Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal.

Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 metastatic biopsies across 100 patients with metastatic ccRCC, including two cases sampledat post-mortem. Metastatic competence was afforded by chromosome complexity, and we identify 9p loss as a highly selected event driving metastasis and ccRCC-related mortality (p = 0.0014). Distinct patterns of metastatic dissemination were observed, including rapid progression to multiple tissue sites seeded by primary tumors of monoclonal structure. By contrast, we observed attenuated progression in cases characterized by high primary tumor heterogeneity, with metastatic competence acquired gradually and initial progression to solitary metastasis. Finally, we observed early divergence of primitive ancestral clones and protracted latency of up to two decades as a feature of pancreatic metastases.

Programs Promoting Virtual Social Connections and Friendships for Youth with Disabilities: A Scoping Review.

AIMS: This scoping review explores what is known about programs that support youth with physical and developmental disabilities to create virtual social connections as a means toward friendships. METHODS: Peer-reviewed studies were searched in six electronic databases: CINAHL, EMBASE, ERIC, MEDLINE, PsycINFO, and Scopus. Two reviewers screened articles that described programs in which participants, ages 8-20, interacted with others online, and reported outcomes related to virtual social connections and friendships in their personal social networks. Data extraction involved program characteristics (e.g., duration, group members, online platform) plus qualitative description outlining access and participation experiences. RESULTS: After screening 12,605 articles, 9 were determined eligible. Programs followed two approaches: (1) training youth to use the internet and technology to access virtual spaces independently; and (2) designing virtual opportunities and activities that encourage youth interaction and collaboration. Each approach was grounded in the principles of fostering privacy and independence (i.e., socializing with peers without relying on caregivers), safety and self-expression (i.e., communicating authentically), plus confidence and capability (i.e., trying new skills). CONCLUSIONS: This scoping review provides guidance on enhancing access and participation of youth with disabilities in virtual spaces where they can develop social connections that increase chances for friendships.

AT1 -R is involved in the development of long-lasting, region-dependent and oxidative stress-independent astrocyte morphological alterations induced by Ketamine.

Astrocytes play an essential role in the genesis, maturation and regulation of the neurovascular unit. Multiple evidence support that astrocyte reactivity has a close relationship to neurovascular unit dysfunction, oxidative stress and inflammation, providing a suitable scenario for the development of mental disorders. Ketamine has been proposed as a single-use antidepressant treatment in major depression, and its antidepressant effects have been associated with anti-inflammatory properties. However, Ketamine long-lasting effects over the neurovascular unit components remain unclear. Angiotensin II AT1 receptor (AT1 -R) blockers have anti-inflammatory, antioxidant and neuroprotective effects. The present work aims to distinguish the acute and long-term Ketamine effects over astrocytes response extended to other neurovascular unit components, and the involvement of AT1 -R, in prefrontal cortex and ventral tegmental area. Male Wistar rats were administered with AT1 -R antagonist Candesartan/Vehicle (days 1-10) and Ketamine/Saline (days 6-10). After 14 days drug-free, at basal conditions or after Ketamine Challenge, the brains were processed for oxidative stress analysis, cresyl violet staining and immunohistochemistry for glial, neuronal activation and vascular markers. Repeated Ketamine administration induced long-lasting region-dependent astrocyte reactivity and morphological alterations, and neuroadaptative changes observed as exacerbated oxidative stress and neuronal activation, prevented by the AT1 -R blockade. Ketamine Challenge decreased microglial and astrocyte reactivity and augmented cellular apoptosis, independently of previous treatment. Overall, AT1 -R is involved in the development of neuroadaptative changes induced by repeated Ketamine administration but does not interfere with the acute effects supporting the potential use of AT1 -R blockers as a Ketamine complementary therapy in mental disorders.

Prospective Evaluation of Focal High Intensity Focused Ultrasound for Localized Prostate Cancer.

