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We have rapidly gained insights into the presence and function of T lymphocytes in non‐lymphoid tissues, the tissue‐resident memory T (TRM) cells. The central pillar of adaptive immunity has been expanded from classic central memory T cells giving rise to progeny upon reinfection and effector memory cells circulating through the blood and patrolling the tissues to include TRM cells that reside and migrate inside solid organs and tissues. Their development and maintenance have been studied in detail, providing exciting clues on how their unique properties used to fight infections may benefit therapies against solid tumors. We provide an overview of CD8 TRM cells and the properties that make them of interest for vaccination and cancer therapies. [ABSTRACT FROM AUTHOR]

In this paper, we present an original experimental approach combining infrared thermography, analysis of voiding, and swelling tests to investigate damage mechanisms in carbon black (CB)‐filled styrene‐butadiene rubber (SBR). Heat exchange and voiding under uniaxial cyclic loading have been observed. A mechanical and electrical percolating filler network was identified by atomic force microscopy and electrical conductivity for the SBR with highest content of fillers (60 phr). SBR materials with a non percolating filler network show a reversible thermal energy dissipation during a series of cyclic loading, concomitant with reversible voiding mechanisms, through the successive formation and closing of voids. The SBR with the percolating network undergoes, during the series of cyclic loading, a high dissipation of energy under the form of heat, concomitantly with irreversible voiding mechanisms. Such mechanisms are shown to be due primarily to (i) the alteration of the filler network and/or filler/rubber interface and to a lower extent to (ii) the rubber matrix alteration (chains scission and/or crosslink breakage) as demonstrated by ex‐situ swelling. [ABSTRACT FROM AUTHOR]

2D MXenes find applications in several technology fields. Solution processing techniques can facilitate the integration of these materials within the technological supply chain. Here, a highly concentrated (up to 1.5 g L−1) and stable dispersion of 2D Ti3C2Tx MXene flakes is produced by an environmentally friendly liquid phase exfoliation process (LPE) in dihydrolevoglucosenone (Cyrene). The flakes preserve their elemental composition after 6 months, while those exfoliated in N‐Methyl‐2‐pyrrolidone (NMP), a commonly used solvent, undergo significant oxidation. The cytotoxicity of the MXene flakes in Cyrene and in NMP is investigated by assessing the cellular viability in a human keratinocyte (HaCaT) cell line, which is a relevant model for skin applications. The data show that the MXene flakes in Cyrene induce cytotoxic effects for a dose > 1 µg cm−2, as similarly observed for the MXene flakes in NMP. Efforts are made to overcome this by collecting the MXene flakes and redispersing them in a solution of bovine serum albumin (BSA). MXene in BSA does not affect cellular viability and cell morphology, possibly due to the formation of a protective protein corona around the individual MXene flakes. These findings illustrate an environmentally friendly strategy to produce biocompatible 2D MXene for biomedical applications. [ABSTRACT FROM AUTHOR]

The article focuses on the emerging importance of managing food–drug interactions within pharmacovigilance systems. It highlights the complexities and risks associated with these interactions, including their impact on drug absorption, metabolism, and efficacy. It underscores the need for enhanced awareness among healthcare providers and the integration of this information into national and international pharmacovigilance frameworks.

Whenever an emergency occurs, such as a change in the system operating environment that prevents regular functioning, one possibility to restore the system to normal operation is to perform immediately the emergency repair process (ERP). This paper introduces the feature‐based emergency repair process (FbERP), which constitutes a feature‐based improvement/extension to ERP. FbERP uses feature models to represent urgent change requests (UCRs) and traces each change to its location in the code base in order to realign documentation and code. Based on real‐world change requests, we evaluated the proposed process using different techniques, including an empirical case study and a small survey. In the empirical case study, we compare FbERP with respect to ERP to check the effectiveness, efficiency, and usability of the proposed process. The results of the evaluation reveal that FbERP can be successfully used by software engineers to respond to UCRs, with an improvement over ERP. [ABSTRACT FROM AUTHOR]

