Oxytocin alleviates cellular senescence through oxytocin receptor-mediated extracellular signal-regulated kinase/Nrf2 signalling.

BACKGROUND: Oxytocin (OT) is a neuropeptide hormone that has many beneficial biological effects, including protection against age-related disorders. However, less is known about its role in intrinsic skin ageing, which is accelerated by an increase in senescent cell fraction in skin tissue. OBJECTIVES: To investigate the novel function and the underlying mechanism of OT in preventing cellular senescence in normal human dermal fibroblasts (NHDFs) isolated from the skin of female donors of different ages. METHODS: NHDFs from young and old donors were exposed to conditioned medium from senescent or control NHDFs in the presence or absence of 10 nmol L-1 OT for 3 days, and were continuously subcultured for 12 days. Subsequently, various age-associated signs of senescence including decreased proliferation rate, elevated p16 and p21 levels, and positivity for senescence-associated ß-galactosidase expression were examined. RESULTS: We found that OT suppressed senescence-associated secretory phenotype-induced senescence in NHDFs, and its effect depended on the age of the donor's NHDFs. The inhibitory effects of OT required signalling by OT receptor-mediated extracellular signal-regulated kinase/Nrf2 (nuclear factor erythroid 2-related factor 2). The age-dependent antisenescence effects of OT are closely related to hypermethylation of the OT receptor gene (OXTR). CONCLUSIONS: Our findings bring to light the role of OT in the prevention of skin ageing, which might allow development of new clinical strategies. What's already known about this topic? Senescent keratinocytes and fibroblasts accumulate with age in the skin and contribute to the loss of skin function and integrity during ageing. Senescent cells secrete senescence-associated secretory phenotype (SASP), which includes the release of proinflammatory cytokines such as interleukin (IL)-6 and IL-1, chemokines, extracellular matrix-remodelling proteases and growth factors. The neuropeptide oxytocin (OT) and its receptor (OXTR) have protective effects against various age-related disorders. What does this study add? OT suppressed SASP-induced cellular senescence in normal human dermal fibroblasts (NHDFs), depending on the age of the NHDFs' donor. The inhibitory effects of OT on cellular senescence required OXTR-mediated phosphorylation of extracellular signal-regulated kinase, which enhanced nuclear localization of Nrf2, a vital factor in the antioxidant defence system. The age-specific antisenescent effects of OT were closely related to hypermethylation of OXTR. What is the translational message? Our results suggest that OT and OXTR agonists could be clinically promising agents for the improvement of age-associated skin ageing, especially in women.

Global transcriptome analysis identifies weight regain-induced activation of adaptive immune responses in white adipose tissue of mice.

OBJECTIVE: Studies have indicated that weight regain following weight loss predisposes obese individuals to metabolic disorders; however, the molecular mechanism of this potential adverse effect of weight regain is not fully understood. Here we investigated global transcriptome changes and the immune response in mouse white adipose tissue caused by weight regain. DESIGN: We established a diet switch protocol to compare the effects of weight regain with those of weight gain without precedent weight loss, weight loss maintenance and chow diet. We conducted a time course analysis of global transcriptome changes in gonadal white adipose tissue (gWAT) during the weight fluctuation. Co-expression network analysis was used to identify functional modules associated with the weigh regain phenotype. Immune cell populations in gWAT were characterized by flow-cytometric immunophenotyping. Metabolic phenotypes were monitored by histological analysis of adipose tissue and liver, and blood-chemistry and body weight/composition analyses. RESULTS: In total, 952 genes were differentially expressed in the gWAT in the weight regain vs the weight gain group. Upregulated genes were associated with immune response and leukocyte activation. Co-expression network analysis showed that genes involved in major histocompatibility complex I and II-mediated antigen presentation and T-cell activation function were upregulated. Consistent with the transcriptome analysis results, flow cytometry demonstrated significant increases in subsets of T cells and proinflammatory M1 macrophages in the gWAT in the weight regain as compared to the weight gain group. In addition, upregulation of adaptive immune responses was associated with high incidence of adipocyte death and upregulation of high mobility group box 1, a well-known component of damage-associated molecular patterns. CONCLUSIONS: Our global transcriptome analysis identified weight regain-induced activation of adaptive immune responses in mouse white adipose tissue. Results suggest that activation of adipocyte death-associated adaptive immunity in adipose tissue may contribute to unfavorable metabolic effects of weight regain following weight loss.

