Search

Genomic alterations in tumors play a pivotal role in determining their clinical trajectory and responsiveness to treatment. Targeted panel sequencing (TPS) has served as a key clinical tool over the past decade, but advancements in sequencing costs and bioinformatics have now made whole-genome sequencing (WGS) a feasible single-assay approach for almost all cancer genomes in clinical settings. This paper reports on the findings of a prospective, single-center study exploring the real-world clinical utility of WGS (tumor and matched normal tissues) and has two primary objectives: (1) assessing actionability for therapeutic options and (2) providing clarity for clinical questions. Of the 120 patients with various solid cancers who were enrolled, 95 (79%) successfully received genomic reports within a median of 11 working days from sampling to reporting. Analysis of these 95 WGS reports revealed that 72% (68/95) yielded clinically relevant insights, with 69% (55/79) pertaining to therapeutic actionability and 81% (13/16) pertaining to clinical clarity. These benefits include the selection of informed therapeutics and/or active clinical trials based on the identification of driver mutations, tumor mutational burden (TMB) and mutational signatures, pathogenic germline variants that warrant genetic counseling, and information helpful for inferring cancer origin. Our findings highlight the potential of WGS as a comprehensive tool in precision oncology and suggests that it should be integrated into routine clinical practice to provide a complete image of the genomic landscape to enable tailored cancer management., (© 2024. The Author(s).)

Self-powered electrical bandages (SEBs), integrated with wearable energy harvesters, can provide an effective and autonomous electrical stimulation (ES) solution for rapid and scarless wound healing. A continuously operating, wireless, and applicable-to-comprehensive-wound ES device is essential for the quick restoration of wounds and convenience. This work illustrates a SEB powered by body-coupled energy harvesting. The SEB continuously treats the wound with 60-Hz sinusoidal electrical potential gained from the coupling of the human body and ambient electrical waves. It is demonstrated that enough level of electrical potential can be applied to the wound, further enhanced by strong capacitive coupling arising from the use of high-permittivity poly(vinylidene fluoride-trifluoroethylene):CaCu 3 Ti 4 O 12 (P(VDF-TrFE):CCTO) nanocomposite. The potential clinical efficacy of the SEB is illustrated by preclinical analysis of human fibroblasts and mouse wound model, thus confirming the successful expedition of wound recovery. This work suggests a new class of wearable devices to provide ES events and its potential for extension to other conventional wound care materials and device technology., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Background: Many people struggle with the choice in a series of processes, from prostate cancer (PCa) diagnosis to treatment. We investigated the degree of regret after the prostate biopsy (PBx) and relevant factors in patients recommended for biopsy for suspected PCa., Methods: From 06/2020 to 05/2022, 198 people who performed PBx at three institutions were enrolled and analyzed through a questionnaire before and after biopsy. Before the biopsy, a questionnaire was conducted to evaluate the sociodemographic information, anxiety scale, and health literacy, and after PBx, another questionnaire was conducted to evaluate the decision regret scale. For patients diagnosed as PCa after biopsy, a questionnaire was conducted when additional tests were performed at PCa staging work-up., Results: 190 patients answered the questionnaire before and after PBx. The mean age was 66.2 ± 7.8 years. Overall, 5.5% of men regretted biopsy, but there was no significant difference between groups according to the PCa presence. Multivariate analysis, to identify predictors for regret, revealed that the case when physicians did not properly explain what the prostate-specific antigen (PSA) test was like and what PSA elevation means (OR 20.57, [95% CI 2.45-172.70], p = 0.005), low media literacy (OR 10.01, [95% CI 1.09-92.29], p = 0.042), and when nobody to rely on (OR 8.49, [95% CI 1.66-43.34], p = 0.010) were significantly related., Conclusions: Overall regret related to PBx was low. Decision regret was more significantly related to media literacy rather than to educational level. For patients with relatively low media literacy and fewer people to rely on in case of serious diseases, more careful attention and counseling on PBx, including a well-informed explanation on PSA test, is helpful., (© 2024. The Author(s).)

Background: The DAPA-HF and DELIVER trials demonstrated the clinical benefits of dapagliflozin in heart failure (HF) patients across the entire ejection fraction (EF) spectrum. However, further investigation is needed for the real-world application of dapagliflozin in HF patients. This study examines the proportion of real-world HF patients eligible for dapagliflozin and evaluates the cost-effectiveness of adding dapagliflozin to current HF therapy., Methods: Data from the nationwide prospective registry, the Korean Acute Heart Failure (KorAHF) registry, were used to determine dapagliflozin eligibility based on the enrollment criteria of the DAPA-HF/DELIVER trials. A cost-utility analysis was conducted using a Markov model to assess the cost-effectiveness of dapagliflozin by comparing it to the standard of care., Results: Out of 5178 KorAHF patients, 48.7% met the enrollment criteria of the DAPA-HF/DELIVER trials, while 89.5% met the label criteria (US Food and Drug Administration, European Medicines Agency, and Korean Ministry of Food and Drug Safety). Eligibility was highest among HF patients with preserved EF (55.3% vs. HF with mildly reduced EF and HF with reduced EF 46.4%). Dapagliflozin proved to be cost-effective, with an incremental cost-effectiveness ratio (ICER) of 4557 US dollar (US$) per quality-adjusted life year, which falls below the US$18,182 willingness-to-pay threshold. The cost-effectiveness benefit was more pronounced in patients with a left ventricular EF (LVEF) ≤ 40% (ICER US$3279 for LVEF ≤ 40% vs. US$8383 for LVEF > 40%)., Conclusions: Discrepancies in dapagliflozin eligibility were observed between real-world data and clinical trial results. The addition of dapagliflozin to HF therapy proved to be highly cost-effective across the entire EF spectrum., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Glycosylation is a crucial attribute for biotherapeutics with significant impacts on quality, stability, safety, immunogenicity, pharmacokinetics, and efficacy. Therefore, to ensure consistent glycosylation, a systematic review of biotherapeutics is absolutely required including the variable glycan structure (micro-heterogeneity) and different occupancy at individual site (macro-heterogeneity) from drug design to upstream and downstream bioprocesses. Various methods have been used for glyco-characterization of biotherapeutics at the glycan, glycopeptide, and intact protein levels. In particular, intact protein analysis is considered a facile and rapid glycoform monitoring approach used throughout the product development lifecycle to determine suitable glycosylation lead candidates and reproducible product quality. However, intact glycoform characterization of diverse and complex biotherapeutics with multiple N- and O-glycosylation sites can be very challenging. To address this, a robust analytical platform that enables rapid and accurate characterization of a biotherapeutics with highly complex multiple glycosylation using two-step intact glycoform mass spectrometry has been developed. We used darbepoetin alfa, a second-generation EPO bearing multiple N- and O-glycosylation sites, as a model biotherapeutics to obtain integrated information on glycan heterogeneity and site occupancy through step-by-step MS of intact protein and enzyme-treated protein. In addition, we performed a comparative assessment of the heterogeneity from different products, confirming that our new method can efficiently evaluate glycosylation equivalence. This new strategy provides rapid and accurate information on the degree of glycosylation of a therapeutic glycoprotein with multiple glycosylation, which can be used to assess glycosylation similarity between batches and between biosimilar and reference during development and production., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This article provides evidence-based recommendations and expert opinions to aid urologists in making optimal decisions regarding managing urolithiasis in various clinical scenarios. The most frequently asked questions by urologists in their clinical practice have been collected and answered in the form of FAQs; based on the latest evidence and expert opinions. The natural history of urolithiasis is divided into active treatment and silent phases, with the active treatment stage divided into typical and special situations and peri-treatment management. The authors address 28 key questions, offering practical guidance for the proper diagnosis, treatment, and prevention of urolithiasis in clinical practice. This article is expected to be served as a valuable resource for urologists., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

Implantable medical devices (IMDs) provide practical approaches to monitor physiological parameters, diagnose diseases, and aid treatment. However, device installation, maintenance, and long-term implantation increase the risk of infection with conventional IMDs. Therefore, medical devices with biocompatibility, controllability, and miniaturization are highly demandable. An ultrasound-driven, biodegradable, and injectable triboelectric nanogenerator (I-TENG) is demonstrated to reduce the risks of implant-related injuries and infections. The injection can be given by subcutaneous injection with a needle to minimize the implantation incision. The stable output of I-TENG is driven by ultrasound (20 kHz, 1 W cm -2 ), with a voltage of 356.8 mV and current of 1.02 µA during in vivo studies and an electric field of about 0.92 V mm -1 during ex vivo experiments. The cell scratch and proliferation assays showed that the delivered electric field effectively increased cell migration and proliferation, indicating a significant potential to accelerate healing with electricity., (© 2023 Wiley-VCH GmbH.)