PURPOSE: We report short-term outcomes of focal high intensity focused ultrasound use for primary treatment of localized prostate cancer. MATERIALS AND METHODS: Single-center prospectively collected data on patients with prostate cancer who underwent primary focal high intensity focused ultrasound from January 2016 to July 2018 were included. All patients underwent a 12-core biopsy with magnetic resonance imaging-ultrasound fusion biopsy depending on the presence of targetable lesions. Any Grade Group was allowed, however only patients with localized disease were included. The primary outcome was oncologic control, defined as negative followup in-field biopsy of treated cancer. Prostate specific antigen, Sexual Health Inventory for Men, International Prostate Symptom Score and Expanded Prostate Cancer Index Composite domain scores were assessed 3-monthly till 12 months. Biopsy was performed at 6 or 12 months for high or low/intermediate risk cancer, respectively. RESULTS: Fifty-two patients with minimum followup of 12 months were included in the study. The majority of patients (67%) had cancer Grade Group 2 or greater. Fifteen patients (28.8%) underwent complete transurethral prostate resection/holmium laser enucleation of prostate procedure for debulking large prostates to avoid postoperative urinary retention. Among 30 (58%) patients who underwent followup biopsies, 25 (83%) had negative in-field biopsy results and 4 (13%) had de-novo positive out-of-field biopsy. Only 5 major complications (all grade III) in 4 patients were noted. Urinary symptoms returned to near baseline questionnaire scores within 3-6 months. Sexual function returned to baseline at 12 months. CONCLUSIONS: Focal high intensity focused ultrasound is a safe and effective treatment for patients with localized clinically significant prostate cancer with acceptable short-term oncologic and functional outcomes. The complications are minimal and patient selection is essential. Short-term oncologic outcomes are promising but longer followup is required to establish long-term oncologic outcomes.

Use and Validation of the AUA/SUO Risk Grouping for Nonmuscle Invasive Bladder Cancer in a Contemporary Cohort.

PURPOSE: We applied nonmuscle invasive bladder cancer AUA (American Urological Association)/SUO (Society of Urologic Oncology) guidelines for risk stratification and analyzed predictors of recurrence and progression. MATERIALS AND METHODS: We retrospectively reviewed the records of 398 patients with nonmuscle invasive bladder cancer treated between 2001 and 2017. Descriptive statistics were used to compare AUA/SUO risk groups. Predictors of recurrence and progression were determined by multivariable regression. Kaplan-Meier analysis was done, a Cox proportional hazards regression model was created and time dependent AUCs were calculated to determine progression-free and recurrence-free survival by risk group. RESULTS: Median followup was 37 months (95% CI 35-42). Of the patients 92% underwent bacillus Calmette-Guérin induction and 46% received at least 1 course of maintenance treatment. Of the patients 11.5% were at low, 32.5% were at intermediate and 55.8% were at high risk. In patients at low, intermediate and high risk the 5-year progression-free survival rate was 93%, 74% and 54%, and the 5-year recurrence-free survival rate was 43%, 33% and 23%, respectively. Kaplan-Meier analysis was done to stratify high grade Ta 3 cm or less tumor recurrence-free and progression-free survival in the intermediate vs the high risk group. Relative to low risk, classification as intermediate and as high risk was an independent predictor of progression (HR 9.7, 95% CI 2.23-42.0, p <0.01, and HR 36, 95% CI 8.16-159, p <0.001, respectively). Recurrence was more likely in patients at high risk than in those at low risk (HR 2.03, 95% CI 1.11-3.71, p=0.022). For recurrence and progression the 1-year AUC was 0.60 (95% CI 0.546-0.656) and 0.68 (95% CI 0.622-0.732), respectively. CONCLUSIONS: The AUA/SUO nonmuscle invasive bladder cancer risk classification system appropriately stratifies patients based on the likelihood of recurrence and progression. It should be used at diagnosis to counsel patients and guide therapy.

Health Related Quality of Life of Patients with Bladder Cancer in the RAZOR Trial: A Multi-Institutional Randomized Trial Comparing Robot versus Open Radical Cystectomy.

