Effectiveness and safety of sofosbuvir-based regimens plus an NS5A inhibitor for patients with HCV genotype 3 infection and cirrhosis. Results of a multicenter real-life cohort.

Patients with HCV genotype 3 (GT3) infection and cirrhosis are currently the most difficult to cure. We report our experience with sofosbuvir+daclatasvir (SOF+DCV) or sofosbuvir/ledipasvir (SOF/LDV), with or without ribavirin (RBV) in clinical practice in this population. This was a multicenter observational study including cirrhotic patients infected by HCV GT3, treated with sofosbuvir plus an NS5A inhibitor (May 2014-October 2015). In total, 208 patients were included: 98 (47%) treatment-experienced, 42 (20%) decompensated and 55 (27%) MELD score >10. In 131 (63%), treatment was SOF+DCV and in 77 (37%), SOF/LDV. Overall, 86% received RBV. RBV addition and extension to 24 weeks was higher in the SOF/LDV group (95% vs 80%, P=.002 and 83% vs 72%, P=.044, respectively). A higher percentage of decompensated patients were treated with DCV than LDV (25% vs 12%, P=.013). Overall, SVR12 was 93.8% (195/208): 94% with SOF+DCV and 93.5% with SOF/LDV. SVR12 was achieved in 90.5% of decompensated patients. Eleven treatment failures: 10 relapses and one breakthrough. RBV addition did not improve SVR (RR: 1.08; P=.919). The single factor associated with failure to achieve SVR was platelet count <75×10E9/mL (RR: 3.50, P=.019). In patients with MELD <10, type of NS5A inhibitor did not impact on SVR12 (94% vs 97%; adjusted RR: 0.49). Thirteen patients (6.3%) had serious adverse events, including three deaths (1.4%) and one therapy discontinuation (0.5%), higher in decompensated patients (16.7% vs 3.6%, P<.006). In patients with GT3 infection and cirrhosis, SVR12 rates were high with both SOF+DCV and SOF/LDV, with few serious adverse events.

State of art of robotic prostatectomy: the way we do it in Catalonia, Spain.

INTRODUCTION AND OBJECTIVE: Robotic-assisted laparoscopic prostatectomy (PLAR) seems to improve functional outcomes, however there is not a consensus of a standard procedure. The aim of this study was to identify the PLAR "state of art" in Catalonia, Spain. MATERIAL AND METHODS: This was a cross-sectional survey-based study conducted among urologists across Catalonia, Spain. The survey was distributed through online platforms and the professional urology society. All statistical analyses were performed using Stata software, v20. RESULTS: 59 urologists completed the survey, revealing PLAR as the most commonly used technique (79.7%). Most urologist (70%) create the pneumoperitoneum using a controlled incision with direct access and 78.3% use the Airseal technology. The intraperitoneal approach is performed in >90% of cases. Endopelvic fascia preservation is not routinely performed. 34.5% of the survey not perform the dorsal vein complex suture. All preserves the bladder neck when oncologically safe. Nerve-vascular bundles bleeding control is performed using standard coagulation or suturing. 34% performed posterior reconstruction. Only use hemostatic devices when evident bleeding and 70% does not routinely left a drainage. Multivariable analysis showed that center volume had a significant independent association with dorsal venous complex suturing (OR 0.073, 95%CI 0.07-0.826), nerve-vascular bundles suturing hemostasis (OR 11.67, 95%CI 1.07-127.60) and endopelvic fascia preservation (OR 13.64, 95%CI 1.087-201.27), but there was no correlation with time the bladder catheter or days hospitalized. CONCLUSIONS: The study provides an overview of the state of PLAR in Catalonia, Spain, showing significant variability and reflecting a commitment to advancing surgical technology and patient care.

Analysis of the lipid profile and atherogenic risk during androgen deprivation therapy in prostate cancer patients.

