Search

Anatoxin-a (ATX-a) is a cyanotoxin whose toxicological profile has been underinvestigated in comparison to other cyanotoxins such as microcystins (MCs) or cylindrospermopsin (CYN). However, its wide distribution, occurrence, and toxic episodes justify more attention. It is classified as a neurotoxin, but it has also been reported to affect other organs and systems. Thus, the aim of this study was to establish, as a first tier in its toxicological evaluation, its cytotoxicity in a wide range of cell lines representative of potential target organs (N2a, SH-SY5Y, HepG2, Caco2, L5178Y Tk+/−, THP-1 and Jurkat). As limited effects were observed after exposure to up to 200 µg/mL of ATX-a for 24 h (only Jurkat and THP-1 cells showed reduced cell viability), cell uptake experiments were performed by ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS). The results showed that the immune system cells had the highest percentage of ATX-a in the intracellular fraction, followed by neuronal cells and finally Caco-2 and HepG2 cells. Moreover, the expression of genes related to cell death mechanisms in THP-1 cells was also analyzed by polymerase chain reaction (PCR) and showed no changes under the conditions tested. Further research is required on ATX-a's toxic effects and toxicokinetics to contribute to its risk assessment. [ABSTRACT FROM AUTHOR]

De Laudibus Sanctae Crucis (DLSC) by Hrabanus Maurus is a seminal work in the medieval Christian literature that explores the Cross as the central structure of the universe through a unique amalgamation of poetry, prose, and visual art. The work employs a multi-layered narrative that enriches the reader's understanding, encouraging a meditative interaction with the text that emphasizes the contemplative over the recitative. This paper analyzes Hrabanus's intricate use of verbal and visual elements to guide his readers into a profound meditation on the universal significance of the Cross. [ABSTRACT FROM AUTHOR]

Anatoxin-a (ATX-a) is a potent neurotoxin produced by several species of cyanobacteria whose exposure can have direct consequences, including neurological disorders and death. The increasing prevalence of harmful cyanobacterial blooms makes the detection and reliable assessment of ATX-a levels essential to prevent the risk associated with public health. Therefore, the aim of this review is to compile the analytical methods developed to date for the detection and quantification of ATX-a levels alone and in mixtures with other cyanotoxins and their suitability. A classification of the analytical methods available is fundamental to make an appropriate choice according to the type of sample, the equipment available, and the required sensitivity and specificity for each specific purpose. The most widely used detection technique for the quantification of this toxin is liquid chromatography–tandem mass spectrometry (LC-MS/MS). The analytical methods reviewed herein focus mainly on water and cyanobacterial samples, so the need for validated analytical methods in more complex matrices (vegetables and fish) for the determination of ATX-a to assess dietary exposure to this toxin is evidenced. There is currently a trend towards the validation of multitoxin methods as opposed to single-ATX-a determination methods, which corresponds to the real situation of cyanotoxins' confluence in nature. [ABSTRACT FROM AUTHOR]

In recent years there has been an increasing interest in expanded hemodialysis (HDx), an emerging renal replacement therapy based on the use of medium cut-off membranes (MCO). Thanks to the internal architecture of these types of membranes, with a higher pore size and smaller fiber inner diameter to favor internal filtration rate, they can increase the removal of larger middle molecules in conventional hemodialysis. Secondarily, several reports suggest that this therapy potentially improve the outcomes for end-stage renal disease patients. However, HDx has not been defined yet and the characteristics of MCO membranes are not well stablished. The aim of this narrative review is to define HDx and summarize the dialyzers that have been used so far to perform this therapy, collect the evidence available on its efficacy and clinical outcomes compared with other hemodialysis techniques and settle the bases for its optimal prescription. [ABSTRACT FROM AUTHOR]

The presence of cyanotoxins and its bioaccumulation in the food chain is an increasingly common problem worldwide. Despite the toxic effects produced by Anatoxin-a (ATX-a), this neurotoxin has been less studied compared to microcystins (MCs) and cylindrospermopsin (CYN). Studies conducted under laboratory conditions are of particular interest because these provide information which are directly related to the effects produced by the toxin. Currently, the World Health Organization (WHO) considers the ATX-a toxicological database inadequate to support the publication of a formal guideline reference value. Therefore, the aim of the present work is to compile all of the in vitro and in vivo toxicological studies performed so far and to identify potential data gaps. Results show that the number of reports is increasing in recent years. However, more in vitro studies are needed, mainly in standardized neuronal cell lines. Regarding in vivo studies, very few of them reflect conditions occurring in nature and further studies with longer periods of oral exposure would be of interest. Moreover, additional toxicological aspects of great interest such as mutagenicity, genotoxicity, immunotoxicity and alteration of hormonal balance need to be studied in depth. [ABSTRACT FROM AUTHOR]

The purpose of this article is to argue that the menstrual blood care practices of Colombia's Iku indigenous women establish a particular relationship with their territory, which means that they can be considered as part of the assemblages that make up territorial governance. This makes sense from an ontological perspective that acknowledges other territories and multiple practices and knowledge that introduce care as part of the management of the commons and that take place in intimate, informal, and non-deliberative spaces. The research was conducted in the iku communities of Nabusímake, between 2016 and 2019, and Katunsama in 2021, through ethnographic observation and semi-structured interviews. I conclude the text by pointing out that governance studies can be enhanced by the feminine practices of caring for blood and territory, as complementary practices to the knowledge of the mamos and authorities. These feminine practices question the separation between the public and the private for the common good, and highlight the centrality of care in the relationships between humans and extrahumans for the continuity of life. The analysis presented here contributes to studies of indigenous women's participation in territorial governance. [ABSTRACT FROM AUTHOR]

