A structurally optimized FXR agonist, MET409, reduced liver fat content over 12 weeks in patients with non-alcoholic steatohepatitis.

BACKGROUND & AIMS: The benefits of farnesoid X receptor (FXR) agonists in patients with non-alcoholic steatohepatitis (NASH) have been validated, although improvements in efficacy and/or tolerability remain elusive. Herein, we aimed to assess the performance of a structurally optimized FXR agonist in patients with NASH. METHODS: In this 12-week, randomized, placebo-controlled study, we evaluated MET409 - a non-bile acid agonist with a unique chemical scaffold - in patients with NASH. Patients were randomized to receive either 80 mg (n = 20) or 50 mg (n = 19) of MET409, or placebo (n = 19). RESULTS: At Week 12, MET409 lowered liver fat content (LFC), with mean relative reductions of 55% (80 mg) and 38% (50 mg) vs. 6% in placebo (p <0.001). MET409 achieved ≥30% relative LFC reduction in 93% (80 mg) and 75% (50 mg) of patients vs. 11% in placebo (p <0.001) and normalized LFC (≤5%) in 29% (80 mg) and 31% (50 mg) of patients vs. 0% in placebo (p <0.05). An increase in alanine aminotransferase (ALT) was observed with MET409, confounding Week 12 changes from baseline (-25% for 80 mg, 28% for 50 mg). Nonetheless, MET409 achieved ≥30% relative ALT reduction in 50% (80 mg) and 31% (50 mg) of patients vs. 17% in placebo. MET409 was associated with on-target high-density lipoprotein cholesterol decreases (mean changes of -23.4% for 80 mg and -20.3% for 50 mg vs. 2.6% in placebo) and low-density lipoprotein cholesterol (LDL-C) increases (mean changes of 23.7% for 80 mg and 6.8% for 50 mg vs. -1.5% in placebo). Pruritus (mild-moderate) occurred in 16% (50 mg) and 40% (80 mg) of MET409-treated patients. CONCLUSION: MET409 lowered LFC over 12 weeks in patients with NASH and delivered a differentiated pruritus and LDL-C profile at 50 mg, providing the first clinical evidence that the risk-benefit profile of FXR agonists can be enhanced through structural optimization. LAY SUMMARY: Activation of the farnesoid X receptor (FXR) is a clinically validated approach for treating non-alcoholic steatohepatitis (NASH), although side effects such as itching or increases in low-density lipoprotein cholesterol are frequently dose-limiting. MET409, an FXR agonist with a unique chemical structure, led to significant liver fat reduction and delivered a favorable side effect profile after 12 weeks of treatment in patients with NASH. These results provide the first clinical evidence that the risk-benefit profile of FXR agonists can be enhanced.

Association between urinary urgency and falls among rural dwelling older women.

AIM: To examine the association between urinary urgency and falls in older women living in rural areas in South Korea. DESIGN: A secondary analysis was conducted using cross-sectional data. METHODS: This study used dataset obtained from 246 women aged 65 years or older living in 15 rural mountain communities in South Korea between February 2016-March 2016. Falls were measured by self-reports including the number, location, reasons of falls during the past year. Frequency of urinary urgency and nocturia were assessed by self-reports. Covariates included age, body mass index, self-reported health problems. Mixed-effects negative binomial regression was used to analyse the association between urinary urgency and the number of falls. RESULTS: The mean age of the 246 women was 77.3 years. Among the sample, 30.1% experienced at least one fall in the past year and 16% had required hospital treatments. The analysis showed that urinary urgency and osteoporosis were significantly associated with a greater number of falls after adjusting for other covariates. Among those who had experienced falls, nearly 60% reported that the reasons for falls were environmental factors, such as slippery floors or uneven sidewalks/thresholds. CONCLUSION: Improving urinary urgency may be a strategy to decrease the fall risk in older women. Accordingly, community nurses can provide intervention programs on lifestyle and behavioural changes such as bladder training, dietary modification and pelvic floor muscle training. Interventions for fall prevention need to be developed while considering the unique features of indoor and outdoor environments. IMPACT: The findings have implications for healthcare providers and policy makers with regard to the development of safer indoor and outdoor environments for older women living in rural areas by remodelling their residential spaces and neighbourhoods. In addition, more prospective studies using larger samples are needed to investigate the causal mechanism between urinary urgency and falls.

