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Purpose: Recent studies indicate that shift work may affect workers' eating habits and overall well-being. This study aimed to assess differences in eating patterns, sleep quality, and mental health between Italian shift and non-shift workers, with a focus on individual chronotype and the type of shift work (day vs. night shift). Methods: The cross-sectional study involved 322 subjects (166 shift and 156 non-shift workers). Eating habits were evaluated using a 7-day diary and the Medi-Lite questionnaire. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI), and mental health with the Depression Anxiety Stress Scales (DASS). Individual chronotype was defined using the Morningness-Eveningness Questionnaire. Results: No significant differences in daily energy, macronutrient, and micronutrient intake between the two groups, nor in the temporal pattern of eating. However, shift workers had significantly (p < 0.05) lower adherence to the Mediterranean diet (MD) (7.6 ± 2.3 vs 8.1 ± 2.2) compared to non-shift workers. Shift workers also reported significantly poorer sleep quality (mean PSQI score 7.6 ± 3.7 vs. 5.8 ± 3.0) and higher levels of anxiety and stress symptoms. Among shift workers, those with an evening chronotype had significantly lower MD adherence than those with a morning chronotypes. Additionally, night shift workers experienced more sleep disturbances compared to day ones. Conclusion: Shift workers reported lower MD adherence, poorer sleep quality, and a higher prevalence of anxiety and stress symptoms compared to a similar group of non-shift workers. Evening chronotypes and night shift work were associated with worse eating habits and sleep quality. [ABSTRACT FROM AUTHOR]

Background/Objective: World Health Organization latest statistics state that 17% of infectious diseases are transmitted by vectors, causing more than 700,000 deaths each year. Particularly, dengue (DENV), Zika (ZIKV) and yellow fever (YFV) viral infections have generated international awareness due to their epidemic proportion and risks of international spread. In this framework, the repositioning strategy of Efavirenz (EFV) represents a key clinical feature to improve different antiviral therapies. Therefore, the development of Soluplus®-based nanomicelles (NMs) loaded with EFV (10 mg/mL) for optimized oral pharmacotherapy against ZIKV, DENV and YFV infections was investigated. Methods: EFV-NMs were obtained by an acetone diffusion technique. Micellar size and in vitro micellar interaction with mucin were assessed by dynamic light scattering. In vitro cytocompatibility was investigated in A549 and Vero cells and micellar in vitro antiviral activity against ZIKV, DENV and YFV was evaluated. In vivo oral bioavailability and histological studies were assessed in Wistar rats. Results: EFV encapsulation within Soluplus® NMs increased the drug's apparent aqueous solubility up to 4803-fold with a unimodal micellar size distribution and a micellar size of ~90 nm at 25 and 37 °C. Micellar in vitro interaction with mucin was also assessed in a pH range of 1.2–7.5 and its storage micellar physicochemical stability at 4 °C was confirmed over 2 years. In vitro cytocompatibility assays in A549 and Vero cells confirmed that EFV micellar dispersions resulted in safe nanoformulations. Interestingly, EFV-loaded NMs exhibited significantly higher in vitro antiviral activity compared with EFV solution for all the tested flaviviruses. In addition, the selectivity index (SI) values reveal that EFV-loaded NMs exhibited considerably more biological efficacy compared to EFV solution in A549 and Vero cell lines and for each viral infection (SI > 10). Further, the drug pharmacokinetics parameters were enhanced after the oral administration of EFV-loaded NMs, being biocompatible by not causing damage in the gastrointestinal segments. Conclusions: Overall, our EFV nanoformulation highlighted its potential as a novel drug delivery platform for optimized ZIKV, DENV and YFV antiviral therapy. [ABSTRACT FROM AUTHOR]

Background: Previous studies employing polymeric micelles and molecular imaging for in vivo nanosystem characterization have led to the development of radionanoprobes (RNPs) designed for diagnosing and monitoring therapeutic interventions in preclinical oncology research, specifically within breast and colon cancer models. These models exhibit high GLUT1 expression on tumor cells and VEGFR expression on the tumor vasculature. We aimed to enhance the tumor-targeting specificity of these RNPs by functionalizing micelles with glucose and bevacizumab. The choice of 99mTc to label the nanoprobes is based on its availability and that direct labeling method is a widespread strategy to prepare radiopharmaceuticals using cold reagents and a 99Mo/99mTc generator. Soluplus® is an attractive polymer for synthesizing micelles that also allows their functionalization. With all the above, the objective of this work was to design, develop and characterize nanoprobes based on polymeric micelles and radiolabeled with 99mTc for the characterization of biological processes associated to the diagnosis, prognosis and monitoring of animal models of breast and colon cancer in preclinical research using molecular images. Results: Four RNPs ([99mTc]Tc-Soluplus®, [99mTc]Tc-Soluplus®+TPGS, [99mTc]Tc-Soluplus®+glucose and [99mTc]Tc-Soluplus®+bevacizumab) were produced with high radiochemical purity (> 95% in all cases) and stability in murine serum for up to 3 h. The RNPs maintained the 100 nm size of the Soluplus® polymeric micelles even when they were functionalized and labeled with 99mTc. The image acquisition protocol enabled the visualization of tumor uptake in two cancer experimental models using the assigned RNPs. In vivo biological characterization showed signal-to-background ratios of 1.7 ± 0.03 for [99mTc]Tc-Soluplus®+TPGS, 1.8 ± 0.02 for [99mTc]Tc-Soluplus®, and 2.3 ± 0.02 for [99mTc]Tc-Soluplus®+glucose in the breast cancer model, and 1.8 ± 0.04 for [99mTc]Tc-Soluplus® and 3.7 ± 0.07 for [99mTc]Tc-Soluplus®+bevacizumab in the colon cancer model. Ex vivo biodistribution, showed that the uptake of the tumors, regardless of the model, is < 2% IA/g while the blood activity concentration is higher, suggesting that the enhanced permeability and retention effect (EPR) would be one of the mechanisms involved in imaging tumors in addition to the active targeting of RNPs. Conclusions: Soluplus®-based polymeric micelles provide a promising nanotechnological platform for the development of RNPs. The functionalization with glucose and bevacizumab enhances tumor specificity enabling effective imaging and monitoring of cancer in animal models. [ABSTRACT FROM AUTHOR]