Recombinant growth hormone therapy for prepubertal children with idiopathic short stature in Korea: a phase III randomized trial.

PURPOSE: Several studies have evaluated the effects of growth hormone (GH) on auxological and biochemical parameters in children with non-GH-deficient, idiopathic short stature (ISS). This study evaluated the efficacy and safety of Growtropin®-II (recombinant human GH) in Korean patients with ISS. METHODS: This was a 1-year, open-label, multicenter, phase III randomized trial of Growtropin®-II in Korean patients with ISS. In total, 70 prepubertal subjects (39 males, 31 females) between 4 and 12 years of age were included in the study. All patients were naive to GH treatment. RESULTS: Annual height velocity was significantly higher in the treatment group (10.68 ± 1.95 cm/year) than the control group (5.72 ± 1.72, p < 0.001). Increases in height and weight standard deviation scores (SDSs) at 26 weeks were 0.63 ± 0.16 and 0.64 ± 0.46, respectively, for the treatment group, and 0.06 ± 0.15 and 0.06 ± 0.28, respectively, for the control group (p < 0.001). Serum insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) increased significantly in the treatment group at week 26 compared to baseline. However, the SDS for body mass index (BMI) at 26 weeks did not change significantly in either group. Growtropin®-II was well tolerated and safe over 1 year of treatment. CONCLUSIONS: One-year GH treatment for prepubertal children with ISS demonstrated increased annualized velocity, height and weight SDSs, and IGF-1 and IGFBP-3 levels, with a favorable safety profile. Further evaluations are needed to determine the optimal dose, final adult height, and long-term effects of ISS treatment.

Empirical combination of a ß-lactam to vancomycin may not improve outcomes of methicillin-susceptible Staphylococcus aureus bacteremia, compared to vancomycin monotherapy.

To evaluate effect of empirical combination of a ß-lactam to vancomycin and vancomycin monotherapy in Staphylococcus aureus bacteremia (MSSA-B), we conducted a retrospective cohort study. Electronic medical records of individuals who were diagnosed with MSSA-B between January 2005 and February 2015 at a tertiary care center were reviewed. Patients were classified into three groups according to empirical antibiotic regimen (BL group, ß-lactam; VAN group, vancomycin; BV group, combination of ß-lactam and vancomycin), and 30-day all-cause mortality of each group was compared. During the study period, 561 patients with MSSA-B were identified. After exclusion of 198 patients (36 with poly-microbial infection, 114 expired within 2 days, and 48 already received parenteral antibiotics) and a matching process, 46 patients for each group were included. Baseline characteristics were similar except for severity and comorbidity scores. The 30-day mortality for all three groups were not significantly different (BL 4.3%, VAN 6.5%, BV 8.7%; P = 0.909). In a multivariate analysis, type of empirical antibiotic regimen was not statistically associated with 30-day all-cause mortality. In comparison with the VAN group, the BV group yielded a HR of 0.579 (95% CI = 0.086-3.890, P = 0.574). Pitt bacteremia score was the only significant factor for mortality. The empirical combination of a ß-lactam to vancomycin was not associated with lower mortality in treating MSSA-B, compared to vancomycin monotherapy.

Suggested new breakpoints of anti-MERS-CoV antibody ELISA titers: performance analysis of serologic tests.