OBJECTIVE: To analyse changes in lipid profiles observed in patients receiving androgen deprivation therapy (ADT) and to evaluate differences between medical castration and maximal androgen blockade (MAB). MATERIAL AND METHODS: Serum levels of total cholesterol (TC), high-density lipoproteins (HDL), low-density lipoproteins (LDL) and triglycerides (TG) were prospectively evaluated in 33 patients with locally advanced or metastatic prostate cancer treated with ADT. The median age was 73.4 years. Serum lipids were measured at baseline and thereafter at 6 and 12 months. The modality of ADT was medical, with 3 months depot LHRH agonist, in 11 patients and MAB, by addition of 50 mg/day of bicalutamide, in 22 patients. RESULTS: TC increased from 210 to 227 mg/dl (p < 0.05), while LDL increased from 132 to 148 mg/dl (p < 0.05) at 6 months. There were no significant changes in HDL or TG levels. There were no significant differences in any of the analysed parameters after 12 months of ADT. The comparison between the group of patients treated with LHRH agonists alone and the group treated with MAB demonstrated no significant differences in any of the analysed parameters at 6 and 12 months (p > 0.05). CONCLUSIONS: Changes observed in TC and LDL after 6 months of ADT were transitory. No significant differences were observed according to the modality of ADT.

Systematic review of methods used to improve the efficacy of magnetic resonance in early detection of clinically significant prostate cancer.

BACKGROUND AND OBJECTIVE: Prostate cancer (PC) is the malignant neoplasm with the highest incidence after lung cancer worldwide. The objective of this study is to review the literature on the methods that improve the efficacy of the current strategy for the early diagnosis of clinically significant PC (csPC), based on the performance of magnetic resonance imaging (RM) and targeted biopsies when suspicious lesions are detected, in addition to systematic biopsy. EVIDENCE ACQUISITION: A systematic literature review was performed in PubMed, Web of Science and Cochrane according to the PRISMA criteria (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), using the search terms: multiparametric magnetic resonance imaging, biparametric magnetic resonance imaging, biomarkers in prostate cancer, prostate cancer y early diagnosis. A total of 297 references were identified and, using the PICO selection criteria, 21 publications were finally selected to synthesize the evidence. EVIDENCE SYNTHESIS: With the consolidation of MRI as the test of choice for the diagnosis of prostate cancer, the role of PSA density (PSAD) becomes relevant as a predictive tool included in prediction nomograms, without added cost. PSAD and diagnostic markers, combined with MRI, offer a high diagnostic power with an area under curve (AUC) above 0.7. Only the SHTLM3 model integrates markers in the creation of a nomogram. Prediction models also offer consistent efficacy with an AUC greater than 0.8 when associating MRI. CONCLUSIONS: The efficacy of MRI in clinically significant prostate cancer detection can be improved with different parameters in order to generate predictive models that support decision making.

Frequency and mechanism of ischemic stroke associated with malignancy: a retrospective series.

BACKGROUND: Cerebrovascular disease is the second most common non-metastatic neurological disorder in oncological patients. The aims of this study were to determine the prevalence of cancer in stroke patients and to compare mechanisms of stroke between patients with and without malignancy. PATIENTS AND METHODS: This retrospective study involved patients with ischemic stroke admitted over 1 year to a Neurology Department. Demographic and clinical data, cardiovascular risk factors, and laboratory findings were recorded. The etiology was classified following the TOAST criteria. Participants were classified as stroke and cancer patients (diagnosis of malignancy before stroke or cancer diagnosed after admission) or as control stroke patients. RESULTS: Over 1 year, 291 stroke patients (268 ischemic) were admitted. Sixteen ischemic patients had a malignancy (5.9%), and in 12 patients, malignancy was the only cause found for the stroke; in 4 patients, malignancy was a coexisting condition. Coexistent stroke and cancer was significantly related to higher median levels of fibrinogen, D-dimers, and erythrocyte sedimentation rate (ESR). Logistic regression analysis showed that D-dimer and ESR levels were independently related to cancer, with odds ratios of 1.004 (95% CI 1.001-1.007, p=0.02) and 1.075 (95% CI 1.031-1.121, p=0.001), respectively. CONCLUSIONS: Almost 6% of ischemic stroke patients had a concomitant malignancy. In most of them, cancer was the only cause of stroke found. Patients with stroke and malignancy exhibited raised D-dimer, fibrinogen, and ESR levels, suggesting the prothrombotic state was a principal mechanism underlying stroke. D-dimer and ESR assessments may be useful in identifying underlying disorders in ischemic stroke.

Reciprocal translocations in cattle: frequency estimation.

