Flexibility of telomerase in binding the RNA template and DNA telomeric repeat.

Telomerase synthesizes telomeres at the ends of linear chromosomes by repeated reverse transcription from a short RNA template. Crystal structures of Tribolium castaneum telomerase reverse transcriptase (tcTERT) and cryoelectron microscopy (cryo-EM) structures of human and Tetrahymena telomerase have revealed conserved features in the reverse-transcriptase domain, including a cavity near the DNA 3' end and snug interactions with the RNA template. For the RNA template to translocate, it needs to be unpaired and separated from the DNA product. Here we investigate the potential of the structural cavity to accommodate a looped-out DNA bulge and enable the separation of the RNA/DNA hybrid. Using tcTERT as a model system, we show that a looped-out telomeric repeat in the DNA primer can be accommodated and extended by tcTERT but not by retroviral reverse transcriptase. Mutations that reduce the cavity size reduce the ability of tcTERT to extend the looped-out DNA substrate. In agreement with cryo-EM structures of telomerases, we find that tcTERT requires a minimum of 4 bp between the RNA template and DNA primer for efficient DNA synthesis. We also have determined the ternary-complex structure of tcTERT including a downstream RNA/DNA hybrid at 2.0-Å resolution and shown that a downstream RNA duplex, equivalent to the 5' template-boundary element in telomerase RNA, enhances the efficiency of telomere synthesis by tcTERT. Although TERT has a preformed active site without the open-and-closed conformational changes, it contains cavities to accommodate looped-out RNA and DNA. The flexible RNA-DNA binding likely underlies the processivity of telomeric repeat addition.

A minimal motif for sequence recognition by mitochondrial transcription factor A (TFAM).

Mitochondrial transcription factor A (TFAM) plays a critical role in mitochondrial transcription initiation and mitochondrial DNA (mtDNA) packaging. Both functions require DNA binding, but in one case TFAM must recognize a specific promoter sequence, while packaging requires coating of mtDNA by association with non sequence-specific regions. The mechanisms by which TFAM achieves both sequence-specific and non sequence-specific recognition have not yet been determined. Existing crystal structures of TFAM bound to DNA allowed us to identify two guanine-specific interactions that are established between TFAM and the bound DNA. These interactions are observed when TFAM is bound to both specific promoter sequences and non-sequence specific DNA. These interactions are established with two guanine bases separated by 10 random nucleotides (GN10G). Our biochemical results demonstrate that the GN10G consensus is essential for transcriptional initiation and contributes to facilitating TFAM binding to DNA substrates. Furthermore, we report a crystal structure of TFAM in complex with a non sequence-specific sequence containing a GN10G consensus. The structure reveals a unique arrangement in which TFAM bridges two DNA substrates while maintaining the GN10G interactions. We propose that the GN10G consensus is key to facilitate the interaction of TFAM with DNA.

How a B family DNA polymerase has been evolved to copy RNA.

We report here crystal structures of a reverse transcriptase RTX, which was evolved in vitro from the B family polymerase KOD, in complex with either a DNA duplex or an RNA-DNA hybrid. Compared with the apo, binary, and ternary complex structures of the original KOD polymerase, the 16 substitutions that result in the function of copying RNA to DNA do not change the overall protein structure. Only six substitutions occur at the substrate-binding surface, and the others change domain-domain interfaces in the polymerase to enable RNA-DNA hybrid binding and reverse transcription. Most notably, F587L at the Palm and Thumb interface stabilizes the open and apo conformation of the Thumb. The intrinsically flexible Thumb domain seems to play a major role in accommodating the RNA-DNA hybrid product distal to the active site. This is reminiscent of naturally occurring RNA-dependent DNA polymerases, including telomerase, which have a dramatically augmented Thumb domain, and of reverse transcriptase, which extends its Thumb with the RNase H domain.

Antibiotic resistance in shellfish and major inland pollution sources in the drainage basin of Kamak Bay, Republic of Korea.