Overall survival (OS) is the most meaningful endpoint in clinical trials. However, owing to their limitations, surrogate endpoints are commonly used and validation studies are required to assess their reliability. Analysis of phase III randomized controlled trials (RCTs) of advanced gastroesophageal cancer (AGC) with > 100 patients, correlation coefficients (r), and determination coefficients (R²) between OS and surrogates were evaluated through meta-analyses. Progression-free survival (PFS), time to progression (TTP), and objective response rate (ORR) were examined to determine their correlations with OS. Analysis of 65 phase III RCTs (29,766 subjects) showed a moderate correlation between PFS/TTP and OS (r = 0.77, R² = 0.59), while ORR correlation was low (r = 0.56, R² = 0.31). Excluding immunotherapy trials improved the PFS/TTP and OS correlations (r = 0.83, R² = 0.70). These findings suggest the potential use of PFS/TTP in AGC phase III investigations, disregarding the use of ORR as a surrogate endpoint. [Display omitted] • Moderate correlation between progression-free survival and overall survival. • A weak association between objective response rate and overall survival. • The surrogate threshold effect predicts survival treatment effects in future trials. • Strong correlation in first-line settings, chemotherapy, and anti-HER2 therapy trials. • The effect of immunotherapy on survival may be better captured by other endpoints. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has accelerated the need to identify new antiviral therapeutics at pace, including through drug repurposing. We employed a Quadratic Unbounded Binary Optimization (QUBO) model, to search for compounds similar to Remdesivir, the first antiviral against SARS-CoV-2 approved for human use, using a quantum-inspired device. We modelled Remdesivir and compounds present in the DrugBank database as graphs, established the optimal parameters in our algorithm and resolved the Maximum Weighted Independent Set problem within the conflict graph generated. We also employed a traditional Tanimoto fingerprint model. The two methods yielded different lists of lead compounds, with some overlap. While GS-6620 was the top compound predicted by both models, the QUBO model predicted BMS-986094 as second best. The Tanimoto model predicted different forms of cobalamin, also known as vitamin B12. We then determined the half maximal inhibitory concentration (IC50) values in cell culture models of SARS-CoV-2 infection and assessed cytotoxicity. We also demonstrated efficacy against several variants including SARS-CoV-2 Strain England 2 (England 02/2020/407073), B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta). Lastly, we employed an in vitro polymerization assay to demonstrate that these compounds directly inhibit the RNA-dependent RNA polymerase (RdRP) of SARS-CoV-2. Together, our data reveal that our QUBO model performs accurate comparisons (BMS-986094) that differed from those predicted by Tanimoto (different forms of vitamin B12); all compounds inhibited replication of SARS-CoV-2 via direct action on RdRP, with both models being useful. While Tanimoto may be employed when performing relatively small comparisons, QUBO is also accurate and may be well suited for very complex problems where computational resources may limit the number and/or complexity of possible combinations to evaluate. Our quantum-inspired screening method can therefore be employed in future searches for novel pharmacologic inhibitors, thus providing an approach for accelerating drug deployment. Author summary: Drug repurposing has emerged as one key strategy in the rapid development of treatments against SARS-CoV-2 infection. Remdesivir (RDV) was the first antiviral approved for human use against SARS-CoV-2. We have employed a novel model which runs on a quantum-inspired device, and compared ours to a more traditional fingerprinting model, in search of compounds similar to RDV. Quantum or quantum-inspired computing allows for handling of complex information such as 3D structures which can increase accuracy, while having shorter execution times than those of regular computers. The two methods yielded different compounds, with some overlap. Our quantum-inspired model predicted BMS-986094 and the fingerprint model predicted different forms of cobalamin, also known as vitamin B12, as second-best candidates. We assessed the effect of different concentrations of BMS-986094 and vitamin B12 forms on SARS-CoV-2 infection in two different cell lines. BMS-986094 and vitamin B12 forms were effective at inhibiting replication of all variants of SARS-CoV-2 assessed, namely England 2 (England 02/2020/407073), B.1.1.7 (Alpha), B.1.351 (Beta) and 55 B.1.617.2 (Delta). Lastly, we demonstrated direct inhibition the viral RNA polymerase by all compounds in vitro. Our data demonstrate the effectiveness of our model, which performed similarly to the well-established Tanimoto fingerprinting in the case of RDV. QUBO may be employed in other disciplines, where local computational resources may not suffice, and quantum-inspired devices may be more appropriate when the modelling of complex structures may otherwise not be feasible. [ABSTRACT FROM AUTHOR]

Cylindrospermopsin (CYN) is a cyanotoxin whose incidence has been increasing in the last decades. Due to its capacity to exert damage at different levels of the organism, it is considered a cytotoxin. Although the main target organ is the liver, recent studies indicate that CYN has potential toxic effects on the nervous system, both in vitro and in vivo. Thus, the aim of the present work was to study the effects of this cyanotoxin on neuronal viability and synaptic integrity in murine primary cultures of neurons exposed to environmentally relevant concentrations (0–1 µg/mL CYN) for 12, 24, and 48 h. The results demonstrate a concentration- and time-dependent decrease in cell viability; no cytotoxicity was detected after exposure to the cyanotoxin for 12 h, while all of the concentrations assayed decreased this parameter after 48 h. Furthermore, CYN was also demonstrated to exert damage at the synaptic level in a murine primary neuronal culture in a concentration- and time-dependent manner. These data highlight the importance of studying the neurotoxic properties of this cyanotoxin in different experimental models. [ABSTRACT FROM AUTHOR]

In the course of experiments aimed at deciphering the inhibition mechanism of mycophenolic acid and ribavirin in hepatitis C virus (HCV) infection, we observed an inhibitory effect of the nucleoside guanosine (Gua). Here, we report that Gua, and not the other standard nucleosides, inhibits HCV replication in human hepatoma cells. Gua did not directly inhibit the in vitro polymerase activity of NS5B, but it modified the intracellular levels of nucleoside di- and tri-phosphates (NDPs and NTPs), leading to deficient HCV RNA replication and reduction of infectious progeny virus production. Changes in the concentrations of NTPs or NDPs modified NS5B RNA polymerase activity in vitro, in particular de novo RNA synthesis and template switching. Furthermore, the Gua-mediated changes were associated with a significant increase in the number of indels in viral RNA, which may account for the reduction of the specific infectivity of the viral progeny, suggesting the presence of defective genomes. Thus, a proper NTP:NDP balance appears to be critical to ensure HCV polymerase fidelity and minimal production of defective genomes. Author summary: Ribonucleoside metabolism is essential for replication of RNA viruses. In this article we describe the antiviral activity of the natural ribonucleoside guanosine (Gua). We demonstrate that hepatitis C virus (HCV) replication is inhibited in the presence of increasing concentrations of this ribonucleoside and that this inhibition does not occur as a consequence of a direct inhibition of HCV polymerase. Cells exposed to increasing concentrations of Gua show imbalances in the intracellular concentrations of nucleoside-diphosphates and triphosphates and as the virus is passaged in these cells, it accumulates mutations that reduce its infectivity and decimate its normal spreading capacity. [ABSTRACT FROM AUTHOR]