Chromosomal anomalies, like Robertsonian and reciprocal translocations, represent a big problem in cattle breeding as their presence induces, in the carrier subjects, a well-documented fertility reduction. In cattle, reciprocal translocations (RCPs, a chromosome abnormality caused by an exchange of material between non-homologous chromosomes) are considered rare as to date only 19 reciprocal translocations have been described. In cattle, it is common knowledge that the Robertsonian translocations represent the most common cytogenetic anomalies, and this is probably due to the existence of the endemic 1;29 Robertsonian translocation. However, these considerations are based on data obtained using techniques that are unable to identify all reciprocal translocations, and thus, their frequency is clearly underestimated. The purpose of this work is to provide a first realistic estimate of the impact of RCPs in the cattle population studied, trying to eliminate the factors that have caused an underestimation of their frequency so far. We performed this work using a mathematical as well as a simulation approach and, as biological data, we considered the cytogenetic results obtained in the last 15 years. The results obtained show that only 16% of reciprocal translocations can be detected using simple Giemsa techniques, and consequently, they could be present in no <0.14% of cattle subjects, a frequency five times higher than that shown by de novo Robertsonian translocations. This data is useful to open a debate about the need to introduce a more efficient method to identify RCP in cattle.

Continence definition and prognostic factors for early urinary continence recovery in posterior rhabdosphincter reconstruction after robot-assisted radical prostatectomy. Post-hoc analysis of a randomised controlled trial.

INTRODUCTION: Urinary incontinence after radical prostatectomy (RP) is an adverse event with high impact on patient's quality of life. Nowadays there is no standardized method for urinary continence measurement. Posterior rhabdosphincter reconstruction (PRR) is a surgical step that can improve early urinary continence after RP. Our objective was to analyse different continence definitions and predictors of urinary continence recovery after robot-assisted RP (RARP). MATERIAL AND METHODS: We conducted a double-blind, randomised controlled trial (NCT03302169) including 152 consecutive patients with localized prostate cancer subjected to RARP. Patients were randomised to single urethrovesical anastomosis (control arm) or PRR before urethrovesical anastomosis (PRR arm). Urinary continence was measured with the EPIC-26 and ICIQ-SF validated questionnaires, and pad use (0-1 pads and no pads), at 7, 15, 30, 90, 180 and 365 days after catheter removal. Prognostic factors for early urinary continence recovery were analysed. RESULTS: 72 patients were included in the control arm and 80 in the PRR arm. Baseline characteristics were similar between arms, except body mass index, which was higher in PRR arm. "No pad" was the only definition assessing the benefit of PRR at 30 days, 33.8% in PRR arm and 18.1% in control arm, p = 0.022; and at 90 days, 58.8 and 43.1% respectively, p = 0.038. Questionnaires did not detect differences in terms of continence recovery. PRR was the only predictor for early continence recovery, p = 0.03. CONCLUSIONS: PRR increased early urinary continence recovery after RARP. Continence definition was critical to assess benefit. The only predictive factor for early continence recovery was PRR.

Famalismo Primero and Puerta Cerrada in Self-Managing Diabetes Among Hispanics: A Qualitative Meta-Synthesis.

INTRODUCTION: Type 2 diabetes (T2D) prevalence is increasing at concerning rates for Hispanics. Researchers have attempted to understand why through quantitative or qualitative studies. This meta-synthesis examines qualitative studies concerning barriers and facilitators that Hispanics face while managing their diabetes. METHOD: Noblit and Hare's (1988) defined method of analysis was used to synthesize 15 qualitative studies on Hispanics' diabetes self-management. RESULTS: Findings revealed two themes: (a) famalismo primero and (b) puerta cerrada, translating to family first and closed door, respectively. In famalismo primero, Hispanics with T2D prioritize family, and receive support, motivation, and knowledge from them first; puerta cerrada is tied to barriers such as cost of services and patient-provider relationships. DISCUSSION: Inclusion of family in diabetes self-management provides support and motivation for Hispanics. Hispanics experience barriers to access health care that may interfere with diabetes self-management, which need to be addressed to promote health equity.

The current value of histological findings in negative prostate biopsies to predict the future risk of clinically significant prostate cancer.