Selective estrogen receptor degraders with novel structural motifs induce regression in a tamoxifen-resistant breast cancer xenograft.

Potent estrogen receptor ligands typically contain a phenolic hydrogen-bond donor. The indazole of the selective estrogen receptor degrader (SERD) ARN-810 is believed to mimic this. Disclosed herein is the discovery of ARN-810 analogs which lack this hydrogen-bond donor. These SERDs induced tumor regression in a tamoxifen-resistant breast cancer xenograft, demonstrating that the indazole NH is not necessary for robust ER-modulation and anti-tumor activity.

Sex differences in factors associated with metabolic syndrome among Korean adults without diabetes mellitus: results from the Korea National Health and Nutrition Examination Survey from 2010 to 2013.

OBJECTIVES: The purpose of this study was to examine sex differences in factors associated with metabolic syndrome in Korean adults without diabetes mellitus. STUDY DESIGN: Cross-sectional design. METHODS: The dataset of Korea National Health and Nutrition Examination Survey from 2010 to 2013 was used. Among a total of 33552 adults aged ≥30, subjects who (i) were diagnosed or had been treated for diabetes mellitus, (ii) had a fasting blood glucose level of 126 mg/dL or higher or (iii) had a glycosylated haemoglobin level of 6.5% or higher were excluded. Subjects who had anaemia or were pregnant were also excluded. Finally, 9406 subjects were included in this study. Sex differences in subjects' characteristics were assessed with Student's t-test and chi-square test. Logistic regressions were used to examine factors associated with metabolic syndrome by sex. RESULTS: The prevalence of metabolic syndrome in Korean adults overall without diabetes mellitus was 12.2%. Glycosylated haemoglobin from 5.7 to 6.5 and increased body mass index were independently associated with metabolic syndrome in both men and women. Current smoking, age and age square were significantly associated with metabolic syndrome in men, whereas age and illiteracy were significantly associated with it in women. CONCLUSIONS: This study confirmed that glycosylated haemoglobin and body mass index can be important indicators of metabolic syndrome in Korean adults without diabetes mellitus.

Changes in Soybean (Glycine max L.) Flour Fatty-Acid Content Based on Storage Temperature and Duration.

Soybeans are low in saturated fat and a rich source of protein, dietary fiber, and isoflavone; however, their nutritional shelf life is yet to be established. This study evaluated the change in the stability and quality of fatty acids in raw and roasted soybean flour under different storage temperatures and durations. In both types of soybean flour, the fatty-acid content was the highest in the order of linoleic acid (18-carbon chain with two double bonds; C18:2), oleic acid (C18:1), palmitic acid (C16:0), linolenic acid (18:3), and stearic acid (C18:0), which represented 47%, 26%, 12%, 9%, and 4% of the total fatty-acid content, respectively. The major unsaturated fatty acids of raw soybean flour-oleic acid, linoleic acid, and linolenic acid-decreased by 30.0%, 94.4%, and 97.7%, and 38.0%, 94.8%, and 98.0% when stored in polyethylene and polypropylene film, respectively, after 48 weeks of storage under high-temperature conditions. These values were later increased due to hydrolysis. This study presents the changes in composition and content of two soybean flour types and the changes in quality and stability of fatty acids in response to storage temperature and duration. This study shows the influence of storage conditions and temperature on the nutritional quality which is least affected by packing material.

Thermochemical Analysis of Molybdenum Thin Films on Porous Alumina.

