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Background: Benign prostatic hyperplasia (BPH) commonly causes lower urinary tract symptoms (LUTS) in men. Holmium (HoLEP) and thulium (ThuLEP) laser enucleation are established techniques for BPH treatment. Thulium fiber laser (TFL) for prostate enucleation (ThuFLEP) shows promising outcomes., Methods: A prospective randomized multicenter study was conducted. Patients with BPH and LUTS unresponsive to medical therapy were enrolled. Preoperative, surgical, perioperative and postoperative data were recorded with follow-up at 3 and 6 months. The primary outcome was functional improvement, and the secondary outcome was safety in terms of complications., Results: Two hundred patients were included (HoLEP 100, ThuFLEP 100). No significant baseline difference was found between groups. At 3 and 6 months we found statistically significant improvements from baseline for both HoLEP and ThuFLEP in efficacy: International Prostatic Symptoms Score (IPSS), IPSS-Quality of Life (QoL), maximum urinary flow rate (Qmax), and post-void residual volume (PVR; P<0.05). At 6 months, mean±SD IPSS, IPSS-QoL, Qmax, and PVR for HoLEP vs. ThuFLEP were 5.8±4.9 vs. 4.8±5.0 points (P=0.57), 1.6±1.4 vs. 0.7±1.1 points (P=0.09), 29.9±12.5 vs. 29.6±8.0 mL/s (P=0.8), and 16.3±17.7 vs. 15.5±13.4 mL (P=0.92), respectively. No intraoperative complication was recorded. No Clavien-Dindo ≥III complications occurred during hospitalization. After 6 months, 8 (8%) and 6 (6%) patients reported mild stress urinary incontinence in HoLEP and ThuFLEP groups, respectively (P=0.24). Urethral stenosis was observed in 3 men (3%) in the HoLEP group and 1 subject (1%) in the ThuFLEP group (P=0.72)., Conclusions: HoLEP and ThuFLEP are effective and safe for BPH treatment, with comparable functional outcomes and complication rates at 6 months. Further research is needed to confirm these findings.

Background: Robot-assisted partial nephrectomy (RAPN) has emerged as the preferred approach for T1 renal-cell-carcinoma. As new robotic platforms like Hugo RAS emerge, we seek to understand their potential in achieving similar RAPN outcomes as the established Da Vinci system., Methods: A prospective single-center comparative study was conducted, and 50 patients selected for RAPN were enrolled (25 Da Vinci Xi; 25 Hugo RAS). The choice of robotic system was based solely on hospital logistics criteria. Surgeries were performed by expert surgeons. Demographic data, tumor characteristics, operative details and postoperative outcomes were collected. SPSS version 22.0 was used for statistical analyses., Results: The average age of patients was 62.52±9.47 years, with no significant differences in median age, sex, and nephrometry scores between groups. Da Vinci group showed a significantly shorter docking time (12.56 vs. 20.08 min; P<0.01), while other intraoperative measures like console time and warm ischemia time were similar. The Hugo RAS group had a shorter renorraphy time (14.33 vs. 18.84 min; P=0.024). Postoperative outcomes and surgical margin positivity showed no significant differences. Each group had one patient (4%) who developed major surgical complications (Clavien IIIa). Trifecta rates were comparable between both groups (Da Vinci 88% vs. Hugo RAS 84%; P=0.93)., Conclusions: Initial findings suggest similar perioperative outcomes for RAPN when using Hugo RAS compared to the Da Vinci system. Further research with long-term follow-up is necessary to evaluate oncological and functional outcomes.

Introduction: Holmium laser enucleation of the prostate has rapidly become the gold standard for the surgical treatment of benign prostate hyperplasia, although thulium fiber laser (TFL) has also been postulated as an effective and safe alternative for prostate enucleation. The aim of this study is to describe our initial experience with the TFL for endoscopic enucleation of the prostate., Material and Methods: All patients proposed to TFL prostate enucleation were included in the analysis, regardless their prostate volume, catheter status and severity of symptoms, in 3 centers. Preoperative characteristics, intraoperative times and functional 3-months follow-up variables were collected, along with complications., Results: Fifty-six patients were available, with a mean age of 68.7 years. Enucleation and morcellation efficiencies were 2.04 and 7.47 g/min, respectively. Median hospital stay was one day. Comparable functional data, pre and 3-month post-surgery was: mean prostate volume 88.9 vs 21.3 g, maximum urinary flow 13.2 vs 27.3 ml/s, post-void residual volume 149 vs 7.8 ml, prostatic specific antigen level 11.2 vs 1 ng/ml, and International Prostate Symptom Score 20.75 vs 3.96. Fourteen out of 56 (25%) patients presented with complications grade ≤2, according to the Clavien-Dindo classification., Discussion: With wider evidence for other urological indications, very recent evidence about the suitability of TFL for prostate enucleation has arisen, since the first case described in 2021. Our results seem to back up these previous successful experiences as long as we obtained good intraoperative and short term follow-up functional results. However, there is still a need of longer follow-up data., Conclusions: TFL represents a novel technology for prostate enucleation, with a good intraoperative and short follow-up functional results, and a safety profile similar to the observed for those techniques that have been wider used for this indication. Further studies with longer follow-up periods and comparative with these other techniques are necessary., (Copyright © 2024. Published by Elsevier España, S.L.U.)

Purpose: To evaluate Hugo RAS against the Da Vinci system for Robot-Assisted Radical Prostatectomy (RARP) in prostate cancer treatment., Methods: We compared outcomes of 150 patients with prostate cancer undergoing RARP with either Hugo or Da Vinci systems. Our analysis included operative, postoperative, pathological, and functional outcomes., Results: Both groups had 75 patients. Baseline characteristics and tumor features were similar. Intraoperatively, Da Vinci had a shorter docking time (10.45 vs. 18.62 min, p = 0.02), but total operative times were comparable (145.34 vs 138.95, p = 0.85). Hugo outperformed in neck dissection and lymphadenectomy times (22 vs 13.67 min, p = 0.027 and 37.82 vs 45.77 min, p = 0.025). Postoperative metrics like stay duration, catheter time, and complications showed no significant difference. Functional results, using IPSS and IIEF5, were similar between systems. Six Da Vinci patients (8%) and nine Hugo patients (12%) experienced social incontinence (p = 0.072). Pathological outcomes like T stage, Gleason Score, and nodes removed were alike. However, Hugo had more positive surgical margins (20% vs. 10.67%, p = 0.034)., Conclusions: RARP outcomes using Hugo RAS were similar to the Da Vinci system in our study. More research and extended follow-up are required to ascertain long-term oncological and functional results., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The availability of multiple treatments for type 1 Gaucher disease increases the need for real-life studies to evaluate treatment efficacy and safety and provide clinicians with more information to choose the best personalized therapy for their patients., Aims: To determine whether treatment with eliglustat produces, in adult GD1 patients, ans optimal response in daily clinical practice., Methods: We designed a real-life study with 2 years of follow-up (TRAZELGA [GEE-ELI-2017-01]) to uniformly evaluate the response and adverse events to eliglustat treatment. This study, conducted in 30 patients across Spain and previously treated with other therapies, included the evaluation of safety and efficacy by assessing visceral enlargement, bone disease (DEXA and T and Z scores), concomitant treatments and adverse events, as well as a quality of life evaluation (SF-36). In addition, the quantification of classical biomarkers (chitotriosidase activity, CCL18/PARC and glucosylsphingosine (GluSph)) and new candidates for GD biomarkers (YKL-40, cathepsin S, hepcidin and lipocalin-2 determined by immunoassay) were also assessed. Non-parametric statistical analysis was performed and p < 0.05 was considered statistically significant., Main Results: Thirty patients were enrolled in the study. The median age was 41.5 years and the male-female ratio was 1.1:1. 84% of the patients had received ERT and 16% SRT as previous treatment. The most common symptoms at baseline were fatigue (42%) and bone pain (38%), no patient had a bone crisis during the study, and two years after switching, 37% had reduced their use of analgesics. Patient-reported outcomes showed a significant increase in physical function scores (p = 0.027) and physical pain scores (p = 0.010). None of the enrolled patients discontinued treatment due to adverse events, which were mild and transient in nature, mainly gastrointestinal and skin dryness. None of the biomarkers show a significant increase or decompensation after switching. CCL18/PARC (p = 0.0012), YKL-40 (p = 0.00004) and lipocalin-2 (p = 0.0155) improved after two years and GluSph after one year (p = 0.0008) and two years (p = 0.0245) of oral therapy., Conclusion: In summary, this real-life study, showed that eliglustat maintains stability and can improve quality of life with few side effects. Significant reductions in classic and other novel biomarkers were observed after two years of therapy., (© 2023. The Author(s).)