Repetitive transcranial magnetic stimulation (rTMS) is attracting attention as a new treatment technique for brain lesions, and many animal studies showing its effects have been reported. However, the findings of animal application researches cannot directly represent the effects of rTMS in human, mainly due to size difference and mechanistic characteristics of rTMS. Therefore, the authors purposed to develop a mouse rTMS to simulate clinical application and to confirm. Firstly, a virtual head model was created according to magnetic resonance images of murine head. Then, simulations of rTMS stimulation with different coils were performed on the murine head phantom, and an rTMS device for mice was fabricated based on the optimal voltage conditions. Lastly, strengths of magnetic fields generated by the two rTMS devices, for human (conventional clinical use) and mouse (newly fabricated), were measured in air and on mouse head and compared. Resultantly, the magnetic field intensity generated by coil of mouse was lower than human's (p < 0.01), and no differences were found between the predicted simulation values and the measured intensity in vivo (p > 0.05). Further in vivo researches using miniaturized rTMS devices for murine head should be followed to be more meaningful for human., (© 2023. The Author(s).)

Hereditary muscle diseases are disabling disorders lacking effective treatments. UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE) myopathy (GNEM) is an autosomal recessive distal myopathy with rimmed vacuoles typically manifesting in late adolescence/early adulthood. GNE encodes the rate-limiting enzyme in sialic acid biosynthesis, which is necessary for the proper function of numerous biological processes. Outside of the causative gene, very little is known about the mechanisms contributing to the development of GNE myopathy. In the present study, we aimed to address this knowledge gap by querying the underlying mechanisms of GNE myopathy using a patient-derived induced pluripotent stem-cell (iPSC) model. Control and patient-specific iPSCs were differentiated down a skeletal muscle lineage, whereby patient-derived GNEM iPSC clones were able to recapitulate key characteristics of the human pathology and further demonstrated defects in myogenic progression. Single-cell RNA sequencing time course studies revealed clear differences between control and GNEM iPSC-derived muscle precursor cells (iMPCs), while pathway studies implicated altered stress and autophagy signaling in GNEM iMPCs. Treatment of GNEM patient-derived iMPCs with an autophagy activator improved myogenic differentiation. In summary, we report an in vitro, iPSC-based model of GNE myopathy and implicate defective myogenesis as a contributing mechanism to the etiology of GNE myopathy., (© 2022. The Author(s).)

Background: Prognostic nutritional index (PNI) is a simple parameter which reflects patient's nutritional and inflammatory status and reported as a prognostic factor for renal cell carcinoma (RCC). Studies were included from database inception until February 2, 2022. The aim of this study is to evaluate prognostic value of PNI by meta-analysis of the diagnostic test accuracy in RCC., Methods and Findings: Studies were retrieved from PubMed, Cochrane, and EMBASE databases and assessed sensitivity, specificity, summary receiver operating characteristic curve (SROC) and area under curve (AUC). Totally, we identified 11 studies with a total of 7,296 patients were included to evaluate the prognostic value of PNI in RCC finally. They indicated a pooled sensitivity of 0.733 (95% CI, 0.651-0.802), specificity of 0.615 (95% CI, 0.528-0.695), diagnostic odds ratio (DOR) of 4.382 (95% CI, 3.148-6.101) and AUC of 0.72 (95% CI, 0.68-0.76). Heterogeneity was significant and univariate meta-regression revealed that metastasis and cut-off value of PNI might be the potential source of heterogeneity. Multivariate meta-regression analysis also demonstrated that metastasis might be the source of heterogeneity., Conclusions: PNI demonstrated a good diagnostic accuracy as a prognostic factor for RCC and especially in case of metastatic RCC., Competing Interests: The authors have declared that no competing interests exist.

Abstract: Sepsis is a highly prevalent cause of death in intensive care units. Characterized by severe immune cell derangements, sepsis is often associated with multiorgan dysfunction. For many sepsis survivors, these deficits can persist long after clinical resolution of the underlying infection. Although many studies report on the impact of sepsis on individual immune cell subtypes, a comprehensive analysis of sepsis-induced alterations within and across the immune cell landscape is lacking. In this study, we used single-cell RNA sequencing to assess sepsis-associated transcriptional changes in immune cells isolated from bone marrow at single-cell resolution. We used a high-survival fecal-induced peritonitis sepsis model using Friend leukemia virus B mice. Single-cell RNA sequencing classified 3402 single cells from control subjects into 14 clusters representing long-term hematopoietic stem cell (HSC), short-term HSC, basophil, dendritic cell, eosinophil, erythroblast, erythrocyte, macrophage, neutrophil, natural killer cell, plasma cell, plasmacytoid dendritic cell, pre-B cell, and T memory cell lineages. One day following experimentally induced sepsis, cell type compositions shifted significantly and included notable decreases in HSC and myeloid cell abundance. In addition to proportional cell composition changes, acute sepsis induced significant transcriptional alterations in most immune cell types analyzed-changes that failed to completely resolve 1 month after sepsis. Taken together, we report widespread and persistent transcriptional changes in diverse immune cells in response to polymicrobial infection. This study will serve as a valuable resource for future work investigating acute and/or long-term sepsis-associated immune cell derangements., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by the Shock Society.)

Introduction: To evaluate the prognostic value of albumin-to-alkaline phosphatase ratio (AAPR) on recurrence and survival in patients with non-metastatic renal cell carcinoma (RCC) treated with radical or partial nephrectomy., Patients and Methods: Between June 1994 and December 2018, 491 patients with RCC who underwent radical or partial nephrectomy at 2 institutions were enrolled in this study. Recurrence-free survival (RFS) and cancer-specific survival (CSS) analyses were performed to distinguish the differences in postoperative recurrence and survival between patients stratified by an optimal cut-off value of AAPR. Multivariable Cox proportional hazards regression models were established to determine the independent prognostic factors after propensity score weighting., Results: Of the total 491 patients, 51 patients (10.4%) developed local recurrence or distant metastasis and 26 patients (5.3%) died of disease during the follow-up period. Patients with AAPR<0.41 had significantly lower rates of RFS and CSS than those of patients with AAPR≥0.41 in multivariate analysis (P < .001 and P = .027, respectively). After propensity scroe matching analyses, this difference was still remained for RFS (P < .001). However, AAPR was not an independent prognostic factor for CSS but the value was almost pregnant (HR = 2.674; 95%CI = 0.872-8.203; P = .086)., Conclusion: AAPR can serve as a novel and useful tool to refine prognosis in patients with non-metastatic RCC treated with partial or radical nephrectomy. These findings suggest that AAPR could be a promising prognostic factor for prediction of recurrence and survival in patients with non-metastatic RCC who undergo nephrectomy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Approximately 80% of pancreatic cancer patients suffer from cachexia, and one-third die due to cachexia-related complications such as respiratory failure and cardiac arrest. Although there has been considerable research into cachexia mechanisms and interventions, there are, to date, no FDA-approved therapies. A major contributing factor for the lack of therapy options could be the failure of animal models to accurately recapitulate the human condition. In this study, we generated an aged model of pancreatic cancer cachexia to compare cachexia progression in young versus aged tumor-bearing mice. Comparative skeletal muscle transcriptome analyses identified 3-methyladenine (3-MA) as a candidate antiwasting compound. In vitro analyses confirmed antiwasting capacity, while in vivo analysis revealed potent antitumor effects. Transcriptome analyses of 3-MA-treated tumor cells implicated Perp as a 3-MA target gene. We subsequently (a) observed significantly higher expression of Perp in cancer cell lines compared with control cells, (b) noted a survival disadvantage associated with elevated Perp, and (c) found that 3-MA-associated Perp reduction inhibited tumor cell growth. Finally, we have provided in vivo evidence that survival benefits conferred by 3-MA administration are independent of its effect on tumor progression. Taken together, we report a mechanism linking 3-MA to Perp inhibition, and we further implicate Perp as a tumor-promoting factor in pancreatic cancer.