Molybdenum (Mo) thin films (thickness <100 nm) were physically deposited by e-beam evaporation on a porous alumina substrate and were analyzed for their stability and reactivity under various thermal and gas conditions. The Mo thin-film composites were stable below 300 °C but had no reactivity toward gases. Mo thin films showed nitrogen incorporation on the surface as well as in the subsurface at 450 °C, as confirmed by X-ray photoelectron spectroscopy. The reactivity toward nitrogen was diminished in the presence of CO2, although no carbon species were detected either on the surface or in the subsurface. The Mo thin films have a very stable native oxide layer, which may further oxidize to higher oxidation states above 500 °C due to the reaction with the porous anodized alumina substrate. The oxidation of Mo thin films was accelerated in the presence of oxidizing gases. At 600 °C in N2, the Mo thin film on anodized alumina was completely oxidized and may also have been volatilized. The results imply that choosing thermally stable and inactive porous supports and operating in nonoxidizing conditions below 500 °C will likely maintain the stability of the Mo composite. This study provides key information about the chemical and structural stability of a Mo thin film on a porous substrate for future membrane applications and offers further insights into the integrity of thin-film composites when exposed to harsh conditions.

Vanadium As a Potential Membrane Material for Carbon Capture: Effects of Minor Flue Gas Species.

Vanadium and its surface oxides were studied as a potential nitrogen-selective membrane material for indirect carbon capture from coal or natural gas power plants. The effects of minor flue gas components (SO2, NO, NO2, H2O, and O2) on vanadium at 500-600 °C were investigated by thermochemical exposure in combination with X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and in situ X-ray diffraction (XRD). The results showed that SO2, NO, and NO2 are unlikely to have adsorbed on the surface vanadium oxides at 600 °C after exposure for up to 10 h, although NO and NO2 may have exhibited oxidizing effects (e.g., exposure to 250 ppmv NO/N2 resulted in an 2.4 times increase in surface V2O5 compared to exposure to just N2). We hypothesize that decomposition of surface vanadium oxides and diffusion of surface oxygen into the metal bulk are both important mechanisms affecting the composition and morphology of the vanadium membrane. The results and hypothesis suggest that the carbon capture performance of the vanadium membrane can potentially be strengthened by material and process improvements such as alloying, operating temperature reduction, and flue gas treatment.

Optimization of an indazole series of selective estrogen receptor degraders: Tumor regression in a tamoxifen-resistant breast cancer xenograft.

Selective estrogen receptor degraders (SERDs) have shown promise for the treatment of ER+ breast cancer. Disclosed herein is the continued optimization of our indazole series of SERDs. Exploration of ER degradation and antagonism in vitro followed by in vivo antagonism and oral exposure culminated in the discovery of indazoles 47 and 56, which induce tumor regression in a tamoxifen-resistant breast cancer xenograft.

Agreement between the spatio-temporal gait parameters from treadmill-based photoelectric cell and the instrumented treadmill system in healthy young adults and stroke patients.

BACKGROUND: Treadmill gait analysis was more advantageous than over-ground walking because it allowed continuous measurements of the gait parameters. The purpose of this study was to investigate the concurrent validity and the test-retest reliability of the OPTOGait photoelectric cell system against the treadmill-based gait analysis system by assessing spatio-temporal gait parameters. MATERIAL AND METHODS: Twenty-six stroke patients and 18 healthy adults were asked to walk on the treadmill at their preferred speed. The concurrent validity was assessed by comparing data obtained from the 2 systems, and the test-retest reliability was determined by comparing data obtained from the 1st and the 2nd session of the OPTOGait system. RESULTS: The concurrent validity, identified by the intra-class correlation coefficients (ICC [2, 1]), coefficients of variation (CVME), and 95% limits of agreement (LOA) for the spatial-temporal gait parameters, were excellent but the temporal parameters expressed as a percentage of the gait cycle were poor. The test-retest reliability of the OPTOGait System, identified by ICC (3, 1), CVME, 95% LOA, standard error of measurement (SEM), and minimum detectable change (MDC95%) for the spatio-temporal gait parameters, was high. CONCLUSIONS: These findings indicated that the treadmill-based OPTOGait System had strong concurrent validity and test-retest reliability. This portable system could be useful for clinical assessments.