BACKGROUND: Repeat prostate biopsy (PBx) is recommended under persistent suspicion of prostate cancer (PCa) or in the face of the following findings: atypical small acinar proliferation (ASAP); extense (≥3 biopsy sites) high-grade prostatic intraepithelial neoplasia (HGPIN); or HGPIN with atypical glands; suspicious for adenocarcinoma (PIN-ATYP). Nowadays; multiparametric magnetic resonance imaging (mpMRI) and mpMRI targeted PBx (MRI-TBx) are recommended in repeat PBx. Our objective was to analyze the current value of ASAP; mHGPIN; PIN-ATYP and other histological findings to predict clinically significant PCa (csPCa) risk. METHODS: Retrospective analysis of 377 repeat PBxs. MRI-TBx was performed when Prostate Imaging-Reporting and Data System (PI-RADS) score >3 and 12-core transrectal ultrasound (TRUS) systematic PBx when ≤2. ASAP; HGPIN; mHGPIN; PIN-ATYP; and 8 other histological findings were prospectively reported in negative PBx. CsPCa was defined as ISUP group grade >2. RESULTS: Incidence of ASAP; multifocal HGPIN (mHGPIN) and PINATYP was 4.2%; 39.7% and 3.7% respectively; and csPCa rate was statistically similar among men with these histological findings. However; the rate of csPCa was 22.2% when proliferative inflammatory atrophy (PIA) was present; and 36.1% when it was not. PIA was the only histological finding which predicted lower risk of csPCa; with an OR of 0.54 (95%CI: 0.308-0.945; P = .031). In addition; PIA was an independent predictor of a model combining clinical variables and mpMRI which reached area under de ROC curve of 0.86 (95%CI: 0.83-0.90). CONCLUSION: PIA emerged as the only predictive histological finding of csPCa risk and can contribute to a predictive model. mHGPIN failed to predict csPCa risk. The low incidence of ASAP (4.2%) and PIN-ATYP (3.7%) prevented us from drawing conclusions.

Monolithic PDMS passband filters for fluorescence detection.

We present the fabrication and characteristics of monolithically integrated ink dyed poly(dimethylsiloxane) (PDMS) filters for optical sensing in disposable lab-on-a-chip. This represents a migration of auxillary functions onto the disposable chip with the goal of producing truly portable systems. Filters made from commercially available ink (Pelikan) directly mixed into PDMS oligomer without the use of any additional solvents were patterned with standard soft lithography technologies. Furthermore, a fabrication process based on capillary forces is presented allowing PDMS coloration of arbitrary shapes. Different filters of varying thickness fabricated using red, green and blue ink in four different concentrations were characterized. The optimal performance was found with filter thicknesses of 250 microm and ink to PDMS ratios of 0.1 (mL ink : mL PDMS oligomer) resulting in a transmittance ranging from -15.1 dB to -12.3 dB in the stopband and from -4.0 dB to -2.5 dB in the passband. Additionally, we demonstrate the robustness of this approach as the ink dyed PDMS filters do not exhibit temporal ageing due to diffusion or autofluorescence. We also show that such filters can easily be integrated in fluorescence systems, with stopbands efficient enough to allow fluorescence measurements under non-optimal conditions (broadband excitation, 180 degrees configuration). Integrated ink dyed PDMS filters add robust optical functionalities to disposable microdevices at a low cost and will enable the use of these devices for a wide range of fluorescence and absorbance based biological and chemical analysis.

In Search for risk predictors at the microscopic scenario of a negative biopsy. A systematic review. / Análisis del escenario microscópico de una biopsia prostática negativa como predictor del riesgo de cáncer de próstata. Una revisión sistemática.

INTRODUCTION: In cases of persistent suspicion of prostate cancer (PC), repeat prostate biopsies (PB) are frequently performed in spite of their low yield. In the context of a negative PB, there is a microscopic scenario (MS), which we define as the group of recognizable non-neoplastic lesions. While some of these lesions seem to have a protective effect, the existence of others increases the risk of PC detection in posterior PB. The objective of this systematic review is to identify the lesions that may belong to the MS of a negative PB and analyse the current evidence of their association with the risk of detecting PC in subsequent PBs. EVIDENCE ACQUISITION: Two independent reviewers conducted a literature search on Medline, Embase and Central Cochrane with the following search terms: small acinar proliferation, ASAP, prostatic intraepithelial neoplasia, HGPIN, adjacent small atypical glands, pinatyp, atrophy, proliferative inflammatory atrophy, pia, prostatic inflammation, prostatitis and prostate cancer. 1,015 references were first identified, and 57 original articles were included in the study, following the PRISMA declaration and the PICO selection principles. EVIDENCE SYNTHESIS: Atypical small acinar proliferation is associated with PC detection in repeat PB with rates ranging between 32 and 48%. High-grade prostatic intraepithelial neoplasia (HGPIN) is related to PC in 13 to 42% of cases. Studies show that HGPIN, when multifocal, is a significant independent risk factor for PC. Prostatic atrophy, inflammatory proliferative atrophy and prostatic inflammation seem to act as protective factors on the detection of PC in repeat PB. On the other hand, the risk of PC detection reduces significantly in male patients with multifocal HGPIN and coexistent PIA. CONCLUSIONS: The MS of a negative PB may include atypical small acinar proliferation, HGPIN, prostatic atrophy, inflammatory proliferative atrophy and prostatic inflammation lesions, since they all seem to be associated with the risk of PC detection in repeat PB. This review has led us to create the hypothesis that the MS of a negative PB might be a valuable and useful tool when considering repeat PB.