Shellfish-growing areas in marine environments are affected by pollutants that mainly originate from land, including streams, domestic wastewater, and the effluents of wastewater treatment plants (WWTPs), which may function as reservoirs of antibiotic-resistant bacteria (ARB) and antibiotic-resistance genes (ARGs). The objective of this study was to identify the occurrence and distribution of antibiotic resistance at five oyster sampling sites and 11 major inland pollution sources in the drainage basin of Kamak Bay, Republic of Korea. Culture-based methods were used to estimate the diversity and abundance of antibiotic-resistant Escherichia coli strains isolated from oysters and major inland pollution sources. The percentages of ARB and multiple antibiotic resistance index values were significantly high in discharge water from small fishing villages without WWTPs. However, the percentages of antibiotic-resistant E. coli isolates from oysters were low, as there was no impact from major inland pollutants. Fourteen ARGs were also quantified from oysters and major inland pollution sources. Although most ARGs except for quinolones were widely distributed in domestic wastewater discharge and effluent from WWTPs, macrolide resistance genes (ermB and msrA) were detected mainly from oysters in Kamak Bay. This study will aid in tracking the sources of antibiotic contamination in shellfish to determine the correlation between shellfish and inland pollution sources.

Relationship between each IPSS item score and erectile dysfunction in the Korean Internet Sexuality Survey (KISS): do men with weak streams have low sexual function?

OBJECTIVES: The current results show that lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are co-prevalent conditions. The objective of this study was to determine which LUTS among seven items on the International Prostate Symptom Scores (IPSS) were related to ED in the general population. METHODS: The Korean Internet Sexuality Survey was performed in 2006 and 2016. We sent emails and surveyed the panelists registered at an Internet survey agency. The inclusion criteria were sexually active men aged between 20 and 69. Data, including the International Index of Erectile Function-5 (IIEF-5) and IPSS scores were extracted from the surveys. Logistic regression analyses were performed to determine the factors related to 'any degree of ED' (IIEF-5 < 22) or 'more than mild ED' (IIEF-5 < 17). RESULTS: The mean age of 1464 men was 39.2 ± 11.4 years. The mean total IPSS and IIEF-5 scores were 7.2 ± 6.5 and 20.8 ± 3.3 points, respectively. The IIEF-5 and total IPSS scores showed significant negative relationships (r = - 0.251, p < 0.001). Among the seven IPSS items, IPSS 5 (weak stream, r = - 0.243, p < 0.001) was most strongly correlated with the IIEF-5 scores. On multivariate analysis, IPSS 3 (intermittency, OR 0.160, 95% CI 1.010-1.333, p = 0.035) and IPSS 7 (nocturia, OR 1.238, 95% CI 1.077-1.423, p = 0.003) were significantly related to 'any degree of ED'. 'More than mild ED' was significantly related to IPSS 5 (weak stream, OR 1.267, 95% CI 1.058-1.518, p = 0.010). CONCLUSIONS: Every LUTS listed in the IPSS items was negatively correlated with erectile function. Among the seven IPSS items, IPSS 5 (weak stream) was the most related to 'more than mild ED'.

Clinical significance of 5-α reductase inhibitor and androgen deprivation therapy in bladder cancer incidence, recurrence, and survival: a meta-analysis and systemic review.

PURPOSE: This study aimed to investigate the effect of androgen suppression therapy (AST), comprising a 5-α reductase inhibitor (5-ARi) and androgen deprivation therapy (ADT), on the risk of bladder cancer incidence, recurrence, and mortality. MATERIALS AND METHODS: We used the PRISMA statement to report the methods and results of this meta-analysis. Bladder cancer incidence, recurrence, and mortality after 5-ARi treatment and ADT were assessed using risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs). The protocol of this study is registered in the PROSPERO database (No. CRD42018118627). RESULTS: We analyzed nine studies (n = 377,427) assessing the secondary effect of AST, with a mean follow-up period of 6 years (range, 2-13 years). Our result showed that the incidence of bladder cancer was significantly reduced when 5-ARi treatment (RR, 0.69; 95% CI, 0.58-0.81; I2 =0%) and ADT (HR, 0.81; 95% CI, 0.70-0.94; I2 =33%) were initiated before diagnosing bladder cancer. When treatment was initiated after diagnosing bladder cancer, 5-ARi treatment reduced cancer-specific mortality (RR, 0.29; 95% CI, 0.20-0.42; I2 =4.1%), whereas ADT reduced bladder cancer recurrence (HR, 0.30; 95% CI, 0.19-0.49; I2 =0%). CONCLUSIONS: This study corroborates that the use of 5-ARi and ADT could be helpful in managing bladder cancer and should not be limited to prostatic abnormalities.