To provide optimal cut-off values of anti-Middle East respiratory syndrome coronavirus (MERS-CoV) serologic tests, we evaluated performance of ELISA IgG, ELISA IgA, IFA IgM, and IFA IgG using 138 serum samples of 49 MERS-CoV-infected patients and 219 serum samples of 219 rRT-PCR-negative MERS-CoV-exposed healthcare personnel and patients. The performance analysis was conducted for two different purposes: (1) prediction of neutralization activity in MERS-CoV-infected patients, and (2) epidemiologic surveillance of MERS-CoV infections among MERS-CoV-exposed individuals. To evaluate performance according to serum collection time, we used 'days post onset of illness (dpoi)' and 'days post exposure (dpex)' assessing neutralization activity and infection diagnosis, respectively. Performance of serologic tests improved with delayed sampling time, being maximized after a seroconversion period. In predicting neutralization activity, ELISA IgG tests showed optimal performance using sera collected after 21 dpoi at cut-off values of OD ratio 0.4 (sensitivity 100% and specificity 100%), and ELISA IgA showed optimal performance using sera collected after 14 dpoi at cut-off value of OD ratio 0.2 (sensitivity 85.2% and specificity 100%). In diagnosis of MERS-CoV infection, ELISA IgG exhibited optimal performance using sera collected after 28 dpex, at a cut-off value of OD ratio 0.2 (sensitivity 97.3% and specificity 92.9%). These new breakpoints are markedly lower than previously suggested values (ELISA IgG OD ratio 1.1, sensitivity 34.8% and specificity 100% in the present data set), and the performance data help serologic tests to be practically used in the field of MERS management.

Generic piperacillin/tazobactam is not associated with galactomannan false-positivity in adult patients with cancer: a case-control study.

Recent products of piperacillin/tazobactam (PTZ) from the original manufacturer, previously considered a major cause of galactomannan (GM) false-positivity, are reported not to be related to it. However, data regarding generic PTZ are limited and controversial. To evaluate the effect of generic PTZ on GM false-positivity in Korea, we performed a case-control study in adult patients with cancer. A case-control study was designed. Electronic medical records of cancer patients who were admitted and tested for serum GM between March and June 2014 at a tertiary care university hospital were reviewed. During the study period, a single generic PTZ (C manufacturer, Korea) was used. Patients who received PTZ within 24 h prior to serum GM testing were enrolled. Age- and GM test date-matched non-PTZ patients were selected as controls. A total of 110 patients received PTZ within 24 h prior to serum GM testing during the study period. The GM optical density index (ODI) of the PTZ group did not vary significantly from that of the control group (p = 0.251). The percentage of false-positive patients in the PTZ group was also similar to that of the control group (p = 0.538). There was no statistical relationship between GM ODI titer and time interval from PTZ administration (p = 0.095) or cumulative PTZ dose (p = 0.416). In a case-control study that evaluated 220 patients, a generic PTZ in Korea was not related to GM false-positivity.

Prostate-specific membrane antigen as a target for cancer imaging and therapy.

The prostate-specific membrane antigen (PSMA) is a molecular target whose use has resulted in some of the most productive work toward imaging and treating prostate cancer over the past two decades. A wide variety of imaging agents extending from intact antibodies to low-molecular-weight compounds permeate the literature. In parallel there is a rapidly expanding pool of antibody-drug conjugates, radiopharmaceutical therapeutics, small-molecule drug conjugates, theranostics and nanomedicines targeting PSMA. Such productivity is motivated by the abundant expression of PSMA on the surface of prostate cancer cells and within the neovasculature of other solid tumors, with limited expression in most normal tissues. Animating the field is a variety of small-molecule scaffolds upon which the radionuclides, drugs, MR-detectable species and nanoparticles can be placed with relative ease. Among those, the urea-based agents have been most extensively leveraged, with expanding clinical use for detection and more recently for radiopharmaceutical therapy of prostate cancer, with surprisingly little toxicity. PSMA imaging of other cancers is also appearing in the clinical literature, and may overtake FDG for certain indications. Targeting PSMA may provide a viable alternative or first-line approach to managing prostate and other cancers.