Postbiotics are defined as a "preparation of inanimate microorganisms and/or their components that confers a health benefit on the host." They can be produced by fermentation, using culture media with glucose (carbon source), and lactic acid bacteria of the genus Lactobacillus, and/or yeast, mainly Saccharomyces cerevisiae as fermentative microorganisms. Postbiotics comprise different metabolites, and have important biological properties (antioxidant, anti‐inflammatory, etc.), thus their cosmetic application should be considered. During this work, the postbiotics production was carried out by fermentation with sugarcane straw, as a source of carbon and phenolic compounds, and as a sustainable process to obtain bioactive extracts. For the production of postbiotics, a saccharification process was carried out with cellulase at 55°C for 24 h. Fermentation was performed sequentially after saccharification at 30°C, for 72 h, using S. cerevisiae. The cells‐free extract was characterized regarding its composition, antioxidant activity, and skincare potential. Its use was safe at concentrations below ~20 mg mL−1 (extract's dry weight in deionized water) for keratinocytes and ~ 7.5 mg mL−1 for fibroblasts. It showed antioxidant activity, with ABTS IC50 of 1.88 mg mL−1, and inhibited elastase and tyrosinase activities by 83.4% and 42.4%, respectively, at the maximum concentration tested (20 mg mL−1). In addition, it promoted the production of cytokeratin 14, and demonstrated anti‐inflammatory activity at a concentration of 10 mg mL−1. In the skin microbiota of human volunteers, the extract inhibited Cutibacterium acnes and the Malassezia genus. Shortly, postbiotics were successfully produced using sugarcane straw, and showed bioactive properties that potentiate their use in cosmetic/skincare products. [ABSTRACT FROM AUTHOR]

Objectives: To characterize orofacial myofunctional structures of elders with Parkinson's disease (PD) and examine the relationship with the stages of PD, pharmacotherapy, and quality of life. Methods: PD Group with 45 elders and a control group (CG) of 10 healthy elders of both sexes were included (60–86 years). Structured interviews, medical records, and clinical examination gathered information on health aspects such as the use of drugs, Hoehn & Yahr stages 1–4, and oral health status. The Mini‐Mental State Examination, Parkinson's Disease Questionnaire, and Orofacial Myofunctional Evaluation with Scores for Elders were applied. Results: Better oral health status was found in participants diagnosed as Hoehn & Yahr stage 1 compared to the later stages. OMES‐Elders scores for appearance/posture, mobility, breathing, and speech functions were different between groups, and decreased overall OMES‐Elders was observed across the Hoehn & Yahr stages. A higher number of masticatory cycles was required for chewing and ingestion of the test food in the PD group compared to CG (p <.05). Significant differences were found in the mobility and daily living activities domains and an overall score of QoL between the Hoehn & Yahr stages 1 and 4, and worst orofacial functioning was accompanied by the worst self‐perception of QoL in the communication domain (rho = −0.32; p =.034). The use of xerogenic drugs did not affect the OMES‐Elders swallowing domain. Conclusion: Worse dental condition and performance of orofacial functions was observed in the elders with PD as the disease progresses, and poorer orofacial performance negatively affects their perception of communication skills. [ABSTRACT FROM AUTHOR]

Carbon‐based materials, such as graphene oxide and reduced graphene oxide membranes have been recently used to fabricate ultrathin, high‐flux, and energy‐efficient membranes for ionic and molecular sieving in aqueous solution. However, these membranes appeared rather unstable during long‐term operation in water with a tendency to swell over time. Membranes produced from pristine, stable, layered graphene materials may overcome these limitations while providing high‐level performance. In this paper, an efficient and "green" strategy is proposed to fabricate µm‐thick, graphene‐based laminates by liquid phase exfoliation in Cyrene and vacuum filtration on a PVDF support. The membranes appear structurally robust and mechanically stable, even after 90 days of operation in water. In ion transport studies, the membranes show size selection (>3.3 Å) and anion‐selectivity via the positively charged nanochannels forming the graphene laminate. In antibiotic (tetracycline) diffusion studies under dynamic conditions, the membrane achieve rejection rates higher than 95%. Sizable antibacterial properties are demonstrated in contact method tests with Staphylococcus aureus and Escherichia coli bacteria. Overall, these "green" graphene‐based membranes represent a viable option for future water management applications. [ABSTRACT FROM AUTHOR]