PURPOSE: We evaluated health related quality of life following robotic and open radical cystectomy as a treatment for bladder cancer. MATERIALS AND METHODS: Using the Randomized Open versus Robotic Cystectomy (RAZOR) trial population we assessed health related quality of life by using the Functional Assessment of Cancer Therapy (FACT)-Vanderbilt Cystectomy Index and the Short Form 8 Health Survey (SF-8) at baseline, 3 and 6 months postoperatively. The primary objective was to assess the impact of surgical approach on health related quality of life. As an exploratory analysis we assessed the impact of urinary diversion type on health related quality of life. RESULTS: Analyses were performed in subsets of the per-protocol population of 302 patients. There was no statistically significant difference between the mean scores by surgical approach at any time point for any FACT-Vanderbilt Cystectomy Index subscale or composite score (p >0.05). The emotional well-being score increased over time in both surgical arms. Patients in the open arm showed significantly better SF-8 sores in the physical and mental summary scores at 6 months compared to baseline (p <0.05). Continent diversion (versus noncontinent) was associated with worse FACT-bladder-cystectomy score at 3 (p <0.01) but not at 6 months, and the SF-8 physical component was better in continent-diversion patients at 6 months (p=0.019). CONCLUSIONS: Our data suggests lack of significant differences in the health related quality of life in robotic and open cystectomies. As robotic procedures become more widespread it is important to discuss this finding during counseling.

Predictors of Recurrence, and Progression-Free and Overall Survival following Open versus Robotic Radical Cystectomy: Analysis from the RAZOR Trial with a 3-Year Followup.

PURPOSE: The RAZOR (Randomized Open versus Robotic Cystectomy) trial revealed noninferior 2-year progression-free survival for robotic radical cystectomy. This update was performed with extended followup for 3 years to determine potential differences between the approaches. We also report 3-year overall survival and sought to identify factors predicting recurrence, and progression-free and overall survival. MATERIALS AND METHODS: We analyzed the per protocol population of 302 patients from the RAZOR study. Cumulative recurrence was estimated using nonbladder cancer death as the competing risk event and the Gray test was applied to assess significance in differences. Progression-free survival and overall survival were estimated by the Kaplan-Meier method and compared with the log rank test. Predictors of outcomes were determined by Cox proportional hazard analysis. RESULTS: Estimated progression-free survival at 36 months was 68.4% (95% CI 60.1-75.3) and 65.4% (95% CI 56.8-72.7) in the robotic and open groups, respectively (p=0.600). At 36 months overall survival was 73.9% (95% CI 65.5-80.5) and 68.5% (95% CI 59.8-75.7) in the robotic and open groups, respectively (p=0.334). There was no significant difference in the cumulative incidence rates of recurrence (p=0.802). Patient age greater than 70 years, poor performance status and major complications were significant predictors of 36-month progression-free survival. Stage and positive margins were significant predictors of recurrence, and progression-free and overall survival. Surgical approach was not a significant predictor of any outcome. CONCLUSIONS: This analysis showed no difference in recurrence, 3-year progression-free survival or 3-year overall survival for robotic vs open radical cystectomy. It provides important prospective data on the oncologic efficacy of robotic radical cystectomy and high level data for patient counseling.

Nasal high flow therapy introduction lowers reintubation risk in a Peruvian paediatric intensive care unit.

