Can Pseudomonas aeruginosa growth be modulated by natural compounds?

Pseudomonas aeruginosa is an opportunistic human pathogen that frequently induces antibiotic resistance, as it mainly tends to form biofilms. Iron chelation may be an intriguing strategy to contrast bacterial growth. Lactoferrin is a natural compound able to chelate iron. A new multi-component medical device also contains lactoferrin. This study analyzed this compound investigating the in vitro capacity to inhibit Pseudomonas aeruginosa growth. In conclusion, this study demonstrated that a multicomponent medical device (Saflovir), also containing lactoferrin, could inhibit the in vitro growth of P. aeruginosa. This activity could be positively used in the prevention of respiratory nasal infections.

Efficient parametric generation in a nonlinear photonic crystal pumped by a dual beam.

We investigate parametric down-conversion in a hexagonally poled nonlinear photonic crystal, pumped by a dual pump with a transverse modulation that matches the periodicity of the χ (2) nonlinear grating. A peculiar feature of this resonant configuration is that the two pumps simultaneously generate photon pairs over an entire branch of modes, via quasi-phase matching with both fundamental vectors of the reciprocal lattice of the nonlinearity. The parametric gain of these modes depends thus coherently on the sum of the two pump amplitudes and can be controlled by varying their relative intensities and phases. We find that a significant enhancement of the source conversion efficiency, comparable to that of one-dimensionally poled crystals, can be achieved by a dual symmetric pump. We also show how the four-mode coupling arising among shared modes at resonance can be tailored by changing the dual pump parameters.

PD-L1 protein expression assessed by immunohistochemistry is neither prognostic nor predictive of benefit from adjuvant chemotherapy in resected non-small cell lung cancer.

Background: The expression of programmed death (PD) ligand 1 (PD-L1) protein expression assessed by immunohistochemistry (IHC) has been correlated with response and survival benefit from anti-PD-1/PD-L1 immune checkpoint inhibitor therapies in advanced non-small cell lung carcinoma (NSCLC). The efficacy of several agents appears correlated with PD-L1 expression. It remains controversial whether PD-L1 is prognostic in NSCLC. We assessed the prognostic value of PD-L1 IHC and its predictive role for adjuvant chemotherapy in early stage NSCLC. Patients and methods: Tumor sections from three pivotal adjuvant chemotherapy trials (IALT, JBR.10, CALGB 9633) using the E1L3N antibody were studied in this pooled analysis. PD-L1 staining intensity and percentage in both tumor cells (TCs) and immune cells (ICs) were scored by two pathologists. The average or consensus PD-L1 expression levels across intensities and/or percent cells stained were correlated with clinicopathological and molecular features, patient survivals and potential benefit of adjuvant chemotherapy. Results: Results from 982 patients were available for analysis. Considering staining at any intensities for overall PD-L1 expression, 314 (32.0%), 204 (20.8%) and 141 (14.3%) tumor samples were positive for PD-L1 staining on TCs using cut-offs at ≥1%, ≥10% and ≥25%, respectively. For PD-L1 expressing ICs, 380 (38.7%), 308 (31.4%) and 148 (15.1%) were positive at ≥ 1%, ≥10% and 25% cut-offs, respectively. Positive PD-L1 was correlated with squamous histology, intense lymphocytic infiltrate, and KRAS but not with TP53 mutation. EGFR mutated tumors showed statistically non-significant lower PD-L1 expression. PD-L1 expression was neither prognostic with these cut-offs nor other exploratory cut-offs, nor were predictive for survival benefit from adjuvant chemotherapy. Conclusions: PD-L1 IHC is not a prognostic factor in early stage NSCLC patients. It is also not predictive for adjuvant chemotherapy benefit in these patients.

An in vitro and in vivo comparison of the effect of Stevia rebaudiana extracts on different caries-related variables: a randomized controlled trial pilot study.

The effect of Stevia extracts on in vitro Streptococcus mutans biofilm formation and in vivo plaque pH was evaluated in this paper. Three 10% solutions containing stevioside, rebaudioside A or sucrose were prepared. MTT assay was used to evaluate microbiological counts in vitro. Twenty volunteers rinsed for 1 min with each solutions, and plaque pH was measured at 7 time points after each rinse. Higher in vitro S. mutans biofilm formation was observed in sucrose solution (p < 0.01). After 5, 10, 15 and 30 min, the sucrose in vivo rinse produced a statistically significantly lower pH value compared to the Stevia extracts (F = 99.45, p < 0.01).Stevia extracts can be considered nonacidogenic.