Purpose: To perform a systematic review and meta-analysis of the Prognostic Nutritional Index (PNI) as a prognostic factor for renal cell carcinoma (RCC)., Materials and Methods: Eligible studies that evaluated the prognostic impact of pretreatment PNI in RCC patients were identified by comprehensive searching the electronic databases PubMed, Cochrane Central Search library, and EMBASE. The end points were overall/cancer-specific survival (OS/CSS) and recurrence-free/disease-free survival (RFS/DFS). Meta-analysis using random-effects models was performed to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs)., Results: In total, 9 retrospective, observational, case-control studies involving 5,976 patients were included for final analysis. Eight studies evaluated OS/CSS, and 5 evaluated RFS/DFS. Our results showed that lower PNI was significantly associated with unfavorable OS/CSS (HR = 1.68, 95% CI 1.44-1.96, P < 0.001, I 2  = 9.2%, P = 0.359) and RFS/DFS (HR = 1.98, 95% CI 1.57-2.50, P < 0.001, I 2  = 18.2%, P = 0.299) in patients with RCC. Subgroup and meta-regression analysis based on ethnicity, study sample size, presence of metastasis, PNI cut-off value, Newcastle-Ottawa quality assessment scale (NOS) score, and gender ratio all showed that lower PNI was associated with poorer OS/CSS and RFS/DFS. Funnel plots and Egger's tests indicated significant publication bias in OS/CSS (P = 0.001), but not in RFS/DFS (P = 0.757)., Conclusion: This meta-analysis indicated that lower PNI was a negative prognostic factor and associated with tumor progression and poorer survival of patients with RCC. Therefore, PNI could be a potential prognostic predictor of treatment outcomes for patients with RCC., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Previous studies on repetitive transcranial magnetic stimulation (rTMS) suggested potential neurorestorative properties in Alzheimer's disease (AD). This study aimed to investigate therapeutic effects of rTMS on an AD mouse model at high and low frequencies. The subject mice were allocated into the AD model group (AD induced by intracerebroventricular amyloid beta 42 oligomer [Aβ42] injection) and the saline-injected control group. Each group was subdivided according to rTMS treatment: high frequency (20 Hz), low frequency (1 Hz), and not rTMS-treated. Behavioural assessments with Y-maze test and novel object recognition task were performed; the results indicated cognition recovery by both the frequencies of rTMS after treatment in the AD model (Ps < 0.01). Tendency of further effects by high frequency compared to low frequency rTMS was also shown in Y-maze test. Neurotransmitter assay showed increment in dopamine concentration and upregulation of dopamine-receptor 4 (DR4) by rTMS in AD mice with higher response by high frequency stimulation (Ps < 0.05). Only high-frequency rTMS induced an elevation of brain-derived neurotrophic factor (BDNF) levels and enhanced the expression of Nestin and NeuN in the brain tissue (Ps < 0.05). Under in vitro conditions, Aβ42 incubated mouse hippocampal cell showed an increase in dopamine levels and BDNF by application of high-frequency rTMS treatment. In conclusion, rTMS might have a potential therapeutic effect on AD, and it seems to be related with dopaminergic activation. High frequency of stimulation seems to induce higher efficacy than that induced by low frequency, with elevated expressions of DR4 gene and neurogenic proteins.

Purpose: To analyze the potential surgical factors affecting postoperative urinary continence, including postoperative membranous urethral length (MUL), in an era where open radical prostatectomy (ORP) and robot-assisted radical prostatectomy (RARP) coexist., Methods: Consecutive patients undergoing either ORP or RARP between April 2009 and June 2017 were included in this study. Pericatheter urethrography (PCU) was performed the day of catheter removal to confirm healing of the vesicourethral anastomosis and to measure PCU-MUL. Daily usage of incontinence pad was self-reported by the patient at each post-operative visit through a questionnaire. Univariate and multivariate analyses were performed to identify factors that influenced recovery of continence., Results: Of the 196 patients included, 121 and 75 patients received ORP and RARP, respectively. The cumulative full continence rates (0 pad/day) at 1 year in the ORP and RARP groups were 87% and 95%, respectively. In the univariate analysis, older age, high preoperative International Prostate Symptom Score (IPSS) irritative symptom domain, ORP, poorer NVB preservation, and shorter PCU-MUL were associated with delayed recovery of full continence. In the multivariate analysis, only older age, high preoperative IPSS irritative symptom domain, and shorter PCU-MUL remained as independent factors significantly associated with delayed recovery of full continence., Conclusions: Our study highlights the importance of saving the MUL as long as possible in terms of continence recovery. This holds true for ORP even in the era of RARP and surgeons should not simply give up the prospect of early urinary continence in exchange for the patient's choice of ORP instead of RARP., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Persistent loss of skeletal muscle mass and function as well as altered fat metabolism are frequently observed in severe sepsis survivors. Studies examining sepsis-associated tissue dysfunction from the perspective of the tissue microenvironment are scarce. In this study, we comprehensively assessed transcriptional changes in muscle and fat at single-cell resolution following experimental sepsis induction., Methods: Skeletal muscle and visceral white adipose tissue from control mice or mice 1 day or 1 month following faecal slurry-induced sepsis were used. Single cells were mechanically and enzymatically prepared from whole tissue, and viable cells were further isolated by fluorescence activated cell sorting. Droplet-based single-cell RNA-sequencing (scRNA-seq; 10× Genomics) was used to generate single-cell gene expression profiles of thousands of muscle and fat-resident cells. Bioinformatics analyses were performed to identify and compare individual cell populations in both tissues., Results: In skeletal muscle, scRNA-seq analysis classified 1438 single cells into myocytes, endothelial cells, fibroblasts, mesenchymal stem cells, macrophages, neutrophils, T-cells, B-cells, and dendritic cells. In adipose tissue, scRNA-seq analysis classified 2281 single cells into adipose stem cells, preadipocytes, endothelial cells, fibroblasts, macrophages, dendritic cells, B-cells, T-cells, NK cells, and gamma delta T-cells. One day post-sepsis, the proportion of most non-immune cell populations was decreased, while immune cell populations, particularly neutrophils and macrophages, were highly enriched. Proportional changes of endothelial cells, neutrophils, and macrophages were validated using faecal slurry and cecal ligation and puncture models. At 1 month post-sepsis, we observed persistent enrichment/depletion of cell populations and further uncovered a cell-type and tissue-specific ability to return to a baseline transcriptomic state. Differential gene expression analyses revealed key genes and pathways altered in post-sepsis muscle and fat and highlighted the engagement of infection/inflammation and tissue damage signalling. Finally, regulator analysis identified gonadotropin-releasing hormone and Bay 11-7082 as targets/compounds that we show can reduce sepsis-associated loss of lean or fat mass., Conclusions: These data demonstrate persistent post-sepsis muscle and adipose tissue disruption at the single-cell level and highlight opportunities to combat long-term post-sepsis tissue wasting using bioinformatics-guided therapeutic interventions., (© 2020 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Obesity and metabolic disorders such as diabetes, heart disease, and cancer, are all associated with dramatic adipose tissue remodeling. Tissue-resident adipose progenitor cells (APCs) play a key role in adipose tissue homeostasis and can contribute to the tissue pathology. The growing use of single cell analysis technologies - including single-cell RNA-sequencing and single-cell proteomics - is transforming the stem/progenitor cell field by permitting unprecedented resolution of individual cell expression changes within the context of population- or tissue-wide changes. In this article, we provide detailed protocols to dissect mouse epididymal adipose tissue, isolate single adipose tissue-derived cells, and perform fluorescence activated cell sorting (FACS) to enrich for viable Sca1 + /CD31 - /CD45 - /Ter119 - APCs. These protocols will allow investigators to prepare high quality APCs suitable for downstream analyses such as single cell RNA sequencing.

