Patient-related risk factors for late rectal bleeding after hypofractionated radiotherapy for localized prostate cancer: a single-center retrospective study.

BACKGROUND: Several studies have reported patient-related risk factors for late rectal bleeding following conventionally fractionated radiotherapy for prostate cancer. We investigated patient-related risk factors for late rectal bleeding after hypofractionated radiotherapy. METHODS: A total of 231 patients with local or locally advanced prostate cancer treated with hypofractionated radiotherapy (70 or 67.2 Gy in 28 fractions) were evaluated retrospectively. All patients received intensity-modulated radiotherapy with daily image guidance. The relationships between late rectal bleeding and risk factors like diabetes, hypertension, cirrhosis, and anticoagulant use were analyzed. RESULTS: During a median follow-up of 23 months, the crude rates of grade ≥ 1, grade ≥ 2, and grade ≥ 3 late rectal bleeding were 23.8%, 16.9%, and 9.5%, respectively. Cirrhosis and anticoagulant use predicted an increased risk of grade ≥ 3 rectal bleeding in multivariable analyses (hazard ratio [HR] 14.37, 95% confidence interval [CI] 3.09-66.87, P = 0.001, and HR 2.93, 95% CI 1.14-7.55, P = 0.026, respectively). The non-anticoagulant group had a significantly superior 5-year freedom from grade ≥ 3 bleeding compared to the anticoagulant group in a propensity-weighted log-rank analysis (88.0% vs. 76.7%, P = 0.041). A receiver operating characteristic curve analysis revealed that rectal bleeding was minimized in the anticoagulant group if the equivalent dose at fractionation of 2 Gy (EQD2) V77 Gy of the rectum was < 4.5% or if the EQD2 V8.2 Gy was < 71.0%. CONCLUSIONS: Patients taking anticoagulants or those with cirrhosis had a significantly higher risk of severe late rectal bleeding than other patients after hypofractionated radiotherapy for prostate cancer in the present study. The bleeding risk could be lowered by minimizing hotspots in patients taking anticoagulants.

Evidence of sleep duration and weekend sleep recovery impact on suicidal ideation in adolescents with allergic rhinitis.

STUDY OBJECTIVES: Sleep problems are common in allergic rhinitis (AR) and are a modifiable risk factor for suicidal ideation. However, the effect of sleep duration and weekend catch-up sleep (WCUS)-sleep time on weekends that exceeds sleep time on weekdays-on suicidal ideation for adolescents with AR is unknown. The objective of this study was to explore whether sleep duration and WCUS have an impact on suicidal ideation among adolescents with AR. METHODS: From the annual Korean Youth Risk Behavior Web-Based Surveys (completed from 2013-2017), data were obtained from a stratified, multistage, clustered sample. Using self-reported questionnaires, students provided doctor-diagnosed AR and sleep time. RESULTS: Among 134,417 and 262,653 adolescents with and without AR, respectively, those with AR compared with those without AR had more sleep dissatisfaction (46.6% vs 40.8%), slept less (sleep duration: 6.71 ± 1.37 hours vs 7.01 ± 1.48 hours), and had longer WCUS (3.46 ± 0.11 hours vs 2.11 ± 0.14 hours). After adjustment, the odds ratio of patients with sleep dissatisfaction was a 1.22 (95% confidence interval, 1.17-1.28) times higher risk of suicidal ideation than in those with sleep satisfaction. For average sleep duration (defining 7-8 hours as the reference), the odds ratio of short sleep (≤ 5 hours) was 1.45 (95% confidence interval, 1.32-1.53). Notably, long WCUS (≥ 2 hours) was significantly associated with decreased suicidal ideation (odds ratio, 0.85; 95% confidence interval, 0.81-0.92). CONCLUSIONS: Although further research is needed to clarify this association, under the condition of sleep deprivation, WCUS at a certain extent may be associated with a low risk for suicidal ideation in adolescents with AR. CITATION: Kim CW, Jeong SC, Hwang SW, Jo SH, Kim SH. Evidence of sleep duration and weekend sleep recovery impact on suicidal ideation in adolescents with allergic rhinitis. J Clin Sleep Med. 2021;17(8):1521-1532.