Nanotechnology has emerged as a possible solution to improve phytochemicals' limitations. The objective of the present study was to encapsulate beetroot extract (BR Ext) within a chitosan (CS)-based nanogel (NG) designed via ionic crosslinking with tripolyphosphate (TPP) for betanin (Bet) delivery, mainly in the ophthalmic environment. BR Ext is rich in betanin (Bet) according to thin layer chromatography (TLC), UV-visible spectroscopy, and HPLC analysis. NG presented a monodisperse profile with a size of 166 ± 6 nm and low polydispersity (0.30 ± 0.03). ζ potential (ζ-Pot) of +28 ± 1 is indicative of a colloidally stable system. BR Ext encapsulation efficiency (EE) was 45 ± 3%. TEM, with the respective 3D-surface plots and AFM, showed spherical–elliptical-shaped NG. The BR Ext release profile was biphasic with a burst release followed by slow and sustained phase over 12 h. Mucoadhesion assay demonstrated interactions between NG with mucin. Moreover, NG provided photoprotection and pH stability to BR Ext. FRAP and ABTS assays confirmed that BR Ext maintained antioxidant activity into NG. Furthermore, in vitro assays using human retinal cells displayed absence of cytotoxicity as well as an efficient protection against injury agents (LPS and H2O2). NGs are a promising platform for BR Ext encapsulation, exerting controlled release for ophthalmological use. [ABSTRACT FROM AUTHOR]

Background: Ursodeoxycholic acid (UDCA) is a therapeutic agent used for the treatment of cholestatic hepatobiliary diseases in pediatric patients. It is a bile acid that presents high lipophilicity, and it belongs to Class II of the Biopharmaceutical Classification System (BCS), which exhibits low water solubility and high intestinal permeability, which leads to poor oral absorption. The objective of this work was to design and optimize UDCA nanosuspensions by means of the precipitation-ultrasonication method to improve the solubility, dissolution, and oral bioavailability of UDCA. Methods: A three-level, three-factor Box–Behnken design was used to optimize formulation variables and obtain uniform, small-particle-size UDCA nanosuspensions. The independent variables were: stabilizer percentage (X1), amplitude (X2), and sonication time (X3), and the dependent variable was the particle size (Y1). In the precipitation–ultrasonication method, UDCA was dissolved in acetone:PEG 400 (1:1 v/v) and quickly incorporated into the antisolvent (pre-cooled aqueous dispersion of HPMC E-15 0.3%), by means of intense sonication at 50 W for 5 min, controlling temperature through an ice water bath. The lyophilization efficacy was evaluated by means of a cryoprotective efficacy test, working with 10% maltose at −80 °C. The nanosuspensions were characterized by dynamic light scattering (DLS), X-ray diffraction, and scanning electron microscopy (SEM). The physicochemical stability was determined at 25 °C and 4 °C at 7, 14, 30, and 60 days, and the UDCA content was analyzed via HPLC-UV. An in vitro dissolution assay and an oral bioavailability study were performed in male Wistar rats. Results: A significant impact was achieved in the optimized nanosuspension with 0.3% (stabilizer), 50 W (amplitude), and 5 min (sonication time), with a particle size of 352.4 nm, PDI of 0.11, and zeta potential of −4.30 mV. It presented adequate physicochemical stability throughout the study and the UDCA content was between 90% and 110%. In total, 86% of UDCA was dissolved in the in vitro dissolution test. The relative oral bioavailability was similar without significant statistical differences when comparing the lyophilized nanosuspension and the commercial tablet, the latter presenting a more erratic behavior. The pharmacokinetic parameters of the nanosuspension and the commercial tablet were Tmax (1.0 ± 0.9 h vs. 2.0 ± 0.8 h, respectively), Cmax (0.558 ± 0.118 vs. 0.366 ± 0.113 µM, respectively), ΔCmax (0.309 ± 0.099 vs. 0.232 ± 0.056, respectively), AUC (4.326 ± 0.471 vs. 2.188 ± 0.353 µg/mL.h, respectively, p < 0.02), and IAUC0–24h (2.261 ± 0.187 µg/mL.h vs. 1.924 ± 0.440 µg/mL.h, respectively). Conclusions: The developed nanosuspension presents an appropriate dosage and administration for pediatric patients. On the other hand, it exhibits an adequate absorption and UDCA oral bioavailability. [ABSTRACT FROM AUTHOR]

