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This study investigates potentiodynamic synthesis of polyaniline (PANI) using pencil graphite electrodes (PGEs), aiming to elucidate deposition mechanisms under simple experimental conditions. By exploring PANI electrosynthesis through electrochemical, spectroscopic, and computational approaches, valuable insights into the physicochemical aspects of aniline polymerization are gained. The proposed synthetic method was challenged for the development of a new molecularly imprinted polymer for chloramphenicol on the surface of PGEs to obtain an innovative impedimetric sensor. The sensing platform shows a linear response in the target concentration range between 0.1 and 17.5 nM, in aqueous solutions, with a limit of detection of 0.03 nM and a limit of quantification of 0.09 nM. The results obtained suggest that the synthesis method proposed provide a way to obtain stable and electroactive polyaniline film with huge potential application. [ABSTRACT FROM AUTHOR]

Cell culture and invertebrate animal models reflect a significant evolution in scientific research by providing reliable evidence on the physiopathology of diseases, screening for new drugs, and toxicological tests while reducing the need for mammals. In this review, we discuss the progress and promise of alternative animal and non-animal methods in biomedical research, with a special focus on drug toxicity. Research Highlights: Alternative methods can be effectively used to screen for toxic materials/drug dosages. The main advantages of the 3D cell culture include a high structural complexity, the simulation of cell-to-cell interactions, and the physiological behavior of cells in tissues. Invertebrate animals have been successfully used in scientific experimentation, with some outcomes similar to those observed in mammals. [ABSTRACT FROM AUTHOR]

The aim of this research was to develop a chalcone-based endodontic irrigant for cleaning and disinfecting the root canal. Minimal inhibitory concentration (MIC) experiments in C. albicans and E. faecalis strains with different aminochalcones (AM) were carried out, and the compound that presented the best activity against both pathogens was chosen. The formulation of an endodontic irrigant was elaborated, tested in mono and dual specie biofilms. Disks were sterilized and then incubated with E. faecalis, C. albicans and E. faecalis and C. albicans mixed for 72 h for biofilm maturation. After contamination, samples were divided in 4 experimental groups and 2 positive control group as follows: Group1: Irrigant; Group2: Irrigant + AM-38; Group3: Chlorhexidine 2% (positive control) and, Group 4: 1.0% sodium hypochlorite (positive control). The samples were analyzed by CFU/ml count. The sample was taken to sonicador to remove the cells and then plated. The toxicity was determined in vitro with human gingival fibroblast cells (HGF) and in vivo using the Galleria mellonella model. Formulation showed antimicrobial activity, with MIC on C. albicans 15.6 and E. faecalis 7.8 µg/ml. Treatment with formulation in concentration 156 µg/ml significantly reduced mono or dual species biofilm formation and viability (p < 0.05). The results were significant against C. albicans and E. faecalis and did not show toxicity in cells and G. mellonella. In general, the formulation showed effective antibiofilm activity, significantly reducing microorganisms, opening paths in search of new endodontic irrigants. [ABSTRACT FROM AUTHOR]

Tanneries are considered some of the most polluting industries due to the heavy use of toxic compounds, most of which are released into water bodies, thus exerting adverse effects on aquatic biota. However, the effects on organisms of treated effluents when released into the natural environment are rarely evaluated. This study aims to assess the physicochemical parameters of a tannery effluent after treatment (TE) at a Common Effluent Treatment Plant as well as the water of the receiving stream and to evaluate cytogenotoxic effects in Allium cepa. Three sampling sites (A: TE discharge point; B: 100 m downstream from site A along the receiving stream; C: 100 m upstream from site A along the stream) were selected. Onion bulbs were exposed to TE (100%, 80%, 60% v/v), water samples from sites B and C, and tap water for 72 h. Chromosomal aberration and mitotic index were analyzed on the root cells of A. cepa. The TE was above the standard limits for ammoniacal nitrogen, COD, and total nitrogen. No cytogenotoxicity was observed in A. cepa exposed to samples from sites A and C. However, the stream water sampled downstream from the TE discharge site significantly reduced the mitotic index, indicating a cytotoxic effect. Therefore, this demonstrates the effects of interactions between the receiving water and the complex chemical mixtures in the TE. The findings thus showed that the toxicity assessment of treated effluents along with the receiving water body would provide valuable and more realistic information about the joint toxicity of chemical pollutants in aquatic environments. [ABSTRACT FROM AUTHOR]

This study aimed to apply the comet assay on Aegla platensis crabs as a suitable non-destructive approach for in situ monitoring of freshwater genotoxicity. Animals were captured during four sampling periods in a stream under minor anthropogenic impacts in Southern Brazil. Crabs were captured with a hand net, then the hemolymph samples were collected, and the animals were released into the stream after a 20-min recovery time. Hemolymph samples were transported to the laboratory and used to perform the alkaline comet assay. Results showed an intermediate level in the DNA damage index (range 107.3–165.0 arbitrary unit). No significant differences were observed among the different sampling periods. Hemolymph was successfully used as a non-lethal source of biological samples, and the comet assay using A. platensis proved to be a feasible approach for genotoxicity studies. [ABSTRACT FROM AUTHOR]

Objective: This systematic review aims to assess the available literature on the clinical efficacy of hand versus power-driven instruments for subgingival instrumentation during surgical periodontal therapy (ST). Materials and methods: A search of the literature was carried out on MEDLINE via Ovid, Embase, Web of Science, the Cochrane Database, LILACS, and Scopus. RCTs comparing the use of powered instruments (test) to hand scalers (control) for subgingival instrumentation in terms of changes in probing pocket depth (PPD) after surgical periodontal treatment were included and screened in duplicate. Descriptive synthesis of the data and risk of bias assessment were undertaken. Results: Four RCTs met the inclusion criteria and were included in this systematic review. ST in all studies was performed by means of open flap debridement. Gracey curettes were the most commonly used hand instruments, while sonic and ultrasonic devices were used in the test group. Sites with initial PPD ≥ 6 mm had pocket reduction ranging from 2.93 to 4.89 mm in the control group and from 2.77 to 3.86 mm in the test group. All studies found no significant difference between the different types of instruments/devices in terms of PPD reduction. Conclusions: Despite the limited number of studies, both manual and power-driven instruments appear to be effective in reducing PPD after surgical treatment of periodontitis. Clinical relevance: Based on the findings of this systematic review, the clinician may make a decision whether to use manual or powered instruments during ST on a case-by-case basis and considering other factors, such as the risk of creating high concentrations of aerosols. [ABSTRACT FROM AUTHOR]