Associated factors for depression, suicidal ideation and suicide attempt among asthmatic adolescents with experience of electronic cigarette use.

INTRODUCTION: While electronic cigarette (EC) use is rapidly increasing among asthmatic adolescents, little is known about the links between EC use and depression or suicidality. We assessed associated factors for depression and suicidality in asthmatic adolescents with experience of EC use. METHODS: We analyzed the data from the 11th to 13th Korea Youth Risk Behavior Web-based Surveys, which were completed from 2015 to 2017. Data were obtained from a stratified, multistage, clustered sample. Students supplied 'yes or no' answers to questions about previous asthma diagnosis by a doctor. Associated factors for depression and suicidality were evaluated by logistic regression models after controlling for potential confounding factors. We targeted 203336 adolescents, and 195847 completed the survey. RESULTS: The proportion of asthma among the respondents was 8.9%. The rate of experience of EC use was higher among asthmatic respondents than non-asthmatic respondents (10.3% vs 8.6%). Asthmatic respondents with experience of EC use had a much higher proportion of negative mental health states including depression and suicidality than subjects without EC experience. In our adjusted models, perception of stress was most strongly associated with depression (adjusted odds ratio, AOR=4.79; 95% CI: 4.12-5.58), and perception of unhappiness was most strongly associated with suicidal ideation (AOR=5.24; 95% CI: 4.51-6.09) and suicide attempt (AOR=4.37; 95% CI: 3.36-5.69). CONCLUSIONS: Many Korean asthmatic adolescents with experience of EC use report relatively high depression and suicidal behaviors. A multidisciplinary approach, including psychological help, may be required to prevent suicide among this population, especially those who report associated factors.

Identification of influencing factors for suicidal ideation and suicide attempts among adolescents: 11-year national data analysis for 788,411 participants.

Suicide is one of the most common causes of death in adolescents. This study identified trends in the prevalence of and factors influencing suicidal ideation and attempts among Korean adolescents. Data were drawn from the third through the thirteenth (2007-2017) annual Korean Youth Risk Behavior Web-based Surveys. Participants included stratified, multistage clustered samples selected from 400 middle schools and 400 high schools annually. Depression, suicidal ideation, and suicide attempts were binary dependent variables (requiring answers of yes or no). A total of 818,684 adolescents were targeted and 788,411 adolescents completed the survey. The prevalence rates of both suicidal ideation and attempts gradually decreased from 23.7% and 5.8%, respectively, in 2007 to 12.1% and 2.6%, respectively, in 2017. Overall, 16.8% of participants had suicidal ideation and 3.9% had suicide attempts during the survey period. During logistic regression analysis, depression was most strongly associated with suicidal ideation (adjusted odds ratio: 5.78 [95% confidence interval: 5.64-5.88]) and suicide attempts (adjusted odds ratio: 5.56, [95% confidence interval: 5.22-5.83]). Despite decreasing trends, the high rate of suicidal behaviors remains a critical public health problem. Depression most strongly predicts suicidal behaviors. Early interventions are essential to treat depression and reduce or prevent suicide.

Epidermal growth factor receptor (EGFR)-MAPK-nuclear factor(NF)-κB-IL8: A possible mechanism of particulate matter(PM) 2.5-induced lung toxicity.

Airway inflammation plays a central role in the pathophysiology of diverse pulmonary diseases. In this study, we investigated whether exposure to particulate matter (PM) 2.5, a PM with an aerodynamic diameter of less than 2.5 µm, enhances inflammation-related toxicity in the human respiratory system through activation of the epidermal growth factor receptor (EGFR) signaling pathway. Through cytokine antibody array analysis of two extracts of PM2.5 [water (W-PM2.5 ) and organic (O-PM2.5 ) soluble extracts] exposed to A549 (human alveolar epithelial cell), we identified eight cytokines changed their expression with W-PM2.5 and three cytokines with O-PM2.5 . Among them, epidermal growth factor (EGF) was commonly up-regulated by W-PM2.5 and O-PM2.5 . Then, in both groups, we can identify the increase in EGF receptor protein levels. Likewise, increases in the phosphorylation of ERK1/2 MAP kinase and acetylation of nuclear factor(NF)-κB were detected. We also detected an increase in IL-8 that was related to inflammatory response. And using the erlotinib as an inhibitor of EGFR, we identified the erlotinib impaired the phosphorylation of EGFR, ERK1/2, acetylation of NF-κB proteins and decreased IL-8. Furthermore, at in vivo model, we were able to identify similar patterns. These results suggest that PM2.5 may contribute to an abnormality in the human respiratory system through EGFR, MAP kinase, NF-κB, and IL-8 induced toxicity signaling. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1628-1636, 2017.