Objective: The objective of this study was to assess the value of a preoperative Prognostic Nutritional Index (PNI) for predicting the survival of patients with nonmetastatic renal cell carcinoma (RCC) treated with partial or radical nephrectomy., Materials and Methods: The medical records of 480 patients with RCC who underwent partial or radical nephrectomy at 2 institutions between June 1994 and July 2017 were retrospectively reviewed. After the exclusion of 21 patients with lymph node or distant metastasis, the data of 459 patients with nonmetastatic RCC were included. The PNI was calculated using a combination of serum albumin level and lymphocyte count in the peripheral blood, as described previously. The prognostic significance of various clinicopathologic variables, including the PNI, was assessed in univariate and multivariate analyses., Results: The univariate analysis identified anemia, PNI, tumor size, T stage, Fuhrman nuclear grade, sarcomatoid differentiation, and lymphovascular invasion as significant prognostic factors of recurrence-free survival (RFS) and cancer-specific survival (CSS). In the multivariate analysis, anemia (P=0.010), PNI (P<0.001), tumor size (P<0.001), T stage (P<0.001), Fuhrman nuclear grade (P=0.023), sarcomatoid differentiation (P=0.003), and lymphovascular invasion (P=0.005) were independent prognostic factors for RFS, versus anemia (P=0.020), PNI (P=0.002), tumor size (P<0.001), T stage (P<0.001), sarcomatoid differentiation (P<0.001), and lymphovascular invasion (P=0.018) for CSS., Conclusions: The PNI is an independent prognostic factor for RFS and CSS in patients with nonmetastatic RCC treated with partial or radical nephrectomy. It may, therefore, be a useful tool for predicting recurrence and survival in these patients.

Objective: The objective of this study was to perform a meta-analysis of the diagnostic test accuracy of Glasgow Prognostic Score (GPS) as a prognostic factor for renal cell carcinoma (RCC)., Materials and Methods: Studies were retrieved from PubMed, Cochrane, and Embase databases, and we performed comprehensive searches to identify studies that evaluated the prognostic impact of pretreatment GPS in RCC patients. We assessed sensitivity, specificity, summary receiver operating characteristic curve, and area under the curve (AUC)., Results: Totally, studies were searched under the prespecified criteria, and 8 studies with a total of 1191 patients were included to evaluate the prognostic impact of GPS in RCC finally. They indicated a pooled sensitivity of 0.785 (95% confidence interval [CI]: 0.705-0.848), specificity of 0.782 (95% CI: 0.656-0.871), diagnostic odds ratio of 13.089 (95% CI: 7.168-23.899), and AUC of 0.83 (95% CI: 0.79-0.86). Heterogeneity was significant, and meta-regression revealed that the presence of metastasis might be the potential source of heterogeneity. Subgroup analysis also demonstrated that the presence of metastasis might be the source of heterogeneity., Conclusion: GPS demonstrated a good diagnostic accuracy as a prognostic factor for RCC and especially in the case of nonmetastatic RCC.

Obesity is a serious health concern and is associated with a reduced quality of life and a number of chronic diseases, including diabetes, heart disease, stroke, and cancer. With obesity rates on the rise worldwide, adipose tissue biology has become a top biomedical research priority. Despite steady growth in obesity-related research, more investigation into the basic biology of adipose tissue is needed to drive innovative solutions aiming to curtail the obesity epidemic. Adipose progenitor cells (APCs) play a central role in adipose tissue homeostasis and coordinate adipose tissue expansion and remodeling. Although APCs are well studied, defining and characterizing APC subsets remains ambiguous because of ill-defined cellular heterogeneity within this cellular compartment. In this study, we used single-cell RNA sequencing to create a cellular atlas of APC heterogeneity in mouse visceral adipose tissue. Our analysis identified two distinct populations of adipose tissue-derived stem cells (ASCs) and three distinct populations of preadipocytes (PAs). We identified novel cell surface markers that, when used in combination with traditional ASC and preadipocyte markers, could discriminate between these APC subpopulations by flow cytometry. Prospective isolation and molecular characterization of these APC subpopulations confirmed single-cell RNA sequencing gene expression signatures, and ex vivo culture revealed differential expansion/differentiation capabilities. Obese visceral adipose tissue featured relative expansion of less mature ASC and PA subpopulations, and expression analyses revealed major obesity-associated signaling alterations within each APC subpopulation. Taken together, our study highlights cellular and transcriptional heterogeneity within the APC pool, provides new tools to prospectively isolate and study these novel subpopulations, and underscores the importance of considering APC diversity when studying the etiology of obesity., (© 2019 Cho et al.)

Background: The World Health Assembly endorsed the WHO Neglected Tropical Disease (NTD) Roadmap in 2013, in which NTDs were suggested as tracers of equity in the assessment of progress towards the Sustainable Development Goals. Nationwide surveys were undertaken in all 18 states of Sudan to identify the geographical distribution and to estimate the prevalence and intensity of schistosomiasis and other intestinal helminthiases from December 2016 to March 2017., Methods: We used two-stage random sampling. Each district was subdivided into one to three different ecological zones (EZs) based on proximity to water bodies. Probability-proportional-to-size sampling was used to select schools from each EZ. We estimated schistosomiasis and intestinal helminthiasis prevalence by the centrifugation method and Kato-Katz smears. Multi-level mixed-effect models were used to investigate the relationship between the prevalence of infections and risk factors, including improved water or latrine status at the household or school level. We estimated the cost-effectiveness of a one-time mass drug administration (MDA) intervention with 75% coverage at the district and EZ levels., Results: A total of 105,167 students from 1772 schools were surveyed. The overall egg-positive rates were: Schistosoma haematobium, 5.2%; S. mansoni, 0.06%; and intestinal helminths, 5.47%. Severe endemic areas were concentrated in East and South Darfur States. Children living in a house or attending schools with an improved latrine were less likely to be infected with schistosomiasis than those without a latrine (adjusted odds ratio, aOR: 0.45, 95% confidence interval, CI: 0.41-0.51 and aOR: 0.75, 95% CI: 0.70-0.81 at the household or the school levels, respectively). Open defecation was strongly associated with schistosomiasis (aOR: 1.50, 95% CI: 1.35-1.66). In community-wide mass treatment at the district level with an 8% threshold for schistosomiasis, 2.2 million people would not benefit from MDA interventions with 75% coverage despite high endemicity, whilst 1.7 million people would receive the MDA intervention unnecessarily. EZ-level MDA was estimated to be more cost-effective than district-level administration under all circumstances., Conclusions: Our findings provide updated prevalence figures to guide preventive chemotherapy programmes for schistosomiasis and intestinal helminthiasis in Sudan. Schistosomiasis was found to be common among the inhabitants of fragile and conflict-affected areas. In addition, we found that MDA interventions would be more cost-effective at the sub-district level than at the district level, and there was a strong association between schistosomiasis prevalence and latrine status, at both the household and school levels. This study will help the Sudanese government and its neighbouring countries develop adequate control and elimination strategies.