Retropubic versus Transobturator Mid Urethral Slings in Patients at High Risk for Recurrent Stress Incontinence: A Systematic Review and Meta-Analysis.

PURPOSE: The efficacy and safety of retropubic and transobturator tension-free vaginal tape mid urethral slings remain controversial in patients with stress urinary incontinence and risk factors for recurrence. We compared the techniques after initial mid urethral sling insertion in select groups, including patients with obesity, intrinsic sphincter deficiency, pelvic organ prolapse and recurrent stress urinary incontinence. MATERIALS AND METHODS: We used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement to report the methods and results of the current review. Randomized controlled trials and observational studies were included. We assessed the objective and subjective cure rates, and the complication rate using the OR with the 95% CI. The protocol of the current meta-analysis was registered on PROSPERO (No. CRD42018102233). RESULTS: We retrieved 28 studies in a total of 2,607 patients to compare the efficacy and safety of retropubic vs transobturator tension-free vaginal tape in select groups (mean followup 26.9 months). Meta-analysis of the objective cure rate showed the significant superiority of retropubic compared to transobturator tension-free vaginal tape in patients overall (OR 3.37, 95% CI 2.55-4.43, p <0.00001, I2 = 37%) and in each subpopulation. The subjective cure rate of retropubic tension-free vaginal tape was also significantly superior to that of transobturator tension-free vaginal tape in in patients overall (OR 2.01, 95% CI 1.45-2.80, p <0.0001, I2 = 0%) and in those with intrinsic sphincter deficiency and recurrent stress urinary incontinence after mid urethral sling insertion. There was no significant difference in overall complications between retropubic and transobturator tension-free vaginal tape (OR 1.22, 95% CI 0.89-1.66, p = 0.21, I2 = 0%). CONCLUSIONS: The meta-analysis showed the superiority of retropubic tension-free vaginal tape over transobturator tension-free vaginal tape in terms of the objective and subjective cure rates in patients with obesity, intrinsic sphincter deficiency, pelvic organ prolapse and recurrent stress urinary incontinence after mid urethral sling insertion. Retropubic tension-free vaginal tape also has morbidity comparable to that of transobturator tension-free vaginal tape.

Clinical outcome of single-incision slings, excluding TVT-Secur, vs standard slings in the surgical management of stress incontinence: an updated systematic review and meta-analysis.

The aim of the present paper was to assess and compare the long-term efficacy and safety of single-incision mini-slings (SIMSs), except tension-free vaginal tape (TVT)-Secur, with standard midurethral slings (SMUSs) for female stress urinary incontinence through an updated systematic review and meta-analysis of randomized controlled trials (RCTs) comparing these two surgical methods. A literature review of all RCTs comparing SIMSs (Mini-Arc, Contasure-Needleless, Ophira, Tissue Fixation System and Ajust), except TVT-Secur, with SMUSs was performed. The Medline, Embase, Scopus, Web of Science and Cochrane Controlled Trial Register databases were reviewed. We retrieved 29 RCTs (including a total of 2 986 patients) that compared SIMSs, except TVT-Secur, with SMUSs. Meta-analysis of long-term results showed no significant difference in the patient-reported cure rate (odds ratio [OR] 0.67, 95% confidence interval [CI] 0.44-1.60); however, we found that SMUSs had a significantly superior objective cure rate (OR 0.68, 95% CI 0.47-0.99; P = 0.04). SIMSs were associated with a significantly shorter operation time, lower immediate postoperative pain based on a visual analogue scale score, lower intra-operative blood loss, and lower postoperative voiding dysfunction. The meta-analysis showed clear evidence of the superiority of SMUSs over SIMSs, except TVT-Secur, in terms of the objective cure rate, after long-term follow-up; however, SIMSs were superior with respect to immediate postoperative pain, intra-operative blood loss, and postoperative voiding dysfunction.

The Potential Role of Arginine Supplements on Erectile Dysfunction: A Systemic Review and Meta-Analysis.