Integrative analysis of mRNA and microRNA expression of a human alveolar epithelial cell(A549) exposed to water and organic-soluble extract from particulate matter (PM)2.5.

MicroRNA (miRNA) is now attracting attention as a powerful negative regulator of messenger RNA(mRNA) levels, and is implicated in the modulation of important mRNA networks involved in toxicity. In this study, we assessed the effects of particulate matter 2.5 (PM2.5 ), one of the most significant air pollutants, on miRNA and target gene expression. We exposed human alveolar epithelial cell (A549) to two types of PM2.5 [water (W-PM2.5 ) and organic (O-PM2.5 ) soluble extracts] and performed miRNA microarray analysis. A total of 37 miRNAs and 62 miRNAs were altered 1.3-fold in W-PM2.5 and O-PM2.5 , respectively. Integrated analyses of miRNA and mRNA expression profiles identified negative correlations between miRNA and mRNA in both W-PM2.5 and O-PM2.5 exposure groups. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses showed that the 35 W-PM2.5 target genes are involved in responses to nutrients, positive regulation of biosynthetic processes, positive regulation of nucleobase, nucleoside, and nucleotide, and nucleic acid metabolic processes; while the 69 O-PM2.5 target genes are involved in DNA replication, cell cycle processes, the M phase, and the cell cycle check point. We suggest that these target genes may play important roles in PM2.5 -induced respiratory toxicity by miRNA regulation. These results demonstrate an integrated miRNA-mRNA approach for identifying molecular events induced by environmental pollutants in an in vitro human model. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 302-310, 2017.

Toxicogenomic analysis of the pulmonary toxic effects of hexanal in F344 rat.

Hexanal is a major component of indoor air pollutants and is a kind of aldehydes; it has adverse effects on human health. We performed an in vivo inhalation study and transcriptomic analysis to determine the mode of toxic actions in response to hexanal. Fischer 344 rats of both sexes were exposed by inhalation to hexanal aerosol for 4 h day-1 , 5 days week-1 for 4 weeks at 0, 600, 1000, and 1500 ppm. Throughout our microarray-based genome-wide expression analysis, we identified 56 differentially expressed genes in three doses of hexanal; among these genes, 11 genes showed dose-dependent expression patterns (10 downregulated and 1 upregulated, 1.5-fold, p < 0.05). Through a comparative toxicogenomics database (CTD) analysis of 11 genes, we determined that five genes (CCL12, DDIT4, KLF2, CEBPD, and ADH6) are linked to diverse disease categories such as cancer, respiratory tract disease, and immune system disease. These diseases were previously known for being induced by volatile organic compounds (VOCs). Our data demonstrated that the hexanal-induced dose-dependent altered genes could be valuable quantitative biomarkers to predict hexanal exposure and to perform relative risk assessments, including pulmonary toxicity. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 382-396, 2017.

Secondary surgery for vesicoureteral reflux after failed endoscopic injection: Comparison to primary surgery.

PURPOSE: As endoscopic treatment for vesicoureteral reflux (VUR) has increased, secondary ureteral reimplantation (UR) after failure of endoscopic treatment has increased. We studied the clinical feature and efficacy of secondary UR after failure of endoscopic treatment compared with primary UR. MATERIALS AND METHODS: Eighty-one children who had UR for VUR were enrolled. Charts were reviewed retrospectively for age, sex, grade of VUR before surgery, operative time, hospitalization period, postoperative complication, and success rate. Primary UR (group A, n=64) was compared with secondary UR after failed endoscopic treatment (group B, n=17). In group B, telephone survey for the satisfaction of endoscopic treatment and surgery was done. RESULTS: Mean age of each group was 49.6±37.1 and 56.6±22.5 months (p=0.236). There was no significant difference between each group in sex, mean operative time, postoperative transfusion, complication rate, and success rate. As telephone survey in group B, eleven responders preferred endoscopic treatment as primary treatment of VUR because it was a simple method and no hospitalization. CONCLUSIONS: Secondary UR after failure of endoscopic treatment was similar to primary UR. Parents preferred endoscopic treatment as first line treatment for VUR in spite of the need for secondary UR after failure of endoscopic treatment.

