The prognostic role of circulating tumor cells (ctc) in high-risk non-muscle-invasive bladder cancer

Circulating tumor cells (CTCs) could represent a promising, noninvasive prognostic and predictive marker in high-risk patients with nonemuscle-invasive bladder cancer. We retrospectively evaluated 155 patients with pT1G3 bladder cancer who underwent transurethral resection of bladder tumor after a blood withdrawal for CTC evaluation. In our analysis, the presence of CTCs was significantly associated with time to first recurrence and time to progression. Introduction: The purpose of this study was to evaluate the impact of circulating tumor cells (CTCs) as a prognostic marker in patients with high-risk nonemuscle-invasive bladder cancer (NMIBC) and assess the efficacy and reliability of 2 different CTC isolation methods. Materials and Methods: Globally, 155 patients with a pathologically confirmed diagnosis of high-risk NMIBC were included (pT1G3 with or without carcinoma in situ) and underwent transurethral resection of bladder tumor (TURB) after a blood withdrawal for CTC evaluation. A total of 101 patients (Group A) had their samples analyzed with the CellSearch automated system, and 54 (Group B) had their samples analyzed with the CELLection Dynabeads manual system. Results: Patients were followed for 28 months, and during this interval, there were a total of 65 (41.9%) recurrences, 27 (17.4%) disease progressions, and 9 (5.8%) lymph node and/or bone metastasis. In our CTC analysis, there were 20 (19.8%) positive patients in Group A and 24 in Group B (44.4%). In our analysis, we found a strong correlation between CTC presence and time to first recurrence; in Group A, we observed an incidence of recurrence in 75% of CTC-positive patients and in Group B of 83% of CTC-positive patients. The time to progression was also strongly correlated with CTCs: 65% and 29%, respectively, of those patients who progressed in those with CTCs in Group A and B. Conclusion: The study demonstrates the potential role of CTCs as a prognostic marker for risk stratification in patients with NMIBC, to predict both recurrence and progression

Exercise Does not Stimulate Citrate Synthase Activity in Cachectic Muscle

Cachexia causes metabolic alterations in skeletal muscle mitochondria stimulated by inflammatory imbalance towards pro-inflammatory signaling. Previous work by our group has demonstrated that exercise significantly increases muscle mass in cases of advanced tumors in transgenic mice. Furthermore, we have discovered that the natural product Nexrutine® has anti-inflammatory properties which can be beneficial in protecting mitochondria. PURPOSE: To compare the effects of exercise and Nexrutine® on mitochondrial density in skeletal muscle taken from transgenic adenocarcinoma of the mouse prostate (TRAMP) models. METHODS: This project is a continuation of a larger study investigating the effects of exercise and Nexrutine® on the attenuation of muscle wasting in TRAMP mice. For this analysis, gastrocnemius from 14 TRAMP mice from control (n=5), Nexrutine® (600 mg/kg; n=5), and voluntary wheel running (VWR) groups (n=4) that completed 20 weeks of intervention were used. Mitochondrial activity was quantified using a commercially available citrate synthase assay (Cayman Chemical, USA). An analysis of variance (ANOVA) with Tukey’s post-hoc was performed. Correlations between muscle mass and citrate synthase activity was performed for each group. Alpha was set at p ≤ 0.05. RESULTS: All mice presented with tumors upon necropsy. VWR mice ran on average 6.67 kilometers per day. Nexrutine® group consumed 1.49 mg Nexrutine® per day on average. No significant differences in muscle mass or citrate synthase were observed between groups. Briefly, the control group had 7.31% and 20.75% greater citrate synthase compared to Nexrutine® and exercise groups, respectively. Exercise group was observed to have 35.25% higher than Nexrutine® group. When all samples were combined, a significant positive correlation was observed between muscle mass and citrate synthase (p= 0.04). CONCLUSION: Contrary to our hypothesis, the results suggest neither exercise nor Nexrutine® positively affect citrate synthase activity in cachectic muscle. Future work by our group will focus on reactive oxygen species and mitochondrial complex activity to further understand how cachexia affects skeletal muscle mitochondrial efficiency

Postoperative vacuum therapy following AMS™ LGX 700® inflatable penile prosthesis placement: penile dimension outcomes and overall satisfaction