Background: Chronic testicular pain (orchialgia) has been defined as intermittent or constant unilateral or bilateral testicular pain that lasts 3 months or longer, significantly interfering with daily activities, and prompting the patient to seek medical attention. In many instances, the etiology of the pain is not identified. The contribution of psychological factors is unclear. The purpose of this study was to identify the categories of mental health (MH) diagnoses that are most frequently associated with orchialgia and determine if a correlation exists between MH diagnoses and orchialgia., Methods: A retrospective review was performed to identify all adult patients within the San Antonio Military Health System with a new diagnosis of orchialgia from January 2005 to April 2015. Patients with acute pathology or recent inguinal/scrotal surgery were excluded. A comparative cohort of all men presenting with hydroceles within the same timeframe was obtained. The presence of coexisting MH diagnoses in both cohorts was then determined., Results: Four hundred and forty-four men met the inclusion criteria for orchialgia, with 133 men presenting with hydroceles. The incidence of orchialgia increased significantly over the study period (P=0.001). MH diagnoses in the study population did trend upward over the years, but not significantly (P=0.063). MH diagnoses were not significantly higher in the cases compared to the controls (21.6% vs. 18.8%, P=0.479). The prevalence of anxiety was twice as high in the cases (9% vs. 4.5%), though not significantly (P=0.075). The prevalence of all MH diagnoses was significantly higher than in the general US population based on National Institute of Mental Health statistics., Conclusions: The incidence of orchialgia rose significantly over time, but it was not significantly associated with MH diagnoses. These results may also be skewed by the overall higher percentage of MH diagnoses in the study population than in the general population., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Tissue-specific stem cells contribute to adult tissue maintenance, repair, and regeneration. In skeletal muscle, many different mononuclear cell types are capable of giving rise to differentiated muscle. Of these tissue stem-like cells, satellite cells (SCs) are the most studied muscle stem cell population and are widely considered the main cellular source driving muscle repair and regeneration in adult tissue. Within the satellite cell pool, many distinct subpopulations exist, each exhibiting differential abilities to exit quiescence, expand, differentiate, and self-renew. In this chapter, we discuss the different stem cell types that can give rise to skeletal muscle tissue and then focus on satellite cell heterogeneity during the process of myogenesis/muscle regeneration. Finally, we highlight emerging opportunities to better characterize muscle stem cell heterogeneity, which will ultimately deepen our appreciation of stem cells in muscle development, repair/regeneration, aging, and disease.

Duchenne muscular dystrophy (DMD) is a musculoskeletal disorder that causes severe morbidity and reduced lifespan. Individuals with DMD have an X-linked mutation that impairs their ability to produce functional dystrophin protein in muscle. No cure exists for this disease and the few therapies that are available do not dramatically delay disease progression. Thus, there is a need to better understand the mechanisms underlying DMD which may ultimately lead to improved treatment options. The muscular dystrophy (MDX) mouse model is frequently used to explore DMD disease traits. Though some studies of metabolism in dystrophic mice exist, few have characterized metabolic profiles of supporting cells in the diseased environment. Using nontargeted metabolomics we characterized metabolic alterations in muscle satellite cells (SCs) and serum of MDX mice. Additionally, live-cell imaging revealed MDX-derived adipose progenitor cell (APC) defects. Finally, metabolomic studies revealed a striking elevation of acylcarnitines in MDX APCs, which we show can inhibit APC proliferation. Together, these studies highlight widespread metabolic alterations in multiple progenitor cell types and serum from MDX mice and implicate dystrophy-associated metabolite imbalances in APCs as a potential contributor to adipose tissue disequilibrium in DMD.

Muscle wasting is a decline in skeletal muscle mass and function that is associated with aging, obesity, and a spectrum of pathologies including cancer. Cancer-associated wasting not only reduces quality of life, but also directly impacts cancer mortality, chemotherapeutic efficacy, and surgical outcomes. There is an incomplete understanding of the role of tumor-derived factors in muscle wasting and sparse knowledge of how these factors impact in vivo muscle regeneration. Here, we identify several cytokines/chemokines that negatively impact in vitro myogenic differentiation. We show that one of these cytokines, CXCL1, potently antagonizes in vivo muscle regeneration and interferes with in vivo muscle satellite cell homeostasis. Strikingly, CXCL1 triggers a robust and specific neutrophil/M2 macrophage response that likely underlies or exacerbates muscle repair/regeneration defects. Taken together, these data highlight the pleiotropic nature of a novel tumor-derived cytokine and underscore the importance of cytokines in muscle progenitor cell regulation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aging is characterized by the development of metabolic dysfunction and frailty. Recent studies show that a reduction in nicotinamide adenine dinucleotide (NAD + ) is a key factor for the development of age-associated metabolic decline. We recently demonstrated that the NADase CD38 has a central role in age-related NAD + decline. Here we show that a highly potent and specific thiazoloquin(az)olin(on)e CD38 inhibitor, 78c, reverses age-related NAD + decline and improves several physiological and metabolic parameters of aging, including glucose tolerance, muscle function, exercise capacity, and cardiac function in mouse models of natural and accelerated aging. The physiological effects of 78c depend on tissue NAD + levels and were reversed by inhibition of NAD + synthesis. 78c increased NAD + levels, resulting in activation of pro-longevity and health span-related factors, including sirtuins, AMPK, and PARPs. Furthermore, in animals treated with 78c we observed inhibition of pathways that negatively affect health span, such as mTOR-S6K and ERK, and attenuation of telomere-associated DNA damage, a marker of cellular aging. Together, our results detail a novel pharmacological strategy for prevention and/or reversal of age-related NAD + decline and subsequent metabolic dysfunction., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Tissue specific stem cells are indispensable contributors to adult tissue maintenance, repair, and regeneration. In skeletal muscle, satellite cells (SCs) are the resident muscle stem cell population and are required to maintain skeletal muscle homeostasis throughout life. Increasing evidence suggests that SCs are a heterogeneous cell population with substantial biochemical and functional diversity. A major limitation in the field is an incomplete understanding of the nature and extent of this cellular heterogeneity. Single cell analyses are well suited to addressing this issue, especially when coupled to unbiased profiling paradigms such as high throughout RNA sequencing. We performed single cell RNA sequencing (scRNA-seq) on freshly isolated muscle satellite cells and found a surprising degree of heterogeneity at multiple levels, from muscle-specific transcripts to the broader SC transcriptome. We leveraged several comparative bioinformatics techniques and found that individual SCs enrich for unique transcript clusters. We propose that these gene expression "fingerprints" may contribute to observed functional SC diversity. Overall, these studies underscore the importance of several established SC signaling pathways/processes on a single cell level, implicate novel regulators of SC heterogeneity, and lay the groundwork for further investigation into SC heterogeneity in health and disease., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Schistosomiasis and soil-transmitted helminthiasis (STHs) are target neglected tropical diseases (NTDs) of preventive chemotherapy, but the control and elimination of these diseases have been impeded due to resource constraints. Few reports have described study protocol to draw on when conducting a nationwide survey. We present a detailed methodological description of the integrated mapping of schistosomiasis and STHs on the basis of our experiences, hoping that this protocol can be applied to future surveys in similar settings. In addition to determining the ecological zones requiring mass drug administration interventions, we aim to provide precise estimates of the prevalence of these diseases., Methods: A school-based cross-sectional design will be applied for the nationwide survey across Sudan. The survey is designed to cover all districts in every state. We have divided each district into 3 different ecological zones depending on proximity to bodies of water. We will employ a probability-proportional-to-size sampling method for schools and systematic sampling for student selection to provide adequate data regarding the prevalence for schistosomiasis and STHs in Sudan at the state level. A total of 108,660 students will be selected from 1811 schools across Sudan. After the survey is completed, 391 ecological zones will be mapped out. To carry out the survey, 655 staff members were recruited. The feces and urine samples are microscopically examined by the Kato-Katz method and the sediment smears for helminth eggs respectively. For quality control, a minimum of 10% of the slides will be rechecked by the federal supervisors in each state and also 5% of the smears are validated again within one day by independent supervisors., Discussion: This nationwide mapping is expected to generate important epidemiological information and indicators about schistosomiasis and STHs that will be useful for monitoring and evaluating the control program. The mapping data will also be used for overviewing the status and policy formulation and updates to the control strategies. This paper, which describes a feasible and practical study protocol, is to be shared with the global health community, especially those who are planning to perform nationwide mapping of NTDs by feces or urine sampling.