The agricultural areas of the world face problems that create difficulties when producing food and the excessive use of fertilizers is generating a negative environmental impact. An alternative that appears as a solution to this problem is the use of nanofertilizers. Within nanofertilizers an area of opportunity is the application of macronutrients, which report an increase in absorption efficiency of 19% compared to conventional fertilizers. Potassium (K) is one of the three macronutrients most used in agriculture and its deficiency affects key processes in plant development, limiting crop production. However, the number of publications where K is used as a nanofertilizer is limited, despite this, products in this form are already on the market. Therefore, the aim of this research work was to study the effect of the foliar application of K nanofertilizer on biomass, yield, nitrogen assimilation and photosynthetic activity in green beans cv. 'Strike'. K was applied in the form of a nanofertilizer in doses of 0, 50, 100 and 200 ppm. The biomass accumulation, yield, nitrate reductase enzyme activity, photosynthetic activity and photosynthetic pigments were evaluated. The dose of 100 ppm of K nanofertilizer obtained a higher accumulation of biomass, nitrate reductase activity, photosynthetic activity, SPAD values and total chlorophyll content. While the 200-ppm dose obtained a higher increase in yield. The results obtained suggest that the application of K nanofertilizers benefits the physiological development of plants. However, more studies are required to compare the application of nanofertilizers with traditional fertilizers. [ABSTRACT FROM AUTHOR]

Introduction: Mild non‐immediate reactions (NIRs) to beta‐lactams (BLs) are the most frequent manifestation of drug allergy in children. The diagnostic approach is complex as the utility of skin tests (STs) and lymphocyte transformation tests (LTTs) is controversial. Drug provocation test (DPT) is the gold standard, although no standardized protocols exist. We aimed to investigate the utility of DPT in a unique dose without previous STs, and LTTs in the diagnosis of NIRs to BLs in children. Methods: We prospectively evaluated children 0–14 years old referred to the Regional University Hospital of Málaga during 2017–2020 reporting NIRs to BLs. We performed a DPT with a unique dose followed by regular treatment at home. If positive, STs and LTTs were done after the reaction had disappeared. Results: We included 194 children, having 24 (12.4%) a positive DPT. The main culprit was AX (70.1%) followed by AX‐clavulanic acid (CLV) (26.8%) and the main symptoms maculopapular exanthema (MPE) (49.5%) and delayed‐urticaria (48.5%). A decrease (p = 0.013) in the interval of days between drug administration and onset of symptoms was observed in positive DPT compared with the original reaction (3.5 vs 6 days), with no differences in the overall percentage of MPE and delayed‐appearing urticaria (p = 0.551). No severe reactions occurred during DPT. Moreover, STs were positive in 13.33% and LTTs in 52.9%. Conclusions: Single‐dose DPT without previous STs is a safe and useful way to assess NIRs to BLs in children. LTT has shown to be useful, confirming a T‐cell mechanism involved in these reactions. [ABSTRACT FROM AUTHOR]

In mountain regions, climate change is resulting in glacial retreat, causing biodiversity loss in glacial‐fed streams (kryal habitat). Diamesa species (Diptera Chironomidae), the main colonizers of the kryal in the Alps, are the aquatic insects more threatened by extinction. In recent years, DNA barcoding was successfully adopted to delimit species of chironomids and provided species identification. We highlighted that for the Diamesa genus, inconsistencies remain between identification on a morphological and molecular basis, mainly within cinerella and zernyi groups, raising doubts about the validity of head colour as a good diagnostic taxonomic character. Molecular phylogeny reconstruction based on mitochondrial (cytochrome oxidase subunits I and II) and one nuclear (ribosomal 18S rRNA) markers revealed that D. bohemani and D. zernyi on one hand, and D. cinerella and D. tonsa on the other hand, represent populations of the same species. Divergence times suggested that the radiation of these alpine species seems to have been driven by the climatic events with the alternation of glacial periods that happened in the Pliocene and Pleistocene. The initial separation of the oriental species D. steinboecki seems to be due to the tectonic movements of the Periadriatic fault system that probably favoured the emergence of lakes and streams, successively colonized by D. steinboecki. This study raises important concerns, from the validity of diagnostic characters used today to identify larval types up to the uncertainty about how many species of Diamesa inhabit the European Alps and what their fate will be within the scenario of climate change. [ABSTRACT FROM AUTHOR]

Background: Three allergic phenotypes of rhinitis have been described in adults: allergic rhinitis (AR), local allergic rhinitis (LAR), and dual allergic rhinitis (DAR, coexistence of AR and LAR). Nevertheless, most centers follow a diagnostic approach only based on skin prick test and serum allergen–specific IgE (collectively called atopy tests, AT). This approach prevents the recognition of LAR and DAR, the diagnosis of which requires a nasal allergen challenge (NAC). Here, we investigate the existence of LAR and DAR phenotypes in children and adolescents, and the misdiagnosis rate associated with a work‐up exclusively based on AT. Methods: Clinical data were obtained during physician‐conducted interviews, and AT and NAC were systematically performed in 5‐ to 18‐year‐old patients with chronic rhinitis. The misdiagnosis rate was defined as the proportion of cases where AT and NAC results were discordant. Results: A total of 173 patients (mean age 15.1 years, 39.9% male) completed the study. AR (positive AT and NAC), LAR (negative AT and positive NAC), DAR (positive AT and NAC for some allergens and negative AT and positive NAC for other allergens), and non‐allergic rhinitis (negative NAC) were diagnosed in 45.7%, 24.9%, 11.6%, and 17.9% of individuals, respectively. The clinical profile was comparable among allergic phenotypes, but allergic patients had a significantly earlier rhinitis onset, higher conjunctivitis prevalence, and more severe disease than NAR individuals. A diagnostic work‐up exclusively based on AT misclassified 37.6% of patients. Conclusions: LAR and DAR represent relevant differential diagnosis in pediatric rhinitis. NAC increases the diagnostic accuracy of clinical algorithms for rhinitis in children and adolescents. [ABSTRACT FROM AUTHOR]