[The French mesothelioma network from 1998 to 2013]. / Mésothéliome: les dispositifs en place en France « le réseau mésothéliome ¼ 1998-2013.

Mesothelioma is a rare disease less than 0.3% of cancers in France, very aggressive and resistant to the majority of conventional therapies. Asbestos exposure is nearly the only recognized cause of mesothelioma in men observed in 80% of case. In 1990, the projections based on mortality predicted a raise of incidence in mesothelioma for the next three decades. Nowadays, the diagnosis of this cancer is based on pathology, but the histological presentation frequently heterogeneous, is responsible for numerous pitfalls and major problems of early detection toward effective therapy. Facing such a diagnostic, epidemiological and medico-legal context, a national and international multidisciplinary network has been progressively set up in order to answer to epidemiological survey, translational or academic research questions. Moreover, in response to the action of the French Cancer Program (action 23.1) a network of pathologists was organized for expert pathological second opinion using a standardized procedure of certification for mesothelioma diagnosis. We describe the network organization and show the results during this last 15years period of time from 1998-2013. These results show the major impact on patient's management, and confirm the interest of this second opinion to provide accuracy of epidemiological data, quality of medico-legal acknowledgement and accuracy of clinical diagnostic for the benefit of patients. We also show the impact of these collaborative efforts for creating a high quality clinicobiological, epidemiological and therapeutic data collection for improvement of the knowledge of this dramatic disease.

Differences in sexual desire between women with clinical versus biochemical signs of hyperandrogenism in polycystic ovarian syndrome.

The role androgens play in female sexual desire remains unclear. We investigated whether androgen sensitivity or elevated androgen levels contributed to sexual desire using a motivational model of sexual desire. Eighty-five women diagnosed with polycystic ovary syndrome (PCOS) were categorized depending on whether they exhibited clinical symptoms of androgen sensitivity or high biochemical androgen levels. Additionally, instead of looking at desire as a uniform construct, we divided desire based on the reasons why women experienced desire, thus distinguishing desire to have sex for relational purposes from the desire to have sex for mating selection or physical pleasure. Findings confirmed that clinical signs suggesting sensitivity to androgen levels, but not biological levels of androgens per se predicted levels of sexual desire. Moreover, in agreement with our hypothesis, we found support for a relationship between androgen sensitivity and some, but not other aspects of sexual desire. Cues that are most closely related to mating selection were significantly associated with androgen sensitivity, but not cues associated with desiring sex to feel emotionally close or create a love bonding with a partner. This study presents a new way to investigate desire and shows some preliminary findings on the importance to consider androgen sensitivity when investigating the relationship between sexual desire and hormones.

Impacts of an urban flood control infrastructure on the limnology and ichthyofauna of a basaltic Cuesta stream (southeast Brazil).

Strategies for flood control associated to extreme precipitation events in urban areas are urgent, in order to prevent not only material damages but also to avoid human losses. The construction of flood contention reservoirs ("piscinões") has become a common engineering intervention in urban and peri-urban areas. However, there is a lack of studies focused on the evaluation of environmental impacts of this type of construction. This study intended to verify the ecological effects of a retention reservoir built directly on the course of the Cascata stream, Botucatu (SP). Three sampling sites were selected, located upstream the reservoir, in the reservoir and downstream. Samplings were carried out in July (winter - dry) and November (late spring - rainy) 2020. In situ measurements were obtained through a multiparameter probe (temperature, pH, electrical conductivity, dissolved oxygen, total dissolved solids, and oxidation-reduction potential) and water samples were collected for laboratory determinations (nitrogen, total phosphorus, thermotolerant coliforms, and chlorophyll-a). For fish sampling, manual trawls, sieves and hand nets were used, with a sampling effort of 10 throws per artefact and site. Despite the small distance between the sampling points (~1,300 m) considerable changes in the limnological conditions and fish community structure were observed. The studied environment is originally a small river surrounded by riparian forest, but this characteristic was abruptly changed in the reservoir stretch, with the direct exposition of a much larger water surface to intense solar radiation and atmosphere exchanges. Consequently, as evidenced by the PCA analysis, there was a considerable (stream-reservoir increase) of temperature, dissolved oxygen and chlorophyll. However, this spatial trend was partially disturbed by an accidental sewage-pipe rupture (posteriorly fixed) adjacent to the first sampling point, due to a previous event of extreme precipitation, which resulted in increased values of nutrients, chlorophyll, conductivity and thermotolerant coliforms. Eleven fish species were collected (two non-native), belonging to seven families and five orders. The upstream reference point (despite not be pristine), was characterized by the predominance of native species, while the reservoir condition favored the development of large populations of the non-native species. Despite the urgency of effective actions to prevent floods in urban areas, construction of contention reservoirs directly on stream courses should be avoided, due to their negative ecological impacts.