Asymmetric training using virtual reality reflection equipment and the enhancement of upper limb function in stroke patients: a randomized controlled trial.

BACKGROUND: Asymmetric movements with both hands contributed to the improvement of spatially coupled motion. Thus, the aim of this study was to investigate the effects of an asymmetric training program using virtual reality reflection equipment on upper limb function in stroke patients. METHODS: Twenty-four stroke patients were randomly allocated to an experimental group (n=12) or a control group (n=12). Both groups participated in conventional physical therapy for 2×30 min/d, 5 d/wk, for 4 weeks. The experimental group also participated in an asymmetric training program using virtual reality reflection equipment, and the control group participated in a symmetric training program. Both asymmetric and symmetric programs were conducted for 30 min/d, 5 d/wk, for 4 weeks. To compare upper limb function before and after intervention, the Fugl-Meyer Assessment (FMA), the Box and Block Test (BBT), grip strength, range of motion (ROM), and spasticity were assessed. RESULTS: Both groups showed significant increases in upper limb function, excepting spasticity, after intervention (P<.05, 1-way repeated-measures analysis of variance [ANOVA]). A significant group-time interaction was demonstrated only for shoulder/elbow/wrist items of FMA, BBT, grip strength, and ROM of wrist flexion, extension, and ulnar deviation (P<.05, 2-way repeated-measures ANOVA). CONCLUSIONS: This study confirms that the asymmetric training program using virtual reality reflection equipment is an effective intervention method for improving upper limb function in stroke patients. We consider that an additional study based on a program using virtual reflection, which is more functional than performing simple tasks, and consisting of tasks relevant to the activities of daily living be conducted.

Effect of Fluid and Caffeine Management on Quality of Life in Older Women with Overactive Bladder in Rural Korea: A Pilot Study.

Purpose: This study aimed to investigate the effectiveness of the simplified intervention, consisting of fluid and caffeine management alone in older women with overactive bladder symptoms. Patients and Methods: A quasi-experimental pretest-posttest design was used. Rural, community-dwelling older women were recruited at four senior centers in South Korea. Of the 63 participants initially enrolled, 34 met the inclusion criteria. One group (n = 15) used fluid and caffeine management alone (FM), and the other group (n = 12) used a combination of fluid and caffeine management and pelvic floor muscle training (FM+PFMT). Urinary symptom-specific health-related quality of life was measured using the Korean version of KHQ. Sleep quality was measured using the Pittsburgh Sleep Quality Index. After the intervention, participants were assessed 4 and 8 weeks. A linear mixed model was used for the analysis. Results: The mean age of the participants was 74.44 ± 5.67 years. Among the nine domains of KHQ, impact on life and physical limitations decreased significantly in both groups, without significant between-group differences. Sleep/energy increased in both groups, and the scores in the FM+PFMT group were significantly improved. The number of micturition episodes per day and the quality of sleep did not differ significantly between the two groups. Conclusion: A simplified intervention, consisting of fluid and caffeine management alone can be considered as the first-line intervention to improve health-related quality of life in rural, community-dwelling, older women with overactive bladder symptoms. Healthcare providers should consider providing a relatively simple, but equally effective intervention to maximize the adherence and effectiveness.

Effectiveness of a Nurse-Led Mobile-Based Health Coaching Program for Patients With Prostate Cancer at High Risk of Metabolic Syndrome: Randomized Waitlist Controlled Trial.