Tuberculosis before hematopoietic stem cell transplantation in patients with hematologic diseases: report of a single-center experience.

BACKGROUND: Few reports discuss the optimal management of patients diagnosed with tuberculosis (TB) before scheduled stem cell transplantation (SCT), who then proceed with transplantation. METHODS: We found 13 patients with TB before SCT (proven, n = 9; probable, n = 3; possible, n = 1) in the medical records of our institution. RESULTS: Most of the patients had pulmonary TB (n = 8; disseminated, n = 2; extrapulmonary, n = 3). Eight of 9 patients with proven disease had SCT after at least 100 days of anti-tuberculous medication, ranging from 103 to 450 days. None of those patients suffered TB-related events after SCT. However, 1 patient with proven pulmonary TB who underwent SCT after only 40 days of anti-tuberculous therapy subsequently died of TB meningitis. Patients with possible and probable disease had their transplants after 6-176 days of anti-tuberculous medication, and all were alive at the time of analysis. The entire duration of anti-tuberculous medication was 12 months in most cases. With a follow-up duration ranging from 0.7 to 87.5 months, 4 patients died, but TB was the cause of death in only 1 case. CONCLUSION: In conclusion, for proven cases of TB, SCT after >100 days of anti-tuberculous medication is probably feasible and safe, in terms of TB control, in patients with various hematologic diseases.

Dental luxation and avulsion injuries in Hong Kong primary school children.

OBJECTIVES: To identify the major causes and types of dental luxation and avulsion injuries, and their associated factors in primary school children in Hong Kong. DESIGN: Case series. SETTING: School dental clinic, New Territories, Hong Kong. PATIENTS: The dental records of children with a history of dental luxation and/or avulsion injury between November 2005 and October 2012 were reviewed. Objective clinical and radiographical findings at the time of injury and at follow-up examinations were recorded using a standardised form. Data analysis was carried out using the Chi squared test and multinomial logistic regression. RESULTS: A total of 220 children with 355 teeth of dental luxation or avulsion injury were recorded. Their age ranged from 6 to 14 years and the female-to-male ratio was 1:1.8. The peak occurrence was at the age of 9 years. Subluxation was the most common type of injury, followed by concussion. Maxillary central incisors were the most commonly affected teeth. The predominant cause was fall and most injuries occurred at school. Incisor relationship was registered in 199 cases: most of them were Class I. Comparison of the incisor relationship in study children and the general Chinese population in another study revealed a higher proportion of Class II and fewer Class III occlusions in the trauma group (P<0.0001). CONCLUSION: Most dental luxation and avulsion injuries in Hong Kong primary school children are caused by fall. Boys are more commonly affected than girls, and a Class II incisor relationship is a significant risk factor.

Risk factors for cytomegalovirus gastrointestinal diseases in adult patients with cancer.

Cytomegalovirus (CMV) gastrointestinal (GI) disease has been noticed frequently in cancer patients, causing abdominal pain, diarrhea, and GI bleeding. However, little is known about its actual incidence, clinical presentation, and the risk factors for its development among cancer patients. To answer these questions, we analyzed all cases that occurred during an 18-year period at our center. A case-control study was performed to identify risk factors for CMV GI disease. Electronic medical records were reviewed from individuals who were admitted and diagnosed with CMV GI disease during the period of January 1995 through March 2013 at a tertiary care center. Two CMV disease-free cancer patients were matched as controls. A total of 98 episodes of CMV GI disease were included in this study, and the overall incidence rate was 52.5 per 100,000 cancer patients, with an increasing trend throughout the study period. According to multivariate analysis, male sex, low body mass index, lymphopenia, hematological malignancy, and steroid use and red blood cell transfusion within 1 month prior to the CMV disease were identified to be independent risk factors. Among these factors, RBC transfusion showed the highest odds ratio (OR = 5.09). Male sex, low body mass index, lymphopenia, hematological malignancy, steroid use, and red blood cell transfusion within 1 month prior to the CMV disease diagnosis were independent risk factors for the development of CMV GI disease in adult patients with cancer.