INTRODUCTION: The efficacy and safety of arginine supplements in erectile dysfunction (ED) remain debatable. AIM: To assess the potential role of arginine supplements on ED as alternatives to phosphodiesterase inhibitors. METHODS: Studies published up to April 2018 that evaluated the efficacy of arginine supplements were identified from multiple databases (Google Scholar, PubMed, Medline, Embase, Kiss, DBpia, and Cochrane databases). Studies comparing arginine supplements with placebo or no treatment; focusing only on patients with mild to moderate severity of ED; and presenting outcomes such as improvement rate, International Index of Erectile Function (IIEF) score, and adverse effects were included. Subgroup analysis for arginine alone and arginine in combination with other substances was further conducted to increase interpretability. MAIN OUTCOME MEASURE: The strength of the association between arginine supplements and ED was assessed using relative odds ratios and weighted mean differences with 95% CI. RESULTS: In total, 10 randomized controlled trials met the inclusion criteria, reporting the outcomes of 540 patients with ED. The analysis demonstrated that arginine supplements with dosage ranging from 1,500 to 5,000 mg significantly improved ED compared with placebo or no treatment (odds ratios, 3.37 [1.29, 8.77], P = .01, I2 = 44). Arginine supplements also caused significant improvements in the IIEF subdomain scores of overall satisfaction, intercourse satisfaction, orgasmic function, and erectile function, whereas the IIEF sexual desire score remain unchanged. The adverse effect rate in the arginine-treated group was 8.3%, and that in the placebo group was 2.3%, none of which were severe. CLINICAL IMPLICATIONS: Arginine supplements can be recommended to patients with mild to moderate ED. STRENGTH & LIMITATIONS: The strength of this study is that it is the first meta-analysis to assess the potential role of arginine supplements in ED compared with placebo or no treatment. A limitation is that the treatment dosage and duration varied among studies, which may have contributed to study heterogeneity. CONCLUSION: The results of our systematic review and meta-analysis provide evidence on the effectiveness of arginine supplements for mild to moderate ED. Rhim HC, Kim MS, Park Y-J, et al. The Potential Role of Arginine Supplements on Erectile Dysfunction: A Systemic Review and Meta-Analysis. J Sex Med 2019;16:223-234.

The change of IPSS 7 (nocturia) score has the maximum influence on the change of Qol score in patients with lower urinary tract symptoms.

PURPOSE: This study evaluated the factors affecting lower urinary tract symptom (LUTS)-related quality-of-life (Qol) scores and the change in the Qol scores following treatment. METHODS: This pooled data analysis study collected the international prostate symptom score (IPSS) with Qol score from five studies which evaluated the change in the IPSS after medication for LUTS. Post-treatment IPSS with Qol scores were measured at 3 months after the initiation of medication. RESULTS: The mean age of 444 men was 62.5 ± 8.5 years. The mean IPSS total and Qol score at baseline were 18.6 ± 6.7 points and 4.0 ± 0.9 points, respectively. Each IPSS item score, except IPSS 3, was found to be an independent factor that had an influence on baseline Qol scores, with IPSS 7 (nocturia) showing the most significant correlation. After 3 months' medication, IPSS total and Qol score were significantly decreased to 11.7 ± 6.4 (p < 0.001) and 2.9 ± 1.2 points (p < 0.001), respectively. On multivariate analysis, the improvements in IPSS item 2, 4, 5, and 7 scores were found to be independent factors that had an influence on the improvement in Qol scores. The improvement in IPSS 7 had maximum influence on the improvement in Qol score. Among men with a decrease in total IPSS score by 5 or more points but without improvement in nocturia, Qol was not improved in one-third of them. CONCLUSIONS: Storage symptoms had a greater influence on QoL scores than voiding symptoms. The improvement in nocturia after treatment was the most important factor for the improvement in Qol.

Novel symptom questionnaire for the differential diagnosis of detrusor underactivity and bladder outlet obstruction in men.