BACKGROUND: Androgen deprivation therapy (ADT), a standard treatment for prostate cancer (PC), causes many physical side effects. In particular, it causes metabolic changes such as fasting glucose abnormalities or accumulation of body fat, and its continuation can lead to metabolic syndrome (MetS), which is closely related to diabetes and cardiovascular disease. Therefore, it is important to maintain and practice a healthy lifestyle in patients with PC. OBJECTIVE: This study aims to evaluate the effectiveness of a nurse-led mobile-based program that aims to promote a healthy lifestyle in patients with PC undergoing ADT with MetS risk factors. METHODS: This was a single-blind, randomized, waitlist control interventional study. A total of 48 patients were randomly assigned to the experimental and waitlist control groups at the urology cancer clinic of a tertiary general hospital in South Korea. The inclusion criteria were patients who had undergone ADT for >6 months, had at least 1 of the 5 MetS components in the abnormal range, and could access a mobile-based education program. The experimental group attended a 4-week mobile-based program on exercise and diet that included counseling and encouragement to maintain a healthy lifestyle, whereas the control group was placed on a waitlist and received usual care during the follow-up period, followed by the intervention. The primary outcome was a change in the lifestyle score. The secondary outcomes were changes in 5 MetS components, body composition, and health-related quality of life. The outcomes were measured at 6 weeks and 12 weeks after the initiation of the intervention. Each participant was assigned to each group in a sequential order of enrollment in a 4×4 permuted block design randomization table generated in the SAS (SAS Institute) statistical program. A linear mixed model was used for statistical analysis. RESULTS: A total of 24 participants were randomly assigned to each group; however, 2 participants in the experimental group dropped out for personal reasons before starting the intervention. Finally, 46 participants were included in the intention-to-treat analysis. The experimental group showed more positive changes in the healthy lifestyle score (ß=29.23; P≤.001), level of each MetS component (fasting blood sugar: ß=-12.0; P=.05 and abdominal circumference: ß=-2.49; P=.049), body composition (body weight: ß=-1.52; P<.001 and BMI: ß=-0.55; P<.001), and the urinary irritative and obstructive domain of health-related quality of life (ß=14.63; P<.001) over time than the waitlist control group. CONCLUSIONS: Lifestyle changes through nurse-led education can improve level of each MetS components, body composition, and ADT side effects. Nurses can induce positive changes in patients' lifestyles and improve the self-management of patients starting ADT through this program. TRIAL REGISTRATION: Clinical Research Information Service KCT0006560; http://tinyurl.com/yhvj4vwh.

Identification of mCMQ069, a novel antimalarial with potential for a single-dose cure and/or 28-day chemoprevention.

In efforts towards eliminating malaria, a discovery program was initiated to identify a novel antimalarial using KAF156 as a starting point. Following the most recent TCP/TPP guidelines, we have identified mCMQ069 with a predicted single oral dose for treatment (∼40-106 mg) and one-month chemoprevention (∼96-216 mg). We have improved unbound MPC and predicted human clearance by 18-fold and 10-fold respectively when compared to KAF156.

Whole-body vibration training improves balance, muscle strength and glycosylated hemoglobin in elderly patients with diabetic neuropathy.

Elderly patients with diabetes and peripheral neuropathy are more likely to experience falls. However, the information available on how such falls can be prevented is scarce. We investigated the effects of whole-body vibration (WBV) combined with a balance exercise program on balance, muscle strength, and glycosylated hemoglobin (HbA1c) in elderly patients with diabetic peripheral neuropathy. Fifty-five elderly patients with diabetic neuropathy were randomly assigned to WBV with balance exercise group, balance exercise (BE) group, and control group. The WBV and BE groups performed the balance exercise program for 60 min per day, 2 times per week, for 6 weeks. Further, the WBV group performed WBV training (up to 3 × 3 min, 3 times per week, for 6 weeks). The control group did not participate in any training. The main outcome measures were assessed at baseline and after 6 weeks of training; namely, we assessed the postural sway and one leg stance (OLS) for static balance; Berg balance scale (BBS), timed up-and-go (TUG) test, and functional reach test (FRT) for dynamic balance; five-times-sit-to-stand (FTSTS) test for muscle strength; and HbA1c for predicting the progression of diabetes. Significant improvements were noted in the static balance, dynamic balance, muscle strength, and HbA1c in the WBV group, compared to the BE and control groups (P < 0.05). Thus, in combination with the balance exercise program, the short-term WBV therapy is beneficial in improving balance, muscle strength and HbA1c, in elderly patients with diabetic neuropathy who are at high risk for suffering falls.