AIM: We examined the impact of introducing high-flow nasal oxygen therapy (HFNT) on children under five with post-extubation respiratory failure in a paediatric intensive care unit (PICU) in Peru. METHODS: This quasi-experimental study compared clinical outcomes before and after initial HFNT deployment in the PICU at Instituto Nacional de Salud del Niño in Lima in June 2016. We compared three groups: 29 received post-extubation HFNT and 17 received continuous positive airway pressure (CPAP) from 2016-17 and 12 historical controls received CPAP from 2012-16. The primary outcome was the need for mechanical ventilation. Adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) were calculated via survival analysis. RESULTS: High-flow nasal oxygen therapy and CPAP did not alter the need for mechanical ventilation after extubation (aHR 0.47, 95% CI 0.15-1.48 and 0.96, 95% CI 0.35-2.62, respectively) but did reduce the risk of reintubation (aHR 0.18, 95% CI 0.06-0.57 and 0.14, 95% CI 0.03-0.72, respectively). PICU length of stay was 11, 18 and 37 days for CPAP, HFNT and historical CPAP and mortality was 12%, 7% and 27%, respectively. There was no effect on the duration of sedative infusions. CONCLUSION: High-flow nasal oxygen therapy provided effective support for some children, but larger studies in resource-constrained settings are needed.

Serum and urinary biomarkers for detection and active surveillance of prostate cancer.

PURPOSE OF REVIEW: To provide a comprehensive review of the available biomarkers for the detection and active surveillance of prostate cancer and simplify decision-making while choosing between them. RECENT FINDINGS: The limitations of PSA and mpMRI and the invasive nature of prostate biopsy has led to a constant search for serum and urinary biomarkers for both the detection and monitoring during active surveillance of prostate cancer. 4K, PHI and PCA3 have been validated in prospective clinical trials for initial detection of prostate cancer and recent evidence points to potential differentiation between indolent and aggressive cancer. However, the usage in monitoring tumor dynamics is debatable because of lack of conclusive evidence. The answer to the existing problems lies in high-quality studies to establish definitive evidence and also to help choose between the plethora of biomarkers available today. SUMMARY: Despite the advancements in innovation and usage of biomarkers in prostate cancer, there exists tremendous potential in improving them to fulfil the unmet need that exists today. Studies to establish conclusive evidence and integration with imaging can tremendously aid diagnosis and monitoring.

Electrical Behavior of a Catalyst Composed of Laminar Manganese Oxide Supported on γ-Al2O3.

The electrical characterization of catalysts composed of layered manganese oxide in the form of birnessite supported on γ-Al2O3, which have been successfully used in the combustion of soot, is presented. The results indicate that the electrical conduction and ion conduction processes are influenced by the amount of the active phase. There was also evidence of Grotthuss-type proton conductivity favored by the presence of surface water on the exposed alumina surface. The above is supported by the porous nature of the catalyst in which the surface area varied between 125.2 ± 1.2 and 159.0 ± 1.1 m2/g, evidencing changes in the alumina surface. The conductivity, determined from measurements of impedance spectroscopy, at low frequency showed changes associated with the amount of the active phase. The values ranged from 2.61 × 10-8 ± 2.1 × 10-9 Ω-1·cm-1 (pure alumina) to 7.33 × 10-8 ± 5.9 × 10-9 Ω-1·cm-1, 7.21 × 10-8 ± 5.8 × 10-9 Ω-1·cm-1 and 4.51 × 10-7 ± 3.6 × 10-8 Ω-1·cm-1 at room temperature for catalysts with nominal active phase contents of 5.0, 10.0 and 20.0%, respectively. Such results indicate that it is possible to modulate the electrical properties with variations in the synthesis parameters.

Cystic Renal Cell Carcinoma: A Report on Outcomes of Surgery and Active Surveillance in Patients Retrospectively Identified on Pretreatment Imaging.