The accumulation of similar interfering experiences hampers our ability to retrieve information. To reduce interference, pattern separation allows the separation of similar memories and build detailed memory representations that are less easily confused. To investigate mnemonic interference, previous research has used a mnemonic discrimination paradigm in which the participants have to mnemonically discriminate between two similar items. Unique from previous studies, electrophysiological brain activity was recorded while 26 healthy participants performed a visual mnemonic discrimination task in which we parametrically manipulated the number of studied exemplars from each category. According to our expectations, as the number of exemplars from the same object category increased, participants were less able to discriminate between old and similar presented items. A 'parietal' old/new effect in a temporal window associated with recollection was observed when interference was higher. Increasing the number of exemplars presented also modulated the ERP amplitude in a temporal window associated with familiarity. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus type-1 (HIV-1) infection is associated with aberrant immune activation, however, most model systems for HIV-1 have been used during established infection. Here, we utilize ultra-sensitive HIV-1 quantification to delineate early events during the HIV-1 eclipse, burst and chronic phases of HIV-1 infection in humanized mice. We show that very early in infection, HIV-1 suppresses peripheral type I interferon (IFN) and interferon-stimulated gene (ISG) responses, including the HIV-1 restriction factor IFI44. At the peak of innate immune activation, prior to CD4 T cell loss, HIV-1 infection differentially affects peripheral and lymphoid TLR expression profiles in T cells and macrophages. This results in a trend towards an altered activation of NFĸB, TBK1 and IRF3. The subsequent type I and III IFN responses result in preferential induction of peripheral ISG responses. Following this initial innate immune activation, peripheral expression of the HIV-1 restriction factor SAMHD1 returns to levels below those observed in uninfected mice, suggesting that HIV-1 interferes with their basal expression. However, peripheral cells, still retain their responsiveness to exogenous type I IFN, whereas splenic cells show a reduction in select ISG in response to IFN. This demonstrates the highly dynamic nature of very early HIV-1 infection and suggests that blocks to the induction of HIV-1 restriction factors contribute to the establishment of viral persistence. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) entry into hepatocytes is mediated via a high-affinity interaction between the preS1 glycoprotein and sodium/bile acid cotransporting polypeptide (NTCP). To date, in vitro model systems rely on high multiplicities of infection to achieve infection of cell lines overexpressing human NTCP. This study investigates a novel regulatory pathway for NTCP trafficking to the cell surface, induced by DMSO-mediated cellular differentiation. DMSO rapidly induces high cell surface expression of NTCP and results in increased susceptibility of cells to HBV infection. Additionally, DMSO treatment induces actin, as well as Tubulin reshaping within the cells. We show that direct disruption of the actin and Tubulin network directly enhances NTCP expression and the subsequent susceptibility of cells to HBV infection. DMSO induces these changes via alterations in the levels of cyclic (c)AMP, which participates in the observed actin rearrangements. Blocking of phosphodiesterases (PDEs), which degrade accumulated cAMP, had the same effect as DMSO differentiation and demonstrates that DMSO prevents phosphodiesterase-mediated cAMP degradation. This identifies adenylate cyclase as a novel target for blocking the entry of HBV via targeting the cell surface accumulation of NTCP. This article is part of the theme issue 'Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses'. [ABSTRACT FROM AUTHOR]

Abstract The occurrence of cyanobacterial toxins is being increasingly reported. This is a reason for concern as they can induce toxic effects both in humans and in the environment. Among them, microcystins (MCs) are the best described and most diverse group of cyanobacterial toxins, and MC-LR and MC-RR are the congeners most widely investigated. However, the number of MC variants has also increased in recent years. Some of these minority variants have been shown to have a different toxicokinetic and toxicodynamic profile, but research focused on them is still limited. Moreover, in some water bodies these minority variants can be the predominant toxins. Nonetheless, MC-LR is the only one used for risk evaluation purposes at present. In order to contribute to more realistic risk assessments in the future, the aim of this review was to compile the available information in the scientific literature regarding the occurrence and concentration of minority MCs in water and food samples, and their toxic effects. The data retrieved demonstrate the congener-specific toxicity of MCs, as well as many data gaps in relation to analytical or mechanistic aspects, among others. Therefore, further research is needed to improve the toxicological characterization of these toxins and the exposure scenarios. Highlights • The occurrence of MCs different to MC-LR and RR is increasing worldwide. • The potential toxicological impact of the minority MCs is emphasized. • Minority MC congeners can show different toxicokinetic and toxikodynamic profiles. • There are many data gaps with regard to their toxicological profile. [ABSTRACT FROM AUTHOR]

[Display omitted] The synthesis of phenylnaphthalic anhydrides, including substitution patterns typically found in the Haemodoraceae and Pontederiacea family of plants, was explored using Suzuki and Ullmann-type aromatic substitutions on acenaphthene. Synthetic challenges were surmounted by tactical changes to determine the order of events. [ABSTRACT FROM AUTHOR]

Background Online haemodiafiltration (OL-HDF) has been shown to reduce all-cause mortality versus conventional haemodialysis (HD); however, it is not always available. In these situations, a novel class of membranes with a higher pore size, medium cut-off (MCO) dialysers, could be promising. The aim of this study is to evaluate the efficacy of an MCO dialyser in the removal of small and medium-size molecules and compare it with standard high-flux (HF) dialysers in HD and OL-HDF. Methods In this crossover study, 18 prevalent HD patients were studied in three single mid-week dialysis treatments during three consecutive weeks as follows: first week with OL-HDF with a standard HF dialyser, second week with conventional HD with a standard HF dialyser and third week with conventional HD with an MCO dialyser. Reduction ratios (RRs) of different-sized molecules and albumin losses were collected for the different dialysers. Results MCO HD provided a greater reduction of middle and larger middle molecules compared with standard HF HD [rate reduction (RR) β2-microglobulin 74.7% versus 69.7%, P=0.01; RR myoglobin 62.5% versus 34.3%, P=0.001; RR prolactin 60% versus 32.8%, P=0.001; RR α1-glycoprotein 2.8% versus −0.1%, P=0.01]. We found no difference in the clearance of small and larger middle molecules comparing MCO HD with OL-HDF. Albumin losses were 0.03  g/session with MCO HD and 3.1  g/session with OL-HDF (P=0.001). Conclusion MCO HD is superior to standard HF HD in the removal of middle and larger middle molecules and it is not inferior to OL-HDF in the clearance of small and larger middle molecules. Thus it could be an alternative in patients in which it is not possible to perform OL-HDF. [ABSTRACT FROM AUTHOR]

Summary: Humanized mice are increasingly appreciated as an incredibly powerful platform for infectious disease research. The often very narrow species tropism of many viral infections, coupled with the sometimes misleading results from preclinical studies in animal models further emphasize the need for more predictive model systems based on human cells rather than surrogates. Humanized mice represent such a model and have been greatly enhanced with regards to their immune system reconstitution as well as immune functionality in the past years, resulting in their recommendation as a preclinical model by the US Food and Drug Administration. This review aims to give a detailed summary of the generation of human peripheral blood lymphocyte‐, CD34+ haematopoietic stem cell‐ and bone marrow/liver/thymus‐reconstituted mice and available improved models (e.g. myeloid‐ or T‐cell‐only mice, MISTRG, NSG‐SGM3). Additionally, we summarize human‐tropic viral infections, for which humanized mice offer a novel approach for the study of disease pathogenesis as well as future perspectives for their use in biomedical, drug and vaccine research. [ABSTRACT FROM AUTHOR]