While cellular metabolism impacts the DNA damage response, a systematic understanding of the metabolic requirements that are crucial for DNA damage repair has yet to be achieved. Here, we investigate the metabolic enzymes and processes that are essential for the resolution of DNA damage. By integrating functional genomics with chromatin proteomics and metabolomics, we provide a detailed description of the interplay between cellular metabolism and the DNA damage response. Further analysis identified that Peroxiredoxin 1, PRDX1, contributes to the DNA damage repair. During the DNA damage response, PRDX1 translocates to the nucleus where it reduces DNA damage‐induced nuclear reactive oxygen species. Moreover, PRDX1 loss lowers aspartate availability, which is required for the DNA damage‐induced upregulation of de novo nucleotide synthesis. In the absence of PRDX1, cells accumulate replication stress and DNA damage, leading to proliferation defects that are exacerbated in the presence of etoposide, thus revealing a role for PRDX1 as a DNA damage surveillance factor. Synopsis: Genetic screens, proteomics, and metabolomics are performed to investigate the crosstalk between metabolism and the DNA damage response. Integrative analyses identify Peroxiredoxin‐1 (PRDX1) as a DNA damage surveillance factor. Systematic approaches following DNA damage induction by etoposide reveal the aspects of metabolism that are crucial for maintaining genome integrity.Loss of electron transport chain enzymes is synthetically viable with etoposide, and some of these enzymes are partially located on chromatin 24 h after etoposide release.The metabolic enzyme PRDX1 contributes to DNA repair and translocates to the nucleus where it reduces DNA damage‐induced nuclear ROS.Loss of PRDX1 lowers aspartate availability and perturbs de novo nucleotide synthesis, which induces replication stress and limits the DNA repair capacities of the cells. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Currently, paclitaxel (PTX) represents the first-line therapy for TNBC; however it presents a hydrophobic behavior and produces severe adverse effects. The aim of this work is to improve the therapeutic index of PTX through the design and characterization of novel nanomicellar polymeric formulations composed of a biocompatible copolymer Soluplus® (S), surface-decorated with glucose (GS), and co-loaded either with histamine (HA, 5 mg/mL) and/or PTX (4 mg/mL). Their micellar size, evaluated by dynamic light scattering, showed a hydrodynamic diameter between 70 and 90 nm for loaded nanoformulations with a unimodal size distribution. Cytotoxicity and apoptosis assays were performed to assess their efficacy in vitro in human MDA-MB-231 and murine 4T1 TNBC cells rendering optimal antitumor efficacy in both cell lines for the nanoformulations with both drugs. In a model of TNBC developed in BALB/c mice with 4T1 cells, we found that all loaded micellar systems reduced tumor volume and that both HA and HA-PTX-loaded SG micelles reduced tumor weight and neovascularization compared with the empty micelles. We conclude that HA-PTX co-loaded micelles in addition to HA-loaded formulations present promising potential as nano-drug delivery systems for cancer chemotherapy. [ABSTRACT FROM AUTHOR]

We have previously demonstrated significant in vitro natriuretic effects of anandamide (AEA) nanoformulation in polymeric nanoparticles, whose size prevents their accumulation in organs, such as the kidneys. Therefore, it is of particular interest to design and test nanostructures that can pharmacologically accumulate in these organs. In this regard, we prepared and characterized polymeric nanomicelles (~14 and 40 nm). Likewise, their biodistribution was determined. Spontaneously hypertensive rats (SHR) and normotensive rats (WKY), n = 3 per group, were divided into five treatment conditions: control, sham, free AEA freshly dispersed in aqueous solution or 24 h after its dispersion, and AEA encapsulated in nanomicelles. The kidneys were the main site of accumulation of the nanoformulation after 24 h. Freshly dispersed free AEA showed its classical triphasic response in SHR, which was absent from all other treatments. Nanoformulated AEA produced a sustained antihypertensive effect over 2 h, accompanied by a significant increase in fractional sodium excretion (FSE %). These effects were not observed in WKY, sham, or free AEA-treated rats after 24 h of its aqueous dispersion. Without precedent, we demonstrate in vivo natriuretic, diuretic, and hypotensive effects of AEA nanoformulation in polymeric nanomicelles, suggesting its possible use as a new antihypertensive agent with intravenous administration and passive renal accumulation. [ABSTRACT FROM AUTHOR]

Prime editing (PE) is a powerful genome engineering approach that enables the introduction of base substitutions, insertions and deletions into any given genomic locus. However, the efficiency of PE varies widely and depends not only on the genomic region targeted, but also on the genetic background of the edited cell. Here, to determine which cellular factors affect PE efficiency, we carry out a focused genetic screen targeting 32 DNA repair factors, spanning all reported repair pathways. We show that, depending on cell line and type of edit, ablation of mismatch repair (MMR) affords a 2–17 fold increase in PE efficiency, across several human cell lines, types of edits and genomic loci. The accumulation of the key MMR factors MLH1 and MSH2 at PE sites argues for direct involvement of MMR in PE control. Our results shed new light on the mechanism of PE and suggest how its efficiency might be optimised. Prime Editing is a versatile genome engineering tool. Here, the authors identify the DNA repair pathway known as mismatch repair as inhibitory for Prime Editing, thus, loss of mismatch repair enhances the efficiency of Prime Editing. [ABSTRACT FROM AUTHOR]