Smoking cession decreases mean platelet volume in healthy Korean populations.

BACKGROUND: Smoking is considered as a major modifiable risk factor for cardiovascular diseases. It has been shown that smoking cessation drops the risk of cardiovascular diseases such as myocardial infarction and also improves platelet function. Because mean platelet volume (MPV) is a simple and convenient indicator for platelet activation, we planned to investigate the effect of smoking status on MPV in healthy populations. METHODS: This study was conducted on 398 individuals who visited our hospital for regular medical check-ups and were confirmed not to have diabetes or hypertension. MPV was measured using EDTA blood on an Advia 2120 (Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA) within 2 hours. RESULTS: Present smokers showed higher MPV levels than present non-smokers. When MPV was compared by taking previous smoking history and present smoking status into account, the smoking cessation group showed significantly lower MPV levels than other groups. CONCLUSIONS: Because this finding was significant only in the female group, the change in MPV according to smoking status was found to be different by gender. We carefully suggest that smoking cessation can lower the risk of cardiovascular diseases through the change in MPV, which can be more effective for women than men.

Factors affecting the success rate of buccal infiltration anaesthesia in the mandibular molar region.

AIM: To compare the anaesthetic efficacy of mandibular second premolar infiltration (SP) with that of mandibular first molar infiltration (FM) in inducing pulpal anaesthesia in the mandibular first molar. To further investigate the mechanisms of action that underlie mandibular infiltration, gender-related differences in the anaesthetic efficacy were also assessed. METHODOLOGY: A total of 29 adult subjects randomly received two sets of SP and FM injections using one cartridge (1.7 mL) of 4% articaine and 1 : 100 000 adrenaline at two separate appointments. The responses of the teeth were assessed using an electronic pulp tester over a 30-min period. A comparison of the anaesthetic success between the SP and FM infiltration routes was analysed using the McNemar's test. Gender-related differences in the anaesthetic success of infiltration routes were assessed using the Fisher's exact test. RESULTS: For the second premolar and the first and second molar teeth, the success rates of SP were 72.4%, 62.1% and 48.3%, whereas the success rates of FM were 75.9%, 51.7% and 55.1%, respectively. There were no significant differences between the success rates of SP and FM or between the rates obtained for each tooth. Significant gender-related differences were observed for the second premolar (P < 0.01) and the first molar (P < 0.05) using FM. However, a significant difference was observed only for the second premolar using SP (P < 0.05). CONCLUSIONS: The differences in the injection sites did not affect the anaesthetic success rates for the mandibular second premolar and molar teeth. However, articaine buccal infiltration produced a higher anaesthetic success rate in the second premolar and first molar teeth of Korean female patients.

Development of machine learning models for the surveillance of colon surgical site infections.

BACKGROUND: Conventional surgical site infection (SSI) surveillance is labour-intensive. We aimed to develop machine learning (ML) models for the surveillance of SSIs for colon surgery and to assess whether the ML could improve surveillance process efficiency. METHODS: This study included cases who underwent colon surgery at a tertiary center between 2013 and 2014. Logistic regression and four ML algorithms including random forest (RF), gradient boosting (GB), and neural networks (NNs) with or without recursive feature elimination (RFE) were first trained on the entire cohort, and then re-trained on cases selected based on a previous rule-based algorithm. We assessed model performance based on the area under the curve (AUC), sensitivity, and positive predictive value (PPV). The estimated proportion of reduction in workload for chart review based on the ML models was evaluated and compared with the conventional method. RESULTS: At a sensitivity of 95%, the NN with RFE using 29 variables had the best performance with an AUC of 0.963 and PPV of 21.1%. When combining both the rule-based algorithm and ML algorithms, the NN with RFE using 19 variables had a higher PPV (28.9%) than with the ML algorithm alone, which could decrease the number of cases requiring chart review by 83.9% compared with the conventional method. CONCLUSION: We demonstrated that ML can improve the efficiency of SSI surveillance for colon surgery by decreasing the burden of chart review while providing high sensitivity. In particular, the hybrid approach of ML with a rule-based algorithm showed the best performance in terms of PPV.