Background: Chronic hypophosphatemia can result from a variety of acquired disorders, such as malnutrition, intestinal malabsorption, hyperparathyroidism, vitamin D deficiency, excess alcohol intake, some drugs, or organ transplantation. Genetic disorders can be a cause of persistent hypophosphatemia, although they are less recognized. We aimed to better understand the prevalence of genetic hypophosphatemia in the population., Methods: By combining retrospective and prospective strategies, we searched the laboratory database of 815,828 phosphorus analyses and included patients 17-55 years old with low serum phosphorus. We reviewed the charts of 1287 outpatients with at least 1 phosphorus result ≤2.2 mg/dL. After ruling out clear secondary causes, 109 patients underwent further clinical and analytical studies. Among them, we confirmed hypophosphatemia in 39 patients. After excluding other evident secondary causes, such as primary hyperparathyroidism and vitamin D deficiency, we performed a molecular analysis in 42 patients by sequencing the exonic and flanking intronic regions of a panel of genes related to rickets or hypophosphatemia (CLCN5, CYP27B1, dentin matrix acidic phosphoprotein 1, ENPP1, FAM20C, FGFR1, FGF23, GNAS, PHEX, SLC34A3, and VDR)., Results: We identified 14 index patients with hypophosphatemia and variants in genes related to phosphate metabolism. The phenotype of most patients was mild, but two patients with X-linked hypophosphatemia (XLH) due to novel PHEX mutations had marked skeletal abnormalities., Conclusion: Genetic causes should be considered in children, but also in adult patients with hypophosphatemia of unknown origin. Our data are consistent with the conception that XLH is the most common cause of genetic hypophosphatemia with an overt musculoskeletal phenotype., (© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

The generation of distinct messenger RNA isoforms through alternative RNA processing modulates the expression and function of genes, often in a cell-type-specific manner. Here, we assess the regulatory relationships between transcription initiation, alternative splicing, and 3' end site selection. Applying long-read sequencing to accurately represent even the longest transcripts from end to end, we quantify mRNA isoforms in Drosophila tissues, including the transcriptionally complex nervous system. We find that in Drosophila heads, as well as in human cerebral organoids, 3' end site choice is globally influenced by the site of transcription initiation (TSS). "Dominant promoters," characterized by specific epigenetic signatures including p300/CBP binding, impose a transcriptional constraint to define splice and polyadenylation variants. In vivo deletion or overexpression of dominant promoters as well as p300/CBP loss disrupted the 3' end expression landscape. Our study demonstrates the crucial impact of TSS choice on the regulation of transcript diversity and tissue identity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

To better understand the causes of hypophosphatemia in children, we evaluated all serum phosphate tests performed in a tertiary hospital with unexpected but persistent temporary or isolated hypophosphatemia over an 18 year period. We collected 29,279 phosphate tests from 21,398 patients, of which 268 (1.2%) had at least one result showing hypophosphatemia. We found that endocrinopathies (n = 60), tumors (n = 10), and vitamin D deficiency (n = 3) were the medical conditions most commonly associated with mild hypophosphatemia, but in many patients the cause was unclear. Among patients with endocrinopathies, those with diabetes mellitus were found to have lower mean serum phosphate levels (mean 3.4 mg/dL) than those with short stature (3.7 mg/dL) or thyroid disorders (3.7 mg/dL). In addition, we found a correlation between glycemia and phosphatemia in patients with diabetes. However, despite the potential relevance of monitoring phosphate homeostasis and the underlying etiologic mechanisms, renal phosphate losses were estimated in less than 5% of patients with hypophosphatemia. In the pediatric age group, malignancies, hypovitaminosis D, and endocrine disorders, mostly diabetes, were the most common causes of hypophosphatemia. This real-world study also shows that hypophosphatemia is frequently neglected and inadequately evaluated by pediatricians, which emphasizes the need for more education and awareness about this condition to prevent its potentially deleterious consequences.

Cell-type-specific gene regulatory programs are essential for cell differentiation and function. In animal neurons, the highly conserved ELAV/Hu family of proteins promotes alternative splicing and polyadenylation of mRNA precursors to create unique neuronal transcript isoforms. Here, we assess transcriptome profiles and neurogenesis success in Drosophila models engineered to express differing levels of ELAV activity in the course of development. We show that the ELAV-mediated establishment of a subset of neuronal mRNA isoforms at the onset of neuron differentiation constitutes a developmental bottleneck that cannot be overcome later by the nuclear activation of the paralog found in neurons (FNE). Loss of ELAV function outside of that critical time window results in neurological defects. We find that FNE, when activated early enough, can restore ELAV-dependent neuronal mRNA isoforms and fully rescue development. Our findings demonstrate the essential role of robust cellular strategies to maintain ELAV activity and intact neuronal signatures in neurogenesis and neuronal function., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Treatment of radio-recurrent prostate cancer (PC) is managed mainly by androgen deprivation therapy. Nonetheless, selected patients could benefit from local salvage treatment options.In this study we present our series of recurrent PC cases submitted to laparoscopic salvage radical prostatectomy (sRP) at our institution., Material and Methods: A total of 29 patients with recurrent PC after primary non-surgical treatment were submitted to laparoscopic sRP at our institution, with a mean follow-up time of 7 years., Results: There were 7 post-operative complications Clavien-Dindo grade ≥2. At the end of the follow-up, 58.6% patients presented biochemical recurrence and five-year recurrence-free survival (RFS) was 50%.Positive lymph nodes, high preoperative prostate-specific antigen (PSA) and TNM stage were correlated with worse RFS. Cox regression analysis demonstrated that stage pT3b was independently associated with worse RFS in comparison with stage pT3a or less.At 12 months, pad-free continence or mild incontinence was observed in 62% of the patients., Conclusions: sRP is a technically challenging surgery, and in our series, we were able to perform this procedure with acceptable operative time and limited blood loss.Post-operative complications, functional results and oncological outcomes were similar to other published studies, being our series, to the best of our knowledge, the one with the longest follow-up, of 7 years.sRP is a feasible local treatment with curative intent for radio-recurrent prostate cancer, with good oncological outcomes and reasonable continence rates in selected patients., Competing Interests: The authors declare no conflicts of interest., (Copyright by Polish Urological Association.)