Cisplatin benefit is predicted by immunohistochemical analysis of DNA repair proteins in squamous cell carcinoma but not adenocarcinoma: theranostic modeling by NSCLC constituent histological subclasses.

BACKGROUND: Most non-small-cell lung cancer (NSCLC) patients receive cisplatin-based chemotherapy though clinical response is restricted to a subset of patients. DNA repair protein levels are possible surrogates for cisplatin-induced DNA adduct (and subsequent cell death) repair efficiency and thus molecular determinants of therapeutic efficacy. The International Adjuvant Lung Trial (IALT)-Bio study previously suggested ERCC1 and MSH2 as predictive of cisplatin-based therapeutic benefit. PATIENTS AND METHODS: DNA repair protein expression (XPF, BRCA1, ERCC1, MSH2, p53, PARP1, and ATM) was assessed by immunohistochemistry on a large subset of patients (N = 769) from the IALT trial. Tissue Microarray slides were digitally scanned and signal quantified by user-defined macros. Statistical analyses (univariate and multivariate) of 5-year disease-free survival (DFS) and 5-year overall survival used binary cut-offs (H score low/high expression). RESULTS: In patients with squamous cell carcinoma (SCC), ATM, p53, PARP1, ERCC1, and MSH2 displayed significant (borderline) predictive values, mainly on DFS with chemotherapy efficacy limited to low marker levels. Adenocarcinoma (ADC) results were not significant. BRCA1 and XPF were not significant for predictive modeling in either SCC or ADCs. CONCLUSION: Here predictive utility of DNA repair enzymes co-segregates with SCC histology, focusing their predictive value to this histological subclass of NSCLC. Distinct mechanisms of chemotherapeutic response or resistance might exist among histological subclasses of solid tumors.

Surgical implications of the new IASLC/ATS/ERS adenocarcinoma classification.

A new adenocarcinoma classification was recently introduced by a joint working group of the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS) and European Respiratory Society (ERS). A distinction is made between pre-invasive lesions, and minimally invasive and invasive adenocarcinoma. The confusing term "bronchioloalveolar carcinoma" is not used any more and new subcategories include adenocarcinoma in situ and minimally invasive adenocarcinoma. Due to a renewed interest in screen-detected nodules and early-stage lung cancers of <2 cm, this classification also has profound implications for thoracic surgeons. In this article, surgical topics are discussed: the role of a minimally invasive approach, especially video-assisted thoracic surgery, limited resection for early-stage lung cancer, the extent of lymph node dissection, the accuracy of intraoperative frozen section analysis, management of multiple lung nodules and prognostic factors in operated patients. Specific key issues are presented based on the current evidence and areas of surgical uncertainty are defined providing a basis for further studies. Thoracic surgeons will play a major role in the application and global introduction of this new adenocarcinoma classification. The remaining controversies regarding the precise diagnosis and management of early-stage lesions will have to be resolved by multidisciplinary and international collaboration.

Experimental observation of a skewed X-type spatiotemporal correlation of ultrabroadband twin beams.

This work presents the experimental observation of the nonfactorable near-field spatiotemporal correlation of ultrabroadband twin beams generated by parametric down-conversion, in an interferometric-type experiment using sum frequency generation, where both the temporal and the spatial degrees of freedom of parametric down-conversion light are controlled with high resolution. The revealed correlation is skewed in space-time in accordance with the X structure predicted by the theory.