New machine learning-based automatic high-throughput video tracking system for assessing water toxicity using Daphnia Magna locomotory responses.

Daphnia magna is an important organism in ecotoxicity studies because it is sensitive to toxic substances and easy to culture in laboratory conditions. Its locomotory responses as a biomarker are highlighted in many studies. Over the last several years, multiple high-throughput video tracking systems have been developed to measure the locomotory responses of Daphnia magna. These high-throughput systems, used for high-speed analysis of multiple organisms, are essential for efficiently testing ecotoxicity. However, existing systems are lacking in speed and accuracy. Specifically, speed is affected in the biomarker detection stage. This study aimed to develop a faster and better high-throughput video tracking system using machine learning methods. The video tracking system consisted of a constant temperature module, natural pseudo-light, multi-flow cell, and an imaging camera for recording videos. To measure Daphnia magna movements, we developed a tracking algorithm for automatic background subtraction using k-means clustering, Daphnia classification using machine learning methods (random forest and support vector machine), and tracking each Daphnia magna location using the simple online real-time tracking algorithm. The proposed tracking system with random forest performed the best in terms of identification (ID) precision, ID recall, ID F1 measure, and ID switches, with scores of 79.64%, 80.63%, 78.73%, and 16, respectively. Moreover, it was faster than existing tracking systems such as Lolitrack and Ctrax. We conducted an experiment to observe the impact of toxicants on behavioral responses. Toxicity was measured manually in the laboratory and automatically using the high-throughput video tracking system. The median effective concentration of Potassium dichromate measured in the laboratory and using the device was 1.519 and 1.414, respectively. Both measurements conformed to the guideline provided by the Environmental Protection Agency of the United States; therefore, our method can be used for water quality monitoring. Finally, we observed Daphnia magna behavioral responses in different concentrations after 0, 12, 18, and 24 h and found that there was a difference in movement according to the concentration at all hours.

Antiangiogenic and antitumor activity of LP-261, a novel oral tubulin binding agent, alone and in combination with bevacizumab.

LP-261 is a novel tubulin targeting anticancer agent that binds at the colchicine site on tubulin, inducing G2/M arrest. Screening in the NCI60 cancer cell lines resulted in a mean GI50 of approximately 100 nM. Here, we report the results of testing in multiple mouse xenograft models and angiogenesis assays, along with bioavailability studies. To determine the antiangiogenic activity of LP-261, both in vitro and ex vivo experiments were performed. Human umbilical vein endothelial cells (HUVECs) were incubated with LP-261 at 50 nM to 10 µM. LP-261 was also tested in a rat aortic ring assay, from 20 nM to 10 µM. Multiple mouse xenograft studies were performed to assess in vivo antitumor activity. LP-261 was tested as a single agent in colon adenocarcinoma (SW620) and prostate cancer (LNCaP and PC3) xenografts, evaluating several different dosing schedules. LP-261 was also used in combination with bevacizumab in the SW620 xenograft model. LP-261 also exhibited high oral bioavailability and apparent lack of efflux by intestinal transporters such as ABCB1. LP-261 is a very potent inhibitor of angiogenesis, preventing microvessel outgrowth in the rat aortic ring assay and HUVEC cell proliferation at nanomolar concentrations. Complete inhibition of tumor growth was achieved in the PC3 xenograft model and shown to be schedule dependent. Excellent inhibition of tumor growth in the SW620 model was observed, comparable with paclitaxel. Combining oral, low dose LP-261 with bevacizumab led to significantly improved tumor inhibition. Oral LP-261 is very effective at inhibiting tumor growth in multiple mouse xenograft models and is well tolerated.

Effectiveness of behavioral sleep interventions on children's and mothers' sleep quality and maternal depression: a systematic review and meta-analysis.

