Association between antibiotic use and subsequent risk of prostate cancer: A retrospective cohort study in South Korea.

OBJECTIVES: Several studies suggest that antibiotic use may affect overall cancer incidence, but the association between antibiotics and prostate cancer is still unclear. This retrospective cohort study aimed to assess the association between antibiotics and the risk of prostate cancer. METHODS: A population-based retrospective cohort study was conducted using the Korean National Health Insurance Service (NHIS) database. 1 032 397 individuals were followed up from January 1, 2007, to December 31, 2019. Multivariable Cox hazards regression was utilized to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the risk of prostate cancer according to accumulative days of antibiotic use and the number of antibiotic classes used from 2002 to 2006. RESULTS: Individuals who used antibiotics for 180 or more days had a higher risk of prostate cancer (aHR, 1.46; 95% CI, 1.11-1.91) than those who did not use antibiotics. Also, individuals who used four or more kinds of antibiotics had a higher risk of prostate cancer (aHR, 1.18; 95% CI, 1.07-1.30) than antibiotic non-users. An overall trend was observed among participants who underwent health examinations. CONCLUSIONS: Our findings suggest that long-term use of antibiotics may affect prostate cancer incidence. Further studies are needed to improve understanding of the association between antibiotic use and prostate cancer incidence.

Pre-operative clonal hematopoiesis is related to adverse outcome in lung cancer after adjuvant therapy.

BACKGROUND: Clonal hematopoiesis (CH) frequently progresses after chemotherapy or radiotherapy. We evaluated the clinical impact of preoperative CH on the survival outcomes of patients with non-small cell lung cancer (NSCLC) who underwent surgical resection followed by adjuvant therapy. METHODS: A total of 415 consecutive patients with NSCLC who underwent surgery followed by adjuvant therapy from 2011 to 2017 were analyzed. CH status was evaluated using targeted deep sequencing of blood samples collected before surgery. To minimize the possible selection bias between the two groups according to CH status, a propensity score matching (PSM) was adopted. Early-stage patients were further analyzed with additional matched cohort of patients who did not receive adjuvant therapy. RESULTS: CH was detected in 21% (86/415) of patients with NSCLC before adjuvant therapy. Patients with CH mutations had worse overall survival (OS) than those without (hazard ratio [95% confidence interval] = 1.56 [1.07-2.28], p = 0.020), which remained significant after the multivariable analysis (1.58 [1.08-2.32], p = 0.019). Of note, the presence of CH was associated with non-cancer mortality (p = 0.042) and mortality of unknown origin (p = 0.018). In patients with stage IIB NSCLC, there was a significant interaction on OS between CH and adjuvant therapy after the adjustment with several cofactors through the multivariable analysis (HR 1.19, 95% CI 1.00-1.1.41, p = 0.041). CONCLUSIONS: In resected NSCLC, existence of preoperative CH might amplify CH-related adverse outcomes through adjuvant treatments, resulting in poor survival results.

Synthesis of Tricyclic Tetrazoles by Cascade Diazotization/Intramolecular Radical C-H Heteroarylation of Arenes.

A cascade diazotization/intramolecular radical C-H heteroarylation of 1-benzyloxy-5-aminotetrazoles and 1-phenethyl-5-aminotetrazoles as substrates using sodium nitrite and acetic acid without any heating, catalysis, irradiation, or electrolysis is reported. This one-pot reaction afforded the desired tricyclic tetrazole products in good yields (up to 94%) without isolation of the diazonium salt intermediate under mild reaction conditions.

Finding of novel lactate utilizing Bacillus sp. YHY22 and its evaluation for polyhydroxybutyrate (PHB) production.

Polyhydroxyalkanoates (PHAs) and their derivatives are biopolymers that have the potential of replacing petroleum-based plastics and can be produced and degraded via bacterial metabolism. However, there are only a few studies on polyhydroxybutyrate (PHB) production using lactate, one of the major waste organic acids that could be implemented in the production of polylactic acid (PLA). Herein, we screened and characterized the PHA-producing microbial strains isolated from saltern soil from Docho Island (South Korea). Among the 24 identified microorganisms that can use lactate as a carbon source, Bacillus sp. YHY22, a newly reported strain, produced the highest amount of PHB: 4.05 g/L with 6.25 g/L dry cell weight, which is 64.7% PHB content under optimal production conditions. Bacillus sp. YHY22 could form the poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer with propionate addition. Moreover, Bacillus sp. YHY22 produced PHB in non-sterilized 2% lactate and 8% NaCl marine broth culture medium, suggesting that its production can occur in high salinity media without additional sterilization steps, rendering fermentation cost- and time-efficient.

Clonal hematopoiesis is associated with risk of severe Covid-19.

Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 525 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we show that CH is associated with severe Covid-19 outcomes (OR = 1.85, 95%=1.15-2.99, p = 0.01), in particular CH characterized by non-cancer driver mutations (OR = 2.01, 95% CI = 1.15-3.50, p = 0.01). We further explore the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH is significantly associated with risk of Clostridium Difficile (HR = 2.01, 95% CI: 1.22-3.30, p = 6×10-3) and Streptococcus/Enterococcus infections (HR = 1.56, 95% CI = 1.15-2.13, p = 5×10-3). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.

Clonal hematopoiesis is associated with risk of severe Covid-19.

Acquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. 1-4 These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. 2,5,6 A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. 7,8 Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 515 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we found that CH was associated with severe Covid-19 outcomes (OR=1.9, 95%=1.2-2.9, p=0.01). We further explored the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH was significantly associated with risk of Clostridium Difficile (HR=2.0, 95% CI: 1.2-3.3, p=6×10 -3 ) and Streptococcus/Enterococcus infections (HR=1.5, 95% CI=1.1-2.1, p=5×10 -3 ). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.

Simultaneous and synergistic effect of heavy metal adsorption on the enhanced photocatalytic performance of a visible-light-driven RS-TONR/TNT composite.

A hydrothermally synthesized rhodium/antimony co-doped TiO2 nanorod and titanate nanotube (RS-TONR/TNT) composite was prepared for removal of heavy metals and organic pollutants from water under visible light irradiation. The composite provides the dual function of simultaneous adsorption of heavy metal ions and enhanced degradation of dissolved organic compounds. Acid treatment transformed titanate nanotubes to irregular tubular structures distributed homogeneously over untransformed RS/TONRs. Synergistic removal and degradation was studied with various heavy metals, Orange (II) dye, and Bisphenol A. The adsorption capacity of the composite for heavy metal ions was Pb(II) > Cd(II) > Cu(II) > Zn(II). The adsorbed metals enhanced photocatalytic degradation of the organic pollutants, but Cu was most effective, with degradation exceeding 70% for the dye and 80% for Bisphenol A after 5 h of treatment. Photocatalytic activity was enhanced more by adsorption than photodeposition of Cu ions. A decrease in XRD rutile peak intensity with adsorbed metal indicates a change in crystallinity which may enhance photocatalytic activity. Thick and bulging nanostructures in FE-SEM images signify ion adsorption within titanate pores. BET analysis indicated titanate nanotubes with adsorbed metal are mesoporous but their tubular structure persists. XPS showed more active Cu 2p3/2 states under light, supporting an active role of Cu+ in photocatalytic ROS generation. Detection of ROS and Cu species using methanol, EDTA, pCBA, and benzoic acid probes provided strong evidence for degradation via a charge transfer mechanism. Findings demonstrate the potential of the RS-TONR/TNT composite for simultaneous removal of heavy metals and degradation of organic pollutants.

A mechanism study on the photocatalytic inactivation of Salmonella typhimurium bacteria by CuxO loaded rhodium-antimony co-doped TiO2 nanorods.

This study presents the first report on the photocatalytic inactivation mechanism for a Salmonella typhimurium pathogen by visible-light active CuxO loaded rhodium-antimony co-doped TiO2 nanorods (CuxO/Rh-Sb-TiO2 NRs) under visible light irradiation (cutoff filter, λ ≥ 420 nm). Remarkably higher pathogenic inactivation of 4 log within 40 min by a CuxO supported Rh-Sb-TiO2 NR photocatalyst was observed. The visible light active photocatalyst mainly produced reduced Cu+ in the lattice of CuxO by charge separation. By this means, photo-generated electrons at the conduction band of Rh-Sb-TiO2 NRs play an important role in reducing Cu2+ to Cu+ through the photocatalytic reduction reaction (PRR), and at the valence band of Rh-Sb-TiO2 NRs, photo-generated holes generate OH˙ radicals through the photocatalytic oxidation reaction (POR). This Cu+ copper species is lethal to microbial pathogens. The inactivation mechanism for the Salmonella typhimurium pathogen was investigated by protein oxidation, HCHO production, and the API-ZYM system. To investigate the role of OH˙ radicals, t-BuOH and MeOH as hole scavengers were used in photocatalytic inactivation reactions. Our experimental results confirmed that the reduced Cu+ species play a major role in bacterial inactivation, while ROS have a major effect on the degradation of organic pollutants.

Study on the Validity of Surface Electromyography as Assessment Tools for Facial Nerve Palsy.