Detection of the ultranarrow temporal correlation of twin beams via sum-frequency generation.

We demonstrate the ultranarrow temporal correlation (6 fs full width half maximum) of twin beams generated by parametric down-conversion by using its reverse process, i.e., sum-frequency generation. The result relies on an achromatic imaging of a huge bandwidth of twin beams and on a careful control of their spatial degrees of freedom. The detrimental effects of spatial filtering and imperfect imaging are shown, along with the theoretical model used to describe the results.

Efficacy of ultrasonic vibration in warm gutta-percha vertical compaction.

AIM: Vertical compaction of warm gutta-percha is a methodology to seal root canals and it might be associated with ultrasonic vibration. The aim of this paper was to determine whether vertical compaction of warm gutta-percha used with ultrasonic vibrations performs better compared to the traditional one. METHODS: Twenty-four single-rooted teeth were endodontically treated and randomly divided into two groups: in the first group (G1), teeth were filled using vertical compaction, while in the other (G2), vertical compaction was used with ultrasonic vibration. A microleakage test was performed after 24 h and 30 days from root canal sealing. RESULTS: After 24 hours, microleakage was similar in both groups (0.013 µL/min; SD 0.008); after 30 days, it was 0.006 µL/min (SD 0.004) in G1 and 0.004 µL/min (SD 0.003) in G2 (P>0.05). CONCLUSION: Under these experimental conditions, ultrasonic vibration used with vertical compaction produced a similar level of sealing as the traditional method.

Microbial contamination of resin composites inside their dispensers: An increased risk of cross-infection?

OBJECTIVES: To evaluate the effects of microorganisms' contamination inside the dispensing syringes of different types of resin-based composites (RBCs). METHODS: This study encompassed two sections. First, an anonymous electronic survey was submitted via Google forms to Italian dentists to acquire information about composite handling during clinical procedures. Then, a bench test was performed on nanohybrid RBCs differing in matrix chemistry and fillers [FiltekTM Supreme XTE (3MTM); Venus Pearl (Kulzer GmbH); Admira Fusion x-tra (Voco)] to evaluate the microbial viability on their surfaces with/out photocuring. Uncured RBCs were exposed to standardized inocula of Streptococcus Mutans, Candida Albicans, Lactobacillus Rhamnosus, or mixt plaque in an in vitro model reproducing clinical restorative procedures. Half of the RBC specimens were cured after exposure. Microbial viability was assessed using an MTT-based test. Statistical analysis included three-way ANOVA and Tukey's tests (p<0.05). RESULTS: Among 300 dentists completing the survey, the majority declared to use the spatula to carry the RBCs from the syringe to the dental cavity (50% same spatula; 35% two spatulas). However, 80% of respondents had personal feelings that using one spatula could be a source of cross-contamination. In vitro results using one spatula showed microbial contamination of all RBCs after one hour of storage. The contamination levels depended on the used strain and RBC type (p<0.0001), but photocuring did not reduce contamination (p = 0.2992). CONCLUSIONS: Microbial species' viability on uncured RBCs and after photocuring shows the existence of a considerable risk of cross-infection. Clinical procedures in Restorative Dentistry need to acknowledge and to reduce such risk during RBCs handling. CLINICAL SIGNIFICANCE: Dentists must be aware of the possibility of cross-infection during restorative procedures, especially when the same spatula is repeatedly used for placing RBC in the cavity.

ERCC1 influence on the incidence of brain metastases in patients with non-squamous NSCLC treated with adjuvant cisplatin-based chemotherapy.