The effects of Piper malacophyllum (C. Pesl) C. DC extracts and its isolated compounds were analysed in a mouse model of primary dysmenorrhoea (PD). Female Swiss mice (6–8 weeks old) on proestrus were intraperitoneally treated with estradiol benzoate for 3 days, to induce PD. Twenty-four hours later, animals were treated 24 h later with vehicle, plant extract, gibbilimbol B, 4,6-dimethoxy-5-E-phenylbutenolide, mixture of 4,6-dimethoxy-5-E-phenylbutenolide and 4,6-dimethoxy-5-Z-phenylbutenolide, or ibuprofen. One hour later, oxytocin was injected and the numbers of abdominal writhing were counted. Then, mice were euthanized and uteri were collected for morphometrical and histological analyses. The effects of P. malacophyllum in inflammation were investigated in mouse peritoneal neutrophils culture stimulated with LPS or fMLP (chemotaxis and mediator release). Finally, uterus contractile and relaxing responses were assessed. Similar to ibuprofen, P. malacophyllum extract and isolated compounds reduced abdominal writhing in mice with PD. Histology indicated a marked neutrophil and mast cell infiltrate in the uterus of PD animals which was attenuated by the extract. The compounds and the extract reduced neutrophil chemotaxis and inflammatory mediator release by these cells. Reduced TNF levels were also observed in uteri of PD mice treated with P. malacophyllum. The extract did not affect spontaneous uterine contractions nor those induced by carbachol or KCl. However, it caused relaxation of oxytocin-induced uterine contraction, an effect blunted by H1 receptor antagonist. Overall the results indicate that P. malacophyllum may represent interesting natural tools for reliving PD symptoms, reducing the triad of pain, inflammation and spasmodic uterus behaviour. [ABSTRACT FROM AUTHOR]

The possibility of constructing a consistent quantum theory of gravitation has motivated the recent interest in gravitational theories that break Lorentz invariance, as it is the case of Einstein aether theory. In this work, we employ Schutz variational formalism to obtain a quantum cosmological Einstein aether model for a spatially flat Universe filled with a barotropic fluid with equation of state p = α ρ . Solutions to the Wheeler–DeWitt equation are obtained by the superposition of stationary quantum states, yielding finite-norm wave packets. The behavior of the scale factor is studied from the point of view of the many-worlds and of the de Broglie–Bohm interpretations of quantum mechanics, indicating non-singular solutions for α < 1 . [ABSTRACT FROM AUTHOR]

Purpose: Aim of the study was to evaluate if the introduction of the imaging checklist TeSLANO would improve the identification of crucial anatomical findings from temporal bone computed tomography (TBCT) scans among a cohort of Otolaryngology residents. Study design: Single-blinded prospective cohort study. Setting: Tertiary care university hospital and referral center for otology and skull base surgery. Methods: The cohort was composed by eight Otorhinolaryngology residents (four junior and four senior) that were individually asked to identify all relevant anatomic findings from preoperative TBCT scans. Supervising surgeon showed to each resident four TBCT scans before and four after the introduction of a systematic checklist evaluation system based on the TeSLANO acronym. Statistical analysis was performed using McNemar's test and results were considered significant with a P value < 0.05. Results: Introduction of the checklist improved global identification of critical anatomical structures from 48.75 to 89.17% (P < 0.05). The postimplementation identification percentage improved for both the senior and junior groups (P < 0.05). Conclusions: The imaging checklist TeSLANO allows a systematic approach to review TBCT scans and significantly improves identification of critical anatomical structures in Otorhinolaryngology residents. [ABSTRACT FROM AUTHOR]

Scopoletin (SP) as a functional monomer for electropolymerization has recently been investigated in the context of molecularly imprinted polymers for biosensing applications. Herein we describe an in-depth analysis of the mechanisms involved in the electropolymerization of SP toward the optimization of the experimental conditions for applications in sensor studies. PolySP films have been in situ synthesized on a standard glassy carbon electrodes by varying three independent experimental parameters, and the output of the analysis has been evaluated in terms of the resulting electroactive area and surface coverage. A quality-by-design approach including design-of-experiments principles and response surface methodology produced unbiased observations on the most relevant parameters to be controlled during the electropolymerization of SP. By combining the output of electroactive area and surface overage, we highlighted a strong dependence on the monomer concentration and scan rate. Thus, an appropriate selection of these two parameters should be sought to have an optimal electropolymerization process, leading to uniform films and homogeneous surface behavior. This study shows that the application of multi-factorial analysis in a comprehensive design of experiments allows the systematic study of polymer electrosynthesis. Therefore, this research is expected to guide further efforts in the electropolymerization of several functional monomers. [ABSTRACT FROM AUTHOR]

The timing of umbilical cord and placental thrombosis in the third trimester intrauterine fetal death (TT-IUFD) may be fundamental for medico-legal purposes, when it undergoes medical litigation due to the absence of risk factors. Authors apply to human TT-IUFD cases a protocol, which includes histochemistry and immunohistochemistry (IHC) for the assessment of thrombi's chronology. A total of 35 thrombi of umbilical cord and/or placenta were assessed: 2 in umbilical artery, 6 in umbilical vein, 15 in insertion, 10 in chorionic vessels, 1 in fetal renal vein, 1 in fetal brachiocephalic vein. Thrombi's features were evaluated with hematoxylin–eosin, Picro-Mallory, Von Kossa, Perls, and immunohistochemistry for CD15, CD68, CD31, CD61, and Smooth Muscle Actin. The estimation of the age of the thrombi was established by applying neutrophils/macrophages ratio taking into consideration, according to literature, the presence of hemosiderophagi, calcium deposition, and angiogenesis. To estimate an approximate age of fresh thrombi (< 1 day), a non-linear regression model was tested. Results were compared to maternal risk factors, fetal time of death estimated at autopsy, mechanism, and cause of death. Our study confirms that the maternal risk factors for fetal intrauterine death and the pathologies of the cord, followed by those of the placental parenchyma, are the conditions that are most frequently associated with the presence of thrombi. Results obtained with histological stainings document that the neutrophile/macrophage ratio is a useful tool for determining placental thrombi's age. Age estimation of thrombi on the first day is very challenging; therefore, the study presented suggests the N/M ratio as a parameter to be used, together with others, i.e., hemosiderophagi, calcium deposition, and angiogenesis, for thrombi's age determination, and hypothesizes that its usefulness regards particularly the first days when all other parameters are negative. [ABSTRACT FROM AUTHOR]