OBJECTIVE: To develop a questionnaire for the differential diagnosis of detrusor underactivity (DUA) and bladder outlet obstruction (BOO) without performing invasive pressure flow studies. STUDY DESIGN AND METHODS: Symptoms of men with DUA were analyzed and compared with those of men with BOO using eight questions from the developing questionnaire. Patients with DUA have a bladder contractility index (PdetQmax+5xQmax) less than 100, whereas those with BOO have a BOO index (PdetQmax-2xQmax) greater than 40 in urodynamic studies (UDS). Men with detrusor overactivity in UDS and neurogenic issues were excluded from the analysis. One urologist reviewed patients' medical records, and responded to eight questions without using information from UDS. Scores in the developing questionnaire were then compared to make a differential diagnosis between DUA and BOO. RESULTS: Overall, 318 men who underwent UDS were included. Symptoms were compared in patients diagnosed with DUA without BOO (n = 165) and BOO without DUA (n = 153). Questions 1, 2, 4, 5, 6, and 7 were significantly different between groups. The sensitivity and specificity of the questionnaire were 95.8% and 95.4%, respectively, for predicting DUA in patients with scores greater than 45 points (cutoff value). CONCLUSIONS: Men with DUA and BOO may be distinguished using a developing questionnaire without invasive evaluation. Men with scores greater than 45 points would be expected to have DUA but not BOO.

Factors that influence lower urinary tract symptom (LUTS)-related quality of life (QoL) in a healthy population.

OBJECTIVES: The aim of this study was to evaluate the factors affecting the lower urinary tract symptoms (LUTS) related quality of life (QoL) score. METHODS: This retrospective study analyzed 29,123 men who underwent health check-ups from January 2007 to July 2011 at a single institution. Those patients who completed the American urologic association symptom index (AUA-SI) with QoL, beck depression inventory (BDI) and state-trait anxiety inventory questionnaires were included in the study. Men with a history of medication for LUTS were excluded from the study. Men who submitted QoL scores of 3 or higher in spite of mild LUTS (total AUA-SI score <8) were defined as having a relatively worse QoL. RESULTS: Mean age of 21,390 men was 48.4 ± 9.5 years. Mean total AUA-SI score was 6.4 ± 5.9 points. The QoL score was well correlated with the total AUA-SI score (r = 0.705, p < 0.001). Among all AUA-SI items, AUA-SI item 1 (incomplete emptying, r = 0.600, p < 0.001) had the strongest correlation with QoL scores. On the multivariate analysis, hypertension, total AUA-SI score, BDI score, and trait anxiety score were found to be independent factors that influenced the QoL scores. A lower age, a higher PSA, a higher AUA-SI score and a higher BDI score were risk factors for relatively worse QoL scores in spite of mild LUTS. CONCLUSIONS: Among the seven items of AUA-SI, AUA-SI item 1 has the strongest correlation with a worse LUTS-related QoL. Psychological status also influences the QoL scores.

Organization of the human mitochondrial transcription initiation complex.

Initiation of transcription in human mitochondria involves two factors, TFAM and TFB2M, in addition to the mitochondrial RNA polymerase, POLRMT. We have investigated the organization of the human mitochondrial transcription initiation complex on the light-strand promoter (LSP) through solution X-ray scattering, electron microscopy (EM) and biochemical studies. Our EM results demonstrate a compact organization of the initiation complex, suggesting that protein-protein interactions might help mediate initiation. We demonstrate that, in the absence of DNA, only POLRMT and TFAM form a stable interaction, albeit one with low affinity. This is consistent with the expected transient nature of the interactions necessary for initiation and implies that the promoter DNA acts as a scaffold that enables formation of the full initiation complex. Docking of known crystal structures into our EM maps results in a model for transcriptional initiation that strongly correlates with new and existing biochemical observations. Our results reveal the organization of TFAM, POLRMT and TFB2M around the LSP and represent the first structural characterization of the entire mitochondrial transcriptional initiation complex.

Prostate-specific antigen lowering effect of metabolic syndrome is influenced by prostate volume.