Early continence after radical prostatectomy: A systematic review. / Variaciones de la prostatectomía radical para una recuperación de la continencia urinaria precoz: una revisión sistemática.

BACKGROUND AND OBJECTIVE: Urinary incontinence is the adverse effect with more impact on patients' quality of life after undergoing radical prostatectomy. The objective of this study is to review the present evidence that describes the variations on surgical techniques which aim to preserve urinary continence after radical prostatectomy. EVIDENCE ACQUISITION: We searched the literature on PubMed, Cochrane, and ScienceDirect according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement, using the PICO review protocol. The search terms were urinary continence, urinary incontinence, urinary leakage, radical prostatectomy, open radical prostatectomy, laparoscopic prostatectomy, robot-assisted laparoscopic prostatectomy, robotic prostatectomy. We identified 1,603 registers, and 27 articles were reviewed for meeting the inclusion criteria. Six of them are randomized clinical trials and 4 of them, meta-analysis. EVIDENCE SYNTHESIS: The surgical techniques more frequently used to achieve early urinary continence are bladder neck and neurovascular bundles preservation, as well as the reconstruction of the rhabdosphincter. The latter has been presented in three randomized clinical trials. Even though some approaches have obtained improved functional outcomes, the lack of consensus on the definition of urinary incontinence and its measurement methods have not advocated for the creation of technical recommendations based on scientific evidence. CONCLUSIONS: The reconstruction of the rhabdosphincter is the only technique that has shown improved functional results through randomized trials. The current evidence is limited and heterogenous, and more studies with consistent criteria are needed in order to establish a standard surgical technique.

Are targeted prostate biopsies ready to replace systematic prostate biopsies? / Las biopsias de próstata dirigidas ¿están listas para reemplazar las biopsias de próstata sistemáticas?

OBJECTIVES: To evaluate the efficacy and efficiency of systematic prostatic biopsy (SPB) and cognitive fusion PB (CFPB) to diagnose prostate cancer (PCa) and significant PCa (SPCa), and to analyse if CFPB could safely replace SPB. MATERIAL AND METHODS: A cohort of 314 consecutive men having PI-RADS ≥2 in a pre-biopsy 3T mp-MRI were prospectively subjected to trans-rectal ultrasound CFPB (two cores per suspicious area until a maximum of three areas) and a 12 peripheral core SPB. SPCa was considered when the WHO grade was higher than 2 (Gleason 4+3 or higher). RESULTS: PCa was diagnosed in 133 patients (42.4%), being 83 (62.4%) SPCa. SPB detected PCa in 114 men (85.7%) while CFPB in 103 (77.4%), P<.001. SPB detected SPCa in 64 men (77.1%) while CFPB in 71 (85.5%), P<.001. In 52 of the 81 men (64.2%) SPCa was detected in SPB and CFPB. In 19 men SPCa was only detected in CFPB (23.5%) while in 10, it was only detected in SPB (12.3%). 33.1 cores were needed to diagnose one PCa in SPB while 8.5 in CFPB, P<.001. 58.9 cores were needed to diagnose one SPCa in SPB, while 12.4 in CFPB, P<.001. CONCLUSIONS: CFPB are more effective and also more efficient than SPBs in detecting SPCa. However, CFPBs still can't safely replace SPBs because they are not able to detect up to 15% of SPCa.