Aims: This study aims to investigate whether HS—when associated with an excessive amount of epicardial adipose tissue—correlates with CAD in subjects with symptoms suggestive of CVD. Methods and results: CCTA images, demographic and clinical variables of 1.182 individuals were retrieved: semi-automated measurements for EFV, CAC, and MLD were obtained. Individuals were grouped into three categories according to the presence of CAD, resulting in absent (CAD0), non-obstructive (CAD1) or obstructive (CAD2) disease-groups, and into two categories based on the presence of HS (with no HS, named HS−, and with HS, named HS+). EFV was significantly higher in HS+ than in HS− group (p < 0.001), whereas MLD was lower in CAD+ than in CAD− subjects (p < 0.001). Two predictive models for CAD were tested: the former included clinical risk factors for CAD along with age, gender, EFV and MLD, whereas the latter did not include clinical variables. The logistic regression analysis of the second proposed model reliably discriminated CAD0 from CAD1 and CAD2 (AUC of 0.712, range 0.682–0.742). Conclusion: Lower MLD was associated with increased EFV, and MLD—as a marker of HS—discriminate symptomatic patients with CAD from whom without. [ABSTRACT FROM AUTHOR]

Garcinia humilis is popularly used to treat digestive, intestinal and inflammatory illness. We investigated the in vivo and in vitro effects of the methanol extract of G. humilis leaves (MEGh) on inflammatory cells behavior (migration and chemical mediators release) and hypersensitivity. Anti-inflammatory activity was investigated using carrageenan-induced inflammation in the subcutaneous tissue of male Swiss mice treated orally with MEGh (0.1–30 mg/kg). Leucocyte migration, chemical mediators secretion (TNF, IL-1β, IL-6 and CXCL1) and protein exudation were quantified in the exudate. The adhesion molecules expression (CD62L and CD18), chemical mediators and chemotaxis was evaluated using neutrophils or macrophages RAW.264.7 previously treated with the extract (1–100 µg/mL) and activated with LPS. The anti-inflammatory activity of the isolated compounds friedelin, canophyllol, amentoflavone and 3-desmethyl-2-geranyl-4-prenylbellidypholine xanthone (10 μM) was evaluated in macrophages nitric oxide (NO) and TNF release. MEGh, given orally (30 mg/kg), significantly reduced neutrophil migration and decreased TNF, IL-1β and CXCL1 levels, without interfering with protein exudation and IL-6. In vitro, the extract significantly reduced IL-1β and IL-6 levels but did not alter TNF and CXCL1. The MEGh also reduced the expression of CD62L and CD18 and consequently neutrophil chemotaxis. The compounds friedelin, amentoflavone and 3-demethyl-2-geranyl-4-prenylbellidypholine xanthone decreased the secretion of NO and TNF by RAW264.7. The MEGh effects were extended to the pain-like behaviour induced by carrageenan in the mice hindpaw. MEGh presented important anti-inflammatory effects probably due to its activity on neutrophil migration and on important chemical mediator release, scientifically reinforcing its use as medicinal plant. [ABSTRACT FROM AUTHOR]

The introduction looks at the constitutional situation in Chile since the demand for a new Constitution erupted in demonstrations all across the country, and argues that the notion of 'constitutional moment' is inadequate to capture the radicality of the popular mobilisation that is sweeping the country as a pure expression of constituent power. [ABSTRACT FROM AUTHOR]

Crystal-phase low-dimensional structures offer great potential for the implementation of photonic devices of interest for quantum information processing. In this context, unveiling the fundamental parameters of the crystal phase structure is of much relevance for several applications. Here, we report on the anisotropy of the g-factor tensor and diamagnetic coefficient in wurtzite/zincblende (WZ/ZB) crystal-phase quantum dots (QDs) realized in single InP nanowires. The WZ and ZB alternating axial sections in the NWs are identified by high-angle annular dark-field scanning transmission electron microscopy. The electron (hole) g-factor tensor and the exciton diamagnetic coefficients in WZ/ZB crystal-phase QDs are determined through micro-photoluminescence measurements at low temperature (4.2 K) with different magnetic field configurations, and rationalized by invoking the spin-correlated orbital current model. Our work provides key parameters for band gap engineering and spin states control in crystal-phase low-dimensional structures in nanowires. [ABSTRACT FROM AUTHOR]

Sulphurous thermal water inhalations have been traditionally used in the treatment of airway diseases. In vivo and in vitro studies reported that they ameliorate mucus rheology, mucociliary clearance and reduce inflammation. Cigarette smoking induces an inflammatory damage, with consequent remodeling of respiratory airways, which in turn affect pulmonary functions. Despite the anti-inflammatory effects of H2S are clinically documented in several airway inflammatory diseases, data on the effects of sulphurous thermal water treatment on pulmonary function and biomarkers of airways inflammation in smokers are still scant. Therefore, we investigated whether a conventional cycle of sulphurous thermal water inhalation produced changes in markers of respiratory inflammation and function. A cohort of 504 heavy current and former smokers underwent 10-day cycles of sulphurous thermal water inhalation. Pulmonary function and metabolic analyses on exhaled breath condensate were then performed at day 0 and after the 10-day treatment. Spirometric data did not change after spa therapy, while exhaled breath condensate analysis revealed that a single 10-day cycle of sulphurous water inhalation was sufficient to induce a statistically significant increase of citrulline levels along with a decrease in ornithine levels, thus shifting arginine metabolism towards a reduced nitric oxide production, i.e. an anti-inflammatory profile. Overall, sulphurous thermal water inhalation impacts on arginine catatabolic intermediates of airways cells, shifting their metabolic balance towards a reduction of the inflammatory activity, with potential benefits for smokers. [ABSTRACT FROM AUTHOR]