Background: While inflammation is associated with obesity and insulin resistance, their inter-relationships in the development of type 2 diabetes or hypertension are not clear., Aim of the Study: To evaluate inflammatory markers in prediction of type 2 diabetes and hypertension., Methods: The study population of this retrospective cohort study consisted of individuals who participated in a comprehensive health screening program with measurement of white blood cell count and C-reactive protein from 2002-2010 (N = 96,606) in nondiabetic and normotensive Koreans. Median follow up time were 3.7 years for incident type 2 diabetes and 3.3 years for hypertension. Multivariate Cox proportional hazards models were performed to assess risk for type 2 diabetes or hypertension by white blood cell or C-reactive protein quartiles with adjustment of various possible confounding factors including insulin resistance., Results: During the follow-up period, 1448 (1.5%) developed type 2 diabetes and 10,405 (10.8%) developed hypertension. Among men, comparison of adjusted hazard ratios (HR) for incident type 2 diabetes in the highest versus lowest white blood cell or C-reactive protein quartiles were 1.48 [95% confidence interval (CI), 1.20-1.83] and 1.30 (95% CI, 1.07-1.57), respectively. Among women, white blood cell but not C-reactive protein was significantly associated with type 2 diabetes [HR 1.79 (95% CI 1.24-2.57)]. White blood cell and C-reactive protein quartiles were also modestly associated with incident hypertension in both sexes., Conclusions: Although white blood cell and C-reactive protein are associated with adiposity and insulin resistance, these inflammatory markers also independently predict type 2 diabetes and/or hypertension., (Copyright © 2017 IMSS. Published by Elsevier Inc. All rights reserved.)

Purpose: Glasgow Prognostic Score (GPS) has been reported to predict oncologic outcomes in various type of cancer. However, their prognostic value in patients with renal cell carcinoma (RCC) is unclear. In this meta-analysis, we evaluated the prognostic significance of GPS in RCC patients., Methods: We performed comprehensive searches of electronic databases to identify studies that evaluated the prognostic impact of pretreatment GPS in RCC patients. The end points were cancer-specific survival (CSS), recurrence-free/disease-free survival (RFS/DFS). Meta-analysis using random-effects models was performed to calculate hazard ratios (HRs) or odds ratios with 95 % confidence intervals (CIs)., Results: Nine retrospective, observational, cohort studies involving 2096 patients were included. Seven studies evaluated CSS, and three evaluated RFS. Our results showed that higher GPS (0 vs. 1 vs. 2) was significantly predictive of poorer CSS (HR 3.68, 95 % CI 2.52-5.40, p < 0.001) and RFS/DFS (HR 2.83, 95 % CI 1.86-4.30, p < 0.001) in patients with RCC. These findings were robust when stratified by sample size, presence of metastasis, and study region. We also conducted subgroup analysis by assessment of Newcastle-Ottawa quality assessment scale (NOS) score, and the HRs were 2.708 (95 % CI 1.969, 3.725) in under 7 points group, 3.685 (95 % CI 2.516, 5.396) in over than 7 points group in CSS. Meta-regression analysis indicated that NOS score group had a significant difference in HRs (p = 0.032)., Conclusions: Higher GPS is associated with tumor progression and is predictive of poorer survival in patients with RCC. Therefore, GPS may help to inform treatment decisions and predict treatment outcomes.

Objective: Previous studies have reported the association among serum uric acid (SUA) levels and cardiovascular and all-cause mortality; however, the results have been inconsistent. The aim of this study was to investigate whether SUA is independently associated with cardiovascular and all-cause mortality in relatively healthy Korean adults., Methods: A total of 396 951 individuals were enrolled for the study between 2002 and 2012. About 39 991 participants were excluded for various reasons. All-cause and cardiovascular mortality data were collected. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals for all-cause and cardiovascular mortality according to baseline uric acid quintiles, and the third, middle SUA quintile was the reference group., Results: A total of 356 960 participants were considered to be eligible for the analysis, and median follow-up duration was 5.88 years. The lowest and highest quintiles of SUA were less than 5.2 and more than 7.1 mg/dl in men, and less than 3.5 and more than 5.0 mg/dl in women, respectively. A total of 2082 deaths (312 from cardiovascular disease and 1770 from other causes) occurred during follow-up. In the highest SUA group, adjusted hazard ratios for all-cause mortality were 1.24 (1.01, 1.51) in men and 1.04 (0.76, 1.42) in women, and for cardiovascular mortality were 1.15 (0.72, 1.83) in men and 1.69 (0.70, 4.04) in women after adjustment for various possible confounding factors., Conclusion: In the current large relatively healthy population-based observational study, SUA showed no significant association with all-cause and cardiovascular mortality.

We derived a stable cell line from Chinese hamster embryonic fibroblasts by transduction of four mouse transcription factors (M 3 O, Sox2, Klf4, and n-Myc) using a lentiviral vector. The cell line possess all the characteristics of an induced pluripotent stem cell (iPSC) line. Given that Chinese hamster ovary (CHO) cells are the predominant host cells used for therapeutic protein production and no pluripotent stem cell line or other normal cell line has been isolated from Chinese hamster, this iPSC line may serve as a useful tool for research using CHO cells or even be used for deriving new cell lines., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The Scientific Report of the Dietary Guidelines Advisory Committee (2015) concluded that restriction of dietary cholesterol is unnecessary in most adults for the prevention of cardiovascular disease., Objective: We aimed to assess the risk for subclinical atherosclerosis according to coronary artery calcium score (CACS), based on dietary cholesterol intake in apparently healthy Korean adults., Methods: This was a cross-sectional study performed in 30,068 participants (mean age 40.8 years; 84.5% men) in a health screening program in Korea. The data were collected from 2001 to 2013 and analyzed in 2015. Total energy intake and dietary cholesterol intake were assessed with a food frequency questionnaire. The participants were stratified according to quartile of dietary cholesterol intake. CACS was measured by multi-detector computed tomography. Lipid profiles were measured, and the participants were divided into 6 groups according to low-density lipoprotein cholesterol (LDL-C) level: <70, 70 to 99, 100 to 129, 130 to 159, 160 to 189, and ≥190 mg/dL., Results: The presence of coronary artery calcification was defined as CACS>0. Dietary cholesterol intake did not correlate with mean value of serum LDL-C level. For both genders, the odds ratio for coronary artery calcification was not significantly greater with greater amounts of dietary cholesterol (as assessed by quartile). The risk for coronary artery calcification was not higher in subjects with LDL-C 70-129 mg/dL compared with those with LDL-C < 70 mg/dL; however, the risk was significantly greater in subjects with LDL-C ≥ 130 mg/dL compared with those with LDL-C < 70 mg/dL., Conclusions: Dietary cholesterol intake did not have an association with LDL-C level or with risk for coronary artery calcification in apparently healthy Korean adults. The results have to be translated with consideration of limitation of population-based studies., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