OBJECTIVES: To investigate the influence of metabolic syndrome on prostate-specific antigen levels by considering prostate volume and plasma volume. METHODS: We retrospectively analyzed 4111 men who underwent routine check-ups including prostate-specific antigen and transrectal ultrasonography. The definition of metabolic syndrome was based on the modified Adult Treatment Panel III criteria. Prostate-specific antigen mass density (prostate-specific antigen × plasma volume / prostate volume) was calculated for adjusting plasma volume and prostate volume. We compared prostate-specific antigen and prostate-specific antigen mass density levels of participants with metabolic syndrome (metabolic syndrome group, n = 1242) and without metabolic syndrome (non-prostate-specific antigen metabolic syndrome group, n = 2869). To evaluate the impact of metabolic syndrome on prostate-specific antigen, linear regression analysis for the natural logarithm of prostate-specific antigen was used. RESULTS: Patients in the metabolic syndrome group had significantly older age (P < 0.001), larger prostate volume (P < 0.001), higher plasma volume (P < 0.001) and lower mean serum prostate-specific antigen (non-metabolic syndrome group vs metabolic syndrome group; 1.22 ± 0.91 vs 1.15 ± 0.76 ng/mL, P = 0.006). Prostate-specific antigen mass density in the metabolic syndrome group was still significantly lower than that in the metabolic syndrome group (0.124 ± 0.084 vs 0.115 ± 0.071 µg/mL, P = 0.001). After adjusting for age, prostate volume and plasma volume using linear regression model, the presence of metabolic syndrome was a significant independent factor for lower prostate-specific antigen (prostate-specific antigen decrease by 4.1%, P = 0.046). CONCLUSIONS: Prostate-specific antigen levels in patients with metabolic syndrome seem to be lower, and this finding might be affected by the prostate volume.

Effect of chronic administration of PDE5 combined with glycemic control on erectile function in streptozotocin-induced diabetic rats.

INTRODUCTION: Chronic treatment with phosphodiesterase type 5 inhibitors (PDE5) is effective in an animal model of diabetes-induced erectile dysfunction (DMED). In addition, recent research indicates that glycemic control can restore DMED. AIMS: We evaluated the effect of chronic administration of PDE5 combined with glycemic control on DMED. METHODS: Sprague-Dawley rats (8 weeks old) were divided into five groups (n = 10 each): normal control (C), diabetes (DM), DM treated with insulin (DM-I), DM treated with PDE5 (DM-P), and DM treated with insulin and PDE5 (DM-I + P). Rats in the diabetic groups received an injection of streptozotocin (45 mg/kg). After 10 weeks of induced diabetes, the DM-I group was treated with a daily injection of neutral protamine Hagedorn, and the DM-P group was treated with a daily dosage of 20 mg/kg PDE5 (DA-8159) for 4 weeks. The DM-I + P group was treated with both treatments simultaneously. After 14 weeks of induced diabetes, an evaluation of erectile function and histological and biochemical markers of corporal tissue was performed. MAIN OUTCOME MEASURES: Erectile function and histological and biochemical markers in corporal tissue. RESULTS: Rats in the DM group showed markedly lower erectile parameters than those in the C group, whereas rats in the DM-I and DM-P groups showed intermediate erectile function between the DM and C groups. Rats in the DM-I + P group showed restored erectile function, comparable with group C. A comparison of apoptotic index, expression of the endothelial marker, and phosphorylation of endothelial nitric oxide synthase and Akt displayed a similar pattern with the results from cavernosometry (DM < DM-I = DM-P < DM-I + P = C, P < 0.05). The distribution of phosphorylated myosin phosphatase target subunit 1 was in the reverse order. CONCLUSIONS: Chronic administration of PDE5 or glycemic control with insulin resulted in restoration of overt DMED. The combination of both treatments was superior to monotherapy with insulin or PDE5.

Prognostic value of systemic inflammatory responses in patients with upper urinary tract urothelial carcinoma.

PURPOSE: To determine the utility of systemic inflammatory response and develop a model based on serum inflammatory indices to aid prognostication in patients with upper urinary tract urothelial carcinoma (UTUC). METHODS: The study population comprised 277 patients with non-metastatic UTUC who underwent nephroureterectomy between 1999 and 2010. Multivariate survival analysis was performed using Cox's proportional hazards model, and a new model was developed to predict recurrence-free (RFS) and disease-specific survival (DSS). The factors considered, in relation to systemic inflammatory responses, were as follows: albumin, white blood cell count, neutrophil count, lymphocyte count, red blood cell count, serum creatinine level, platelet count, prognostic nutritional index, platelet/lymphocyte ratio, neutrophil/lymphocyte ratio (NLR), and derived NLR. RESULTS: The final model consisted of bladder cuffing, pathologic T stage, lymphovascular invasion, and derived NLR. The bootstrap-concordance indices of the model were 0.778 [95 confidence interval (CI) 0.730-0.826] for RFS and 0.802 (95 % CI 0.752-0.851) for DSS, respectively, and integrated area under the curve value for time to RFS and DSS for patients was 0.738 and 0.760, respectively. When we generated calibration curves, the nomograms were reasonably calibrated. CONCLUSIONS: Derived NLR may be used in combination with conventional staging techniques and other clinicopathological parameters to improve the prediction of survival in patients with UTUC.