Objectives: Laboratory animal allergy is a highly prevalent occupational disease among exposed workers. The aim of the study was to validate the biomarkers of airway inflammation in laboratory animal (LA) care workers.Methods: All of the participants in this observational study (63 LA care workers and 64 controls) were administered a clinical questionnaire, underwent spirometry and a skin prick or radioallergosorbent test for common and occupational aeroallergens, and the fraction of exhaled nitric oxide (FeNO50), exhaled breath condensate hydrogen peroxide (EBC H2O2) and serum pneumoprotein levels were measured. Multivariate analysis (ANCOVA) was used to assess the interactions of the variables.Results: FeNO50 levels correlated with exposure (p = 0.002), sensitisation (p = 0.000) and age (p = 0.001), but there was no interaction between exposure and sensitisation when age was considered in the model (p = 0.146). EBC-H2O2 levels were higher in the sensitised workers than in the sensitised controls [0.14 (0.08-0.29) µM vs 0.07 (0.05-0.12) µM; p < 0.05]. Serum surfactant protein A (SP-A) levels were unaffected by exposure, sensitisation or age, although higher levels were observed in symptomatic workers; however, SP-D levels were influenced by exposure (p = 0.024) and age (p = 0.022), and club cell 16 levels were influenced by sensitisation (p = 0.027) and age (p = 0.019).Conclusions: The presence of the clinical symptoms associated with LA exposure and high FeNO levels should prompt further medical assessments in LA workers. Although EBC-H2O2 levels do not seem to reflect eosinophilic inflammation, serum SP-A levels could be used to monitor progression from rhinitis to asthma. [ABSTRACT FROM AUTHOR]

Colloidal nanocrystals can self-assemble into highly ordered superlattices. Recent studies have focused on changing their morphology by tuning the nanocrystal interactions via ligandbased surface modification for simple particle shapes. Here we demonstrate that this principle is transferable to and even enriched in the case of a class of branched nanocrystals made of a CdSe core and eight CdS pods, so-called octapods. Through careful experimental analysis, we show that the octapods have a heterogeneous ligand distribution, resembling a cone wrapping the individual pods. This induces location-specific interactions that, combined with variation of the pod aspect ratio and ligands, lead to a wide range of planar superlattices assembled at an air-liquid interface. We capture these findings using a simple simulation model, which reveals the necessity of including ligand-based interactions to achieve these superlattices. Our work evidences the sensitivity that ligands offer for the self-assembly of branched nanocrystals, thus opening new routes for metamaterial creation. [ABSTRACT FROM AUTHOR]

B Introduction, third paragraph line 3-8 should read: b We shed light on the use of 3D cell culture (organoids) and U alternative animal u models, such as I Galleria mellonella i larvae, zebrafish, Brine Shrimp ( I Artemia salina i ), roundworms ( I Caenorhabditis elegans i ), and Fruit fly ( I Drosophila melanogaster i ). B Alternative animals, first paragraph should read: b U Alternative animals u have been successfully used in scientific experimentation, with some outcomes similar to those observed in mammals (Table 2). B Abstract, first line should read: b Cell culture and U alternative animal u models reflect a significant evolution in scientific research by providing reliable evidence... B Research Highlights, topic 3 should read: b U Alternative animals u have been successfully used in scientific experimentation, with some outcomes similar to those observed in mammals. [Extracted from the article]

The molecule-substrate interaction plays a key role in charge injection organic-based devices. Charge transfer at molecule-metal interfaces strongly affects the overall physical and magnetic properties of the system, and ultimately the device performance. Here, we report theoretical and experimental evidence of a pronounced charge transfer involving nickel tetraphenyl porphyrin molecules adsorbed on Cu(100). The exceptional charge transfer leads to filling of the higher unoccupied orbitals up to LUMO+3. As a consequence of this strong interaction with the substrate, the porphyrin's macrocycle sits very close to the surface, forcing the phenyl ligands to bend upwards. Due to this adsorption configuration, scanning tunneling microscopy cannot reliably probe the states related to the macrocycle. We demonstrate that photoemission tomography can instead access the Ni-TPP macrocycle electronic states and determine the reordering and filling of the LUMOs upon adsorption, thereby confirming the remarkable charge transfer predicted by density functional theory calculations. [ABSTRACT FROM AUTHOR]

Very low doses of recombinant interleukin-2 (rIL-2) and interferon-alpha (rIFN-alpha) induce, in patients with advanced renal cell carcinoma (RCC) clinical response rate and median survival time comparable to other protocols, other than immunological response in terms of expansion of NK cells and cT lymphocytes. The aim of this pilot study was to verify whether very low dose immunotherapy can enhance NK cell cytotoxicity against tumoral target cells. Eight patients with advanced and 13 patients with localised disease received 4-week cycles of rIL-2 (total dose per week 7 MIU/m(2), s.c.) and rIFN-alpha (total dose per week 3.6 MUI/m(2), i.m.) according to the scheme proposed by Buzio et al. Neutrophils, monocytes, eosinophils, NK cells (CD56+bright, CD56+dimmer, CD3-CD56 +), NK-T cells (CD3+CD56+), Th-lymphocytes, cT-lymphocytes, HLA-DR+ and CD25+ lymphocytes and NK cell cytotoxicity were evaluated before and after cycle. The treatment led to the significant expansion of eosinophils (P < 0.001), NK cells (P < 0.001), CD56+bright (P < 0.001), CD56+dimmer (P < 0.001), Th-lymphocytes (P = 0.001), cT-lymphocytes (P = 0.014), HLA-DR+ (P = 0.007) and CD25+(P = 0.002) cells. Neutrophils significantly decreased (P = 0.001), whereas no significant effect was observed on monocytes (P = 0.22) or NK-T cells (P = 0.20). Patients with localised disease responded significantly better to treatment than metastatic patients in terms of the expansion of CD56+bright (P = 0.038), DR+ (P = 0.021), CD25+ (P = 0.006) and Th-lymphocytes (P = 0.014). The NK cell cytotoxicity was significantly increased by the immunotherapy in the whole population (P = 0.021) and similarly in the two groups of patients (P = 0.860); a reverse relation, even if not significant, was seen between the variation of NK-T cells and NK cells cytotoxicity (r = -0.39; P = 0.074). [ABSTRACT FROM AUTHOR]