The differentiation of human pluripotent stem cells toward the hepatocyte lineage can potentially provide an unlimited source of functional hepatocytes for transplantation and extracorporeal bioartificial liver applications. It is anticipated that the quantities of cells needed for these applications will be in the order of 10 9 -10 10 cells, because of the size of the liver. An ideal differentiation protocol would be to enable directed differentiation to the hepatocyte lineage with simultaneous cell expansion. We introduced a cell expansion stage after the commitment of human embryonic stem cells to the endodermal lineage, to allow for at least an eightfold increase in cell number, with continuation of cell maturation toward the hepatocyte lineage. The progressive changes in the transcriptome were measured by expression array, and the expression dynamics of certain lineage markers was measured by mass cytometry during the differentiation and expansion process. The findings revealed that while cells were expanding they were also capable of progressing in their differentiation toward the hepatocyte lineage. In addition, our transcriptome, protein and functional studies, including albumin secretion, drug-induced CYP450 expression and urea production, all indicated that the hepatocyte-like cells obtained with or without cell expansion are very similar. This method of simultaneous cell expansion and hepatocyte differentiation should facilitate obtaining large quantities of cells for liver cell applications.

In early mouse pre-implantation development, primitive endoderm (PrE) precursors are platelet-derived growth factor receptor alpha (PDGFRα) positive. Here, we demonstrated that cultured mouse embryonic stem cells (mESCs) express PDGFRα heterogeneously, fluctuating between a PDGFRα+ (PrE-primed) and a platelet endothelial cell adhesion molecule 1 (PECAM1)-positive state (epiblast-primed). The two surface markers can be co-detected on a third subpopulation, expressing epiblast and PrE determinants (double-positive). In vitro, these subpopulations differ in their self-renewal and differentiation capability, transcriptional and epigenetic states. In vivo, double-positive cells contributed to epiblast and PrE, while PrE-primed cells exclusively contributed to PrE derivatives. The transcriptome of PDGFRα + subpopulations differs from previously described subpopulations and shows similarities with early/mid blastocyst cells. The heterogeneity did not depend on PDGFRα but on leukemia inhibitory factor and fibroblast growth factor signaling and DNA methylation. Thus, PDGFRα + cells represent the in vitro counterpart of in vivo PrE precursors, and their selection from cultured mESCs yields pure PrE precursors., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This study was to estimate salt preference and sodium intake of pregnant women, and identify the relationship between salt preference and sodium intake., Methods: Research design was a cross sectional correlational survey with 197 pregnant women who visited outpatient clinics for antenatal care. The sodium intake levels were estimated by the amounts of sodium intake using the 24-hour recall method and sodium concentration in spot urine. The data were analyzed using descriptive statistics, t-test, ANOVA and Pearson's correlation., Results: Sodium intake using 24-hour recall method was 3,504±1,359 mg. Sodium intake levels had statistically significant differences depending on income. The average amount of sodium in spot urine was 2,882±878mg/day. Sodium excretion levels had statistically significant differences depending on whether participants had preexisting hypertension in their family history and Body Mass Index (BMI) pre-conception. Salt preference was 62.61±20.96 out of 180 points. Salt preference had significant differences depending on income, parity, gestational age, BMI pre-conception and showed negative correlation with sodium quantity in spot urine., Conclusion: Sodium intake in pregnant women recommended by World Health Organization recommended is 175%. Salt preference was not significantly different between sodium intake levels, however it was negatively correlated with sodium quantity in spot urine among pregnant women.

The objective was to evaluate the effect of TeamSTEPPS on operating room efficiency and patient safety. TeamSTEPPS consisted of briefings attended by all health care personnel assigned to the specific operating room to discuss issues unique to each case scheduled for that day. The operative times, on-time start rates, and turnover times of all cases performed by the urology service during the initial year with TeamSTEPPS were compared to the prior year. Patient safety issues identified during postoperative briefings were analyzed. The mean case time was 12.7 minutes less with TeamSTEPPS (P < .001). The on-time first-start rate improved by 21% with TeamSTEPPS (P < .001). The mean room turnover time did not change. Patient safety issues declined from an initial rate of 16% to 6% at midyear and remained stable (P < 0.001). TeamSTEPPS was associated with improved operating room efficiency and diminished patient safety issues in the operating room., (© The Author(s) 2015.)

Objective The aim of this study was to evaluate the usefulness of the modified Glasgow Prognostic Score (mGPS) as a prognostic factor in patients with non-metastatic clear cell renal cell carcinoma (RCC). Materials and methods Between June 1994 and July 2012, 469 patients with RCC underwent radical or partial nephrectomy at two hospitals. Among these patients, 65 with non-clear cell type histology and 16 with lymph-node or distant metastasis were excluded. The medical records of the remaining 388 patients were retrospectively reviewed. The mGPS was calculated using a selective combination of C-reactive protein (CRP) and albumin as previously described. The prognostic significance of various clinicopathological variables including mGPS was analyzed using univariate and multivariate analyses. Results Of the total 388 patients, 40 patients (10.3%) developed local recurrence or distant metastasis and 18 patients (4.6%) died of disease during the follow-up period. The univariate analysis identified CRP, mGPS, thrombocytosis, T stage, Fuhrman's nuclear grade and lymphovascular invasion as significant prognostic factors for recurrence-free survival (RFS) and cancer-specific survival (CSS). The multivariate analysis indicated that mGPS (p < 0.001), T stage (p = 0.024) and lymphovascular invasion (p = 0.046) were independent prognostic factors for RFS, whereas mGPS (p = 0.001) was the only independent prognostic factor for CSS. Conclusions The mGPS is an independent prognostic factor for RFS and CSS in patients with non-metastatic clear cell RCC treated with radical or partial nephrectomy. These findings suggest that mGPS should be used for predicting recurrence or survival in patients undergoing nephrectomy for non-metastatic clear cell RCC.

Background: Ureteral stent removal using an extraction string is advantageous because it can obviate an invasive cystoscopy, but there is a paucity of data on how patients feel about it, and how bothersome or beneficial it is. We performed this study to evaluate patients' preference for stent removal using an extraction string and which parameters could affect it., Methods: In total, 114 consecutive patients undergoing ureteral stent insertion after ureteroscopic stone removal (URS) for unilateral recurrent ureter stones were enrolled. Patients were randomized to a string group or a no string group. Stent removal was performed on the first visit within 7 days postoperatively. All patients were asked to complete the ureteral stent symptom questionnaire, to rate the degree of pain during stent removal using a visual analog scale (VAS) and to answer to questions regarding their preference., Results: No significant differences were found in domain total scores including urinary symptoms (p = 0.17), pain (p = 0.62), general health (p = 0.37), work performance (p = 0.41). However, regarding separate questions for 'dysuria' and 'difficulties with heavy physical activity', there were significant intergroup differences (p = 0.03 and p = 0.04, respectively). Particular, a significantly higher proportion of patients in the string group checked 'stoppage of sexual intercourse due to stent-related problems' than in the no string group (p = 0.03). VAS score on stent removal was significantly higher in the no string group than the string group (p = 0.005). Among the patients who remember the experience of an indwelling ureteral stent in the past, 85% (17/20) of the no string group answered 'No' to the question of 'difference between the methods used in this time and in the past'. On the contrary, 84.2% (16/19) answered 'Yes' to the same question in the string group. And, all 16 patients of the string group who noted differences between the methods preferred ureteral stent removal using an extraction string to the past method., Conclusions: Despite of minor increased morbidity related to the extraction string, patients preferred ureteral stent removal using the extraction string after URS. The patients with the extraction string felt less pain on stent removal than flexible cystoscopic stent removal., Trial Registration: KCT0001700 . The trial was registered in the Clinical Research Information Service (CRiS), Republic of Korea; registration date: 18/11/2015.