Usefulness of contrast-enhanced 3-dimensional T1-VISTA in the diagnosis of facial neuritis: comparison with contrast-enhanced T1-TSE.

BACKGROUND AND PURPOSE: Compared with 2-dimensional imaging, 3D-reformatted imaging is a valuable technique that offers improved anatomic accuracy with minimal flow artifact and thinner sections without gaps between slices. Our aim was to evaluate the usefulness of CE 3D T1-VISTA with fat suppression sequences compared with CE T1-TSE with fat suppression sequences in patients with facial neuritis. MATERIAL AND METHODS: The study enrolled 32 consecutive patients who underwent IAC MR imaging for Bell's palsy. IAC MR scanning, including CE T1-VISTA and CE T1-TSE, was performed in all patients using a 3T scanner. The order of the scans was random. Signal intensity was measured at three segments (canalicular, labyrinthine, and anterior genu) of the facial nerve by drawing a ROI along the affected side and the normal side in each segment. We compared the quantitative CR of the two MR sequences with paired t-tests. RESULTS: In all three segments, the lesion-to-normal contrast ratios on CE 3D T1-VISTA (canalicular: 2.32; labyrinthine: 2.22; anterior genu: 1.97) were greater than those on CE T1-TSE (canalicular: 2.17; labyrinthine: 1.72; anterior genu: 1.68). The labyrinthine and anterior genu segments had significantly higher lesion-to-normal contrast ratios on CE 3D T1-VISTA in patients with facial neuritis (labyrinthine: P<0.001; anterior genu: P=0.002). CONCLUSION: CE 3D T1-VISTA was superior to CE T1-TSE in terms of image contrast between lesions and the normal facial nerve.

Intrathyroidal parathyroid carcinoma mimicking a thyroid nodule in a MEN type 1 patient.

A 59-year-old woman with classic manifestations of hyperparathyroidism associated with multiple endocrine neoplasia type 1 presented with a right adrenal mass and two pituitary microadenomas on imaging studies. For evaluation of hypercalcemia, (99m) Tc-MIBI scintigraphy was done and showed focal uptake at the thyroid level of the right anterior neck. Subsequent neck sonography showed several thyroid nodules, but there was no parathyroid tumor. Percutaneous fine-needle aspiration of the dominant thyroid nodule indicated a follicular nodule. After surgery, final histopathology revealed intrathyroidal parathyroid carcinoma. This case illustrates the difficulty in diagnosing parathyroid carcinoma via fine-needle aspiration.

Preoperative serum albumin as a prognostic factor in patients with upper urinary tract urothelial carcinoma.

PURPOSE: The study evaluated whether preoperative measures of the C-reactive protein-systemic inflammatory response may predict cancer survival independent of tumor stage in patients with upper urinary tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: Between September 1999 and October 2010, 181 patients submitted to radical nephroureterectomy were available for evaluation. Multivariate survival analyses were performed using Cox's proportional hazards model and the coefficient for each factor was divided by the highest coefficient, multiplied by 4, and rounded to the nearest integer. RESULTS: Multivariate analyses showed that tumor location, pathologic T stage, lymphovascular invasion, margin status, and albumin level were independent contributors. The bootstrap-corrected C statistics of the model were 0.813 for disease-specific survival and 0.755 for overall survival, respectively. For time to disease-specific and overall mortality for patients, integrated area under the curve values were 0.792 and 0.739, respectively. When patients were clustered into three groups according to their model-predicted survival, the 5-year disease-specific survival in the low-, intermediate- and high-risk group was 95.4%, 76.2%, and 36.9%, respectively (p<0.001), and were 87.8%, 54.4%, and 31.8%, respectively, for overall survival (p<0.001). Decision curve analysis revealed that the use of model was associated with net benefit gains relative to the treat-all strategy. CONCLUSIONS: Pretreatment albumin is a simple biomarker based on routinely available well-standardized measures, and is not an expensive and time-consuming process. Hypoalbuminemia is an independent marker of poor prognosis in patients with upper urinary tract urothelial carcinoma.