To capture the global gene network regulating the differentiation of immature T cells in an unbiased manner, large-scale forward genetic screens in zebrafish were conducted and combined with genetic interaction analysis. After ENU mutagenesis, genetic lesions associated with failure of T cell development were identified by meiotic recombination mapping, positional cloning, and whole genome sequencing. Recessive genetic variants in 33 genes were identified and confirmed as causative by additional experiments. The mutations affected T cell development but did not perturb the development of an unrelated cell type, growth hormone-expressing somatotrophs, providing an important measure of cell-type specificity of the genetic variants. The structure of the genetic network encompassing the identified components was established by a subsequent genetic interaction analysis, which identified many instances of positive (alleviating) and negative (synthetic) genetic interactions. Several examples of synthetic lethality were subsequently phenocopied using combinations of small molecule inhibitors. These drugs not only interfered with normal T cell development, but also elicited remission in a model of T cell acute lymphoblastic leukaemia. Our findings illustrate how genetic interaction data obtained in the context of entire organisms can be exploited for targeted interference with specific cell types and their malignant derivatives., (© 2021. The Author(s).)

Importance: Current guidelines recommend brain magnetic resonance imaging (MRI) for clinical management of patients with severe herpes simplex encephalitis (HSE). However, the prognostic value of brain imaging has not been demonstrated in this setting., Objective: To investigate the association between early brain MRI data and functional outcomes of patients with HSE at 90 days after intensive care unit (ICU) admission., Design, Setting, and Participants: This multicenter cohort study was conducted in 34 ICUs in France from 2007 to 2019 and recruited all patients who received a clinical diagnosis of encephalitis and exhibited cerebrospinal fluid positivity for herpes simplex virus DNA in the polymerase chain reaction analysis. Data analysis was performed from January to April 2020., Exposures: All patients underwent a standard brain MRI during the first 30 days after ICU admission., Main Outcomes and Measures: MRI acquisitions were analyzed by radiologists blinded to patients' outcomes, using a predefined score. Multivariable logistic regression and supervised hierarchical classifiers methods were used to identify factors associated with poor outcome at 90 days, defined by a score of 3 to 6 (indicating moderate-to-severe disability or death) on the Modified Rankin Scale., Results: Overall, 138 patients (median [interquartile range {IQR}] age, 62.6 [54.0-72.0] years; 75 men [54.3%]) with an admission median (IQR) Glasgow Coma Scale score of 9 (6-12) were studied. The median (IQR) delay between ICU admission and MRI was 1 (1-7) days. At 90 days, 95 patients (68.8%) had a poor outcome, including 16 deaths (11.6%). The presence of fluid-attenuated inversion recovery MRI signal abnormalities in more than 3 brain lobes (odds ratio [OR], 25.71; 95% CI, 1.21-554.42), age older than 60 years (OR, 7.62; 95% CI, 2.02-28.91), and the presence of diffusion-weighted MRI signal abnormalities in the left thalamus (OR, 6.90; 95% CI, 1.12-43.00) were independently associated with poor outcome. Machine learning models identified bilateral diffusion abnormalities as an additional factor associated with poor outcome (34 of 39 patients [87.2%] with bilateral abnormalities had poor outcomes) and confirmed the functional burden of left thalamic lesions, particularly in older patients (all 11 patients aged >60 years had left thalamic lesions)., Conclusions and Relevance: These findings suggest that in adult patients with HSE requiring ICU admission, extensive MRI changes in the brain are independently associated with poor functional outcome at 90 days. Thalamic diffusion signal changes were frequently observed and were associated with poor prognosis, mainly in older patients.

Backgrounds: High flow nasal cannula (HFNC) is an alternative therapy for acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). This study aimed first to describe outcomes of patients suffering from COVID-19-related ARDS treated with HFNC; secondly to evaluate safety of HFNC (patients and healthcare workers) and compare patients according to respiratory outcome., Methods: A retrospective cohort was conducted in French general hospital intensive care unit (ICU). Patients were included if receiving HFNC for hypoxemia (saturation pulse oxygen (SpO 2 ) <92% under oxygen ⩾6 L/min) associated with ARDS and positive SARS-CoV-2 polymerase chain reaction (PCR). Main clinical characteristics and outcomes are described in patients: (a) with do not intubate order (HFNC-DNIO); (b) who did not need intubation (HFNC-only); and (c) eventually intubated (HFNC-intubation). Medians are presented with (1st-3rd) interquartile range., Results: From 26 February to 30 June 2020, 46 patients of median age 75 (70-79) years were included. In the HFNC-DNIO group ( n  = 11), partial arterial oxygen pressure (PaO 2 )/inhaled fraction of oxygen (FiO 2 ) ratio median worst PaO 2 /FiO 2 ratio was 109 (102-172) and hospital mortality was 54.5%. Except the HFNC-DNIO patients ( n  = 35), 20 patients (57%) were eventually intubated (HFNC-intubation group) and 15 were only treated by HFNC (HFNC-only). HFNC-intubation patients presented higher worst respiratory rates per minute in ICU [37 (34-41) versus 33 (24-34) min, p  < 0.05] and worsened ICU admission PaO 2 /FiO 2 ratios [121 (103-169) versus 191 (162-219), p  < 0.001] compared with HFNC-only patients. Hospital mortality was 35% ( n  = 7/20) in HFNC-intubation group, 0% in HFNC-only group with a global mortality of these two groups of 20% ( n  = 7/35). Among tests performed in healthcare workers, 1/12 PCR in symptomatic healthcare workers and 1.8% serologies in asymptomatic healthcare workers were positive. After review of each case, COVID-19 was likely to be acquired outside hospital., Conclusions: HFNC seems to be useful for COVID-19-related ARDS and safe for healthcare workers. ARDS severity with PaO 2 /FiO 2 <150 associated with respiratory rate >35/min could be regarded as a predictor of intubation. The reviews of this paper are available via the supplemental material section.