MicroRNA response of inhalation exposure to hexanal in lung tissues from Fischer 344 rats.

In previous studies, we have investigated the relationships between environmental chemicals and health risk based on omics analysis and identified significant biomarkers. Our current findings indicate that hexanal may be an important toxicant of the pulmonary system in epigenetic insights. MicroRNA (miRNA) is an important indicator of biomedical risk assessment and target identification. Hexanal is highly detectable in the exhaled breath of patients with chronic obstructive pulmonary disease (COPD) and chronic inflammatory lung disease. In this study, we aimed to identify hexanal-characterized miRNA-mRNA correlations involved in lung toxicity. Microarray analysis identified 56 miRNAs that commonly changed their expression more than 1.3-fold in three doses (600, 1000, and 1500 ppm) within hexanal-exposed Fischer 344 rats by inhalation, and 226 genes were predicted to be target genes of miRNAs through TargetScan analysis. By integrating analyses of miRNA and mRNA expression profiles, we identified one anti-correlated target gene (Chga; chromogranin A; parathyroid secretory protein 1). Comparative toxicogenomics database (CTD) analysis of this gene showed that Chga is involved with several disease categories such as cancer, respiratory tract disease, nervous system disease, and cardiovascular disease. Further research is necessary to elucidate the mechanisms of hexanal-responsive toxicologic pathways at the molecular level. This study concludes that our integrated approach to miRNA and mRNA enables us to identify molecular events in disease development induced by hexanal in an in vivo rat model. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1909-1921, 2016.

Clinical characteristics and treatment of cryptorchidism in adults: a single center experience.

PURPOSE: We evaluated the clinical and therapeutic characteristics of adult cryptorchidism, which have been difficult to establish, given the small number of patients presenting to outpatient clinics. MATERIALS AND METHODS: A retrospective study of 20 adult patients with cryptorchid testis was performed. We analyzed their palpation of testis, location, surgical method, marital status, number of children, histologic findings, and semen analysis. RESULTS: In 17 cases with unilateral cryptorchidism, the mean age at surgery was 31.1±12.5 years. Fourteen patients had a palpable, small cryptorchid testis. The location of the testis, as verified, was inguinal in 14, prepubic in 2, and intra-abdominal in 1, respectively. We performed orchiopexy in 14 out of 15 patients who sought to have this procedure. Four among 6 married patients had children. Testis biopsy was performed in 12 patients, and all showed abnormal histologic findings. Three among 4 patients, performed semen analysis, showed abnormal findings. In three cases of bilateral cryptorchidism, the mean age at surgery was 35.7±12.5 years. All of these patients had palpated cryptorchid testes in the inguinal area and sought to have a bilateral orchiopexy. Two patients have been married but had no children. All showed abnormal findings in both testis biopsy and semen analysis. No testicular neoplasm was detected during the duration of follow-up. CONCLUSIONS: Most adult patients with cryptorchidism preferred orchiopexy to orchiectomy. However, most of patients showed abnormal histology of the testis and semen analysis. Therefore, orchiopexy with regular scrotal examination may be considered a suitable treatment options for adult cryptorchidism.

Characterisation of a new antihypertensive angiotensin I-converting enzyme inhibitory peptide from Pleurotus cornucopiae.

