard deviation, 2.7) years for girls (p = .047). The final estimated diagnoses were psychogenic fever, physical disorder, infection of unknown origin, and miscellaneous in 18, 12, 12, and 5 patients, respectively. The most common comorbidity in these pediatric patients with psychogenic fever was postural tachycardia syndrome. CONCLUSION: Psychogenic fever was a common cause of fever of unknown origin in pediatric patients, and postural tachycardia was prevalent among children with psychogenic fever. Enhanced sympathetic response to stress might play an important role in both psychogenic fever and postural tachycardia.

Japanese clinical guidelines for chronic pain in children and adolescents.

Chronic pain is a common problem in pediatric practice. The prevalence of chronic pain in children is >30%. Because pain indicates emotional expression as well as the physiological reaction toward infection, injury, and inflammation, both physiological and psychological assessments are essential to determine primary interventions for chronic pain. The Japanese Society of Psychosomatic Pediatrics Task Force of clinical practice guidelines for chronic pain in children and adolescents compiled clinical evidence and opinions of specialists associated with the primary care of pediatric chronic pain in the Japanese 'clinical guidelines for chronic pain in children and adolescents' in 2009, which are presented herein. The guidelines consist of three domains: general introduction to chronic pain; chronic abdominal pain; and chronic headache. Each section contains information on the physiological mechanism, psychological aspects, assessment methods, and primary interventions for pediatric chronic pain. These guidelines are expected to help disseminate knowledge on primary interventions for chronic pain in children and adolescents.

Two types of orthostatic dysregulation assessed by diameter of inferior vena cava.

AIMS: Orthostatic dysregulation (OD) is common in adolescents. This study was conducted to evaluate the usefulness of the measurement of the diameter of the inferior vena cava (IVC) for objective assessment of patients with OD. METHODS: Twenty children with OD (median 14 years, range 9-15 years) and 23 age-matched healthy children (median 12 years, range 10-15 years) were enrolled. A diameter of IVC was measured by an abdominal echogram before and after a head-up tilt table testing (HUT). Changes in IVC was assessed by an arbitrary parameter, collapse index (CI) as the following equation: [(maximal IVC diameter in the supine position - maximal IVC diameter in the standing position)/(maximal IVC diameter in the supine position)]× 100. CI was evaluated 4 weeks after treatment with an adrenergic agent. RESULTS: Children with OD demonstrated either higher CI or lower CI compared to that in control children: CI was more than 50 (range 50-71) in 12 patients with OD while that was equal to or less than 0 (range -225 to 0) in eight out of 20 patients. In contrast, CI was between 0 and 50 (range 1-26) in 23 healthy children. Pharmacological treatment induced the normalization in the CI in both higher and lower CI group. CONCLUSION: OD can be classified into two subtypes: by HUT, one is characterized by an increase of IVC diameter while another is characterized by its decrease. Measurement of IVC diameter by HUT is useful to understand the pathophysiology and to assess the efficacy of treatment.

A case of WHIM syndrome associated with diabetes and hypothyroidism.

The WHIM syndrome is a rare immunological disorder characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. We hypothesized that immunological or genetic mechanisms may link WHIM syndrome and type 1 diabetes. We report that the young girl with WHIM syndrome developed diabetes and transient hypothyroidism. A nonsense mutation (C-->T) truncating the CXC chemokine receptor 4 (CXCR4) C-terminal cytoplasmic tail domain occurred at nucleotide position 1000(R334X) of the CXCR4 gene in one allele of the patient was identified, and the person was diagnosed as having WHIM syndrome. Recent observation suggested that the CXCR4, a G-protein-coupled receptor with a unique ligand, CXCL12, might be involved in the pathogenesis for type 1 diabetes. Taken into consideration the concurrent prevalence of the two disorders and the speculated common pathogenesis associated with the CXCR4, our patient may enable us to understand the genetic damage related to accelerated apoptosis.

Measurement of inferior vena cava diameter for evaluation of venous return in subjects on day 10 of a bed-rest experiment.

We evaluated the usefulness of measurements of the inferior vena cava (IVC) diameters on abdominal echograms as an indicator of changes of venous return in subjects with orthostatic intolerance (OI) induced by simulated microgravity. We performed a standing test and recorded the IVC diameters on abdominal echograms in 12 subjects placed on a 20-day 6 degrees head-down-tilt bed-rest experiment. We found that different patterns of changes in IVC diameter occurred in the standing test on day 10 of the experiment; in five subjects with a marginal decrease in pulse pressure, IVC diameters in the upright position were markedly decreased compared with those in the supine position. In five subjects with feelings of discomfort, the IVC diameters in the upright position distended or did not decrease from those in the supine position. These results suggested that the changes in IVC diameter on the standing test indicated the presence of various types of hemodynamic responses of OI caused by simulated microgravity. In this study, we also evaluated changes in body-water compartments by conducting multifrequency bioelectrical impedance analysis. Longitudinal data analysis showed that the total body-water-to-fat-free mass and extracellular fluid-to-fat-free mass ratios decreased during the experimental period and recovered thereafter, and that the ratio of intracellular fluid to fat-free mass decreased during the experiment. No significant difference in changes in body-water compartments was seen among subjects with different patterns of changes in IVC diameters. Measurement of IVC diameter was useful to estimate hemodynamic changes in subjects with OI.