Commercial topical medications for oral conditions are scarce and the vehicles used are not very suitable. Therefore, formulations containing active ingredients in vehicles specially designed for oral application must often be prepared. Drug compounding offers other advantages, including the possibility of combining several active ingredients in a single vehicle and prescribing drugs that are in short supply. In this article, we describe the main pharmaceutical formulations used to treat the most common diseases of the oral mucosa., (Copyright © 2020 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

We describe the case of a 74-year-old woman with previous history of gastric signet cell carcinoma who develops bladder metastasis as first sign of recurrence 6 years later. Bladder metastasis due to signet cell carcinoma is extremely rare with only 19 cases reported. Treatment includes radical cystectomy or chemotherapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction and Objectives: Nodal prostate cancer recurrence is a challenging scenario. Current guidelines recommend the use of androgen deprivation therapy, tailored treatment or clinical trials. We studied the impact of Salvage lymph node dissection in selected patients., Material and Methods: We retrospectively reviewed records of 23 consecutive patients with prostate cancer and previous Radical prostatectomy or Radiotherapy who underwent SLND from December 2005 to November 2015., Results: We found that in patients that showed biochemical response the introduction of ADT was delayed 14.9 months compared to patients that did not responded (2.8 months) P=.00026. Furthermore although statistical significance was not reached (P=.072) PSA-DT could be a potential prognostic factor of radiological recurrence since patients with PSA-DT<6 months developed radiological recurrence 7.6 months earlier compared to their counterparts., Conclusions: Salvage lymph node dissection is a potential treatment that could delay ADT in selected patients., (Copyright © 2018 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Homologous recombination (HR) enables the exchange of genetic material between and within species. Recent studies suggest that this process plays a major role in the microevolution of microbial genomes, contributing to core genome homogenization and to the maintenance of cohesive population structures. However, we still have a very poor understanding of the possible adaptive roles of intraspecific HR and of the factors that determine its differential impact across clades and lifestyles. Here we used a unified methodological framework to assess HR in 338 complete genomes from 54 phylogenetically diverse and representative prokaryotic species, encompassing different lifestyles and a broad phylogenetic distribution. Our results indicate that lifestyle and presence of restriction-modification (RM) machineries are among the main factors shaping HR patterns, with symbionts and intracellular pathogens having the lowest HR levels. Similarly, the size of exchanged genomic fragments correlated with the presence of RM and competence machineries. Finally, genes exchanged by HR showed functional enrichments which could be related to adaptations to different environments and ecological strategies. Taken together, our results clarify the factors underlying HR impact and suggest important adaptive roles of genes exchanged through this mechanism. Our results also revealed that the extent of genetic exchange correlated with lifestyle and some genomic features. Moreover, the genes in exchanged regions were enriched for functions that reflected specific adaptations, supporting identification of HR as one of the main evolutionary mechanisms shaping prokaryotic core genomes. IMPORTANCE Microbial populations exchange genetic material through a process called homologous recombination. Although this process has been studied in particular organisms, we lack an understanding of its differential impact over the genome and across microbes with different life-styles. We used a common analytical framework to assess this process in a representative set of microorganisms. Our results uncovered important trends. First, microbes with different lifestyles are differentially impacted, with endosymbionts and obligate pathogens being those less prone to undergo this process. Second, certain genetic elements such as restriction-modification systems seem to be associated with higher rates of recombination. Most importantly, recombined genomes show the footprints of natural selection in which recombined regions preferentially contain genes that can be related to specific ecological adaptations. Taken together, our results clarify the relative contributions of factors modulating homologous recombination and show evidence for a clear a role of this process in shaping microbial genomes and driving ecological adaptations., (Copyright © 2019 González-Torres et al.)

Context: Kidney transplantation from donors with expanded criteria has increased the pool of kidneys at the cost of a higher risk of short and long-term graft dysfunction. The main issue lies in determining which kidneys will offer acceptable function and survival compared with the risk represented by surgery and subsequent immunosuppression., Objective: The objective of our article is to review the current evidence on the tools for predicting the functionality of kidney transplantation from cadaveric donors with expanded criteria and determining the validity for their use in standard practice., Acquisition of Evidence: We conducted a systematic literature review according to the PRISM criteria, through Medline (http://www.ncbi.nlm.nih.gov) and using the keywords (in isolation or in conjunction) "cadaveric renal transplantation; kidney graft function appraisal, graft function predictors". We selected prospective and retrospective series and review articles. A total of 375 articles were analysed, 39 of which were ultimately selected for review., Summary of the Evidence: The predictors of functionality include the following: The donor risk indices; the calculation of the renal functional weight or the assessment of the nephronic mass; the measurement of vascular resistances during perfusion in hypothermia; the measurement of the donor's biomarkers in urine and in the perfusion liquid; the measurement of functional and reperfusion parameters in normothermia; and the measurement of morphological parameters (microscopic and macroscopic) of the target organ. In this article, we present an explanatory summary of each of these parameters, as well as their most recent evidence on this issue., Discussion: None of the reviewed parameters in isolation could reliably predict renal function and graft survival. There is a significant void in terms of the macroscopic assessment of kidney transplantation., Conclusions: We need to continue developing predictors of renal functionality to accurately define the distribution of each currently available donor kidney., (Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: European guidelines recommend primary HPV testing for cervical cancer screening. However, the starting age remains to be defined, with an undecided window between 30 and 35 years. This pilot study compares the effectiveness of primary HPV testing to that of cytology for the detection of high-grade (CIN2+) lesions stratified by age., Methods: Cotesting with LBC cytology and APTIMA ® HPV (AHPV) was performed in 5053 women aged 25-65 in an opportunistic screening program in Madrid. AHPV-positive cases were referred to colposcopy and genotyped for HPV16 and 18/45 (AHPV-GT). Results were analyzed stratified in four age groups., Results: 454 cases (9.0%) were AHPV-positive. Women under 35 had a 30.2% CIN2+ rate, compared to 21.9% and 20.4% for women aged 35-44 or 45-54. There was a significant increase (P < .05) in the rate of CIN2+ in AHPV-GT-positive women when compared to that for other HPV types (AHPV-other), being 43.3% versus 15.7%. AHPV-GT-positive women under 35 had significantly higher rates of CIN2+ lesions than any other age-group. The sensitivity of cytology for cervical CIN2+ in APHV-positive women was 60.6%. All 4 carcinomas, including one AHPV-negative endometrial adenocarcinoma, had abnormal cytology. All cervical CIN2+ lesions biopsied were AHPV-positive., Conclusions: Aptima HPV shows a significantly higher sensitivity for cervical CIN2+ lesions than cytology alone. Unexpectedly, AHPV-positive women under 35 had the highest incidence of CIN2+ lesions, particularly when they are HPV16/18/45-positive. Reconsidering HPV primary screening before the recommended age of 35 is warranted., (© 2017 Wiley Periodicals, Inc.)

Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious disease and a major concern in animal health worldwide. We have previously reported the use of RNA transcripts mimicking structural domains in the non-coding regions of the FMDV RNA as potent type-I interferon (IFN) inducers showing antiviral effect in vivo, as well as their immunomodulatory properties in combination with an FMD vaccine in mice. Here, we describe the enhancing effect of RNA delivery on the immunogenicity and protection induced by a suboptimal dose of a conventional FMD vaccine in pigs. Animals receiving the RNA developed earlier and higher levels of neutralizing antibodies against homologous and heterologous isolates, compared to those immunized with the vaccine alone, and had higher anti-FMDV titers at late times post-vaccination. RNA delivery also induced higher specific T-cell response and protection levels against FMDV challenge. Peripheral blood mononuclear cells from pigs inoculated with RNA and the vaccine had a higher IFN-γ specific response than those from pigs receiving the vaccine alone. When challenged with FMDV, all three animals immunized with the conventional vaccine developed antibodies to the non-structural viral proteins 3ABC and two of them developed severe signs of disease. In the group receiving the vaccine together with the RNA, two pigs were fully protected while one showed delayed and mild signs of disease. Our results support the immunomodulatory effect of these RNA molecules in natural hosts and suggest their potential use for improvement of FMD vaccines strategies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Many clinical anatomy studies have looked into how variations in the acromion, coracoacromial ligament (CAL) and subacromial space are associated with rotator cuff injuries. However, no study up to now had defined anatomically the fibro-osseous canal that confines the supraspinatus muscle in the subcoracoacromial space. Through an anatomical study of the scapula, we defined the bone-related parameters of this canal and its anatomical variations., Materials and Methods: This study on dry bones involved 71 scapulas. With standardised photographs in two orthogonal views (superior and lateral), the surface area of the subcoracoacromial canal and the anatomical parameters making up this canal were defined and measured using image analysis software. The primary analysis evaluated the anatomical parameters of the canal as a function of three canal surface area groups; the secondary analysis looked into how variations in the canal surface area were related to the type of acromion according to the Bigliani classification., Results: Relative to glenoid width, the group with a large canal surface area (L) had significantly less lateral overhang of the acromion than the group with a small canal surface area (S), with ratios of 0.41±0.23 and 0.58±0.3, respectively (P=0.04). The mean length of the CAL was 46±8mm in the L group and 39±9mm in the S group (P=0.003). The coracoacromial arch angle was 38°±11° in the L group and 34°±9° in the S group; the canal surface area was smaller in specimens with a smaller coracoacromial arch angle (P=0.20)., Conclusion: Apart from acromial morphology, there could be innate anatomical features of the scapula that predispose people to extrinsic lesions to the supraspinatus tendon (lateral overhang, coracoacromial arch angle) by reducing the subcoracoacromial canal's surface area., Level of Evidence: Anatomical descriptive study., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Lymphocytes represent basic components of vertebrate adaptive immune systems, suggesting the utility of non-mammalian models to define the molecular basis of their development and differentiation. Our forward genetic screens in zebrafish for recessive mutations affecting early T cell development revealed several major genetic pathways. The identification of lineage-specific transcription factors and specific components of cytokine signaling and DNA replication and/or repair pathways known from studies of immunocompromised mammals provided an evolutionary cross-validation of the screen design. Unexpectedly, however, genes encoding proteins required for pre-mRNA processing were enriched in the collection of mutants identified here. In both zebrafish and mice, deficiency of the splice regulator TNPO3 impairs intrathymic T cell differentiation, illustrating the evolutionarily conserved and cell-type-specific functions of certain pre-mRNA-processing factors for T cell development., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

In this work we have tested the potential antiviral activity of silver nanoparticles formulated as Argovit™ against Rift Valley fever virus (RVFV). The antiviral activity of Argovit was tested on Vero cell cultures and in type-I interferon receptor deficient mice (IFNAR (-/-) mice) by two different approaches: (i) different dilutions of Argovit were added to previously infected cells or administrated to animals infected with a lethal dose of virus; (ii) virus was pre-incubated with different dilutions of Argovit before inoculation in mice or cells. Though the ability of silver nanoparticles to control an ongoing RVFV infection in the conditions tested was limited, the incubation of virus with Argovit before the infection led to a reduction of the infectivity titers both in vitro and in vivo. These results reveal the potential application of silver nanoparticles to control the infectivity of RVFV, which is an important zoonotic pathogen., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The use of prostatic multiparametric MRI (mpMRI) has increased significantly over the last years, and has emerged as a crucial test for diagnosis, staging and treatment of prostate cancer (PCa). The use of the various available sequences (T2W, T1W, diffusion, perfusion and spectroscopy), as well as the different parameters they associate, not only enables to determine the group of patients subsidiary of focal ablative therapy, but also to perform a proper determination of the áreas to treat, as well as to monitor the development of therapy and to evaluate both oncological results and possible therapeutic failures. Despite the excellent results showed in the different studies, it is necessary to reach a consensus about its use on the different features associated with focal therapy, since it is a technique that requires not only large experience in its operation but also standardization. All this make it a complex technique and not free of difficulties in its interpretation.

We retrospectively analyzed the findings of a prospective cohort of 75 children referred for thyroid nodules between 2008 and 2013. Prevalence of papillary differentiated thyroid carcinoma was 18.7%. Thyrotropin >2.5 mIU/L, multinodular goiter, solid nodules, irregular margins, and pathologic lymphadenopathies were identified as independent predictors of malignancy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: In many centers patients are hospitalised to perform a renal allograft biopsy., Aim: To evaluate the safety and efficacy of outpatient renal allograft biopsies., Methods: Since December 2011 we perform renal allograft biopsies as an outpatient procedure. Exclusion criteria for performing an outpatient biopsy included: 1.) anticoagulant treatment, 2.) thrombocytopenia &lt;50,000/mm3, 3.) body mass index &gt;35kg/m2 and 4.) uncontrolled hypertension. The number and severity of complications were compared with an historical cohort of 124 biopsies done between 2007 and 2011 when all patients were hospitalised for the procedure and with 42 patients biopsied during hospitalisation between 2011 and 2013., Results: Between 2011 and 2013, 210 (95%) out of 230 biopsies indicated in the outclinic were performed as an outpatient procedure (95%). The incidence of major complications (bleeding requiring blood transfusion and/or embolisation) was 0.8% between 2007 and 2011 and 2.4% in biopsies between 2011 and 2013 in hospitalised patients (p=0.475). No major complications were observed in the outpatient biopsy group. Minor complications (hematuria, hematoma or fistula not requiring transfusion or embolisation) were also not different between groups (3.2%, 7.1% and 2.7%; respectively). Sample size adequacy according to the Banff criteria was not different among groups (p=0.052)., Conclusion: Ambulatory renal allograft biopsy is a safe and efficient procedure.

Background: Plantar ulcers, which commonly occur in leprosy patients, tend to recur increasing physical disability. The aim of this study is to identify both the bacteriological profile of these ulcers and the antibiotic susceptibility of the isolated bacteria., Materials and Methods: 68 leprosy patients with chronic ulcers attending the in-patient department of Gambo General Hospital, West Arsi, were included in this study. Proper sample collection, inoculation on culture media, and final identification using biochemical methods were undertaken., Results: 66 patients (97.1%) had a positive culture. A total of 81 microorganisms were isolated. Multiple organisms (two or more) were isolated in 15 (22.7% out of positive culture) patients. The main isolation was Proteus spp (30.9%), followed by Escherichia coli (21.0%), Staphylococcus aureus (18.5%) and Pseudomonas aeruginosa (9.9%). In the total number of the isolated bacteria, the antibiotics with less resistance were gentamicin (18.5%), fosfomycin (22.2%) cefoxitin (24.7%), ceftriaxone (25.9%) ciprofloxacin (25.9%), and amoxicillin-clavulanic acid (28.49%)., Conclusion: The bacteriological study of plantar ulcers of leprosy patients revealed Enterobacteriaceae and S. aureus as the main pathogens involved in such infections. The results of this study may guide empirical therapy in a rural area hospital where culture and susceptibility testing facilities are scarce.