PURPOSE: We evaluated the outcomes of surgical intervention and active surveillance in patients diagnosed with cystic renal cell carcinoma at our hypothesized radiological cutoff of greater than 50% cystic. MATERIALS AND METHODS: We identified all 430 patients with a pathologically confirmed cystic renal mass that fit our criteria from 2000 to 2015. The 292 patients with a lack of computerized tomography, tumors less than 50% cystic on imaging, multifocal tumors and prior renal cell carcinoma were excluded from study. Patients were stratified into benign or malignant subgroups, and radiological, clinicopathological and oncologic features were determined. Univariate and multivariate associations between clinicoradiological parameters in each group were analyzed. We similarly reviewed the records of a separate cohort of patients treated with active surveillance for cystic renal cell carcinoma. RESULTS: Of the 138 identified cases of cystic renal cell carcinoma 102 (73.9%) were renal cell carcinoma and 36 (26.1%) were benign masses. Of the tumors 77.5% were Fuhrman grade 1-2, 83.4% were stage pT2 or less and 65.9% showed clear cell histology. On univariate analysis male gender, a solid component and increasing Bosniak classification were significant for malignancy. In a separate cohort we identified 38 patients on active surveillance. The growth rate was 1.0 mm per year overall and 2.3 mm per year for the solid component. At a median followup of more than 4 years in all cohorts there was no evidence of recurrence or metastasis of cystic renal cell carcinoma. CONCLUSIONS: Patients with unifocal cystic renal cell carcinoma evaluated using a standardized radiological threshold of greater than 50% cystic had an excellent prognosis on active surveillance and after surgical resection.

Clinical Outcome of Patients with Fibrosis/Necrosis at Post-Chemotherapy Retroperitoneal Lymph Node Dissection for Advanced Germ Cell Tumors.

PURPOSE: Fibrosis accounts for approximately 50% of histological findings at post-chemotherapy retroperitoneal lymph node dissection, and is associated with reported relapse rates of 10% to 15%. We characterized patients with fibrosis at post-chemotherapy retroperitoneal lymph node dissection and identified predictors of adverse outcomes in this group. MATERIALS AND METHODS: We reviewed the medical records of men who underwent post-chemotherapy retroperitoneal lymph node dissection between 1989 and 2013 with histological findings of necrosis/fibrosis. With few exceptions post-chemotherapy retroperitoneal lymph node dissection after 1999 was performed with a bilateral template. Clinical, pathological and treatment related data were reported. Cox regression models were built to identify predictors of disease recurrence. RESULTS: The study cohort included 598 men with a median age of 32 years (IQR 25-38). Most cases (397 of 547, 73%) were classified as IGCCCG good risk, with no significant differences in risk classification before and after 1999 (p=0.55). Median followup was 7.3 years (IQR 3.2-12.3). The 5-year recurrence-free and overall survival rates were 94% and 96%, respectively. Overall 36 patients had disease recurrence, most of which was distant or outside the retroperitoneal lymph node dissection template. Procedures performed after 1999 and the presence of embryonal cell carcinoma on primary histology were associated with improved recurrence-free survival on multivariate analysis (p <0.01). CONCLUSIONS: Disease recurrence in patients with fibrosis at post-chemotherapy retroperitoneal lymph node dissection is an uncommon yet significant event, which is less likely to occur in patients treated after 1999 and in those with embryonal carcinoma on primary histology.

Cooperative Behavior of Fluoroquinolone Combinations against Escherichia coli and Staphylococcus aureus.

The effects of different combinations of ciprofloxacin (CIP) and norfloxacin (NOR) against Escherichia coli and Staphylococcus aureus were studied using checkerboard, fractional inhibitory concentration (FIC) and time-kill analysis methods. Results obtained by the checkerboard method showed that the more effectives combinations against Escherichia coli were 0.0009 µg/mL CIP+0.0312 µg/mL NOR and 0.0037 µg/mL CIP+0.0075 µg/mL NOR with a FIC index of 0.62. For Staphylococcus aureus, the combination of 0.0625 µg/mL CIP+0.2500 µg/mL NOR showed a synergistic effect, with a FIC index of 0.50. The results of the time-kill method demonstrated either indifference or additivity of the combinations 0.0009 µg/mL CIP+0.0312 µg/mL NOR, 0.0018 µg/mL CIP+0.0312 µg/mL NOR, 0.0037 µg/mL CIP+0.0075 µg/mL NOR and 0.0037 µg/mL CIP+0.0156 µg/mL NOR at 24 h against E. coli. The combination 0.0037 µg/mL CIP+0.0312 µg/mL NOR showed synergistic activity. All the analyzed combinations evidenced bactericidal effects at 4 h. The combinations 0.0625 µg/mL CIP+0.2500 µg/mL NOR and 0.0625 µg/mL CIP+0.0625 µg/mL NOR showed indifference or additivity against S. aureus. None of them generated bactericidal effect at 4 h. Moreover, this last equimolecular combination (equivalent to 1/4 minimum inhibitory concentration (MIC) CIP+1/16 MIC NOR) generated higher reduction of nitro blue tetrazolium than drugs alone. By another way, combinations not equimolecular of CIP and NOR assayed, generated less levels of reactive oxygen species (ROS) than the components alone.