OBJECTIVES: The purpose of this study was to find out validity of Surface Electromyography(sEMG) compared with Nerve Conduction Study and clinical assessment scale as assessment factors for facial palsy. METHODS: We investigated 50 cases of patients with peripheral facial palsy who had records of sEMG and NCS to check. Then we analyzed the correlation between sEMG and NCS that carried out around 1 week after onset. And we analyzed the correlation between sEMG and clinical assessment scales that were measured three times around 1 week, 3-4 weeks and 5-6 weeks after onset. Clinical assessment scales used in this study were House-brackmann grade, Yanagihara unweighted grading scale and Sunnybrook facial grading system. We used Pearson's correlation for statistical analysis. RESULTS: sEMG and NCS, measured at similar times, were statistically correlated. Especially, the correlation with the forehead region was high. And sEMG and clinical assessment scale, measured at same time, were statistically correlated, especially after 5 weeks from onset. CONCLUSION: According to this study, sEMG is expected to be useful to assessment facial palsy.

Boosting Photocatalytic Performance of Inactive Rutile TiO2 Nanorods under Solar Light Irradiation: Synergistic Effect of Acid Treatment and Metal Oxide Co-catalysts.

In the present work, we accomplish the boosting of photocatalytic performance by the synergistic effect of acid treatment and transition metal oxide co-catalysts on molten salt rutile TiO2 nanorods. FT-IR and XPS (oxygen deconvolution) results confirmed that the amount of hydroxyl groups increased on the surface of rutile TiO2 nanorods (TO-NRs) after acid treatment. HR-TEM analysis revealed fine dispersion of metal oxide on the surface of acid treated TiO2 nanorods (ATO-NRs). The photocatalytic activities of as-prepared (TO-NRs), acid treated (ATO-NRs), metal oxide loaded (MTO-NRs), and both acid treated and metal oxide loaded (MATO-NRs) nanorods were compared based on the rate kinetics and dye degradation efficiencies. Cobalt oxide (1 wt %) loaded and 1.0 M acid treated TiO2 nanorods (Co/ATO-NR) exhibited the higher photocatalytic degradation efficiency for Orange-II dye degradation and inactivation of S. typhimurium pathogen compared to other photocatalysts under solar irradiation. Photoelectrochemical analysis demonstrated that the charge transfer process in Co/ATO-NR is significantly higher than that in the untreated samples. The improved photocatalytic activity of inactive TO-NRs might be due to enhanced charge transfer of finely dispersed metal oxides on the OH-rich surface of acid treated TiO2 nanorods.

Metabolomic Analysis Reveals Cyanidins in Black Raspberry as Candidates for Suppression of Lipopolysaccharide-Induced Inflammation in Murine Macrophages.

The extracts produced by multisolvent extraction and subfractionation with preparative liquid chromatography of black raspberry (Rubus coreanus Miquel) cultivated in Gochang, South Korea, were tested for their anti-inflammatory effects. The metabolomic profiling and analysis by orthogonal partial least-squares discriminant analysis (OLPS-DA) suggested that cyanidin, cyanidin-3-glucoside (C3G), and cyanidin-3-rutinoside (C3R) were key components for the anti-inflammatory responses in the most active fraction BF3-1, where they were present at 0.44, 1.26, and 0.56 µg/mg of BF3-1, respectively. Both BF3-1 and mixture of these cyanidins at the same ratio reduced lipopolysaccharide (LPS)-induced protein level of iNOS expression and suppressed mRNA and protein expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß through inhibiting the phosphorylation of mitogen-activated protein kinases (MAPKs) and STAT3 in murine macrophage RAW264.7 cells. Overall, the results suggested that co-administration of cyanidin, C3G, and C3R is more effective than that of cyanidin alone and that the coexistence of these anthocyanin components in black raspberry plays a vital role in regulating LPS-induced inflammation even at submicromolar concentrations, making it possible to explain the health beneficial activity of its extracts.

Ellagic acid identified through metabolomic analysis is an active metabolite in strawberry ('Seolhyang') regulating lipopolysaccharide-induced inflammation.

This study employed the metabolomic approach to identify the key constituent exerting anti-inflammatory activity in murine macrophage RAW 264.7 cells. Among the six different fractions (SF1-SF6) of the strawberry 'Seolhyang', SF4 showed more significant inhibition on iNOS expression than SF3, and ellagic acid was determined as the most significant different component between SF4 and SF3 using orthogonal partial least-squares discriminant analysis. Ellagic acid (0.3 and 1.0 µM) and SF4 (100 µg/mL) were found to regulate the same inflammatory mediators, inhibitory κB (IκB) and mitogen-activated protein kinases (MAPKs), which led to the reduction of tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), and iNOS expressions. These results demonstrate that ellagic acid from strawberry 'Seolhyang' is the major component playing a crucial role in inflammation, suggesting the possible application of metabolomic analysis to determining the key ingredients having biological functions in the complicated food matrix.