To modulate the expression of genes involved in nitrogen assimilation, the cyanobacterial PII-interacting protein X (PipX) interacts with the global transcriptional regulator NtcA and the signal transduction protein PII, a protein found in all three domains of life as an integrator of signals of the nitrogen and carbon balance. PipX can form alternate complexes with NtcA and PII, and these interactions are stimulated and inhibited, respectively, by 2-oxoglutarate, providing a mechanistic link between PII signaling and NtcA-regulated gene expression. Here, we demonstrate that PipX is involved in a much wider interaction network. The effect of pipX alleles on transcript levels was studied by RNA sequencing of S. elongatus strains grown in the presence of either nitrate or ammonium, followed by multivariate analyses of relevant mutant/control comparisons. As a result of this process, 222 genes were classified into six coherent groups of differentially regulated genes, two of which, containing either NtcA-activated or NtcA-repressed genes, provided further insights into the function of NtcA-PipX complexes. The remaining four groups suggest the involvement of PipX in at least three NtcA-independent regulatory pathways. Our results pave the way to uncover new regulatory interactions and mechanisms in the control of gene expression in cyanobacteria.

Unlabelled: No differences in either bone mineral density or serum 25OHD levels have been found between 205 women with fibromyalgia (both pre- and postmenopausal) and their controls. However, a lack of the expected 25OHD summer rise was observed in patients., Introduction: Contradictory data have been published regarding a possible association between fibromyalgia and osteoporosis or hypovitaminosis D. Most studies, however, have been performed in small size samples and have excluded postmenopausal women. We decided to study this association in a larger sample of fibromyalgia patients including both pre- and postmenopausal women., Methods: Two hundred five patients were recruited from a clinic specializing in fibromyalgia and 205 healthy controls were enrolled from the census of a Primary Care Center. Controls were matched with patients by age and the time of the year they were included in the study. Bone mineral density (BMD) was measured by DXA. Serum 25OHD, iPTH, P1NP, and CTX were also determined., Results: BMD was similar in both groups (lumbar spine, 0.971 ± 0.146 g/cm(2) in patients and 0.970 ± 0.132 g/cm(2) in controls; femoral neck, 0.780 ± 0.122 g/cm(2) and 0.785 ± 0.117 g/cm(2), respectively). 25OHD levels were also similar: 23.0 ± 9.5 ng/ml and 24.1 ± 9.6 ng/ml. However, while controls showed the usual summer rise in 25OHD, fibromyalgia patients did not. PTH did not show seasonal changes, but on average was higher in patients (51 pg/ml vs. 48 pg/ml; p = 0.034). P1NP or CTX were similar in both groups., Conclusions: No differences in BMD were found between patients and controls. As for 25OHD, a lack of its expected summer rise was observed. It is doubtful whether this has any homeostatic consequence. We consider that the association reported in other studies is merely circumstantial, and not due to the intrinsic characteristics of these disorders.

Compounding continues to play a key role in the treatment of skin conditions, despite the abundance of products made by the pharmaceutical industry. Right from the earliest days of dermatology, compounding proved very useful in the treatment of diseases for which no specific drugs were available. However, as new products came onto the market, this usefulness was called into question, and doubts over safety, stability, and effectiveness were raised. Today, compounding is regaining the place it once held in routine dermatological practice. We review the advantages and disadvantages of compounding, the most common indications, current legislation in our setting, and the latest developments in active ingredients and vehicles., (Copyright © 2011 Elsevier España, S.L. and AEDV. All rights reserved.)

We have recently described the antiviral effect in mice of in vitro-transcribed RNAs mimicking structural domains in the non-coding regions of the foot-and-mouth disease virus (FMDV) genome RNA. These small, synthetic and non-infectious RNA molecules (ncRNAs) are potent type-I interferon (IFN) inducers in vivo. In this work, the immunomodulatory effect of the ncRNA corresponding to the internal ribosome entry site (IRES) on immunization with two different FMD vaccine formulations, both based on inactivated virus, including or not a commercial adjuvant, was analyzed in the mice model. The effect of the time interval between RNA inoculation and immunization was also studied. RNA delivery consistently increased the titers of specific anti-FMDV antibodies, including neutralizing antibodies, elicited after vaccination. Moreover, at day 2 after immunization, significant differences in mean antibody titers could be detected between the groups of mice receiving either vaccine co-administered with the RNA and the control group, unlike those immunized with the vaccine alone. When vaccinated mice were challenged with FMDV, the mean values of viral load were lower in the groups receiving the RNA together with the vaccine. Our results show the enhancing effect of the IRES RNA on the immune response elicited after vaccination and suggest the potential of this molecule as an adjuvant for new FMD vaccine design., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

African horse sickness virus (AHSV) belongs to the genus Orbivirus. We have now engineered naked DNAs and recombinant modified vaccinia virus Ankara (rMVA) expressing VP2 and NS1 proteins from AHSV-4. IFNAR((-/-)) mice inoculated with DNA/rMVA-VP2,-NS1 from AHSV-4 in an heterologous prime-boost vaccination strategy generated significant levels of neutralizing antibodies specific of AHSV-4. In addition, vaccination stimulated specific T cell responses against the virus. The vaccine elicited partial protection against an homologous AHSV-4 infection and induced cross-protection against the heterologous AHSV-9. Similarly, IFNAR((-/-)) mice vaccinated with an homologous prime-boost strategy with rMVA-VP2-NS1 from AHSV-4 developed neutralizing antibodies and protective immunity against AHSV-4. Furthermore, the levels of immunity were very high since none of vaccinated animals presented viraemia when they were challenged against the homologous AHSV-4 and very low levels when they were challenged against the heterologous virus AHSV-9. These data suggest that the immunization with rMVA/rMVA was more efficient in protection against a virulent challenge with AHSV-4 and both strategies, DNA/rMVA and rMVA/rMVA, protected against the infection with AHSV-9. The inclusion of the protein NS1 in the vaccine formulations targeting AHSV generates promising multiserotype vaccines.

The protective efficacy of recombinant vaccines expressing serotype 8 bluetongue virus (BTV-8) capsid proteins was tested in a mouse model. The recombinant vaccines comprised plasmid DNA or Modified Vaccinia Ankara viruses encoding BTV VP2, VP5 or VP7 proteins. These constructs were administered alone or in combination using either a homologous prime boost vaccination regime (rMVA/rMVA) or a heterologous vaccination regime (DNA/rMVA). The DNA/rMVA or rMVA/rMVA prime-boost were administered at a three week interval and all of the animals that received VP2 generated neutralising antibodies. The vaccinated and non-vaccinated-control mice were subsequently challenged with a lethal dose of BTV-8. Mice vaccinated with VP7 alone were not protected. However, mice vaccinated with DNA/rMVA or rMVA/rMVA expressing VP2, VP5 and VP7 or VP2 alone were all protected.