Growing data have provided encouraging results on the use of interleukin (IL)-1 inhibitors in Behçet's disease (BD). This study was aimed at reporting the largest experience with anti-IL-1 agents in BD patients. We evaluated 30 BD patients receiving treatment with anti-IL-1 agents. The primary aims of the study were to evaluate the efficacy of anakinra (ANA) and canakinumab (CAN) in a cohort of BD. The secondary aims were to evaluate the overall safety profile of the treatments, explore the timing of response to therapy and any adjustment of dosage and frequency of drugs studied, and investigate predictive factors of response to therapy. The frequency of first line therapy was 90 % with ANA and 10 % with CAN. The overall number of subjects in complete remission after 12 months of therapy with anti-IL-1 drugs was 13: 6 maintained the initial therapy regimen, 1 maintained the same initial anti-IL-1 drug with further therapeutic adjustments, and the remaining 6 shifted from ANA to CAN. Among them, 3 used CAN for at least 12 months without therapeutic adjustments, 1 had therapeutic adjustments, and 3 had an overall history of a 12-month complete remission. Adverse events (AEs) were reported in 15 % patients who received ANA, represented in all cases by local cutaneous reactions, while no AE were observed in patients who received CAN; we did not observe any serious AEs (SAEs) during the follow-up period. Our data have confirmed that the use of anti-IL-1β drugs is efficacious and safe with an overall acceptable retention on treatment. [ABSTRACT FROM AUTHOR]

The authors report the cumulative incidence of Restless Legs Syndrome (RLS) over a 3 years follow-up period in 92 de novo Parkinson's disease patients under chronic dopaminergic therapy and the clinical course of the sensory-motor disorder over 12 months as from its onset. The overall cumulative incidence of RLS was found by 15.3 %, i.e. 14 incident cases, and by 11.9 %, i.e. 11 incident cases, after the exclusion of possible 'secondary' forms of the disorder. These figures are higher than those reported in general population in Germany (Study of Health in Pomerania), confirming our previous findings of incidence rate of the disorder. At the end of the 3 years follow-up period the prevalence of 'current' RLS was significantly higher than that previously found in drug naïve Parkinson's disease patients and in controls, supporting the view that RLS emerging in the course of chronic dopaminergic therapy is the main determinant of the co-morbid association with Parkinson's disease. During the 12 months period of observation the RLS showed a frequency of occurrence of 6.08 episodes per month on average and a remittent clinical course was prevailing in the 11 incident cases, with a significant frequency decrease in the second as compared to the first 6 months, i.e. 3.26 versus 8.9 episodes per month, and none of the patients developed augmentation in the same period. It is hypothesized that the remittent course could be due to long-term adaptation (downregulation) of the hypersensitive post-synaptic dopamine receptors in the spinal cord to a continuous dopaminergic stimulation, possibly coupled with compensatory up-regulation of pre-synaptic dopamine re-uptake mechanism, in the patients in which the hypothalamic A11 area, site of origin of the dopamine-mediated diencephalo-spinal pathway, is involved in the neurodegenerative process. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the chemical parameters and the cytotoxic and genotoxic potential of raw domestic sewage and effluents from treatment with activated sludge and a floating emergent-macrophyte filter from a domestic wastewater treatment plant in the city of Novo Hamburgo, Rio Grande do Sul, Brazil. The physicochemical analysis revealed that both treatment systems achieved the legal emission pattern for biochemical oxygen demand, chemical oxygen demand, and suspended solids, but ammoniacal nitrogen and E. coli values were above the limits in the macrophyte treatment effluent. Phosphorous values were above the maximum permitted for both treatments. The results obtained from the Allium cepa test and the micronuclei test in fish did not demonstrate any significant differences in both cytotoxicity (mitotic index) and genotoxicity (chromosome aberration and micronucleus) endpoints between the negative control group and the exposed groups. However, the comet assay in fish revealed a DNA damage increase in animals exposed to the 30 % concentration of the macrophyte effluent and two concentrations of the activated sludge treatment effluent (10 and 75 %), which suggests that these two treatment systems may increase wastewater genotoxicity. [ABSTRACT FROM AUTHOR]

It is currently controversial if and in which terms Parkinson's disease (PD) and restless legs syndrome (RLS) are linked in co-morbid association. In a cohort of 106 de novo PD patients (67 male and 39 female, aged 42-83 years), 15 of them developed RLS, which was prospectively assessed at 6-month intervals from the starting of dopamine(DA)ergic therapy. The incidence rate of total RLS was 47 per 1,000 case/person per year and 37 per 1,000 case/person per year after the exclusion of possible 'secondary' forms of the disorder ( n = 3). These figures are higher than those reported in an incidence study conducted in German general population (Study of Health in Pomerania), in which the method of ascertainment of RLS similar to ours has been used. An incidence rate of total RLS significantly higher than that reported in the above-mentioned study was found in the age ranges 55-64 years and in the age range 45-74 years standardized to European general population 2013 (70 and 53 per 1,000 case/person per year, respectively, p < 0.01). Ten out of 12 patients (83.3 %) developed RLS within 24 months from the starting of DAergic medication (median latency 7.5 months). These findings support the view that sustained DAergic therapy could represent the critical factor inducing an increased incidence of RLS in patients with PD and that the latter disease should be regarded as the condition predisposing to the occurrence of the former and not viceversa as previously hypothesized. The mechanism underlying the increased incidence of RLS remains unclear and deserves further investigation. [ABSTRACT FROM AUTHOR]

Starting from a simplified model of the Ptolemaic system in the complex plane, we show that Copernicus' innovation did not merely consist of choosing a reference frame in which the planetary motions were simpler, but in finding the size of the planetary orbits expressed in what we now call astronomical units. In modern times a misleading appeal to relativity and a comparison only on the grounds of precision has led some to consider the Ptolemaic and the Copernican systems as basically equivalent. This erroneous point of view has resulted in the neglect of the main scientific content of the Copernican theory and has left Copernicus only to historians and philosophers of science. It is time to restore Copernicus to the teachers of physics as an incomparable opportunity to show the formidable power of theoretical investigation. [ABSTRACT FROM AUTHOR]