Automatic detection of seizure termination during electroconvulsive therapy using sample entropy of the electroencephalogram.

Determining the exact duration of seizure activity is an important factor for predicting the efficacy of electroconvulsive therapy (ECT). In most cases, seizure duration is estimated manually by observing the electroencephalogram (EEG) waveform. In this article, we propose a method based on sample entropy (SampEn) that automatically detects the termination time of an ECT-induced seizure. SampEn decreases during seizure activity and has its smallest value at the boundary of seizure termination. SampEn reflects not only different states of regularity and complexity in the EEG but also changes in EEG amplitude before and after seizure activity. Using SampEn, we can more precisely determine seizure termination time and total seizure duration.

No association of functional polymorphisms in methlylenetetrahydrofolate reductase and the risk and minor physical anomalies of schizophrenia in Korean population.

Methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate metabolism, plays an important role in DNA methylation. It has been suggested that abnormal DNA methylation contributes to the pathogenesis of schizophrenia and congenital anomalies. The previous findings regarding the genetic relationship between MTHFR and schizophrenia are controversial. This study investigated the association of the two functional polymorphisms of MTHFR, C677T and A1298C, with the risk for schizophrenia. Furthermore, we conducted an updated meta-analysis on the two polymorphisms. In addition, we investigated the relationship between the polymorphisms and minor physical anomaly (MPA), which may represent neurodevelopmental aberrations in 201 schizophrenia patients and 350 normal control subjects. There was no significant association between either of the two polymorphisms and the risk of schizophrenia (chi-square = 0.001, df = 1, P = 0.971 for C677T; chi-square = 1.319, df = 1, P = 0.251 for A1298C). However, in meta-analysis, the C677T polymorphism showed a significant association in the combined and Asian populations (OR = 1.13, P = 0.005; OR = 1.21, P = 0.011, respectively) but not in the Korean and Caucasian populations alone. Neither polymorphism was associated with MPAs measured by the Waldrop scale (chi-square = 2.513, df = 2, P = 0.285). In conclusion, the present findings suggest that in the Korean population, the MTHFR polymorphisms are unlikely to be associated with the risk for schizophrenia and neurodevelopmental abnormalities related to schizophrenia.

No association between AKT1 polymorphism and schizophrenia: a case-control study in a Korean population and a meta-analysis.

V-akt murine thymoma viral oncogene homolog 1 (AKT1) has been suggested to be involved in the pathophysiology of schizophrenia. Recent, independent studies in Caucasian, Japanese, Iranian, and Chinese populations have reported that the AKT1 gene may be associated with schizophrenia, but these results have yet to be replicated in other populations. In the present study, we performed a case-control association study between AKT1 and schizophrenia in a Korean population. We genotyped six single nucleotide polymorphisms (SNP1 (rs3803300), SNP2 (rs1130214), SNP3 (rs3730358), SNP4 (rs1130233), SNP5 (rs2494732), SNP A (rs2498804)) of AKT1, selected from previous reports, in a sample of 283 subjects with schizophrenia and 350 controls. No significant difference in single marker polymorphisms or haplotype frequencies of the six SNPs in the AKT1 gene was observed between controls and subjects with schizophrenia. In addition, we carried out an updated meta-analysis of the six SNPs, and found no evidence for an association between the six SNPs and schizophrenia. Taken together, our results do not support the hypothesis that AKT1 is a susceptibility gene for schizophrenia.

Differential pattern of heart rate variability in patients with schizophrenia.

The cardiac autonomic dysfunction has been reported in patients with schizophrenia. Heart rate variability (HRV) provides non-invasive indices of cardiac autonomic modulation. This study examined whether patients with schizophrenia may show a distinctive pattern of HRV compared to healthy controls. Nine measures of time, frequency and complexity domains were extracted from 5-min resting evaluation of HRV in 30 unmedicated patients with schizophrenia and 30 age- and gender-matched controls. In addition to inferential statistics, a hierarchical clustering (HC) was used to examine difference in the interrelationships among HRV measures between the two groups. Multivariate analysis of variance revealed a significant group effect. Significantly lower sample entropy (SampEn) and a trend towards a higher ratio of low- to high frequency (LF/HF) were observed in the schizophrenia group. In the results of HC using Ward's method, SampEn co-clustered with LF/HF ratio in patients with schizophrenia compared to the separation of LF/HF ratio in healthy controls. In concert with decreased parasympathetic activity, low complexity of heart rate dynamics may reduce adaptability of cardiovascular system to changes in internal or external environment, thus increasing the risk of cardiovascular events. Diverse HRV measures combined in a multivariate fashion appear to be useful in understanding the pattern of neurocardiac modulation in patients with schizophrenia.