The role of STAT3 protein as a prognostic factor in the clear cell renal carcinoma. Systematic review. / Valor de la proteína STAT3 como factor pronóstico en el carcinoma renal de célula clara. Revisión sistemática.

CONTEXT AND OBJECTIVE: There have been significant advances in the knowledge of renal carcinogenesis n the last years. Nowadays, renal tumors are classified according to their genetic profile and specific treatments based on the identification of therapeutic targets have also been developed. However, no prognostic markers have yet been identified. The aim of this review is to analyse literature that has evaluated the expression of the STAT3 protein as a molecular marker in clear cell renal carcinoma (ccRCC). EVIDENCE ACQUISITION: In January 2018 a systematic review was conducted in Pubmed, Cochrane library and Sciencedirect databases, from papers published from 1990. Search terms were"renal cell carcinoma"and"STAT3"or"STAT-3"and"prognostic factor. Following the principles of the PRISMA declaration and the PICO selection strategy, original articles with series of patients diagnosed with localized or metastatic ccRCC, and where the activity of STAT3 is analysed as a prognostic marker, were selected. A total of 132 publications were identified, of which 10 were finally revised, for they met the inclusion criteria. EVIDENCE SYNTHESIS: STAT3 activation (phosphorylation) through Ser727 is important during ccRCC development and progression. PSTAT3 expression seems to be a prognostic marker and an antiangiogenic-resistance marker in metastatic patients. There is little evidence as prognostic marker in patients with localized disease. CONCLUSIONS: STAT3 (Ser 727) expression in the nucleus of the ccRCC cells can be a prognostic marker and an antiangiogenic-resistance marker. Current scientific evidence is limited and more studies are needed to demonstrate its usefulness.

Preoperative magnetic resonance imaging in predicting early continence recovery after robotic radical prostatectomy. / La resonancia magnética preoperatoria predice la recuperación temprana de la continencia urinaria tras la prostatectomía radical robótica.

INTRODUCTION AND AIMS: Urinary incontinence is a common complication after radical prostatectomy. The aim of our study was to describe the preoperative anatomical features using magnetic resonance imaging in order to predict early continence recovery after robotic radical prostatectomy. MATERIAL AND METHODS: 72 patients who underwent robotic radical prostatectomy were prospectively analysed. EPIC questionnaire (1, 6 and 12 mo) and first self-reported continence were used to assess functional outcomes. Membranous urethral length (MUL) and MUL-prostate axis angle (aMULP) were assessed preoperatively on T2 weighted sagittal images. RESULTS: Continence rate was 67.2%, 92.6% and 95.2% at 1, 6 and 12 months, respectively. Early continence was achieved in patients with the lower aMULP. At 1 month, average aMULP in continent patients was 107.21° (IC 95% 90.3-124.6) vs. 118.5° (IC 95% 117.7-134) in incontinent ones (P=.014). At 6 month differences in aMULP among groups were found: 114.24° (IC 95% 104.6-123.9) in continents vs. 142° (IC 95% 126.5-157.6) in incontinents (P=0.015). At 12 month, continent group showed a significantly higher preoperative aMULP. aMULP was revealed as the only independent predictor of urinary continence at 6 mo in multivariate analysis, OR 0.007 (IC 95% 0.002-0.012), P=0.012. CONCLUSIONS: Preoperative anatomical parameters assessment prior surgery can help to identified those patients will achieve early continence recovery and it supports therapeutic decisions making.

A systematic review of methods for quantifying serum testosterone in patients with prostate cancer who underwent castration. / Métodos para cuantificar la testosterona sérica en pacientes con cáncer de próstata sometidos a castración: una revisión sistemática.

BACKGROUND: The clinical practice guidelines recommend measuring serum testosterone in patients with prostate cancer (PC) who undergo castration. The serum testosterone concentration should be <50ng/dL, a level established by using a radioimmunoassay method. The use of chemiluminescent immunoassays (IA) has become widespread, although their metrological characteristics do not seem appropriate for quantifying low testosterone concentrations. The objective of this review is to analyse the methods for quantifying testosterone and to establish whether there is scientific evidence that justifies measuring it in patients with PC who undergo castration, through liquid chromatography attached to a mass spectrometry in tandem (LC-MSMS). MATERIAL AND METHODS: We performed a search in PubMed with the following MeSH terms: measurement, testosterone, androgen suppression and prostate cancer. We selected 12 studies that compared the metrological characteristics of various methods for quantifying serum testosterone compared with MS detection methods. RESULTS: IAs are standard tools for measuring testosterone levels; however, there is evidence that IAs lack accuracy and precision for quantifying low concentrations. Most chemiluminescent IAs overestimate their concentration, especially below 100ng/dL. The procedures that use LC-MSMS have an adequate lower quantification limit and proper accuracy and precision. We found no specific evidence in patients with PC who underwent castration. CONCLUSIONS: LC-MSMS is the appropriate method for quantifying low serum testosterone concentrations. We need to define the level of castration with this method and the optimal level related to better progression of the disease.