This systematic review and meta-analysis was conducted to investigate the effectiveness of behavioral sleep interventions (BSIs) on the number of child night awakenings, and maternal sleep quality and depression. The search followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA) using PubMed, CINAHL, Cochrane, and EMBASE databases and retrieved studies published until April 2021. We calculated the odds ratios (ORs) and 95% confidence intervals (CIs) for child sleep problems, and the mean differences (MD) and 95% CI for the number of child night awakenings, and maternal sleep quality and depression. Ten studies of 1628 initial searched were included in the final analysis. Two of the 10 studies were divided into two subgroups by participants and intervention type; thus, 12 subgroups were included in the meta-analysis. BSIs significantly reduced child sleep problems (OR 0.51; 95% CI 0.37-0.69) and improved maternal sleep quality (MD - 1.30; 95% CI - 1.82 to - 0.77) in the intervention group. There were no significant differences in the number of child night awakenings and maternal depression between the two groups. More RCTs to examine the effect of BSIs considering children's age, duration of intervention, and outcome measuring time points are needed.

Quality of life patterns and its association with predictors among non-muscle invasive bladder cancer survivors: A latent profile analysis.

Objective: This study identified group patterns in the quality of life (QOL), as well as examining factors associated with group membership, among non-muscle invasive bladder cancer (NMIBC) survivors. Methods: This was a cross-sectional study involving 278 participating NMIBC survivors. Mplus version 7.2 was used to perform the latent profile analysis of QOL using the EORTC QLQ-NMIBC-24. The participants' social support, self-efficacy, knowledge level, depression, perceived severity of and susceptibility of cancer recurrence, and their demographic and clinical characteristics were compared between the subgroups, with a logistic regression analysis being adopted to examine the factors associated with the QOL subgroups. Results: The NMIBC survivors based on the QOL were classified into two subgroups: "QOL-high" (81.3%) and "QOL-low" (18.7%). Having ≥ 3 disease recurrences, perceived susceptibility toward and severity of cancer recurrence, and having depressive symptoms were significantly associated with the "QOL-low" group. Conclusions: Participants with frequent recurrences of NMIBC, higher perceived susceptibility and severity levels, and depressive symptoms had lower QOL. Therefore, it is necessary to develop intervention programs targeting participants with these characteristics to improve their QOL.

Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD).

Discovery of a new class of DFG-out p38α kinase inhibitors with no hinge interaction is described. A computationally assisted, virtual fragment-based drug design (vFBDD) platform was utilized to identify novel non-aromatic fragments which make productive hydrogen bond interactions with Arg 70 on the αC-helix. Molecules incorporating these fragments were found to be potent inhibitors of p38 kinase. X-ray co-crystal structures confirmed the predicted binding modes. A lead compound was identified as a potent (p38α IC(50)=22 nM) and highly selective (≥ 150-fold against 150 kinase panel) DFG-out p38 kinase inhibitor.

Factors Associated with Subsequent Childbirth between Marriage Years in Korea.

This study aimed to identify differences in factors associated with subsequent childbirth between the marriage years of 1996-2005 (Group 1) and 2006-2015 (Group 2) using the 2015 National Survey. A total of 5097 eligible participants (2492 and 2605 women in each group, respectively) were included. The main variables consisted of demographic characteristics, socio-economic status, value for child and son, and social support for raising child. For statistical analysis, discrete-time hazard models were used. The common factors associated with subsequent childbirth in both groups were son preference (Group 1: HR = 1.16; 95% CI = 1.06-1.27, Group 2: HR = 1.14; 95% CI = 1.04-1.24) and the favorable value on children (HR = 1.12; 95% CI = 1.01-1.25, HR = 1.11; 95% CI = 1.01-1.22). Only in Group 2, age at the first childbirth (HR = 1.35; 95% CI = 1.31-1.39) and more monthly income (≥4600, <6000: HR = 1.18; 95% CI = 1.04-1.33, ≥6000: HR = 1.15; 95% CI = 1.00-1.32) were significantly associated with subsequent children. Whereas, working women (HR = 0.86; 95% CI = 0.78-0.94) were less likely to have subsequent children. To increase fertility in Korea, the government must provide childcare and deal with factors associated with low fertility considering the reduction in role incomparability for women due to changes in demographic characteristics.