Purpose: The main aim of the study was to provide evidence whether professional cleaning was associated with biomarkers of lung damage in non-invasively collected biological fluids (exhaled air and exhaled breath condensate-EBC). Materials and methods: This cross-sectional study involved 40 cleaners regularly exposed to cleaning detergents and 40 controls. The subjects completed a standard questionnaire from European Community Respiratory Health Survey (ECRHS II) and underwent a spirometry. Fractional exhaled nitric oxide (FNO) was measured online, and pH, ammonium (NH), HO and 4-hydroxynonenal (4-HNE) were assayed in EBC. Results: Among the cleaners, the frequency of asthma and rhinitis was, respectively, 2.5 and 20%. The most frequently reported symptoms were sneezing (27.5%), nasal and/or pharyngeal pruritus (25%), ocular pruritus (22.5%) and cough (22.5%). There were no significant differences in comparison with the control group. Median FNO levels were higher in African than in Caucasian cleaners (21.5 [16.5-30.0] ppb and 18.0 [13.5-20.5] ppb; p < 0.05). HO-EBC (0.26 [0.09-0.53] μM vs. 0.07 [0.04-0.15] μM; p < 0.01), NH-EBC (857 [493-1,305] μM vs. 541 [306-907] μM; p < 0.01) and pH-EBC (8.17 [8.09-8.24] vs. 8.06 [7.81-8.10]; p < 0.01) were higher in the cleaners than in the controls. Finally, the cleaners showed significant correlations between pH-EBC and NH-EBC ( r = 0.33, p < 0.05) and a weak correlation between 4-HNE-EBC and HO-EBC ( r = 0.37, p < 0.05). Conclusion: The promising role of EBC analysis in biomonitoring of exposed workers was confirmed. It was also possible to identify the potential biomarkers of exposure to alkaline products (increased ammonium-EBC and pH-EBC levels) and potential biomarkers of oxidative stress (increased HO-EBC levels correlated with 4-HNE-EBC levels) in workers with no signs of airway diseases. [ABSTRACT FROM AUTHOR]

We report on ab-initio calculations of the electronic structure and optical absorption response of the black dye sensitizer in gas phase. We show that, despite the large size of this molecule, the second-order multiconfiguration quasi-degenerate perturbation theory (MC-QDPT) can be used to calculate vertical excitation energies, oscillator strengths and optical absorption spectra. The zeroth-order reference states entering perturbation calculations are complete active space (CAS) configuration interaction (CI) wave functions computed for 12 active electrons distributed in 12 active orbitals. We found that the CI approach is not enough for taking into account the strong dynamical correlation effects in this system. In fact, the excitation energies of the CAS-CI target states are strongly renormalized by the MC-QDPT calculations. In the calculated absorption spectra, the analysis of the perturbed wavefunctions revealed that the stronger absorption bands correspond to metal-to-ligand and ligand-to-ligand charge transfer processes. Comparison with independent time-dependent extension (TDDFT) calculations performed with different functionals shows that corrections to the long-range behavior of the functional is pivotal to achieve agreement with the MC-QDPT results. [ABSTRACT FROM AUTHOR]

MeHg (0.5 mg/kg/day) and/or PCB153 (5 mg/kg/day) effects, administered orally to rat dams (GD7-PND21), were explored in PND21 and PND36 offspring brain in terms of density (Bmax) and affinity (Kd) of dopamine D1-like (D1-Rs) and D2-like receptors (D2-Rs), by saturation binding studies. D1-Rs decreased density in both cortex and striatum (15-30%) by MeHg and PCB153, either alone or combined, without additivity in PND21 males. Changes disappeared by PND36. In females, only MeHg caused a 15% Bmax decrease in striatum. D2-Rs enhanced density (23-50%) and reduced affinity in cortex to a similar extent by all treatments in both weanling and pubertal males. Affinity was also decreased in females by all types of exposure at both ages, while density was enhanced by PCB153 only in a delayed manner (PND36). No changes were detected in striatum. In MeHg and MeHg + PCB153 pup cortex, Hg concentrations ranged, on PND21, between 0.25 and 0.89 and 0.94-1.40 μg/g tissue, respectively, and were 5- to sixfold lower 2 weeks later. PCB153 levels, in PCB153 ± MeHg treated rats, were about 15 μg/g tissue (PND21) and 4-8 μg/g tissue (PND36). In striatum, the Hg and PCB153 concentrations were similar to those in cortex. Brain kinetics trend also applied to blood PCB153 or Hg levels. Perinatal exposure to MeHg and/or PCB153 affects D1- and D2-Rs in a gender-, time-, and brain area-dependent manner. Combined treatment does not exacerbate the neurochemical effects of the individual compounds. [ABSTRACT FROM AUTHOR]

Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are widespread environmental pollutants commonly found as contaminants in the same food sources. Even though their neurotoxic effects are established, the mechanisms of action are not fully understood. In the present study, we have used the mouse hippocampal neuronal cell line HT22 to investigate the mechanisms of neuronal death induced by MeHg, PCB 153, and PCB 126, alone or in combination. All chemicals induced cell death with morphological changes compatible with either apoptosis or necrosis. Mitochondrial functions were impaired as shown by the significant decrease in mitochondrial Ca uptake capacity and ATP levels. MeHg, but not the PCBs, induced loss of mitochondrial membrane potential and release of cytochrome c into the cytosol. Also, pre-treatment with the antioxidant MnTBAP was protective only against cell death induced by MeHg. While caspase activation was absent, the Ca-dependent proteases calpains were activated after exposure to MeHg or the selected PCBs. Furthermore, lysosomal disruption was observed in the exposed cells. Accordingly, pre-treatment with the calpain specific inhibitor PD150606 and/or the cathepsin D inhibitor Pepstatin protected against the cytotoxicity of MeHg and PCBs, and the protection was significantly enhanced when the two inhibitors were combined. Simultaneous exposures to lower doses of MeHg and PCBs suggested mostly antagonistic interactions. Taken together, these data indicate that MeHg and PCBs induce caspase-independent cell death via parallel activation of calpains and lysosomal proteases, and that in this model oxidative stress does not play a major role in PCB toxicity. [ABSTRACT FROM AUTHOR]