Penile shortening after inflatable penile prosthesis for erectile dysfunction is a common postoperative patient complaint and can reduce overall satisfaction with the procedure. In this prospective study we report our results regarding penile dimensions and patient satisfaction outcomes after 1 year of follow-up from AMS™LGX700® penile prosthesis implant with 6 months of vacuum erectile device therapy. Seventy-four selected patients with medically refractory erectile dysfunction underwent AMS™ LGX 700® IPP placement. Postoperatively, patients were assigned vacuum device therapy for 5 min twice daily. Follow-up continued for 1 year after surgery. Dimensional and functional results were assessed. Baseline median preoperative stretched penile length and girth were 14 cm (range 10–17) and 9 cm (range 7–12), respectively. At the end of the study penile median dimensional outcomes were 17 cm (range 13–23) for length and 11 cm (range 10–13) for girth while a median number of 24 pumps (range 18–29) to fully inflate the device was seen. Baseline median International Index of Erectile Function (IIEF-5) score was 9 (range 5–11), at 6 months 20 (range 18–26) and at 1 year was 25 (range 20–27) (p < 0.0001). Median Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) score at the end of the follow-up was 74 (range 66–78). Our postoperative rehabilitation program is feasible and should be recommended after prothesis surgery in order to increase overall satisfaction with the procedure. Penile postoperative dimensional outcomes were statistically significant improved and complications were negligible

Subjects With Early-Onset Type 2 Diabetes Show Defective Activation of the Skeletal Muscle PGC-1α/Mitofusin-2 Regulatory Pathway in Response to Physical Activity

Objective: Type 2 diabetes is associated with insulin resistance and skeletal muscle mitochondrial dysfunction. We have found that subjects with early-onset type 2 diabetes show incapacity to increase Vo2max in response to chronic exercise. This suggests a defect in muscle mitochondrial response to exercise. Here, we have explored the nature of the mechanisms involved. Research design and methods: Muscle biopsies were collected from young type 2 diabetic subjects and obese control subjects before and after acute or chronic exercise protocols, and the expression of genes and/or proteins relevant to mitochondrial function was measured. In particular, the regulatory pathway peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha/mitofusin-2 (Mfn2) was analyzed. Results: At baseline, subjects with diabetes showed reduced expression (by 26%) of the mitochondrial fusion protein Mfn2 and a 39% reduction of the alpha-subunit of ATP synthase. Porin expression was unchanged, consistent with normal mitochondrial mass. Chronic exercise led to a 2.8-fold increase in Mfn2, as well as increases in porin, and the alpha-subunit of ATP synthase in muscle from control subjects. However, Mfn2 was unchanged after chronic exercise in individuals with diabetes, whereas porin and alpha-subunit of ATP synthase were increased. Acute exercise caused a fourfold increase in PGC-1alpha expression in muscle from control subjects but not in subjects with diabetes. Conclusions: Our results demonstrate alterations in the regulatory pathway that controls PGC-1alpha expression and induction of Mfn2 in muscle from patients with early-onset type 2 diabetes. Patients with early-onset type 2 diabetes display abnormalities in the exercise-dependent pathway that regulates the expression of PGC-1alpha and Mfn2.</p

Creativity in Engineering Education

The paper examines the creativity in engineering education. The authors substantiate the topicality of the training of creative professionals in Russia and abroad and present training of creative professionals experience at the Department of Engineering Entrepreneurship of NR TPU. The empirical basis of the paper is the definition of the algorithm and conditions of the training of creative professionals

Metformin Attenuates Palmitate-Induced Endoplasmic Reticulum Stress, Serine Phosphorylation of IRS-1 and Apoptosis in Rat Insulinoma Cells

Lipotoxicity refers to cellular dysfunctions caused by elevated free fatty acid levels playing a central role in the development and progression of obesity related diseases. Saturated fatty acids cause insulin resistance and reduce insulin production in the pancreatic islets, thereby generating a vicious cycle, which potentially culminates in type 2 diabetes. The underlying endoplasmic reticulum (ER) stress response can lead to even β-cell death (lipoapoptosis). Since improvement of β-cell viability is a promising anti-diabetic strategy, the protective effect of metformin, a known insulin sensitizer was studied in rat insulinoma cells. Assessment of palmitate-induced lipoapoptosis by fluorescent microscopy and by detection of caspase-3 showed a significant decrease in metformin treated cells. Attenuation of β-cell lipotoxicity was also revealed by lower induction/activation of various ER stress markers, e.g. phosphorylation of eukaryotic initiation factor 2α (eIF2α), c-Jun N-terminal kinase (JNK), insulin receptor substrate-1 (IRS-1) and induction of CCAAT/enhancer binding protein homologous protein (CHOP). Our results indicate that the β-cell protective activity of metformin in lipotoxicity can be at least partly attributed to suppression of ER stress

The CroHort Study: Cardiovascular Behavioral Risk Factors in Adults, School Children and Adolescents, Hospitalized Coronary Heart Disease Patients, and Cardio Rehabilitation Groups in Croatia