Mutation in the protocadherin 19 (PCDH19) gene is an increasingly recognized cause of epilepsy in females. This disorder is frequently associated with mental retardation and psychiatric features. We describe two unrelated females with novel PCDH19 missense mutations. One was de novo, and the other was inherited from her unaffected father. Both had mild mental impairment but had remarkable behavioral problems. We reviewed the cognitive and behavioral profiles of previously reported PCDH19-positive cases. Intellectual disability appeared in 75% of patients, ranging from borderline to severe. More than half of the individuals presented behavioral disturbances, which could be divided into two different groups: autistic and non-autistic. The majority of patients with autism already had some degree of cognitive impairment. It appears that seizures tend to diminish or even stop in adolescence, so non-epileptic problems can become the most important and disabling issue in adult patients with PCDH19 mutation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

In mammals, the cytokine IL-7 is a key regulator of various aspects of lymphocyte differentiation and homeostasis. Because of the difficulty of identifying cytokine homologs in lower vertebrates and the paucity of assay systems and reagents, the degree of functional conservation of cytokine signaling pathways, particularly those pertaining to lymphocyte development, is unclear. In this article, we report on the analysis and characterization of three zebrafish mutants with severely impaired thymopoiesis. The identification of affected genes by positional cloning revealed components of the IL-7 signaling pathway. A presumptive null allele of the zebrafish homolog of the IL-7Rα-chain causes substantially reduced cellularity of the thymus but spares B cell development in the kidney. Likewise, nonsense mutations in the zebrafish homologs of janus kinases JAK1 and JAK3 preferentially affect T cell development. The functional interactions of the cytokine receptor components were examined in the three groups of fish hetero- or homozygous for either il7r and jak1, il7r and jak3, or jak1 and jak3 mutations. The differential effects on T cell development arising from the different genotypes could be explained on the basis of the known structure of the mammalian IL-7R complex. Because IL-7 signaling appears to be a universal requirement for T cell development in vertebrates, the mutants described in this article represent alternative animal models of human immunodeficiency syndromes amenable to large-scale genetic and chemical screens.

Background: Altered blood glucose concentration is commonly observed in patients with sepsis, even among those without hypoglycemic treatments or history of diabetes mellitus. These alterations in blood glucose are potentially detrimental, although the precise relationship with outcome in patients with bacteremia has not been yet determined., Methods: A retrospective cohort study design for analyzing patients with Gram negative rod bacteremia was employed, with the main outcome measure being in-hospital mortality. Patients were stratified in quintiles accordingly deviation of the blood glucose concentration from a central value with lowest mortality. Cox proportional-hazards regression model was used for determining the relationship of same day of bacteremia blood glucose and death., Results: Of 869 patients identified 63 (7.4%) died. Same day of bacteremia blood glucose concentration had a U-shaped relationship with in-hospital mortality. The lowest mortality (2%) was detected in the range of blood glucose concentration from 150 to 160 mg/dL. Greater deviation of blood glucose concentration from the central value of this range (155 mg/dL, reference value) was directly associated with higher risk of death (p = 0.002, chi for trend). The low-risk group (quintile 1) had a mortality of 3.3%, intermediate-risk group (quintiles 2, 3 and 4) a mortality of 7.1%, and the high-risk group (quintile 5) a mortality of 12.05%. In a multivariable Cox regression model, the hazard ratio for death among patients in the intermediate-risk group as compared with that in the low risk group was 2.88 (95% confidence interval, 1.01 to 8.18; P = 0.048), and for the high risk group it was 4.26 (95% confidence interval, 1.41 to 12.94; P = 0.01)., Conclusions: Same day of bacteremia blood glucose concentration is related with outcome of patients with Gram-negative rod bacteremia. Lowest mortality is detected in patients with blood glucose concentration in an interval of 150-160 mg/dL. Deviations from these values are associated with an increased risk of death.

This paper describes the generation of monoclonal antibodies directed to immunogenic nucleoprotein N epitopes of Rift Valley fever virus (RVFV), and their application in diagnostics, both for antibody detection in competitive ELISA and for antigen capture in a sandwich ELISA. Monoclonal antibodies (mAbs) were generated after DNA immunization of Balb/c mice and characterized by western blot, ELISA and cell immunostaining assays. At least three different immunorelevant epitopes were defined by mAb competition assays. Interestingly, two of the mAbs generated were able to distinguish between RVFV strains from Egyptian or South African lineages. These monoclonal antibodies constitute useful tools for diagnosis, especially for the detection of serum anti-RVFV antibodies from a broad range of species by means of competitive ELISA.

Background: There is limited information about the effect of diabetes on the prognosis of patients with bacterial infections. We performed a retrospective cohort study to investigate possible correlations between diabetes and prognosis in patients with Enterobacteriaceae bacteremia., Methods: We reviewed the medical charts of 1112 patients who were treated at a community teaching hospital for Enterobacteriaceae bacteremia from January 1997 through June 2007. Factors associated with in-hospital mortality were analyzed by logistic regression analysis., Results: Among the 1112 patients with Enterobacteriaceae bacteremia, 181 (16.3%) were diabetic patients; 90 patients (8.1%) died while in the hospital. Compared to non-diabetic patients, diabetic patients were older (75.4 +/- 11.9 years vs. 70 +/- 16.6 years, p < 0.001) and had more comorbidities. However, mortality among diabetic and non-diabetic patients was not different [7.2% vs. 8.2%, RR 1.13; 95% CI (0.67-1.9); p = 0.39]. In a multivariate analysis, the variables associated with in-hospital mortality were age, the origin of the bacteremia, and the presence of immunosuppression. Diabetes was not associated with outcome., Conclusion: In this cohort of patients with Enterobacteriaceae bacteremia, diabetes was not associated with a poorer prognosis.

Introduction: In the 10 last years, the increase of international travels and immigration from low income countries to Spain was related with an increased of prevalence of parasitic diseases., Source: Critical review of the literature., Structure: Firstly, several general considerations were made on the antiparasitic drugs revised in this paper. Chemical structures and mechanisms of action of the main drugs with antiparasitic effect were considered in the second part of the review. Further, antiparasitic spectrum of selected drugs, main pharmacokinetical characteristics, usual posology, possible side effects and contraindications were detailed. Finally, some practical aspects, such as interactions and the methods for practical obtention of these drugs are indicated. This information is relevant because in Spain many anti-parasitic drugs may be obtained using non conventional methods., Conclusion: In Spain, the increase of parasitic diseases necessitates an update on antiparasitics drugs for their treatment.