Contactless monitoring with photoelectron microspectroscopy of the surface potential along individual nanostructures, created by the X-ray nanoprobe, opens exciting possibilities to examine quantitatively size- and surface-chemistry-effects on the electrical transport of semiconductor nanowires (NWs). Implementing this novel approach-which combines surface chemical microanalysis with conductivity measurements-we explored the dependence of the electrical properties of undoped GaAs NWs on the NW width, temperature and surface chemistry. By following the evolution of the Ga 3d and As 3d core level spectra, we measured the position-dependent surface potential along the GaAs NWs as a function of NW diameter, decreasing from 120 to ?20 nm, and correlated the observed decrease of the conductivity with the monotonic reduction in the NW diameter from 120 to ~20 nm. Exposure of the GaAs NWs to oxygen ambient leads to a decrease in their conductivity by up to a factor of 10, attributed to the significant decrease in the carrier density associated with the formation of an oxide shell. [ABSTRACT FROM AUTHOR]

Water is the renewable, bulk chemical that nature uses to enable carbohydrate production from carbon dioxide. The dream goal of energy research is to transpose this incredibly efficient process and make an artificial device whereby the catalytic splitting of water is finalized to give a continuous production of oxygen and hydrogen. Success in this task would guarantee the generation of hydrogen as a carbon-free fuel to satisfy our energy demands at no environmental cost. Here we show that very efficient and stable nanostructured, oxygen-evolving anodes are obtained by the assembly of an oxygen-evolving polyoxometalate cluster (a totally inorganic ruthenium catalyst) with a conducting bed of multiwalled carbon nanotubes. Our bioinspired electrode addresses the one major challenge of artificial photosynthesis, namely efficient water oxidation, which brings us closer to being able to power the planet with carbon-free fuels. [ABSTRACT FROM AUTHOR]

Several differences have been described between neonatal and adult immune responses. The predisposition in early life to Th2-type response or tolerance makes it a susceptible period for infections and allergic sensitization. The aim of this work was to evaluate the effects of CpG-containing oligodeoxynucleotides on neonatal and adult immunization with ovalbumin and Blomia tropicalis extract and compare the CpG effects on B and T cells of neonatal and adult mice. Mice that received CpG showed reduced immunoglobulin E (IgE) antibody production in both neonatal and adult periods, in parallel to increased IgG2a antibody levels. We observed that spleen cells of mice that received CpG in early life produced increased amounts of interferon-γ upon anti-CD3 stimulation. Negative regulation of IgE response was more pronounced in adult than neonate mice; further, CpG decreased anaphylactic antiovalbumin IgG1 only in adults. Also, an upregulation of toll-like receptor 9 expression was detected in adult B cells, but not in neonatal, upon CpG stimuli. Neonatal B cells showed enhanced interleukin (IL)-10 expression and decreased IL-6 levels than adult B cells in response to CpG. When we analyzed in vitro activation of CD4+ T cells, an increased expression of B7 molecules on T cells in neonates was suppressed by CpG. Altogether, we verified qualitative and quantitative evidences regarding CpG effect on neonatal and adult allergens immunizations, which points to the importance of understanding neonatal immune system to establish immunomodulatory strategies for prevention of allergic diseases. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the misclassification of cause of death for breast cancer cases, and to evaluate the differential misclassification between cases detected in an organized screening program and cases found in current clinical practice. All deaths occurring between 1999 and 2002 within breast cancer cases were linked to hospital discharge records. Death certificates and latest available hospital discharge notes were classified into various categories. We created a classification algorithm defining which combinations of categories (of death certificates and hospital discharge notes) suggested the probability of misclassification and the need for an in-depth diagnostic review. Questionable cases were reviewed by a team of experts in order to reach a consensus on cause of death. Based on our algorithmic classification and diagnostic review results, the agreement between original cause of death and that resulting from the assessment process was analyzed stratifying for every variable of interest. According to death certificates, breast cancer was the cause of death in 66.9% of subjects, and after assessment this figure changed to 65.7%. The misclassification rate was 4.3% and did not differ significantly between screen-detected (4.7%) and non-screen-detected (4.3%) cases. Higher misclassification rates in favor of false positivity (cause of death wrongly attributed to breast cancer in death certificates) was observed for subjects with multiple cancers (6.5% vs. 1.9%), with no admission in the year before death (4.6% vs. 2.4%) and with an unknown cancer stage (4.9% vs 2.4% or 2.3%). The cause of death misclassification rate is modest, causing a slight overestimate of deaths attributed to breast cancer, and is not affected by modality of diagnosis. The study confirmed the validity of using cause-specific mortality for service screening evaluation. [ABSTRACT FROM AUTHOR]

Allelic deletions on human chromosome 12q24 are frequently reported in a variety of malignant neoplasms, indicating the presence of a tumor suppressor gene(s) in this chromosomal region. However, no reasonable candidate has been identified so far. In this study, we report the cloning and functional characterization of a novel mitochondrial protein with tumor suppressor activity, henceforth designated MITOSTATIN. Human MITOSTATIN was found within a 3.2-kb transcript, which encoded a ∼62 kDa, ubiquitously expressed protein with little homology to any known protein. We found homozygous deletions and mutations of MITOSTATIN gene in ∼5 and ∼11% of various cancer-derived cells and solid tumors, respectively. When transiently overexpressed, MITOSTATIN inhibited colony formation, tumor cell growth and was proapoptotic, all features shared by established tumor suppressor genes. We discovered a specific link between MITOSTATIN overexpression and downregulation of Hsp27. Conversely, MITOSTATIN knockdown cells showed an increase in cell growth and cell survival rates. Finally, MITOSTATIN expression was significantly reduced in primary bladder and breast tumors, and its reduction was associated with advanced tumor stages. Our findings support the hypothesis that MITOSTATIN has many hallmarks of a classical tumor suppressor in solid tumors and may play an important role in cancer development and progression.Oncogene (2009) 28, 257–269; doi:10.1038/onc.2008.381; published online 20 October 2008 [ABSTRACT FROM AUTHOR]

Due to their wurzite structure, GaN quantum wells and dots arecharacterized by large built-in piezoelectric fields.These induce a spatial separation between the confined electron andholes, thus favouring the formation of electric dipoles.Here, we theoretically investigate the effects of the long-range,dipole-dipole interaction between two excitons in a GaN/AlxGa1-xNmicrodisk.These Coulomb interactions are shown to strongly affect the biexcitonground state. In particular, they induce strong spatial correlationsbetween the two excitons and result in biexciton binding energiesof the order of 1 meV. [ABSTRACT FROM AUTHOR]