Regulation of Pseudomonas aeruginosa virulence factors by two novel RNA thermometers.

In a number of bacterial pathogens, the production of virulence factors is induced at 37 °C; this effect is often regulated by mRNA structures formed in the 5' untranslated region (UTR) that block translation initiation of genes at environmental temperatures. At 37 °C, the RNA structures become unstable and ribosomes gain access to their binding sites in the mRNAs. Pseudomonas aeruginosa is an important opportunistic pathogen and the expression of many of its virulence-associated traits is regulated by the quorum-sensing (QS) response, but the effect of temperature on virulence-factor expression is not well-understood. The aim of this work is the characterization of the molecular mechanism involved in thermoregulation of QS-dependent virulence-factor production. We demonstrate that traits that are dependent on the QS transcriptional regulator RhlR have a higher expression at 37 °C, correlating with a higher RhlR concentration as measured by Western blot. We also determined, using gene fusions and point mutations, that RhlR thermoregulation is a posttranscriptional effect dependent on an RNA thermometer of the ROSE (Repression Of heat-Shock gene Expression) family. This RNA element regulates the expression of the rhlAB operon, involved in rhamnolipid production, and of the downstream rhlR gene. We also identified a second functional thermometer in the 5' UTR of the lasI gene. We confirmed that these RNA thermometers are the main mechanism of thermoregulation of QS-dependent gene expression in P. aeruginosa using quantitative real-time PCR. This is the first description, to our knowledge, of a ROSE element regulating the expression of virulence traits and of an RNA thermometer controlling multiple genes in an operon through a polar effect.

Pseudomonas aeruginosa ATCC 9027 is a non-virulent strain suitable for mono-rhamnolipids production.

Rhamnolipids produced by Pseudomonas aeruginosa are biosurfactants with a high biotechnological potential, but their extensive commercialization is limited by the potential virulence of P. aeruginosa and by restrictions in producing these surfactants in heterologous hosts. In this work, we report the characterization of P. aeruginosa strain ATCC 9027 in terms of its genome-sequence, virulence, antibiotic resistance, and its ability to produce mono-rhamnolipids when carrying plasmids with different cloned genes from the type strain PAO1. The genes that were expressed from the plasmids are those coding for enzymes involved in the synthesis of this biosurfactant (rhlA and rhlB), as well as the gene that codes for the RhlR transcriptional regulator. We confirm that strain ATCC 9027 forms part of the PA7 clade, but contrary to strain PA7, it is sensitive to antibiotics and is completely avirulent in a mouse model. We also report that strain ATCC 9027 mono-rhamnolipid synthesis is limited by the expression of the rhlAB-R operon. Thus, this strain carrying the rhlAB-R operon produces similar rhamnolipids levels as PAO1 strain. We determined that strain ATCC 9027 with rhlAB-R operon was not virulent to mice. These results show that strain ATCC 9027, expressing PAO1 rhlAB-R operon, has a high biotechnological potential for industrial mono-rhamnolipid production.

Evaluation of Antibacterial Activity and Reactive Species Generation of N-Benzenesulfonyl Derivatives of Heterocycles.