IgE-mediated anaphylaxis and allergic reactions to idursulfase in patients with Hunter syndrome.

BACKGROUND: Enzyme replacement therapy (ERT) with recombinant human idursulfase is effective for the treatment of Hunter syndrome, mucopolysaccharidosis (MPS) type II. However, various adverse events can occur by the infusion of idursulfase. The purpose was to evaluate the occurrence of infusion-related allergic reactions, including anaphylaxis, to idursulfase in patients with MPS II receiving ERT and to elucidate its possible mechanism. METHODS: A total of 34 patients with MPS II were enrolled to receive ERT with Elaprase(®) at a dose of 0.5 mg/kg intravenously once a week. Information regarding the symptoms, frequency, and timing of anaphylaxis during treatment was analyzed. Presence of anti-idursulfase IgE antibody was assessed by skin prick test (SPT) and enzyme-linked immunosorbent assay (ELISA). Western blotting was performed to confirm the reaction between idursulfase and specific IgE. RESULTS: Three patients (8.8%) showed anaphylaxis by infusion of idursulfase. No deaths occurred during the study. Anti-idursulfase IgE antibody was detected by SPT and ELISA. Immunoblotting with patients' sera and Elaprase(®) showed a single band of specific IgE binding to the protein around 70 kD, and idursulfase did not display amino acid sequence homology to known allergens. SPT with idursulfase demonstrated positive results in all patients with anaphylaxis. However, we failed to reveal any risk factors for the development of infusion-related immediate-type allergic reactions. CONCLUSIONS: Anaphylaxis related to infusion of idursulfase is mediated by anti-idursulfase IgE antibody, which might be produced by de novo synthesis. SPT is useful in predicting the occurrence of anti-idursulfase IgE-mediated anaphylaxis during infusion.

Stylet- or forceps-guided tube exchanger to facilitate GlideScope intubation in simulated difficult intubations--a randomised controlled trial.

The GlideScope videolaryngoscope is widely used in the management of the difficult airway. However, passing the tracheal tube through the vocal cords can be awkward, and the use of a stylet to guide insertion is recommended. This randomised controlled trial evaluated a forceps-guided tube exchanger as an alternative to the stylet to aid intubation with the GlideScope in patients undergoing anaesthesia, with a simulated difficult airway created by the application of a semi-rigid cervical collar. Data were analysed from 178 patients randomly assigned to undergo intubation using either the stylet (n = 88) or a forceps-guided tube exchanger (n = 90). All intubations were completed successfully, with first attempt rates of 93.2% using the stylet and 94.4% using the exchanger (p = 0.597). The mean (SD) intubation time was 67.8 (28.7) s in the stylet group and 66.1 (15.5) s in the forceps-guided tube exchanger group (p = 0.11). The frequency of sore throat 1 h after extubation was 34.1% in the stylet group and 2.2% in the tube exchanger group (p < 0.001); 24 h after extubation the corresponding figures were 40.0% and 11.1% (p < 0.001). Using a forceps-guided tube exchanger may offer an advantage over a stylet in guiding tracheal intubation when the GlideScope is used.

Differences in prostate cancer detection rates according to the level of glomerular filtration rate in patients with prostate specific antigen levels of 4.0-10.0 ng/ml.