BACKGROUND: We recently demonstrated that excision repair cross-complementing group 1 protein (ERCC1) is predictive of adjuvant cisplatin-based chemotherapy benefit in resected non-small-cell lung cancer (NSCLC). Non-squamous cell carcinomas (non-SCCs) carry an increased risk of brain metastases (BMs). We hypothesised that there might be an increased incidence of BMs in ERCC1-negative non-SCCs when treated with adjuvant cisplatin-based chemotherapy. PATIENTS AND METHODS: Incidence of BMs and histoclinical parameters were analysed in a population of 761 patients enrolled in the International Adjuvant Lung Cancer Trial. A subgroup analysis was carried out in patients with ERCC1-negative non-SCCs. RESULTS: Of 761 patients, 98 developed BMs alone or in association with other metastatic sites, with a 5-year incidence rate of 18.0% (14.7%-21.8%). In the multivariate analysis, the clinical parameters associated with the occurrence of BMs were the nodal status (P = 0.02) and histological type [give hazard ratio (HR) for non-squamous to quantify introduction assertion, P = 0.002]. Chemotherapy had no effect on BMs [HR = 1.4 (0.90-2.1), P = 0.14]. In patients with non-SCC histology (n = 335), adjuvant chemotherapy was associated with an increased risk of BMs [HR = 2.1 (1.01-4.3), P = 0.04] for ERCC1-negative tumours, whereas there was no evidence of an effect on BMs for ERCC1-positive tumours [HR = 1.1 (0.38-3.0), P = 0.90]. Nevertheless, these two effects are not different (P = 0.30 for interaction) possibly due to a lack of power in this subgroup. CONCLUSIONS: This study suggests that adjuvant cisplatin-based chemotherapy is associated with an increased risk of BMs in patients with resected chemosensitive non-SCCs. If confirmed, these data could provide a rationale for new follow-up and/or prophylactic strategies.

Primary lung adenocarcinoma: characteristics by smoking habit and sex.

The incidence of adenocarcinoma is increasing, particularly among females. We sought to assess the role of tobacco consumption in clinical presentation according to sex. In this retrospective study, 848 patients diagnosed between 1997 and 2006 at Grenoble University Hospital (Grenoble, France) were stratified into four groups according to smoking habits. Differences between sexes and two contrasting female profiles emerged. Female current smokers were younger than female never-smokers (median 51 versus 69 yrs; p < 0.001), more often had surgery (62.7% versus 39%; p = 0.01) and had a median (95% CI) estimated survival of 26.2 (18.1-49.2) versus 15.1 (12.8-22.2) months (p = 0.002). Both groups had similar survival when taking treatment into account. Among males, smoking did not influence presentation. Male current smokers were older than female current smokers (median 59 yrs; p < 0.001) and fewer had surgery (48.8%; p = 0.015), although the percentage of stage IIIb-IV disease was similar (53% and 46%; nonsignificant) and they had a poorer estimated survival of 14.3 (13.0-18.5) months (p = 0.0024). Males smoked more than females (median 41 versus 30 pack-yrs; p < 0.001). Quitting smoking delayed age at diagnosis by 11 yrs for females (p = 0.0035) and 8 yrs for males (p < 0.001). Our results support the hypothesis that carcinogenesis differs between males and females, and between female smokers and never-smokers.

Aeromonas rivuli sp. nov., isolated from the upstream region of a karst water rivulet.

Two freshwater isolates (WB4.1-19(T) and WB4.4-101), sharing 99.9 % 16S rRNA gene sequence similarity, were highly related to Aeromonas sobria (99.7 % similarity; 6 bp differences). A phylogenetic tree derived from a multi-locus phylogenetic analysis (MLPA) of the concatenated sequences of five housekeeping genes (gyrB, rpoD, recA, dnaJ and gyrA; 3684 bp) revealed that both strains clustered as an independent phylogenetic line next to members of Aeromonas molluscorum and Aeromonas bivalvium. The DNA-DNA reassociation value between the two new isolates was 89.3 %. Strain WB4.1-19(T) had a DNA-DNA relatedness value of <70 % with the type strains of the other species tested. Phenotypic characterization differentiated the two novel strains from all other type strains of species of the genus Aeromonas. It is concluded that the two new strains represent a novel species of the genus Aeromonas, for which the name Aeromonas rivuli sp. nov. is proposed, with the type strain WB4.1-19(T) (=CECT 7518(T)=DSM 22539(T)=MDC 2511(T)).

A new urinary catheter design reduces in-vitro biofilm formation by influencing hydrodynamics.