Reports on the occurrence of the cyanobacterial toxin cylindrospermopsin (CYN) have increased worldwide because of CYN toxic effects in humans and animals. If contaminated waters are used for plant irrigation, these could represent a possible CYN exposure route for humans. For the first time, a method employing solid phase extraction and quantification by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) of CYN was optimized in vegetables matrices such as lettuce (Lactuca sativa). The validated method showed a linear range, from 5 to 500 ng CYN g-1 of fresh weight (f.w.), and detection and quantitation limits (LOD and LOQ) of 0.22 and 0.42 ng CYN g-1 f.w., respectively. The mean recoveries ranged between 85 and 104%, and the intermediate precision from 12.7 to 14.7%. The method showed to be robust for the three different variables tested. Moreover, it was successfully applied to quantify CYN in edible lettuce leaves exposed to CYN-contaminated water (10 μg L-1 ), showing that the tolerable daily intake (TDI) in the case of CYN could be exceeded in elderly high consumers. The validated method showed good results in terms of sensitivity, precision, accuracy, and robustness for CYN determination in leaf vegetables such as lettuce. More studies are needed in order to prevent the risks associated with the consumption of CYN-contaminated vegetables. [ABSTRACT FROM AUTHOR]

Improving the knowledge about the distribution of threatened species is a fundamental step forward for implementing effective measures for species conservation. Distribution maps of herpetological species are often inferred from morphological identification but, in some cases, morphology alone is not reliable for assessing the distribution of lookalike species. The common lizard Zootoca vivipara includes several lineages which, to date, cannot be distinguished by any conventional morphological traits. Therefore, a reliable taxonomic identification for the main Zootoca lineages is only feasible with genetic data. In this study, we identify a morphological trait that can be used to distinguish individuals of the parapatric Z. v. vivipara and Z. carniolica, without the support of molecular analyses. This method may provide a cost-effective tool to better depict the distribution of the threatened Z. carniolica and therefore prioritize the conservation of the locations where the oviparous Alpine lineage is found. [ABSTRACT FROM AUTHOR]

Cylindrospermopsin (CYN) has become increasingly important as a freshwater algal toxin, showing cytotoxic effects. This toxin is able to bioaccumulate in freshwater food webs, representing a serious human health problem. Normally, fish is cooked before consumption, and CYN concentration can be altered. For the first time, the effects of microwaving and broiling for 1 and 2 min on CYN concentration and its decomposition products in fish muscle (Oreochromis niloticus) contaminated in the laboratory were investigated, using UPLC-MS/MS and Orbitrap. The results show that cooking the fish reduced unconjugated CYN levels by 11, 10 and 15% after microwaving for 1 and 2 min, and broiling for 2 min, respectively, compared to control fish. Different CYN decomposition products with m/z 416.1234 (7-epi-CYN) and m/z 336.16663 (diasteroisomers C-3A, C-3C, C-3D, C-3E, C-3F) are generated in fish samples submitted to cooking. Based on the relative abundance of the decomposition products, the possible degradation pathways taking place by microwaving may be through the formation of 7-epi-CYN and m/z 336.16663 compounds, whereas in the case of broiling the last route is the only one observed in this study. The influence of cooking and the toxicity characterization of the degradation products generated in CYN-contaminated fish are of importance for more realistic risk evaluation related to their consumption. [ABSTRACT FROM AUTHOR]

Processing and mechanical behaviour of fine grained (diameter ≈0.5–3 µm) and pure β-TCP materials with different levels of porosity (up to 19%) is described. Pores with diameters, d 50 ≈13–14 µm were formed fromcorn starch during sintering. Comprehensive mechanical characterisation –Young´s modulus, strength and toughness– has been done paying special attention to toughness determined in stable fracture tests. The dependence of Young´s modulus and strength with porosity was well fitted to the minimum solid area models while toughness values did not. The competitive processes occurring during fracture impede the degradation of toughness associated to the decrease in Young´s modulus as porosity increases. Materials present similar values of the critical energy release rate G IC , which describes crack initiation. A maximum of the specific fracture energy, G F , which averages crack propagation, has been obtained for the material with the highest porosity. [ABSTRACT FROM AUTHOR]

Highlights from the article: Mixed cryoglobulinaemia (MCG) is one of the most severe extrahepatic hepatitis C virus (HCV)-associated complications, MCG prognosis relies on HCV response to antiviral treatment We report a case of a patient with chronic HCV infection treated with DAA who developed MCG vasculitis despite the For HCV (including hepatitis C virus (HCV)-polymerase chain reac-.

Aim In birds, patterns of migratory connectivity are influenced by landscape structure experienced throughout the annual cycle. Assessing how landscape patterns drive the movements and distributions of migratory species is important for understanding the evolution of migration and determining conservation priorities. We determined migratory connectivity in the Canada Warbler ( Cardellina canadensis), a declining Neotropical migratory bird, and evaluated the degree to which the Andean mountains influence winter population distribution in this montane forest specialist. Location Seven study regions across the Western, Central, and Eastern Andes of Colombia. Methods We inferred breeding and natal origins of Canada Warblers overwintering in Colombia by analysing stable hydrogen isotope values (δ2H) in feathers and assigning wintering populations to breeding origins using an established feather δ2H isoscape for North America. Results We found strong evidence for parallel migration between breeding and wintering sites, giving rise to moderately strong migratory connectivity between breeding and wintering regions. The model best explaining population distribution in the Colombian Andes implied that populations were most similar within basins or valleys. Such segregation is notable, given that basins are separated by less than 300 km on the wintering grounds, while breeding populations may be separated by more than 3000 km from east to west. Main conclusions Our results suggest that the high spine of each Andean cordillera acts to shape the winter distribution of individuals from different breeding populations. To our knowledge, this is the first demonstration that the topography of the Andean mountains can act to shape the winter distribution of populations of a migratory bird. The strength of migratory connectivity found in Canada Warblers may inhibit evolutionary responses to environmental change, and the more rapid population declines recorded in some eastern breeding populations may be related to habitat loss and local environmental conditions in the Eastern Andes, where individuals from these populations were more likely to overwinter. [ABSTRACT FROM AUTHOR]

Virgin olive oil (VOO) stability needs to be controlled to guarantee that the oil keeps the quality declared on the label during distribution. However, the stability is changing as storage progresses and its estimation under moderate conditions are difficult to accomplish, due to the challenge of implementing rapid stability evaluation under the environmental variables given in long storage periods. The main objective of this work was to study the dynamic changes of VOO stability taking place during storage. For this purpose, a realistic storage approach of 27 months was designed. The stability of the oils was evaluated at different months by incubating the oil on mesh cell and scanning FTIR spectra during this incubation (mesh cell-FTIR). Although the storage of the oils did not show remarkable spectral changes, the spectra from mesh cell incubation showed variations at different months, which evidenced a change in the stability as the oil aged. The results revealed that the stability changes were abrupt during VOO ageing. In general terms, the results showed that these changes mainly occurred during the first 6 months. The incubation in mesh cell-FTIR spectroscopy is able to detect the minor chemical changes occurring in VOO during storage under moderate conditions. [Display omitted] • Dynamic measurements of stability were conducted during virgin olive oil storage. • Mesh cell-FTIR spectra reflected changes in the stability during storage. • The main changes of stability mostly occurred during the first 6 months of storage. • Mesh cell incubation amplify small spectral changes, undetectable in raw spectra. • The PCA results allowed differentiate the samples according to their ageing. [ABSTRACT FROM AUTHOR]