Cisplatin induces DNA crosslinks that are highly cytotoxic. Hence, platinum complexes are frequently used in the treatment of a broad range of cancers. Efficiency of cisplatin treatment is limited by the tumor-specific DNA damage response to the generated lesions. We reasoned that better tools to investigate the repair of DNA crosslinks induced by cisplatin would therefore be highly useful in addressing drug limitations. Here, we synthesized a series of cisplatin derivatives that are compatible with click chemistry, thus allowing visualization and isolation of DNA-platinum crosslinks from cells to study cellular responses. We prioritized one alkyne and one azide Pt(II) derivative, Pt-alkyne-53 and Pt-azide-64, for further biological characterization. We demonstrate that both compounds bind DNA and generate DNA lesions and that the viability of treated cells depends on the active DNA repair machinery. We also show that the compounds are clickable with both a fluorescent probe as well as biotin, thus they can be visualized in cells, and their ability to induce crosslinks in genomic DNA can be quantified. Finally, we show that Pt-alkyne-53 can be used to identify DNA repair proteins that bind within its proximity to facilitate its removal from DNA. The compounds we report here can be used as valuable experimental tools to investigate the DNA damage response to platinum complexes and hence might shed light on mechanisms of chemoresistance. [ABSTRACT FROM AUTHOR]

Among respiratory infections, tuberculosis was the second deadliest infectious disease in 2020 behind COVID-19. Inhalable nanocarriers offer the possibility of actively targeting anti-tuberculosis drugs to the lungs, especially to alveolar macrophages (cellular reservoirs of the Mycobacterium tuberculosis). Our strategy was based on the development of a mannose-decorated micellar nanoformulation based in Soluplus® to co-encapsulate rifampicin and curcumin. The former is one of the most effective anti-tuberculosis first-line drugs, while curcumin has demonstrated potential anti-mycobacterial properties. Mannose-coated rifampicin (10 mg/mL)–curcumin (5 mg/mL)-loaded polymeric micelles (10% w/v) demonstrated excellent colloidal properties with micellar size ~108 ± 1 nm after freeze-drying, and they remain stable under dilution in simulated interstitial lung fluid. Drug-loaded polymeric micelles were suitable for drug delivery to the deep lung with lung accumulation, according to the in vitro nebulization studies and the in vivo biodistribution assays of radiolabeled (99mTc) polymeric micelles, respectively. Hence, the nanoformulation did not exhibit hemolytic potential. Interestingly, the addition of mannose significantly improved (5.2-fold) the microbicidal efficacy against Mycobacterium tuberculosis H37Rv of the drug-co-loaded systems in comparison with their counterpart mannose-free polymeric micelles. Thus, this novel inhaled nanoformulation has demonstrated its potential for active drug delivery in pulmonary tuberculosis therapy. [ABSTRACT FROM AUTHOR]

Prime editing (PE) is a powerful genome engineering approach that enables the introduction of base substitutions, insertions and deletions into any given genomic locus. However, the efficiency of PE varies widely and depends not only on the genomic region targeted, but also on the genetic background of the edited cell. Here, to determine which cellular factors affect PE efficiency, we carry out a focused genetic screen targeting 32 DNA repair factors, spanning all reported repair pathways. We show that, depending on cell line and type of edit, ablation of mismatch repair (MMR) affords a 2–17 fold increase in PE efficiency, across several human cell lines, types of edits and genomic loci. The accumulation of the key MMR factors MLH1 and MSH2 at PE sites argues for direct involvement of MMR in PE control. Our results shed new light on the mechanism of PE and suggest how its efficiency might be optimised. Prime Editing is a versatile genome engineering tool. Here, the authors identify the DNA repair pathway known as mismatch repair as inhibitory for Prime Editing, thus, loss of mismatch repair enhances the efficiency of Prime Editing. [ABSTRACT FROM AUTHOR]

Copyright of Revista Argentina de Cardiología is the property of Sociedad Argentina de Cardiologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Ecologia Austral is the property of Asociacion Argentina de Ecologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Bile acids (BAs) are bioactive molecules that have potential therapeutic interest and their derived salts are used in several pharmaceutical systems. BAs have been associated with tumorigenesis of several tissues including the mammary tissue. Therefore, it is crucial to characterize their effects on cancer cells. The objective of this work was to analyse the molecular and cellular effects of the bile salts sodium cholate and sodium deoxycholate on epithelial breast cancer cell lines. Bile salts (BSs) effects over breast cancer cells viability and proliferation were assessed by MTS and BrdU assays, respectively. Activation of cell signaling mediators was determined by immunobloting. Microscopy was used to analyze cell migration, and cellular and nuclear morphology. Interference of membrane fluidity was studied by generalized polarization and fluorescence anisotropy. BSs preparations were characterized by transmission electron microscopy and dynamic light scattering. Sodium cholate and sodium deoxycholate had dual effects on cell viability, increasing it at the lower concentrations assessed and decreasing it at the highest ones. The increase of cell viability was associated with the promotion of AKT phosphorylation and cyclin D1 expression. High concentrations of bile salts induced apoptosis as well as sustained activation of p38 and AKT. In addition, they affected cell membrane fluidity but not significant effects on cell migration were observed. In conclusion, bile salts have concentration-dependent effects on breast cancer cells, promoting cell proliferation at physiological levels and being cytotoxic at supraphysiological ones. Their effects were associated with the activation of kinases involved in cell signalling. [ABSTRACT FROM AUTHOR]