Based on repeated measurement of health behaviors the CroHort Study showed that health behavior explains a great deal more of class inequalities in mortality than observed in previous studies. These include decreasing prevalence of smoking and increase in obesity, hypertension and diabetes mellitus. The lowest prevalence of health risks was recorded among children and adolescents, followed by general adult population from the CroHort Study. Hospitalized coronary heart disease patients had higher risks prevalence than general population, while the highest prevalence of risks was recorded among patients in cardiac rehabilitation program. The higher levels of stress were associated to lower financial conditions, poorer social functioning and poorer mental health for bothmen and women. Higher levels of stress were also associated with heart problems, higher alcohol consumption in men while in women stress was associated to poorer general health, higher age and lower levels of education

Modified Glasgow Prognostic Score as a Predictor of Recurrence in Patients with High Grade Non-Muscle Invasive Bladder Cancer Undergoing Intravesical Bacillus Calmette–Guerin Immunotherapy

Background: A systemic inflammatory marker, the modified Glasgow prognostic score (mGPS), could predict outcomes in non-muscle-invasive bladder cancer (NIMBC). We aimed to investigate the predictive power of mGPS in oncological outcomes in HG/G3 T1 NMIBC patients undergoing Bacillus Calmette–Guérin (BCG) therapy. Methods: We retrospectively reviewed patient’s medical data from multicenter institutions. A total of 1382 patients with HG/G3 T1 NMIBC have been administered adjuvant intravesical BCG therapy, every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months. The analysis of mGPS for recurrence and progression was performed using multivariable and univariable Cox regression models. Results: During follow-up, 659 patients (47.68%) suffered recurrence, 441 (31.91%) suffered progression, 156 (11.28%) died of all causes, and 67 (4.84%) died of bladder cancer. At multivariable analysis, neutrophil to lymphocyte ratio [hazard ratio (HR): 7.471; p = 0.0001] and erythrocyte sedimentation rate (ESR) (HR: 0.706; p = 0.006 were significantly associated with recurrence. mGPS has no statistical significance for progression (p = 0.076). Kaplan–Meier survival analysis showed a significant difference in survival among patients from different mGPS subgroups. Five-year OS was 93% (CI 95% 92–94), in patients with mGPS 0, 82.2% (CI 95% 78.9–85.5) in patients with mGPS 1 and 78.1% (CI 95% 60.4–70) in mGPS 2 patients. Five-year CSS was 98% (CI 95% 97–99) in patients with mGPS 0, 90% (CI 95% 87–94) in patients with mGPS 1, and 100% in mGPS 2 patients. Limitations are applicable to a retrospective study. Conclusions: mGPS may have the potential to predict recurrence in HG/G3 T1 NMIBC patients, but more prospective, with large cohorts, studies are needed to study the influence of systemic inflammatory markers in prediction of outcomes in NMIBC for a definitive conclusion

Multiparametric magnetic resonance imaging and frozen-section analysis efficiently predict upgrading, upstaging, and extraprostatic extension in patients undergoing nerve-sparing robotic-assisted radical prostatectomy

To evaluate the role of multiparametric magnetic resonance imaging (mpMRI) in predicting upgrading, upstaging, and extraprostatic extension in patients with low-risk prostate cancer (PCa). MpMRI may reduce positive surgical margins (PSM) and improve nerve-sparing during robotic-assisted radical prostatectomy (RARP) for localized prostate cancer PCa.This was a retrospective, monocentric, observational study. We retrieved the records of patients undergoing RARP from January 2012 to December 2013 at our Institution. Inclusion criteria were: PSA <10\u200ang/mL; clinical stage <T3a; biopsy Gleason score <7; prostate mpMRI performed preoperatively at our Institution; intraoperative FSA of the posterolateral aspects of the specimen.All the identified lesions were scored according to the Prostate Imaging Reporting and Data System (PIRADS). We considered the lesion with the highest PIRADS score as index lesion. All the included patients underwent nerve-sparing RARP. During surgery, the specimen was sent for FSA of the posterolateral aspects. The surgeon, according to the localization scheme provided by the mpMRI, inked the region of the posterolateral aspect of the prostate that had to be submitted to FSA.We evaluated association between clinical features and PSM, upgrading, upstaging, and presence of unfavorable disease.Two hundred fifty-four patients who underwent nerve-sparing RARP were included. PSM rate was 29.13% and 15.75% at FSA and final pathology respectively. Interestingly, the use of FSA reduced PSM rate in pT3 disease (25.81%). Higher PIRADS scores demonstrated to be related to high probability of upgrading and upstaging. This significativity remains even when considering PIRADS 2-3 versus 4 versus 5 and PIRADS 2-3 versus 4-5. Also PSM at FSA were associated with higher probability of upgrading and upstaging.PIRADS score and FSA resulted to be strictly related to grading and staging, thus being able to predict upgrading and/or upstaging at final pathology