Background: Injections of filler materials in orofacial tissues is a growing practice and may be followed by a reaction involved from small inflammatory nodules to large and diffuse granulomas. They may develop months or years after de procedure making it difficult to diagnose Purpose: Identify histopathological features of a reaction to filler materials through a literature review and the report of three cases in the orofacial region. Method: An exhaustive search of journal articles related to filler materials commonly used in the orofacial region and clinical cases of foreign body reaction by filler material with emphasis in the histopathological features were carried out. The search was made in the database PubMed and the browser Google Scholar between 2004 and 2015. Additionally, three cases diagnosed as foreign body reaction by exogenous material in an oral pathology laboratory of the Venezuelan state Anzoátegui were documented. Results: There were only 10 articles with clinical cases describing histopathological features. Other 3 review articles explained specific characteristics for each filler material. Based on this review, the diagnosis of the 3 cases was confirmed. Conclusions: Few studies describe the histopathological features of filler material reactions and the type of material. Nevertheless, characteristics were collected to confirm the cases. [ABSTRACT FROM AUTHOR]

Modern food packaging has made great advances as result of global trends and consumer preferences, which are oriented to obtain improved food quality and safety. In this regard, clay minerals, and mainly Montmorillonite (Mt) are attracting considerable interest in food packaging because of the improvements developed in mechanical and barrier properties. Hence, the present work aim to assess the toxicity of four Montmorillonite-based clay minerals, an unmodified clay, Cloisite®Na+ (CNa+), and three modified Mt clays: Cloisite®30B (C30B), a commercial clay, and Clay1 and Clay2, two novel modified organoclays developed by the Packaging, Transport, & Logistics Research Institute (ITENE). First, the cytotoxic effects were studied in the Human Umbilical Vein Endothelial Cells (HUVEC). In addition, the potential mutagenicity of the clays was evaluated by the Ames test. Clay1 did not induce any cytotoxic effects in HUVEC, although it exhibited potential mutagenicity in TA98 Salmonella typhimurium strain. In contrast, Clay2 produced cytotoxicity in endothelial cells but no mutagenicity was recorded. However, CNa+ was not cytotoxic neither mutagenic. And finally, C30B showed positive results in both assays. Therefore, results showed that clay minerals have a different toxicity profile and a case by case toxicity evaluation is required. [ABSTRACT FROM AUTHOR]

Basic relationships between the microstructure and the texture of refractories and their toughness have been established. A series of commercial materials has been chosen in order to highlight the influence of microstructural characteristics on fracture behaviour and associated toughness. Silica, silica–alumina and silica–alumina–zirconia based shaped refractories and a calcium aluminate cement bonded concrete have been analysed. Extensive microstructural characterisation has been performed using a combination of techniques, including chemical analysis by X-ray fluorescence, X-ray diffraction, reflected light optical microscopy and scanning electron microscopy with analysis by dispersive energies. Fracture has been characterised using stable fracture tests of SENB tested in 3 point bending. Stability was reached in displacement and crack mouth opening displacement controlled tests. Size effect has been analysed by using two different specimen sizes and relative notch lengths. For the range of microstructures studied, the obtained results have allowed to characterise toughness and establish the relationships toughness-microstructure and texture. [ABSTRACT FROM AUTHOR]

Currently, antimicrobial additives derived from essential oils (Eos) extracted from plants or spices, such as Origanum vulgare , are used in food packaging. Thymol and carvacrol, the major EO compounds of O. vulgare , have demonstrated their potential use as active additives. These new applications use high concentrations, thereby increasing the concern regarding their toxicological profile and especially their genotoxic risk. The aim of this work was to investigate the potential in vitro genotoxicity of thymol (0–250 μM) and carvacrol (0–2500 μM) at equivalent doses to those used in food packaging. The micronucleus (MN) test and the mouse lymphoma (MLA) assay on L5178Y/ Tk ± mouse lymphoma cells were used. The negative results for thymol with the MN with and without the S9 fraction and also with the MLA assay reinforce the view that this compound is not genotoxic in mammalian cells. However, carvacrol presented slight genotoxic effects, but only in the MN test at the highest concentration assayed (700 μM) and in the absence of metabolic activation. The lack of genotoxic response in the MLA assay after 4 and 24 h of exposure indicates a low genotoxic potential for carvacrol. Alternatively, the general negative findings observed in both assays suggest that the MN results of carvacrol are marginal data without biological relevance. These results can be useful to identify the appropriate concentrations of these substances to be used as additives in food packaging. [ABSTRACT FROM AUTHOR]

This article aims to show the importance of the human subject in considering the experience of time. Breaking away from a usual ontologization of the concept often found in classical authors, we bring forward those aspects about time that time itself allows us to perceive clearly. On the premise that human beings can become aware of time, and establishing relations between the concepts of time found in Wittgentstein, Heidegger and Merleau-Ponty, we look for a new way to comprehend the dynamics of past, present and future, that would fit the human subject. This concept merges past, present and future in a whole unit that is the foundation of meaningful human experience. [ABSTRACT FROM AUTHOR]

Highlights: [•] Pyrolytic techniques are a potential tool for CYN analysis from cyanobacterial blooms. [•] Specific molecular fragments can be used as CYN markers in environmental samples. [•] A diagnostic ion (m/z 194) could be used for CYN detection by conventional Py-GC/MS. [•] The characteristic peak (m/z 336) could have diagnostic value to detect CYN by TCh-GC/MS. [Copyright &y& Elsevier]

One of the major challenges in the analysis of closely related species, speciation and phylogeography is the identification of variable sequence markers that allow the determination of genealogical relationships in multiple genomic regions using coalescent and species tree approaches. Rodent species represent nearly half of the mammalian diversity, but so far no systematic study has been carried out to detect suitable informative markers for this group. Here, we used a bioinformatic pipeline to extract intron sequences from rodent genomes available in databases and applied a series of filters that allowed the identification of 208 introns that adequately fulfilled several criteria for these studies. The main required characteristics of the introns were that they had the maximum possible mutation rates, that they were part of single-copy genes, that they had an appropriate sequence length for amplification, and that they were flanked by exons with suitable regions for primer design. In addition, in order to determine the validity of this approach, we chose ten of these introns for primer design and tested them in a panel of eleven rodent species belonging to different representative families. We show that all these introns can be amplified in the majority of species and that, overall, 79% of the amplifications worked with minimum optimization of the annealing temperature. In addition, we confirmed for a pair of sister species the relatively high level of sequence divergence of these introns. Therefore, we provide here a set of adequate intron markers that can be applied to different species of Rodentia for their use in studies that require significant sequence variability. [ABSTRACT FROM AUTHOR]