Despite their potential as a sustainable source of soil nutrients and organic matter, waste organic residues are often discarded rather than utilized in agriculture. This review examines the current state‐of‐the‐art in the application of organic residues in agricultural production systems by analysing trends and results in published research conducted on their use for soil health and crop production purposes. For this, a bibliographic analysis was conducted on 81 papers collected from the Web of Science database. Our research shows a growing trend in the field, particularly in recent years, with articles from India, China and the United States at the forefront. The most commonly evaluated organic residues were compost, animal manure, crop residues, municipal solid waste and biochar. Soil pH, bulk density and especially organic matter/total organic carbon (TOC) were the chemical, physical and biological attributes most frequently evaluated, respectively. This review indicates that the application of organic residues improves soil health, positively affecting crop productivity in crops such as maize, wheat and rice. However, further research is needed to address the potential risk of soil contamination from potentially toxic metals (PTMs) associated with organic residues, as well as to identify best practices to guarantee food safety and environmental preservation. [ABSTRACT FROM AUTHOR]

Background: The prosthetic screw fixes the prostheses to the implants. Upon osteointegration, the untightening of the prosthetic screw is the most common problem in oral rehabilitation with implants. Objective: To study the deformation of the implant retaining hexagonal screw head. Methods: This investigation used two methods for evaluating the screw head's area of deformation (mm2): a stereoscopic microscopy and micro computed tomography (microCT). For stereoscopic microscopy, 16 titanium alloy (T) and 16 titanium gold‐plated alloy (G) screws of the Zimmer Biomet™ brand were used, divided into eight groups: group 0 (control group), groups T1 and G1 (screws tightened 10 times to 20 Ncm), the groups T2 and G2 (screws tightened 20 times to 20 Ncm) and the groups T3 and G3 (screws tightened 10 times to 30 Ncm). In the study with microCT, one screw was randomly chosen from each of the groups described above to perform the scanning by microCT. Results: When comparing the type of screw material using stereoscopic microscopy, no statistically significant differences were found (p > 0.05). Contrarily, different number of successive grips and different torque value showed statistically significant differences in the head section of the retaining screws (p < 0.05). The observation by microCT showed the torque applied is crucial to the head deformation in titanium screws. In gold‐plated screws the successive tightening appears to be pivotal. Conclusion: Titanium and gold screws tend to behave similarly. By increasing the tightening cycles and the torque values of protocols greater levels of deformations can be expected. In general, microCT data showed better results for gold‐plated titanium alloy. Clinical Significance: To control severe screw head deformation and the impossibility of untightening the implant's restoration, clinicians should avoid extreme torque values and prevent surpassing 10 tightening cycles. [ABSTRACT FROM AUTHOR]

Histamine is involved in several central nervous system processes including cognition. In the last years, H3 receptor (H3R) antagonists have been widely explored for their potential on dementias and other cognitive dysfunctions, and the cooperative role between histamine and acetylcholine neurotransmissions on cognitive processes is widely known in literature. This motivated us to assess the potential of 1‐[(2,3‐dihydrobenzofuran‐1‐yl)methyl]piperazines (LINS01 compounds) as inhibitors of cholinesterases, and thus this work presents the inhibitory effect of such compounds against acetyl (AChE) and butyrylcholinesterase. A set of 16 selected compounds were evaluated, being compounds 2d and 2e the most potent inhibitors of both cholinesterases (IC50 13.2–33.9 μM) by competitive mechanism, as indicated by the kinetic assays. Molecular docking simulations suggested that the allylpiperazine and dihydrobenzofuran motifs present in these compounds are important to perform π‐interactions with key tryptophan residues from the enzymes, increasing their affinity for both H3R and cholinesterases. Metric analysis support that compound 2d (LINS01022) should be highlighted due to its balanced lipophilicity (ClogP 2.35) and efficiency (LE 0.32) as AChE inhibitor. The results add important information to future design of dual H3R‐cholinesterases ligands. [ABSTRACT FROM AUTHOR]