We present an optical gas sensor based on the classical nondispersive infrared technique using ultracompact photonic crystal gas cells. The ultracompact device is conceptually based on low group velocities inside a photonic crystal gas cell and low-reflectivity antireflection layers coupling light into the device. Experimentally, an enhancement of the CO2 infrared absorption by a factor of 2.6 to 3.5 as compared to an empty cell, due to slow light inside a 2D silicon photonic crystal gas cell, was observed; this is in excellent agreement with numerical simulations. We show that, theoretically, for an optimal design enhancement factors of up to 60 are possible in the region of slow light. However, the overall transmission of bulk photonic crystals, and thus the performance of the device, is limited by fluctuations of the pore diameter. Numerical estimates suggest that the positional variations and pore diameter fluctuations have to be well below 0.5% to allow for a reasonable transmission of a 1 mm device. [ABSTRACT FROM AUTHOR]

Thin and porous SnO2 films (70 nm thick with grain size between 10 and 30 nm) have been prepared by e-beam evaporation onto alumina substrate provided with platinum electrodes. The Ohmic character of the contacts was preserved in all measurement conditions utilized for investigations. The dependence of electrical conduction on the composition of the ambient atmosphere has been studied by means of Hall and four point conductance measurements. The experiments were performed in different gas atmospheres containing N2, O2, and CO and at different operation temperatures (between room temperature and 420 °C). A relatively low effective mobility (5–30 cm2 V-1 s-1) and a high charge carrier effective concentration (1018–1019 cm-3) were deduced when using the single crystals recipe, as required by the established models for granular materials. The analysis of these experimental data showed the inadequacy of the geometrical models and effective medium theories to correctly extract the electrokinetic parameters from conductance and Hall measurements in the case of gas sensitive layers and to predict their temperature and gas composition dependences. The conventional approach fails because it considers the samples at different temperatures as one physical system while, in fact, the surface chemistry in oxygen atmosphere leads to new trap generation, which is equivalent to the doping level modification. The use of a nonconventional approach, taking into account the film interaction with the ambient through quasichemical equations, and associated mass action laws together with the surface scattering influence on the carrier mobility allowed for the understanding of the involved mechanisms and good fits for the experimental data. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the genotoxic potential of surface waters located in a rural area in the north east of Buenos Aires province (Argentina) using the Allium cepa test. Water samples were collected at four sites located in a drainage channel and two sites on the Burgos stream that receives water from the channel, taking into account the sowing and harvesting months and rainfall periods. Analytical determinations revealed high total concentrations of Cd, Cu, Pb, and Zn (maximum values: 0.030, 0.252, 0.176, and 0.960 mg L−1, respectively), and concentrations of glyphosate and its metabolite aminomethylphosphonic acid (AMPA), with maximum values of 13.6 and 9.75 μg L−1, respectively. Statistically positive correlations were observed between the total metal concentrations and precipitation. No cytotoxicity (mitotic index MI) was observed in A. cepa. However, several water samples showed significant increases in micronucleus (MN) frequencies with respect to the controls. No correlations were observed between MN and the abiotic variables or precipitation. These results showed a state of deterioration in the water quality at the rural area studied in Buenos Aires province, and heavy metal contamination may contribute to the genotoxic activity. A. cepa was shown to be a useful tool for the detection of genotoxicity in water samples from areas with agricultural and livestock activities. [ABSTRACT FROM AUTHOR]

The toxicity of chlortetracycline (CTC), oxytetracycline (OTC) and enrofloxacin (ENF) was tested on two green algal species: the international standard Pseudokirchneriella subcapitata and the native Argentine species Ankistrodesmus fusiformis. All three antibiotics inhibited the algal growth. The most sensitive species was P. subcapitata, for which the EC for CTC, OTC and ENF were 1.19 ± 0.53, 0.92 ± 0.30 and 5.18 ± 3.80 mg L, respectively. The EC for A. fusiformis, were 3.23 ± 0.53, 7.15 ± 2.69 and 10.6 ± 1.28 mg L, respectively. The genotoxicity of these veterinary antibiotics was also assessed using chromosome aberration (CA) and micronuclei (MN) induction in Allium cepa roots. Three concentrations were tested (0.1, 1 and 10 mg L). Only ENF at 1 and 10 mg L showed any significant MN induction. These data revealed that CTC, OTC and ENF could cause toxicity on green algae, whereas ENF could cause genotoxicity on A. cepa plants. [ABSTRACT FROM AUTHOR]