Cloning of the glucocorticoid receptor (GR) in gilthead seabream (Sparus aurata). Differential expression of GR and immune genes in gilthead seabream after an immune challenge.

In order to determine the cortisol response after an immune challenge in the gilthead seabream (Sparus aurata), a cortisol receptor (GR) was cloned, sequenced and its expression determined after lipopolysaccharide (LPS) treatment. To clone the gilthead seabream GR (sbGR), consecutive PCR amplifications and screening of a pituitary cDNA library were performed. We obtained a clone of 4586 bp encoding a 784aa protein. Northern blot analysis from head kidney, heart and intestine revealed that the full length sbGR mRNA was approximately 6.5 Kb. A LPS treatment, used as an acute stress model, was employed to characterise the expression of sbGR and some selected genes involved in the immune response (IL-1beta, TNF-alpha, Mx protein, cathepsin D and PPAR-gamma). All genes were expressed in all tissues examined and responses were tissue and time dependent revealing differential gene expression profiles after LPS administration. Furthermore, analysis of plasma cortisol levels after LPS injection, showed an acute response to inflammatory stress with a significant increase two and six h after injection, recovering to basal levels 12 h post-stress in all LPS concentrations tested.

Constitutive model for fiber-reinforced materials with deformable matrices.

A great number of biological structures are composed of fibers (elastin, collagen, etc.) dispersed on an aqueous matrix in such a complex way that a detailed mechanical analysis based on microconstituents is, for practical purposes, out of reach. Consequently, the preferred approach to the mechanical behavior of these materials is based on setting up of constitutive equations that homogenize the behavior while capturing their main microstructural features. This work presents a simple macroscopic model for fiber-reinforced materials with deformable matrices, especially suited to many biological structural tissues. The constitutive equation is derived by imposing equivalence between the virtual works of both the fiber-reinforced and the equivalent continuum media, showing that it is independent of the control volume used for such equivalence. The model is particularized to incompressible materials, and an extension to orthotropic biological fibers is shown. Numerical simulations of uniaxial tests on silk fibers demonstrate the model's ability to capture the progressive alignment of the microconstituents under large deformations.

Transcriptional analysis of LPS-stimulated activation of trout (Oncorhynchus mykiss) monocyte/macrophage cells in primary culture treated with cortisol.

Primary immune responses to pathogen invasion are mediated by the innate immune system in which tissue macrophages play a key role. During infectious processes glucocorticoids generally may function to dampen inflammatory responses. In this study, the ability of cortisol to directly modulate the transcriptional response of rainbow trout macrophages to the cellular activator lipopolysaccharide (LPS) was investigated. The results indicate that cortisol significantly inhibits the well-described LPS-dependent induction of the expression of TNF-alpha2, a pro-inflammatory cytokine. In order to further characterize the molecular effects of LPS and the immunomodulatory role of cortisol, the in vitro macrophage response to LPS in the absence or presence of 12-h cortisol exposure was analyzed utilizing a salmonid-specific microarray platform. Genes that were stimulated or inhibited with LPS plus cortisol fell into several major functional groups. The first, a general "response" group comprising genes within ontology classes including the response to external stimuli, stress, humoral immunity and apoptosis, exhibited a significant increase after LPS stimulation, whereas suppression of this response was observed in the presence of cortisol. LPS stimulated other genes in a second group involved in cell signalling and also genes in a third group involved in the activation of transcription. Categories activated with cortisol were mainly related to various aspects of metabolism (including protein biosynthesis, binding and transport of ions) and structural proteins (mainly cytoskeleton and microtubules). The immunomodulatory action of cortisol on LPS-stimulated macrophages therefore appears more complex than simply the antagonism of LPS-induced transcriptional responses.