Two N-benzenesulfonyl (BS) derivatives of 1,2,3,4-tetrahydroquinoline (THQ) were designed, prepared, and screened for antibacterial activity. This approach was based on combining the two privileged structures, BS and THQ, which are known to be active. The objective of this study was to evaluate the antibacterial activity of BS-THQ and its analogue 4-NH2BS-THQ, and to investigate the roles of reactive oxygen species and reactive nitrogen species in their lethality. Both showed bactericidal activity against Staphylococcus aureus ATCC 29213 and methicillin-resistant S. aureus (MRSA) ATCC 43300, with transmission electron microscopy revealing a disturbed membrane architecture. Furthermore, an increase of reactive oxygen species (ROS) in strains treated with BS-THQ with respect to the control was detected when fluorescent microscopy and spectrophotometric techniques were used. The analogue 4-NH2BS-THQ demonstrated a broader spectrum of activity than BS-THQ, with a minimum inhibitory concentration of 100 µg/mL against reference strains of S. aureus, Escherichia coli and Pseudomonas aeruginosa. The assayed compounds represent promising structures for the development of new synthetic classes of antimicrobials.

Examining the Preliminary Efficacy of a Dating Violence Prevention Program for Hispanic Adolescents.

The purpose of this study is to evaluate the preliminary efficacy of a dating violence (DV) prevention program for Cuban American adolescents (JOVEN/YOUTH: Juntos Opuestos a la Violence Entre Novios/Together Against Dating Violence). A randomized-controlled experimental design with a delayed condition was used to evaluate the effects on DV victimization and perpetration (N = 82). Self-administrated assessments were completed at baseline, 1 week, 3 months, and 12 months after the intervention to assess for psychological victimization and perpetration and physical and sexual victimization and perpetration. Effect sizes were estimated, and generalized estimating equations were generated to test intervention effects over time and potential gender interactions. The intervention had medium to strong effects on DV victimization and perpetration for male participants but not for females. However, intervention effects were not statistically significant over time. More research is needed to enhance intervention effects of JOVEN on DV outcomes and to evaluate these effects among a larger and more diverse sample.

Pseudomonas aeruginosa clinical and environmental isolates constitute a single population with high phenotypic diversity.

BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen with a high incidence of hospital infections that represents a threat to immune compromised patients. Genomic studies have shown that, in contrast to other pathogenic bacteria, clinical and environmental isolates do not show particular genomic differences. In addition, genetic variability of all the P. aeruginosa strains whose genomes have been sequenced is extremely low. This low genomic variability might be explained if clinical strains constitute a subpopulation of this bacterial species present in environments that are close to human populations, which preferentially produce virulence associated traits. RESULTS: In this work, we sequenced the genomes and performed phenotypic descriptions for four non-human P. aeruginosa isolates collected from a plant, the ocean, a water-spring, and from dolphin stomach. We show that the four strains are phenotypically diverse and that this is not reflected in genomic variability, since their genomes are almost identical. Furthermore, we performed a detailed comparative genomic analysis of the four strains studied in this work with the thirteen previously reported P. aeruginosa genomes by means of describing their core and pan-genomes. CONCLUSIONS: Contrary to what has been described for other bacteria we have found that the P. aeruginosa core genome is constituted by a high proportion of genes and that its pan-genome is thus relatively small. Considering the high degree of genomic conservation between isolates of P. aeruginosa from diverse environments, including human tissues, some implications for the treatment of infections are discussed. This work also represents a methodological contribution for the genomic study of P. aeruginosa, since we provide a database of the comparison of all the proteins encoded by the seventeen strains analyzed.

Aspartame-stabilized gold-silver bimetallic biocompatible nanostructures with plasmonic photothermal properties, antibacterial activity, and long-term stability.

Gold-silver core-shell nanoparticles stabilized with a common sweetener, aspartame (AuNP@Ag@Asm), combine the antimicrobial properties of silver with the photoinduced plasmon-mediated photothermal effects of gold. The particles were tested with several bacterial strains, while biocompatibility was verified with human dermal fibroblasts.