Introduction: We investigate the influence of stretched membranous urethral length (SUL) and urethral circumference (UC) on postoperative recovery of continence after radical prostatectomy (RP)., Methods: To evaluate the distal continence zone intraoperatively, we individually measured and recorded stretched membranous urethral length (distance between the urogenital diaphragm and the prostate apex with cephalad retraction, SUL) and urethral circumference (UC) after exposure of the urethra. We analyzed the association between magnetic resonance imaging-measured membranous urethral length (MRIL) and urethral diameter (MRID) and intraoperative SUL and UC and influence on return to continence., Results: The mean patient age, SUL and UC were 66.5 ± 6.0 years, 24.2 ± 3.3 mm, and 27.5 ± 4.4 mm, respectively. MRIL and MRID were 11.3 ± 1.6 mm and 10.6 ± 1.9mm, respectively. In the bivariate correlation analysis, there was no statistically significant correlation between SUL and MRIL (p = 0.201) and between UC and MRID (p = 0.124). In the Kaplan-Meier curve analysis, cumulative continence rates between the two groups dichotomized at the median value according to age (p = 0.0519), SUL (p = 0.6583), UC (p = 0.4031), MRIL (p = 0.4042), and MRID (p = 0.8191) were not significantly different. High SUL-to-MRIL ratio (>2.2) was the only significant predictor of lower cumulative continence rate (p = 0.0457)., Conclusions: MRIL measured during surgery was not associated with postoperative continence recovery after RP. We observed that an excessively long membranous urethra compared to the urethral length on preoperative MRI is predictive of poorer postoperative continence recovery. However, small sample size and potential confounding surgical factors limit the significance of this study.

Purpose: The aim of the study was to assess and identify gender differences in factors associated with prevalence, awareness, and treatment of osteoporosis., Methods: Data for 3,071 men and 3,635 women (age ≥ 50) from the Korea National Health and Nutrition Examination Survey 2008~2011 were included. Osteoporosis was defined by World Health Organization T-score criteria. Impact factors and odds ratios were analysed by gender using multivariate logistic regression., Results: Osteoporosis prevalence rates were 7.0% in men and 40.1% in women. Osteopenia rates were 45.5% and 46.0% respectively. Among respondents with osteoporosis, 7.6% men and 37.8% women were aware of their diagnosis. Also 5.7% men with osteoporosis and 22.8% women were treated. Higher prevalence was found among respondents who were older, at lower socioeconomic levels, with lower body mass index and shorter height in both genders, and among women with fracture history, and non-hormonal replacement therapy. Awareness and treatment rates for the risk groups were similar compared to the low risk controls for both genders. Fracture history increased awareness and treatment rates independently for both genders. Women with perceived poor health status and health screening had increased awareness and treatment rates, but not men., Conclusion: Results indicate that postmenopausal women have a higher prevalence of osteoporosis than men and awareness and treatment rates were higher than for men. Despite gender difference in prevalence, osteoporosis was underdiagnosed and undertreated for both genders. Specialized public education and routine health screenings according to gender could be effective strategies to increase osteoporosis awareness and treatment.

Aim: We investigated the proportion of people who would qualify for statin treatment with an atherosclerotic cardiovascular disease (ASCVD) 10-year risk of ≥7.5% and who exhibit an LDL cholesterol (LDL-C) of 70 to 189 mg/dL according to the new ACC/AHA guidelines for the treatment of increased cardiovascular risk., Methods: The study population (8,742 subjects) included individuals who underwent health examinations at Kangbuk Samsung Hospital in South Korea in 2010. We also evaluated the data obtained from the 2008-2010 Korea National Health and Nutrition Examination Survey (KNHANES) of 16,892 adults., Results: Approximately 90% of men ≥60 years of age and women ≥70 years of age had an ASCVD 10-year risk of ≥7.5% and LDL-C level of ≥70 mg/dL. The proportions of subjects with a Framingham 10-year risk of ≥10%, coronary artery calcium score of >20 and >100 and fatty liver each increased in association with an increasing ASCVD 10-year risk quartile in both sexes. Furthermore, age was significantly associated with the ASCVD 10-year risk in both sexes (all p-value <0.001). The KNHANES data also showed that over 85.0% of men ≥60 years of age and 95.0% of women ≥70 years of age had an ASCVD 10-year risk of ≥7.5% and an LDL-C level of ≥70 mg/dL., Conclusions: Adopting the new ASCVD prevention guidelines would result in the treatment of almost all Korean men and women (≥60 years and ≥70 years of age, respectively) without evidence of cardiovascular disease. Therefore, Asian-specific guidelines are needed to avoid unnecessary over treatment in an aging global population.

Introduction: In this article, we aim to present our novel experience of bladder stone removal under pneumovesicoscopic field using a laparoscopic entrapment sac., Technical Considerations: We retrospectively reviewed the medical records of 21 patients who had pneumovesicoscopic bladder stone removal to assess a variety of patient characteristics and surgical outcomes. We considered stone burden, stone removal time including pneumovesicoscopic procedure time, postoperative catheter indwelling duration, postoperative hospital stay, and complications. The procedure was performed in the following steps: Under cystoscopy filled with saline solution, a 10-mm suprapubic transvesical trocar was inserted. After changing optical transmission medium from saline to CO(2) gas, pneumovesicoscopic procedure was performed to put stones in an entrapment sac inserted through the trocar. The stones trapped in the sac were extracorporeally broken with a lithotripter via the suprapubic route. The mean patient age was 58.95 ± 22.03 years. The mean stone burden was 4.88 ± 2.63 cm. Eleven patients had a single stone, whereas 10 had multiple stones. All stones were completely removed. The mean operative time was 31.66 ± 7.25 minutes, including the pneumovesicoscopic procedure time of 13.81 ± 7.30 minutes. In all but 6 patients with a cystostomy or a combined transurethral resection of the prostate, the urethra catheter was removed on the day after surgery; the mean postoperative hospital stay was 1.67 ± 0.49 days. There were 5 postoperative complications of Clavien grade I or II., Conclusion: We report the technical feasibility of pneumovesicoscopic bladder stone removal using a laparoscopic entrapment sac as a minimally invasive method. This technique will likely become more important as a useful option for treating bladder stones., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Under the Kyoto Protocol, a global governmental response to climate change, protocol signatories make an effort to cut their greenhouse gas emissions. South Korea is not included in the list of Annex I countries; yet, South Korea is the seventh highest emitter of CO2. The South Korean government has enacted various institutional policies to encourage greenhouse gas reductions. While previous studies have focused on the guidance that reflects the stance of suppliers in the carbon market, this study focuses on South Korean firms' actual demand for forest carbon credits. By applying the contingent valuation method, we estimated domestic firms' willingness to pay for forest carbon credits. We then applied a rank-ordered logistic regression to confirm whether the rank of forest carbon credits, as compared to any other carbon credit, is influenced by a firm's characteristics. The results showed that Korean firms are willing to pay 5.45 USD/tCO2 and 7.77 USD/tCO2 for forest carbon credits in domestic and overseas forest carbon projects, respectively. Therefore, the introduction of forest carbon credits in the Korean carbon market seems reasonable. Analysis of the priority rankings of forest carbon credits, however, demonstrated that forestry projects were least likely to be ranked by firms as their first priority. Although relative preferences for forest carbon credits were influenced by individual firms' characteristics such as prior experience of environmental CSR related activities and whether the firm established an emissions reduction plan, the impact of perceived behavior control, whether the firm was included in the emissions target management scheme on forest carbon credits was negligible. Therefore, forest carbon credits are not a feasible solution without strong government support or institutional instruments. The results of this study are expected to provide policy makers with realistic approaches to formulate climatic change-related policies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)