AIM: To evaluate the performance of a new catheter design based on different hydrodynamics aiming to reduce the development of biofilm, and compare it with a conventional Foley catheter (FC). METHODS: The new proposed design (NPD) catheter is a modification of the FC, based on asymmetric positioning of the balloon and additional drainage holes allowing continuous urine drainage and complete voiding of the bladder. A first experiment was undertaken to assess drainage capability, and a second experiment was performed using a bioreactor with a set-up simulating the bladder and using the test catheter as a flow-through system. The biofilm formation of five bacterial species associated with catheter-associated urinary tract infection (CAUTI) was determined after 24 h of incubation using an MTT assay. Morphological evaluation was performed using scanning electron microscopy. In-vitro determination of residual fluid, and quantitative and morphological data on biofilm formation on the intravesical and intraluminal parts of the tested catheters were assessed. RESULTS: Residual fluid was significantly higher in the FC (5.60 ± 0.43 mL) compared with the NPD catheter (0.2 ± 0.03 mL). The NPD catheter showed significantly less biofilm formation (P<0.0001) than the FC. Catheter design had a variable effect on biofilm formation depending on the bacterial strain tested. There was significantly less intraluminal biomass compared with intravesical biomass in both catheters (P<0.0001). Multi-layered biofilms that covered the FC surfaces completely were seen for all tested strains, while the NPD catheter surfaces showed reduced biofilm formation. CONCLUSIONS: Modifications of the hydrodynamic characteristics of a catheter can significantly reduce bacterial colonization. Integrated design approaches combining chemical, mechanical and topographical elements can help to reduce the occurrence of CAUTI.

Antibacterial and antibiofilm effects of radioactive thermal water.

OBJECTIVE: Most of the infections of the upper respiratory tract are caused by biofilm-forming microorganisms belonging to the Pseudomonas, Streptococcus, Staphylococcus, and Enterobacter genus. Many of these microorganisms also show antibiotic resistance, partly related to biofilm formation. The treatment of these affections may include inhalation of radioactive thermal water (RTW). The present study aimed to evaluate the in vitro antibiofilm effect of RTW collected from Merano springs, Italy. MATERIALS AND METHODS: A series of experiments were performed evaluating the effect of RTW against planktonic cultures (1 h exposure) and on biofilms (10 min and 1 h exposure) formed by Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. Viable biomass was assessed using a colorimetric assay. A model based on the infection by the same strains of a reconstituted human respiratory epithelium (RHRE) was used to morphologically evaluate the antibiofilm effect of RTW. RESULTS: RTW decreased the viability of S. aureus and S. pneumoniae planktonic cultures by about 20%. RTW also decreased biofilm viability by all strains except for E. coli at both time points. In the RHRE model, bacterial adherence and colonization occurred in all specimens, showing a particular affinity for the epithelium's cilia. Bacterial infections caused significant alterations in the epithelium structure, showing enlargement of the intercellular spaces, and damage to the cell structure. Specimens infected with S. aureus showed slightly lower colonization levels after RTW treatment. CONCLUSIONS: Results of this in vitro study showed a significant effect of RTW against Gram-positive planktonic bacterial cells as well as a significant antibiofilm activity.

Pathogenesis of lung cancer signalling pathways: roadmap for therapies.

Lung cancer is the major cancer killer worldwide, and 5-yr survival is extremely poor (

EUELC project: a multi-centre, multipurpose study to investigate early stage NSCLC, and to establish a biobank for ongoing collaboration.

The European Early Lung Cancer (EUELC) project aims to determine if specific genetic alterations occurring in lung carcinogenesis are detectable in the respiratory epithelium. In order to pursue this objective, nonsmall cell lung cancer (NSCLC) patients with a very high risk of developing progressive lung cancer were recruited from 12 centres in eight European countries: France, Germany, southern Ireland, Italy, the Netherlands, Poland, Spain and the UK. In addition, NSCLC patients were followed up every 6 months for 36 months. A European Bronchial Tissue Bank was set up at the University of Liverpool (Liverpool, UK) to optimise the use of biological specimens. The molecular-pathological investigations were subdivided into specific work packages that were delivered by EUELC Partners. The work packages encompassed mutational analysis, genetic instability, methylation profiling, expression profiling utilising immunohistochemistry and chip-based technologies, as well as in-depth analysis of FHIT and RARbeta genes, the telomerase catalytic subunit hTERT and genotyping of susceptibility genes in specific pathways. The EUELC project engendered a tremendous collaborative effort, and it enabled the EUELC Partners to establish protocols for assessing molecular biomarkers in early lung cancer with the view to using such biomarkers for early diagnosis and as intermediate end-points in future chemopreventive programmes.