Correlation among particles in finite quantum systems leads to complex behaviour and novel states of matter. One remarkable example is predicted to occur in a semiconductor quantum dot, where at vanishing electron density the Coulomb interaction between electrons rigidly fixes their relative positions as those of the nuclei in a molecule. In this limit, the neutral few-body excitations are roto-vibrations, which have either rigid-rotor or relative-motion character. In the weak correlation regime, on the contrary, the Coriolis force mixes rotational and vibrational motions. Here, we report evidence for roto-vibrational modes of an electron molecular state at densities for which electron localization is not yet fully achieved. We probe these collective modes by using inelastic light scattering in quantum dots containing four electrons. Spectra of low-lying excitations associated with changes of the relative-motion wavefunction—the analogues of the vibration modes of a conventional molecule—do not depend on the rotational state represented by the total angular momentum. Theoretical simulations by the configuration-interaction method are in agreement with the observed roto-vibrational modes and indicate that such molecular excitations develop at the onset of short-range correlation. [ABSTRACT FROM AUTHOR]

Chromium in exhaled breath condensate (EBC) has recently been proposed as a biomarker of pulmonary exposure. The aim of this study was to measure the Cr levels in the EBC and pulmonary tissue of patients with early, operable non-small cell lung cancer (NSCLC) who had not been occupationally exposed to Cr before and after tumour resection and to correlate Cr in lung tissue with that in EBC. Cr levels in the EBC and pulmonary tissue of 20 NSCLC patients were measured by means of electrothermal atomic absorption before and after tumour resection. Cr levels were also measured in the urine of 15 of these patients. The pre-surgery EBC Cr levels of the NSCLC patients were not different from those of the controls, but both EBC and urinary Cr levels increased after surgery. There was a significant correlation between Cr levels in EBC and pulmonary tissue ( R = 0.55, P = 0.01), but not between these and urinary Cr levels. Cr levels in EBC and urine of NSCLC patients were increased after surgical intervention. Measured Cr EBC levels were by one order of magnitude lower than those observed in moderately exposed workers. This fact, together with the correlation between Cr in EBC and in pulmonary tissue, confirms that EBC is a promising biological fluid to test pulmonary exposure to Cr, giving complementary information to that provided by urinary Cr, not correlated with EBC and tissue. [ABSTRACT FROM AUTHOR]

The article discusses rapidity, the inversion of hyperbolic tangent and the passing to the hyperbolic angle in special relativity. It stresses that rapidity denotes a simple physical meaning. It presents a mathematical problem wherein slope was given importance and angle was ignored. Also provided is a graph showing that for small values, rapidity is almost equal to velocity.

LS 5039 is the only X-ray binary persistently detected at TeV energies by the Cherenkov HESS telescope. It is moreover a γ-ray emitter in the GeV and possibly MeV energy ranges. To understand important aspects of jet physics, like the magnetic field content or particle acceleration, and emission processes, such as synchrotron and inverse Compton (IC), a complete modeling of the multiwavelength data is necessary. LS 5039 has been detected along almost all the electromagnetic spectrum thanks to several radio, infrared, optical and soft X-ray detections. However, hard X-ray detections above 20 keV have been so far elusive and/or doubtful, partly due to source confusion for the poor spatial resolution of hard X-ray instruments. We report here on deep (∼300 ks) serendipitous INTEGRAL hard X-ray observations of LS 5039, coupled with simultaneous VLA radio observations. We obtain a 20–40 keV flux of 1.1±0.3 mCrab (5.9 (±1.6) ×10−12 erg cm−2 s−1), a 40–100 keV upper limit of 1.5 mCrab (9.5×10−12 erg cm−2 s−1), and typical radio flux densities of ∼25 mJy at 5 GHz. These hard X-ray fluxes are significantly lower than previous estimates obtained with BATSE in the same energy range but, in the lower interval, agree with extrapolation of previous RXTE measurements. The INTEGRAL observations also hint to a break in the spectral behavior at hard X-rays. A more sensitive characterization of the hard X-ray spectrum of LS 5039 from 20 to 100 keV could therefore constrain key aspects of the jet physics, like the relativistic particle spectrum and the magnetic field strength. Future multiwavelength observations would allow to establish whether such hard X-ray synchrotron emission is produced by the same population of relativistic electrons as those presumably producing TeV emission through IC. [ABSTRACT FROM AUTHOR]

Leucine-rich repeats and immunoglobulin-like domains-1 (LRIG1) is a transmembrane protein with an ectodomain containing 15 leucine-rich repeats (LRRs) homologous to mammalian decorin and the Drosophila kekkon1 gene. In this study, we demonstrate that a soluble ectodomain of LRIG1, containing only the LRRs, inhibits ligand-independent epidermal growth factor receptor (EGFR) activation and causes growth inhibition of A431, HeLa and MDA-468 carcinoma cells. In contrast, cells that do not express detectable levels of EGFR fail to respond to soluble LRIG1. However, when a functional EGFR gene is introduced in these cells, they become growth-inhibited by soluble LRIG1 protein. Furthermore, we demonstrate the existence of high-affinity (Kd=10 nM) binding sites on the A431 cells that can be competitively displaced (up to 75%) by molar excess of EGF. Even more powerful effects are obtained with a chimeric proteoglycan harboring the N-terminus of decorin, substituted with a single glycosaminoglycan chain, fused to the LRIG1 ectodomain. Both proteins also inhibit ligand-dependent activation of the EGFR and extracellular signal-regulated protein kinase 1/2 signaling in a rapid and dose-dependent manner. These results suggest a novel mechanism of action evoked by a soluble ectodomain of LRIG1 protein that could modulate EGFR signaling and its growth-promoting activity. Attenuation of EGFR activity without physical downregulation of the receptor could represent a novel therapeutic approach toward malignancies in which EGFR plays a primary role in tumor growth and survival.Oncogene (2007) 26, 368–381. doi:10.1038/sj.onc.1209803; published online 17 July 2006 [ABSTRACT FROM AUTHOR]