Assessing effects of winter habitat quality and environmental conditions on fitness of migratory birds is important to understand factors that regulate migratory bird populations throughout the annual cycle. We evaluated effects of winter habitat occupancy, as inferred from tissue stable-carbon (δC) and -nitrogen (δN) isotope values, on nutritional condition and arrival date of seven long-distance Nearctic-Neotropical migratory species sampled at Delta Marsh Bird Observatory (DMBO, Manitoba, Canada) during their spring migration to more northerly breeding areas. Additionally, we used a long-term dataset of DMBO to assess the effect of May minimum temperature, May minimum daily temperature, and El Niño-Southern Oscillation (ENSO) index on body condition and spring arrival date. A positive effect of assumed mesic winter habitat on nutritional condition and arrival phenology was detected primarily in species overwintering in the Caribbean (Palm Warbler Setophaga palmarum, Northern Waterthrush Parkesia novaboracensis). We caution, then, against generalizing the results of previous isotopic studies inferring winter habitat use applied to Neotropical migrants wintering in the Caribbean (e.g., American Redstart Setophaga ruticilla) to those species or populations wintering elsewhere and especially away from dichotomous mangrove versus scrub habitats. In general, birds arrived later and in lower nutritional condition during colder springs, and early migrants did not adjust their timing of migration to spring temperature. Early arrival was associated with poorer nutritional condition, and most species had their lowest nutritional condition during the coldest periods of migration. ENSO, probably through its influence on weather and food availability during winter, carried over to northern latitudes and affected both spring arrival date and nutritional condition. [ABSTRACT FROM AUTHOR]

Abstract: A lab-scale, gas-lift anaerobic membrane bioreactor (Gl-AnMBR) was developed and evaluated for its ability to treat and recover resources from sewage. Gl-AnMBR is a hybrid treatment technology that combines anaerobic biological process with low-pressure membrane filtration. A synthetic sewage, mimicking household wastewater, was used as feed to the 10L suspended-growth bioreactor, which is coupled to a tubular PVDF ultrafiltration membrane (with biogas as sparge gas) for sludge/water separation. A series of rapid filterability assessments of flocculant anaerobic sludge was performed and a flux of 18L/m2 h (LMH) could be obtained under the tested conditions. Under continuous operation (100d), the flux gradually settled to a stable range of 10–15LMH when weekly manual fouling control was applied. When frequent backwash (for 5min every 4h) was applied, an average flux of 50LMH was sustained. Gl-AnMBR showed excellent removal efficiencies of sewage organic matter (up to 98% and 95% in chemical oxygen demand and organic carbon removal, respectively), while producing methane as biogas (4.5L/d), which can be used for membrane scrubbing and energy recovery. The high-clarity permeate contained soluble nutrients derived from sewage organic matter (95.5% and 93.4% cumulative recovery for nitrogen and phosphorous, respectively, after 100d), which may potentially be used for combined fertilization/irrigation (fertigation). The study demonstrates that Gl-AnMBR is a promising technology for wastewater reuse and resource recovery. [Copyright &y& Elsevier]

Lethal mutagenesis, or virus extinction produced by enhanced mutation rates, is under investigation as an antiviral strategy that aims at counteracting the adaptive capacity of viral quasispecies, and avoiding selection of antiviral-escape mutants. To explore lethal mutagenesis of hepatitis C virus (HCV), it is important to establish whether ribavirin, the purine nucleoside analogue used in anti-HCV therapy, acts as a mutagenic agent during virus replication in cell culture. Here we report the effect of ribavirin during serial passages of HCV in human hepatoma Huh-7.5 cells, regarding viral progeny production and complexity of mutant spectra. Ribavirin produced an increase of mutant spectrum complexity and of the transition types associated with ribavirin mutagenesis, resulting in HCV extinction. Ribavirin-mediated depletion of intracellular GTP was not the major contributory factor to mutagenesis since mycophenolic acid evoked a similar decrease in GTP without an increase in mutant spectrum complexity. The intracellular concentration of the other nucleoside-triphosphates was elevated as a result of ribavirin treatment. Mycophenolic acid extinguished HCV without an intervening mutagenic activity. Ribavirin-mediated, but not mycophenolic acid-mediated, extinction of HCV occurred via a decrease of specific infectivity, a feature typical of lethal mutagenesis. We discuss some possibilities to explain disparate results on ribavirin mutagenesis of HCV. [ABSTRACT FROM AUTHOR]

This article is an advance of a wider investigation, in which the objective is to analyze overall maintenance management in public institutions of higher education in the municipality Cabimas, hence in this development describes the elements of the management maintenance present in these institutions. Authors were consulted such as Duffuaa et al. (2010), Clemenza (2010), Zambrano and Leal (2006) , Robbins and Coulter (2005) y Martínez (2007) among others. The research is descriptive, non-experimental design, transactional and field. We used a population census, for a total of twentythree (23) research subjects, belonging to the Universidad del Zulia Núcleo Costa Oriental del Lago, Universidad Nacional Experimental Rafael Maria Baralt and Instituto Universitario Tecnológico Cabimas. To collect data, a questionnaire was composed of twenty-two (22) items, which was validated by the trial of six (6) experts, with 0.99 reliability by Cronbach alpha coefficient. We conclude that the elements planning, organizing, scheduling, execution and control, have a high presence in maintenance management, not the human resource and security elements. [ABSTRACT FROM AUTHOR]

A new method for determining dissolved cylindrospermopsin (CYN) in waters using solid-phase extraction (SPE) with graphitized carbon cartridges and quantification by liquid chromatography coupled with tandem mass spectrometry is described and discussed. The method has been suitably validated: the linear range covered is from 0.900 to 125 µg CYN/L. Limits of detection and quantification were 0.5 and 0.9 µg CYN/L, respectively, and allow CYN determination at concentrations below the guideline proposed of 1 µg CYN/L in natural waters. The method exhibits mean recoveries from 83 to 95%, and intermediate precision (relative standard deviation (%)) values from 5 to 12%, ensuring adequacy against the Association of Official Analytical Chemists guidelines. The method is robust against the following three influential factors considered in the cleanup stage: the batch of the graphitized carbon cartridges, the flow rate of the water sample through the cartridge, and the final redissolved water volume after SPE treatment. The method has been successfully applied to detection and quantification of CYN in water samples from aquaria of a toxicological in vivo laboratory experiment. Environ. Toxicol. Chem. 2012; 31: 2233-2238. © 2012 SETAC [ABSTRACT FROM AUTHOR]