Cytokines make up a network of molecules involved in the regulation of immune response and organ functional homeostasis. Cytokines coordinate both physiological and pathological processes occurring in the liver during viral infection, including infection control, inflammation, regeneration, and fibrosis. Hepatitis B and hepatitis C viruses interfere with the complex cytokine network brought about by the immune system and liver cells in order to prevent an effective immune response, capable of viral control. This situation leads to intrahepatic sequestration of nonspecific inflammatory infiltrates that release proinflammatory cytokines, which in turn favor chronic inflammation and fibrosis. The therapeutical administration of cytokines such as interferon alpha may result in viral clearance during persistent infection, and revert this process.

Acalculous cholecystitis has been associated with several infectious agents, but its relation with Plasmodium falciparum infection has not been clearly defined. This is the first case of acalculous cholecystitis produced by Plasmodium falciparum infection that is directly documented and should be included among the differential diagnoses of acalculous cholecystitis.

Noroviruses (NoVs) are responsible for the majority of gastroenteritis outbreaks in humans. Recently, NoV strains which are genetically closely related to human genogroup II (GII) NoVs have been detected in fecal specimens from swine. These findings have raised concern about the possible role of pigs as reservoirs for NoVs that could infect humans. To better understand the epidemiology of swine NoVs in both the swine and the human populations, rapid immunoassays are needed. In this study, baculovirus recombinants were generated to express the capsid gene of a swine NoV GII genotype 11 (GII.11) strain which self-assembled into virus-like particles (VLPs). Subsequently, the purified VLPs were used to evoke monoclonal antibodies (MAbs) in mice. A panel of eight promising MAbs was obtained and evaluated for their ability to bind to heterologous VLPs, denaturated antigens, and truncated capsid proteins. The MAbs could be classified into two groups: two MAbs that recognized linear epitopes located at the amino-terminal half (shell domain) of the swine NoV GII.11 VLPs and that cross-reacted with human GII.4 NoV VLPs. The other six MAbs bound to conformational epitopes and did not cross-react with the human GII.4 VLPs. To our knowledge, this is the first report on the characterization of MAbs against swine NoVs. The swine NoV VLPs and the MAbs described here may be further used for the design of diagnostic reagents that could help increase our knowledge of the prevalence of NoV infections in pigs and the possible role of pigs as reservoirs for NoVs.

In this work, an analysis of the emission of different pollutants when replacing partially the fuel type used in a cement kiln is done. The wastes used to feed the kiln were tyres and two types of sewage sludge. The increasing mass flow of sludge is between 700 kg h(-1) and 5,500 kg h(-1)1, for a total production of clinker of 150th(-1), whereas the fed tyres were in the flow range of 500-1,500 kg h(-1). Dioxins and furans, polycyclic aromatic hydrocarbons (PAHs) and other hydrocarbons, heavy metals, HCl and HF, CO, CO(2), NO(x) and other parameters of the stack were analyzed, according to the standard methods of sampling and determination, through more than 1 year in six series: one blank (no sewage sludge) and five more with increasing amount of sludge and/or tyres. The emission of PAHs and dioxins seems to increase with the amount of tyres fed to the kiln, probably due to the fed point used for this waste.

Fluoride complexes of metallic ions are one of the main problems when processing industrial effluents with high content of fluoride anion. The most important case is derived from pickling treatment of stainless steel, which is performed with HNO3/HF mixtures to remove oxides scale formed over the metal surface. Waste from this process, spent pickling liquor, must be treated for recovering metallic and acid content. Conventional treatments produce a final effluent with high quantity of fluoride complexes of iron and chromium. This work proposes a hydrolysis treatment of these solid metal fluorides by reacting them with a basic agent. Metal oxides are obtained, while fluoride is released to solution as a solved salt, which can be easily recovered as hydrofluoric acid. Solid iron and chromium fluorides, mainly K2FeF5(s) and CrF3(s), obtained in the UCM treatment process, were employed in this work. Optimal hydrolysis operating conditions were obtained by means of a factorial design: media must be basic but pH cannot be higher than 9.5, temperature from 40 to 70 degrees C and alkali concentration (potassium hydroxide) below 1.1 mol L(-1). Secondary reactions have been detected, which are probably due to fluoride adsorption onto obtained oxides surface. Mechanism of reaction consists of several stages, involving solid fluoride dissolution and complexes decomposition. Hydrolysis kinetics has been modeled with classical crystal dissolution kinetics, based on mass transfer phenomena.

Hepatitis B virus (HBV) infection is a worldwide public health problem. There are an estimated 350 million persons with chronic HBV infection that could progress to cirrhosis and hepatocarcinoma with nearly one million deaths per year. In the last few years the therapeutic options in chronic hepatitis B have increased and currently six treatments are authorized: standard interferon (IFN)-alpha, pegylated interferon-alpha (PEG-IFNalpha), lamivudine, adefovir, entecavir, and telbivudine. For the last 25 years, conventional IFNalpha has been used as the treatment of chronic hepatitis B (CHB) and currently PEG-IFNalpha is indicated due to its greater effectiveness. Both drugs are first line options for HBeAg(+) and HBeAg(-) CHB. The advantages of IFNalpha and PEG-IFNalpha are that these drugs are administered for a limited time period, they achieve a higher sustained response rate and do not induce HBV mutants with antiviral resistance. These drugs achieve greater HBeAG and HBsAG clearance due to their antiviral and immunomodulatory activity. PEG-IFNalpha induces sustained biochemical and virological response in approximately one third of patients with HBeAg(+) CHB. The best response to IFNalpha and PEG-IFNalpha is obtained in patients with elevated transaminase levels, moderate viral load and HBV genotypes A and B. The disadvantages of IFNalpha and PEG-IFNalpha are their adverse effects and contraindications. These drugs cannot be administered in patients with decompensated cirrhosis. The combination of nucleos(t)ide analogs with PEG-IFNalpha could achieve much higher sustained response rates; however, which treatment constitutes the most suitable therapeutic strategy requires investigation.

The time from the start of incubation to a positive reading of blood cultures (time-to-positivity; TTP) is related to the concentration of bacteria in blood. Information concerning the correlation of TTP with clinical parameters, and its usefulness as a prognostic factor in patients with Escherichia coli bacteraemia, is limited. To investigate the relationship of TTP to clinical parameters, 459 cases of monomicrobial E. coli bloodstream infections from a single institution between 1997 and 2005 were reviewed. All cases involved patients who were not undergoing antibiotic treatment at the time of blood sampling. The in-hospital mortality rate was 6.3%. Median TTP was significantly shorter for patients who died than for those who survived (9.7 h, inter-quartile range 7.85-11.05 h vs. 11.2 h, inter-quartile range 10.1-11.4 h; p <0.001). Patients with TTP in the lowest quartile were more likely to be female, to have a non-urinary tract or an unknown origin of bacteraemia, to have severe sepsis or shock, and to subsequently die. In a multivariable Cox regression model, the hazard ratio for death from any cause for patients with a short TTP was 3.13 (95% CI 1.28-7.64; p 0.01). TTP in patients with E. coli bacteraemia provides prognostic information beyond that provided by the presence of haematological illness, a Charlson score > or =3, a non-urinary tract origin of bacteraemia, and the presence of severe sepsis or shock.