AIMS: To investigate differences in prostate cancer detection rates according to the level of glomerular filtration rates (GFR). MATERIALS AND METHODS: Patients with prostate-specific antigen (PSA) levels of 4.0-10.0 ng/ml were analysed. Age, serum creatinine, estimated GFR, body mass index, total PSA (tPSA), free PSA (fPSA), per cent free PSA (%fPSA), comorbidities, biopsy Gleason sum and per cent positive core were retrospectively reviewed. All parameters were compared to show whether patients with GFR <60 ml/min/1.73 m(2) (group A) have higher risk of prostate cancer than patients with GFR ≥ 60 (group B). The primary endpoint was cancer detection rate and the secondary endpoints were differences in mean tPSA, fPSA, %fPSA and pathologic outcomes. RESULTS: A total of 1092 men (243 cancer patients) were included. Mean age was 65.8 ± 7.7 years. No differences in mean age and tPSA were found between groups A and B. Mean fPSA, %fPSA and cancer detection rate were significantly higher in group A than group B. The incidence of %fPSA <25% was significantly lower in group A than in group B. GFR <60 ml/min/1.73 m(2) , fPSA and %fPSA <25% were significant predictors for the presence of prostate cancer in patients with tPSA between 4 and 10 ng/ml. However, %fPSA <25% was not a significant predictor for group A. CONCLUSIONS: Because of the increased cancer detection rates in patients with CKD of stage ≥ 3 whose tPSA levels are 4.0-10.0 ng/ml, performing prostate biopsy should be actively considered in patients with CKD.

A retrospective study of clinical outcomes of α-blocker or finasteride monotherapy followed by combination therapy: determination of the period of combination therapy of α-blocker and finasteride.

AIMS: We investigated outcomes after discontinuing alpha-blockers or finasteride in patients who initially received combination therapy and compared differences by duration of combination therapy. METHODS: Patients with international prostate symptom score ≥ 8, serum prostatic-specific antigen (PSA) < 4 ng/ml, prostate volume > 25 cm(3) and combination therapy of alpha-blockers and finasteride for more than 6 months were classified into three groups. Group 1 continued combination therapy; group 2, alpha-blockers monotherapy; and group 3, finasteride monotherapy. All parameters were evaluated before and after changing to monotherapy. Patients who received combination therapy for 6-9 months and those who received combination therapy for longer were comparatively analysed. RESULTS: Mean age of the 106 patients was 66.9 ± 7.8 years. No significant differences in baseline symptom scores, PSA or prostate volume were found. Following combination therapy, symptom scores, and quality of life (QoL) decreased for all groups. Group 1 maintained decreased PSA and prostate volume, and improved uroflowmetric profiles. No differences in uroflowmetric parameters were found after 6 months. Group 2 maintained improved symptoms, QoL and uroflowmetric profiles, although PSA and prostate volume returned to baseline. Group 3 maintained lowered PSA and prostate volume, whereas Qmax returned to baseline. QoL scores showed no change. Patients who received combination therapy for ≥9 months improved more in symptoms and QoL than those who received shorter combination therapy. CONCLUSIONS: Discontinuation of alpha-blockers or finasteride after combination therapy for ≥ 6 months maintained improvements in symptoms. The appropriate period of combination therapy was ≥ 9 months.

METTL3-mediated downregulation of splicing factor SRSF11 is associated with carcinogenesis and poor survival of cancer patients.