Objectives--To determine the pharmacokinetics of a commercial formulation of doxycycline hyclate after IM administration of a single dose to sheep. Animals--11 healthy domestic sheep. Procedures--For each sheep, doxycycline was administered as a single dose of 20 mg/kg, IM. Blood samples were obtained prior to and for 84 hours after doxycycline administration. Plasma concentrations of doxycycline were determined via high-performance liquid chromatography with UV detection. Pharmacokinetic data were analyzed with noncompartmental methods. Results--Mean ± SD values for pharmacokinetic parameters included maximum plasma concentration (2.792 ± 0.791 µg/mL), time to reach maximum plasma concentration (0.856 ± 0.472 hours), mean residence time (91.1 ± 40.78 hours), elimination half-life (77.88 ± 28.45 hours), and area under the curve (65.67 ± 9.877 µg•h/mL). Conclusions and Clinical Relevance--Results indicated that doxycycline had prolonged absorption and elimination in sheep after IM administration. A daily dose of 20 mg/kg would be sufficient to reach effective plasma concentrations against Chlamydia spp (minimum inhibitory concentration, 0.008 to 0.031 µg/mL) and Staphylococcus aureus (minimum inhibitory concentration, 0.12 µg/mL). Doxycycline administered IM could be an option for therapeutic use in sheep, although further studies are needed. [ABSTRACT FROM AUTHOR]

The article presents a study on geographic origins and the timing of fall migration of veery in Sierra Nevada de Santa Marta, northern Colombia. The study analyses stable hydrogen isotopes (δD) in feathers and values expected from feathers' δD in the long-term isoscape. Result shows that most of the veery originated from the southwest or the northeast regions. Moreover, a chain migration was suggested as there is no correlation found between the δD and timing of arrival.

Abstract: Understanding the factors that contribute to the risk from fish consumption is a relevant public health concern due to potential adverse effects of cyanobacterial toxins. The aim of this work was to study the influence of two usual cooking practices, microwave oven and boiling, on the microcystin (MCs) concentration in fish muscle (Tilapia, Oreochromis niloticus) spiked with a stock solution (500μL) containing a mixture of three toxins (MC-LR, MC-RR, and MC-YR) (1.5μg/mL of each toxin). Two different variables were investigated: time of cooking in the microwaves treatment (1 or 5min), and way of boiling, “boiled muscle” or “continuously heated muscle”. All samples were then lyophilized and MCs were extracted and purified (Oasis HLB cartridge) and quantified by HPLC-MS. Furthermore, the waters in which the samples boiled were also analyzed after their purification. The results suggest a reduction on MC-LR (36%) and MC-YR (24.6%) in samples cooked in the microwave for 5min. Major changes were found when the fish was cooked by the continuous boiling, with a decrease of 45.0% (MC-RR), 56.4% (MC-YR) and 59.3% (MC-LR). More studies are necessary to elucidate the mechanisms involved when aquatic food is submitted to usual cooking practices. [Copyright &y& Elsevier]

Abstract: The effect of operation regime and culture system on carotenoid productivity by the halotolerant alga Dunaliella salina has been analyzed. Operation strategies tested included batch and semi continuous regime, as well as a two-stage approach run simultaneously in both, open tanks and closed reactor. The best results were obtained with the closed tubular photobioreactor. The highest carotenoid production (328.8mgcarotenoidl−1 culture per month) was achieved with this culture system operated following the two-stage strategy. Also, closed tubular photobioreactor provided the highest carotenoid contents (10% of dry weight) in Dunaliella biomass and β-carotene abundance (90% of total carotenoids) as well as the highest 9-cis to all-trans β-carotene isomer ratio (1.5 at sunrise). [ABSTRACT FROM AUTHOR]

Abstract: The present study investigates the effects of the oral administration of N-acetylcysteine (NAC), a glutathione (GSH) precursor, on the pathological changes induced by Microcystic cyanobacterial cells containing microcystins (MCs) in an important aquaculture fish species, tilapia (Oreochromis niloticus). Fish were exposed to a single oral dose of 120μg MC-LR/fish and sacrificed in 24h. Pathological lesions in the hepatic and renal tissues, intestines, heart, and gills were investigated in the absence and presence of 20.0, 44.0 and 96.8mg NAC/fish/day. Results showed a protective role of NAC mainly at the median dose used (44.0mg NAC/fish/day), which reduced tissue lesions probably due to its antioxidant activity. The highest dose, however, induced toxic effects even in fish exposed only to NAC. Therefore, it can be considered a useful chemoprotectant in the prophylaxis and prevention of MC-related intoxications in fish. However, particular attention must be paid to its application dose because of its pathological activity, which was shown by the present study to start from 96.8mg NAC/fish/day. [Copyright &y& Elsevier]

In the Early Middle Ages reading and writing become marginal activities, but their social extension is wider than expected. This paper explores the methods used to teach both skills as well as the results of this teaching. [ABSTRACT FROM AUTHOR]

Fish can be exposed to toxic cyanobacterial cells in natural waters and fish farms and suffer from oxidative damage. The present study investigates the effects of N-acetylcysteine (NAC), a glutathione (GSH) precursor, on the oxidative stress induced by Microcystis cyanobacterial cells containing microcystins (MCs) in tilapia fish (Oreochromis niloticus). Variation in lipid peroxidation (LPO) levels, carbonyl group content, reduced glutathione to oxidized glutathione ratio (GSH:GSSG), and catalase (Enzyme Commission [EC] 1.11.1.6), superoxide dismutase (SOD; EC 1.15.1.1), glutathione reductase (GR; EC 1.8.1.7), glutathione peroxidase (GPx; EC 1.11.1.9), and glutathione S-transferase (EC 2.5.1.18) activities in liver and kidney of tilapia exposed to a single oral dose of 120 μg MC-LR (with leucine [L] and arginine [R])/fish and killed in 24 h were investigated in the absence and presence of 20.0, 44.0, and 96.8 mg NAC/fish/d. Results showed a protective role of NAC, depending on the dose and the biomarker considered. The increase in LPO (1.9- and 1.4-fold in liver and kidney, respectively) and the decreased protein content and GSH: GSSG in the liver induced by MCs were recovered mainly by the lower doses of NAC employed. Antioxidant enzyme activities increased (range, 1.4- to 1.7-fold) by MCs also were ameliorated by NAC, although the highest level used induced significant alteration of some enzymatic activities, such as SOD, GPx, and GR. Thus, NAC can be considered to be a useful chemoprotectant that reduces hepatic and renal oxidative stress in the prophylaxis and treatment of MC-related intoxications in fish when careful attention is given to its application dose because of its own pro-oxidant activity, as shown in the present study at 96.8 mg NAC/ fish/d. [ABSTRACT FROM AUTHOR]