This study describes the characterisation of a new angiotensin I-converting enzyme (ACE) inhibitory peptide from the fruiting body of Pleurotus cornucopiae which could be used as a functional food or nutraceutical compounds. After purification of the ACE inhibitor in an ultrafiltration, Sephadex G-25 column chromatography, successively C(18) and SCX solid-phase extraction and reverse-phase HPLC, two types of the purified ACE inhibitors with IC(50) values of 0.46 and 1.14mg/ml were obtained. The two purified ACE inhibitors were analysed, showing two types of oligopeptides. The amino acid sequences of the two purified oligopeptides were found to be RLPSEFDLSAFLRA and RLSGQTIEVTSEYLFRH. The molecular mass of the purified ACE inhibitors was estimated to be 1622.85 and 2037.26Da, respectively. Water extracts of P. cornucopiae fruiting body showed a clear antihypertensive effect on spontaneously hypertensive rats at a dosage of 600mg/kg.

Digestion Pattern of Antihypertensive Angiotensin I-Converting Enzyme Inhibitory Peptides from Saccharomyces cerevisiae in a Successive Simulated Gastricintestinal Bioreactor.

A cell-free extract of Saccharomyces cerevisiae containing the angiotensin I-converting enzyme (ACE) inhibitory peptide was treated in a successive simulated gastric-intestinal bioreactor (step 1: amylase digestion, step 2: gastric fluid digestion, step 3: intestinal fluid digestion) to illustrate the absorption pattern of antihypertensive ACE inhibitory peptide, and the ACE inhibitory activities of each step were determined. Total ACE inhibitory activities of step 1, step 2, and step 3 were 55.96%, 80.09%, and 76.77%, respectively. The peptide sequence of each steps was analyzed by MS/MS spectrophotometry. Eleven kinds of representative peptide sequences were conserved in each step, and representative new peptides including RLPTESVPEPK were identified in step 3.

Isolation and characterization of a novel platelet aggregation inhibitory peptide from the medicinal mushroom, Inonotus obliquus.

This study describes the extraction and characterization of a platelet aggregation inhibitory peptide from Inonotus obliquus. Ethanol extract from I. obliquus ASI 74006 mycelia showed the highest platelet aggregation inhibitory activity (81.2%). The maximum platelet aggregation inhibitory activity was found when the mycelia of I. obliquus ASI 74006 was extracted with ethanol at 80 degrees C for 12 h. The platelet aggregation inhibitor was purified by systematic solvent fractionation, ultrafiltration, Sephadex G-10 column chromatography, and reverse-phase HPLC. The purified platelet aggregation inhibitor is a novel tripeptide with a molecular mass of 365 Da, having a sequence of Trp-Gly-Cys. The purified platelet aggregation inhibitor also showed high platelet aggregation inhibitory activity in Institute of Cancer Research (ICR) mice.

Production of Antihypertensive Angiotensin I-Converting Enzyme Inhibitor from Malassezia pachydermatis G-14.

To produce a novel antihypertensive angiotensin I-converting enzyme (ACE) inhibitor from yeast, a yeast isolate, designated G-14 showing the highest ACE inhibitory activity was obtained and identified as Malassezia pachydermatis based on morphological, biochemical and cultural characteristics. The maximal extracellular ACE inhibitor production was obtained from M. pachydermatis G-14 when the strain was cultured in YEPD medium containing 0.5% yeast extract, 3.0% peptone and 2.0% glucose at 30℃ for 24 h and the final ACE inhibitory activity was 48.9% under the above condition.

Production of ribonucleotides by autolysis of Pichia anomala mutant and some physiological activities.

Various mutants of Pichia anomala were isolated by ethyl methanesulfonate (EMS) treatment and UV irradiation through cycloheximide resistance and KCl sensitivity. The selected mutant HA-2 accumulated a higher content of RNA and grew faster than the wild-type strain in yeast extract-malt (YM) broth. Autolysis of the HA-2 mutant at 60 degrees C and pH 7.0 for 6 h was the best condition to obtain maximum yields of 5'-ribonucleotides, inosinic monophosphate (IMP) (6.2 mg/g biomass) and guanylic monophosphate (GMP) (35.5 mg/g biomass). The yield of adenylic monophosphate (AMP) (7.8 mg/g biomass) was optimal at 60 degrees C at pH 6.5 for 6 h. The inhibitory activity of the angiotensin-converting enzyme and the nitrite-scavenging activity for autolysates of the HA-2 mutant were about 13.0% and 47.0% higher than those of native strain, respectively.