Objectives Carvedilol ( CAR) is a poorly water-soluble beta-blocker. Its encapsulation within nanomicelles ( NMs) could improve drug solubility and its oral bioavailability, allowing the development of a paediatric liquid CAR formulation with commercially available copolymers: D-α-tocopheryl polyethylene glycol 1000 succinate ( TPGS) and poly(vinyl caprolactam)-poly(vinyl acetate)-poly(ethylene glycol) (Soluplus®). Methods Drug-loaded NMs were prepared by copolymer and CAR dispersion in distilled water. Micellar size and morphology were characterized by dynamic light scattering and transmission electron microscopy, respectively. In-vitro drug permeation studies were evaluated by conventional gut sac method. In-vivo CAR oral bioavailability from NMs dispersions and drug control solution was evaluated in Wistar rats. Key findings Carvedilol apparent aqueous solubility was increased (up to 60.4-folds) after its encapsulation within NMs. The micellar size was ranged between 10.9 and 81.9 nm with a monomodal size distribution. There was a significant enhancement of CAR relative oral bioavailability for both copolymers vs a micelle-free drug solution ( P < 0.05). This improvement was higher for TPGS-based micelles (4.95-fold) in accordance with the in-vitro CAR permeation results. Conclusions The present investigation demonstrates the development of highly concentrated CAR liquid micellar formulation. The improvement on drug oral bioavailability contributes to the potential of this NMs formulation to enhance CAR paediatric treatment. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) can undergo double-strand breaks (DSBs), caused by defective replication, or by various endogenous or exogenous sources, such as reactive oxygen species, chemotherapeutic agents or ionizing radiations. MtDNA encodes for proteins involved in ATP production, and maintenance of genome integrity following DSBs is thus of crucial importance. However, the mechanisms involved in mtDNA maintenance after DSBs remain unknown. In this study, we investigated the consequences of the production of mtDNA DSBs using a human inducible cell system expressing the restriction enzyme PstI targeted to mitochondria. Using this system, we could not find any support for DSB repair of mtDNA. Instead we observed a loss of the damaged mtDNA molecules and a severe decrease in mtDNA content. We demonstrate that none of the known mitochondrial nucleases are involved in the mtDNA degradation and that the DNA loss is not due to autophagy, mitophagy or apoptosis. Our study suggests that a still uncharacterized pathway for the targeted degradation of damaged mtDNA in a mitophagy/autophagy-independent manner is present in mitochondria, and might provide the main mechanism used by the cells to deal with DSBs. [ABSTRACT FROM AUTHOR]

The discharge of sewage effluents into low-order streams has negative effects on water quality. Macrophytes can be efficient in the treatment of this wastewater due to the removal of the main pollutants. The genotoxicity of sewage-polluted water discharging into La Choza stream was evaluated by testing with Allium cepa. Also, a phytoremediation assay with continuous recirculation of the residual water was conducted for 12 days. Three treatments were carried out. One treatment (Hr) was performed with a macrophyte ( Hydrocotyle ranunculoides), and two treatments were conducted without macrophytes: with lighting (Ai) and without lighting (Ao). The wastewater was toxic according to all the evaluated indexes (mitotic index, frequency of chromosomal aberrations and micronucleus). High concentrations of ammonium, dissolved inorganic nitrogen (DIN), total (TP) and soluble reactive phosphorous (SRP) and indicators of faecal contamination were determined in the wastewater. The ammonium, DIN, SRP and TP loads at the end of the assay were significantly lower in the treatments with light (Hr and Ai). So, the nutrient removal was due to their absorption and adsorption by the periphyton and H. ranunculoides. Our results lead us to recommend the maintenance and planting of macrophytes in lowland streams subject to sewage pollution. [ABSTRACT FROM AUTHOR]

Treatment of agro-industrial effluents can be carried out via phytoremediation with mono- or multi-specific macrophyte crops. A 6 day phytoremediation assay was performed in mesocosms with continuous recirculation of wastewater from a poultry industry with the macrophytes Lemna gibba and/or Hydrocotyle ranunculoides. The plant effects over removal of nutrients (N, P and C), fecal contamination indicators (total coliforms and Escherichia coli) and the genotoxicity of wastewater by the Allium cepa test were evaluated. A decrease by about 97.6% of total coliforms and E. coli, without significant differences between treatments was observed. The highest removal rates of ammonium (77.9%), dissolved inorganic nitrogen (77.9%), soluble reactive phosphorus (47.6%), total phosphorus (60.6%), and particulate organic carbon (82.1%) were observed in mesocosms with L. gibba + H. ranunculoides, although there were no significant differences ( p > 0.05) with respect to the monospecific culture of L. gibba. Lower rates of nutrients removal were observed in monospecific cultures of H. ranunculoides. Moreover, the use of both species meant a reduction of the genotoxicity of wastewater, with no chromosomal aberrations and micronuclei in meristematic root cells of A. cepa. The obtained results confirm the benefits of the joint use of H. ranunculoides and L. gibba for phytoremediation of wastewater from the poultry industry, being preferable to the use of monospecific crops. [ABSTRACT FROM AUTHOR]

The imazethapyr herbicide (formulation Verosil) was evaluated for phytotoxicity and genotoxicity using a battery of bioassays: (1) the growth inhibition of the green alga Pseudokirchneriella subcapitata, (2) the root growth and germination of the higher plant Lactuca sativa, (3) the genetic damage using the Salmonella/microsome test, and (4) the aneugenic and clastogenic effects on Allium cepa. The Verosil formulation was highly toxic to the non-target green alga (median effective concentration (EC50) = 1.05 ± 0.05 mg active ingredient (a.i.) L), and concentrations above 10 mg a.i. L inhibited root elongation in lettuce: relative growth index (RGI) between 0.28 ± 0.01 and 0.66 ± 0.10. No genotoxic effect was observed in S almonella typhimurium at 100 mg a.i. L, either with or without the microsomal fraction. However, significant differences in the frequency of chromosomal aberrations in anaphases and telophases (bridges, chromosome fragments, and vagrants) were observed in A. cepa at concentrations between 0.01 and 1 mg a.i. L with respect to the control. The frequencies of micronuclei showed significant differences with respect to the control at concentrations between 0.001 and 0.1 mg a.i. L. A very high mitotic index (MI = 93.8 ± 5.8) was observed associated with a high number of cells in the prophase stage at 100 mg a.i. L, indicating cytotoxicity. These results showed that imazethapyr is toxic to the non-target populations in both aquatic and terrestrial ecosystems. This herbicide might also exert clastogenic and aneugenic mitotic damage in higher plants. Therefore, the imazethapyr formulation may constitute an environmental risk to plants. [ABSTRACT FROM AUTHOR]