OBJECTIVE: N6-methyladenosine (m6A) is one of the most abundant post-transcriptional modifications in eukaryotic RNA. As m6A modifications play an important role in RNA processing, abnormal m6A regulation caused by aberrant expression of m6A regulators is closely related to carcinogenesis. In this study, we aimed to determine the role of METTL3 expression in carcinogenesis, regulation of splicing factor expression by METTL3, and their effects in survival period and cancer-related metabolisms. MATERIALS AND METHODS: We investigated the correlation between each splicing factor and METTL3 in breast invasive ductal carcinoma (BRCA), colon adenocarcinoma (COAD), lung adenocarcinoma (LUAD) and gastric adenocarcinoma (STAD). Survival analysis was performed based on the expression of each splicing factor. To determine the molecular mechanism of SRSF11 in carcinogenesis, gene set enrichment analysis using RNA sequencing data was performed according to SRSF11 expression. RESULTS: Among the 64 splicing factors used for correlation analysis, 13 splicing factors showed a positive correlation with METTL3 in all four cancer types. We found that when METTL3 expression was decreased, the expression of SRSF11 was also decreased in all four types of cancer tissue when compared to that in normal tissue. Decreased SRSF11 expression was associated with poor survival in patients with BRCA, COAD, LUAD, and STAD. Gene set enrichment analysis according to SRSF11 expression showed that the p53/apoptosis, inflammation/immune response, and ultraviolet/reactive oxygen species stimulus-response pathways were enriched in cancers with decreased SRSF11 expression. CONCLUSIONS: These results suggest that METTL3 regulates SRSF11 expression, which could influence mRNA splicing in m6A modified cancer cells. METTL3-mediated downregulation of SRSF11 expression in cancer patients correlates with poor prognosis.

Immunological impact of Taekwondo competitions.

Immunological changes in elite adolescent female athletes during Taekwondo competitions were investigated on-field. 6 female athletes (16.7 ± 0.8 year-old) volunteered and performed 5 bouts of demonstration Taekwondo competitions simulating real tournaments in intensity, duration, and break-time intervals on the same day. Blood samples were taken before, after the competitions and during the recovery, respectively. Immunological changes and oxidative stress in peripheral blood mononuclear cells were evaluated by flow-cytometry. During the competitions, exercise intensity was 92.2 ± 3.8% (86.1~95.7) of the maximal heart rate. Blood lactate increased immediately after the competitions (p=0.0165) and decreased to baseline during recovery. Intracellular reactive oxygen species (ROS) in the peripheral blood increased continuously during recovery (p<0.05, respectively). Natural killer cells increased immediately after the competitions (p=0.0006), and decreased during recovery. B and T cells increased immediately after the competitions and remained elevated throughout recovery (p<0.05, respectively). CD4/CD8 ratio after the competitions was decreased (p=0.0091) and returned to baseline during recovery. These results suggest that the immunological function of the elite female adolescent athletes could be attenuated after Taekwondo competitions. Further large-scaled Taekwondo studies on immunologic and apoptotic changes related to oxidative stress should be performed for improving and protecting the health of adolescent athletes.

Erectile response to type 5 phosphodiesterase inhibitor could be preserved with the addition of simvastatin to conventional insulin treatment in rat model of diabetes.

Enhanced RhoA/Rho-kinase pathway plays anti-erectile role and is associated with reduced response to type 5 phosphodiesterase inhibitor (PDE5I) in diabetic animals. We tested whether adjunctive simvastatin to conventional insulin treatment would restore PDE5I-induced as well as basal erectile response in diabetic rat model of erectile dysfunction. Forty 8-week-old male Sprague-Dawley rats were equally divided into four groups, (n=10) i.e. the diabetic group (D), age-matched control (C), conventional insulin treatment (I) and adjunctive simvastatin to conventional insulin treatment (S). Following 10weeks of intraperitoneal injection of streptozotocin (STZ, 35mg/kg), the group I and S received insulin (10U NPH/day) for 4weeks. Concurrently, group S received simvastatin (20mg/kg/day). Following 14weeks of diabetes induction, basal and PDE5I (intravenous mirodenafil 1mg/kg)-elicited erectile response were assessed during cavernous nerve electrostimulation. Then, penile tissues were processed for molecular assessment. Although group I failed to restore basal and PDE5I-induced erectile response, group S showed normalized erectile responses. Furthermore, group I showed improvement of only eNOS-related pathway, whereas group S effectively controlled both eNOS-related and RhoA/Rho-kinase pathway. Conclusively, adjunctive use of simvastatin to conventional insulin treatment showed more effectiveness in restoring erectile responses of diabetic rats by controlling the RhoA/Rho-kinase pathway than conventional insulin treatment alone.