Background: Coadministration of rifampicin (RIF)/isoniazid (INH) is clinically recommended to improve the treatment of tuberculosis. Under gastric conditions, RIF undergoes fast hydrolysis (a pathway hastened by INH) and oral bioavailability loss. Aim: We aimed to assess the chemical stabilization and the oral pharmacokinetics of RIF nanoencapsulated within poly(ε-caprolactone)- b-PEG- b-poly(ε-caprolactone) 'flower-like' polymeric micelles. Materials & methods: The chemical stability of RIF was evaluated in vitro under acid conditions with and without INH, and the oral pharmacokinetics of RIF-loaded micelles in rats was compared with those of a suspension coded by the US Pharmacopeia. Results: Nanoencapsulation decreased the degradation rate of RIF with respect to the free drug. Moreover, in vivo data showed a statistically significant increase of RIF oral bioavailability (up to 3.3-times) with respect to the free drug in the presence of INH. Conclusion: Overall results highlight the potential of this nanotechnology platform to develop an extemporaneous liquid RIF/INH fixed-dose combination suitable for pediatric administration. Original submitted 6 April 2013; Revised submitted 7 August 2013 [ABSTRACT FROM AUTHOR]

Hospital wastewater (HWW) constitutes a potential risk to the ecosystems and human health due to the presence of toxic and genotoxic chemical compounds. In the present work we investigated toxicity and genotoxicity of wastewaters from the public hospital of Buenos Aires (Argentina). The effluent from the sewage treatment plant (STP) serving around 10 million inhabitants was also evaluated. The study was carried out between April and September 2012. Toxicity and genotoxicity assessment was performed using the green algae Pseudokirchneriella subcapitata and the Allium cepa test, respectively. Toxicity assay showed that 55% of the samples were toxic to the algae (%I of growth between 23.9 and 54.8). The A. cepa test showed that 40% of the samples were genotoxic. The analysis of chromosome aberrations (CA) and micronucleus (MN) showed no significant differences between days and significant differences between months. The sample from the STP was not genotoxic to A. cepa but toxic to the algae (%I = 41%), showing that sewage treatment was not totally effective. This study highlights the need for environmental control programs and the establishment of advanced and effective effluent treatment plants in the hospitals, which are merely dumping the wastewaters in the municipal sewerage system. [ABSTRACT FROM AUTHOR]

One of the fundamental aims of education is the integration of theory and practice. The case method is a teaching strategy in which students must apply their knowledge to solve real-life situations. They have to analyze the case described and propose the best possible solution. Although the case may be written, the use of new information and communication technologies can develop the case plan in ways that would achieve greater realism and widen the possibilities for discussion. This paper describes our experience in implementing the case method to teach food safety in the Chair of Hygiene. At first this methodology was used to improve the teaching of good practices in food preparation, later practical work was implemented where small groups of students designed and carried out the microbiological analysis of suspected food. This practical work was presented online as a multimedia activity; students were given face-to-face and on-line tutoring. Evaluation was based both on students' performance and on a survey they had to answer. More than 92% of students regarded the methodology used for the understanding of the unit as sound. Professors collaboration on providing guidance and multimedia presentation were also positively assessed. The bringing together of face-to-face and virtual tasks and small-group discussion of cases under professors guidance contributed to making good use of the positive aspects of this methodology in order to improve the understanding of problems which do not always have a single answer. [ABSTRACT FROM AUTHOR]

ABSTRACT Aromatic caramel results from the heat treatment of sugars under specific temperature conditions. Because of its richness in aroma compounds and its pleasant organoleptic properties, caramel is widely used in the food industry. However, the composition of the volatile odorant fraction has not been completely elucidated. The aim of this work was thus to identify the volatile odorant compounds responsible for caramel sensory properties using a multivariate statistical technique. Four aromatic caramels differing in terms of their carbohydrate composition and cooking process were chosen. Odorant compounds were screened by gas chromatography-olfactometry (GC-O) and identified by GC-mass spectrometry (GC-MS). GC-O data were processed using a detection frequency method. A total of 76 odorant zones were detected and 49 aroma compounds identified, some of them being reported for the first time in caramel. In parallel, descriptive sensory profiles of the caramels were performed with a panel of ten trained assessors. Odour properties appeared to be closely related to the cooking properties of the caramel. The relationship between the intensities of sensory descriptors and the 76 odorant zones was modelled by partial least squares regression (PLS-R). The first PLS-R component explained 93% of the variance in sensory descriptors and 39% in GC-O data. Sensory descriptors were mainly separated on the first axis, opposing sweet-like descriptors (cooked-syrup, fruity, honey) to burnt sugar descriptors (strong, pungent, roasted). Heterocycles, carbocyclic compounds and acids appeared to be the principal odorants for burnt sugars. They were mainly described by empyreumatic notes in GC-O and correlated to burnt sugar descriptors in the PLS model. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract  Functional micro- and nanosized metal oxide thin film structures are very promising candidate for future gas-sensors. Their reduced size offers an increased surface to volume ratio thus improving sensitivity and sensor performance. Whilst most experimental nanostructures are produced using a bottom-up approach, a top-down sputtering technique for structuring nano-sized gas sensitive metal oxide areas is presented in this letter. Oxidised silicon wafers were used as substrates. The silicon dioxide film of 1 μm thickness was prepared by thermal oxidation in order to insulate the gas sensing elements from the substrate. The sensor chips had an overall size of (1.5 × 1.5) mm2 onto which a Ta/Pt film (20/200 nm thickness) was deposited and patterned to act as electrodes, heater and temperature sensor. In a second step micro-scaled tin dioxide layers (60 nm thick, 5 μm width) were deposited by sputtering techniques and photolithographical patterning between the platinum micro-electrodes (4 μm gap). Finally, the width of the stripes was reduced using focused ion beam technology to obtain the desired size and structure. This enables the control of the dimensions of the structures down to the resolution limit of the FIB-system which is about 10 nm. The structural and electrical characterisation of the sensors and their responses during exposure to several test gases including O2, CO, NO2 and H2O are presented as well. [ABSTRACT FROM AUTHOR]

The article cites a study conducted to determine the mutagenicity of samples of antineoplastic agents before and after autoclaving treatment was tested with the Salmonella mutagenicity assay. The antineoplastic drugs assayed were selected between the most widely used in cancer therapy. The lack of in-depth information on effects of different hospital waste treatments on antitumor agents points to an obvious need for research to develop this important baseline set of data. Results obtained when 5-fluorouracil, doxorubicin, cisplatin, carboplatin did not show any variation in mutagenic activity after autoclaving. The same concentration-response curves were found before and after treatment.

This article presents information related to water pollution in the Urban Argentine River. Chemical stress in aquatic ecosystems is increasing. Water pollution assessment and its possible effects upon river biotic communities, is required for development of control and management strategies. The Matanza-Riachuelo, a temperate lowland river, is one of the most polluted rivers of Latin America, representing a risk for human health. Its mixed pollution derives from farming, grazing, and wastewater from domestic sewage and thousands of industries.

The article examines the interference of sterilized river water samples on the genotoxicity detection of environmental mutagen called potassium dichromate from a river in Buenos Aires, Argentina. The researcher had chosen chromium as an environmental genotoxic pollutant because of its toxic and mutagenic properties that were easy to understand. The results demonstrated that there were interference in the genotoxic activity of potassium dichromate because of compounds found in the soluble fraction of the river water.

The article presents a study on the concentrates of polluted water through genetic alteration induction in Saccharomyces cerevisiae D7 strain. It states the reverse point mutation and mitotic gene conversion are the effects which viewed as gentotoxicity indicator. It also mentions that the water samples were examined by the XAD2 resin column. Result shows that the Saccharomyces cerevisiae D7 strain genotoxicity were positive when the study frequencies surpass the controls.

The article presents a study on the detection of genotoxicants in waste waters through a yeast system. The study used a strain of Saccharomyces cerevisiae that allows to detect mutation and genetic recombination as well as incubation of yeast cells. Results showed that there were variations in the genotoxic response of the samples and that a two-fold dilution of raw water led to a ten-fold reduction in the gene conversion frequencies induced.

Vismodegib is a first-in-class inhibitor for advanced basal cell carcinoma treatment. Its daily oral doses present a high distribution volume and several side effects. We evaluated its skin penetration loaded in diverse nanosystems as potential strategies to reduce side effects and drug quantities. Ultradeformable liposomes, ethosomes, colloidal liquid crystals, and dendrimers were able to transport Vismodegib to deep skin layers, while polymeric micelles failed at this. As lipidic systems were the most effective, we assessed the in vitro and in vivo toxicity of Vismodegib-loaded ultradeformable liposomes, apoptosis, and cellular uptake. Vismodegib emerges as a versatile drug that can be loaded in several delivery systems for topical application. These findings may be also useful for the consideration of topical delivery of other drugs with a low water solubility. [ABSTRACT FROM AUTHOR]

Metabolism is a fundamental cellular process that can become harmful for cells by leading to DNA damage, for instance by an increase in oxidative stress or through the generation of toxic byproducts. To deal with such insults, cells have evolved sophisticated DNA damage response (DDR) pathways that allow for the maintenance of genome integrity. Recent years have seen remarkable progress in our understanding of the diverse DDR mechanisms, and, through such work, it has emerged that cellular metabolic regulation not only generates DNA damage but also impacts on DNA repair. Cancer cells show an alteration of the DDR coupled with modifications in cellular metabolism, further emphasizing links between these two fundamental processes. Taken together, these compelling findings indicate that metabolic enzymes and metabolites represent a key group of factors within the DDR. Here, we will compile the current knowledge on the dynamic interplay between metabolic factors and the DDR, with a specific focus on cancer. We will also discuss how recently developed high-throughput technologies allow for the identification of novel crosstalk between the DDR and metabolism, which is of crucial importance to better design efficient cancer treatments. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains as the second most-deadly infection right behind the HIV/AIDS. Actually, in 2016, TB incidence was estimated in 10.4 million cases. Although an efficient and low-cost TB pharmacotherapy has been available for the last 50 years, the development of multi- and extra-drug-resistant Mycobacterium tuberculosis (Mtb) strains has put on the spot the necessity of improved TB regimens. In this framework, this review article presents the main relevant research outcomes of nanotechnology in TB. The novel delivery systems for antituberculosis drugs have been discussed. Moreover, the active-targeted nanomedicines to the Mtb reservoirs enlighten the possibility to eradicate low-replicant mycobacteria and diminish latent TB. Finally, we present an overview of the TB socio-economic impact and the cost-related features of TB regimens associated with the use of nanoformulations. [ABSTRACT FROM AUTHOR]