Microcystins (MC) are hepatotoxic for organisms. Liver MC accumulation and structural change are intensely studied, but the functional hepatic enzymes and energy metabolism have received little attention. This study investigated the liver and hepatocyte structures and the activity of key hepatic functional enzymes with emphasis on energetic metabolism changes after subchronic fish exposure to cyanobacterial crude extract (CE) containing MC. The Neotropical erythrinid fish, Hoplias malabaricus, were exposed intraperitoneally to CE containing 100 μg MC‐LR eq kg−1 for 30 days and, thereafter, the plasma, liver, and white muscle was sampled for analyses. Liver tissue lost cellular structure organization showing round hepatocytes, hyperemia, and biliary duct obstruction. At the ultrastructural level, the mitochondria and the endoplasmic reticulum exhibited disorganization. Direct and total bilirubin increased in plasma. In the liver, the activity of acid phosphatase (ACP) increased, and the aspartate aminotransferase (AST) decreased; AST increased in plasma. Alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were unchanged in the liver, muscle, and plasma. Glycogen stores and the energetic metabolites as glucose, lactate, and pyruvate decrease in the liver; pyruvate decreased in plasma and lactate decreased in muscle. Ammonia levels increased and protein concentration decreased in plasma. CE alters liver morphology by causing hepatocyte intracellular disorder, obstructive cholestasis, and dysfunction in the activity of key liver enzymes. The increasing energy demand implies glucose mobilization and metabolic adjustments maintaining protein preservation and lipid recruitment to supply the needs for detoxification allowing fish survival. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is characterized by social cognition deficits, including difficulties inferring the intentions of others. Although deficits in attribution of intentions (AI) have been consistently replicated in ASD, their exact nature remains unexplored. Here we registered the electrophysiological correlates of a nonverbal social cognition task to investigate AI in autistic adults. Twenty‐one male autistic adults and 30 male neurotypical volunteers performed a comic strips task depicting either intentional action (AI) or physical causality with or without human characters, while their electroencephalographic signal was recorded. Compared to neurotypical volunteers, autistic participants were significantly less accurate in correctly identifying congruence in the AI condition, but not in the physical causality conditions. In the AI condition a bilateral posterior positive event‐related potential (ERP) occurred 200–400 ms post‐stimulus (the ERP intention effect) in both groups. This waveform comprised a P200 and a P300 component, with the P200 component being larger for the AI condition in neurotypical volunteers but not in autistic individuals, who also showed a longer latency for this waveform. Group differences in amplitude of the ERP intention effect only became evident when we compared autistic participants to a subgroup of similarly performing neurotypical participants, suggesting that the atypical ERP waveform in ASD is an effect of group, rather than a marker of low‐task performance. Together, these results suggest that the lower accuracy of the ASD group in the AI task may result from impaired early attentional processing and contextual integration of socially relevant cues. Lay Summary: To understand why autistic people have difficulties in inferring others' intentions, we asked participants to judge the congruence of the endings of comic strips depicting either intentional actions (e.g., fetching a chair to reach for something) or situations solely following physical rules (e.g., an apple falling on someone's head), while their electrical brain activity was recorded. Autistic individuals had more difficulties in inferring intentions than neurotypical controls, which may reflect impaired attention and contextual integration of social cues. [ABSTRACT FROM AUTHOR]

In the context of bridge management, three main types of maintenance actions can be considered. Maintenance actions can be taken preventively before the predefined limit condition is reached, or as a corrective measure in case those limits have been reached. The third possibility corresponds to the so-called "doing nothing" scenario, in which no action is taken on the bridge. To be able to implement preventive maintenance, it is necessary to know the current condition of the bridge, as well as to be able to predict its performance. On the other hand, it is also important to be able to identify potentially threatening events that might occur in the analysis life period. This paper describes an integrated methodology to help bridge managers in defining an efficient maintenance program, considering the specific case of a railway bridge. The novelty of the methodology is focused on updating an existing methodology proposed by COST TU1406, by extending it to railway bridges and also by including the resilience analysis in case of a sudden event occurrence. The analysis considers a multi-hazard future scenario, in which a flood event occurs while corrosion phenomena were already in place. The results show the feasibility of the proposed methodology as a support for the establishment of an efficient maintenance schedule to prevent bridge severe degradation, as well as to establish recovery plans in case of a sudden event. [ABSTRACT FROM AUTHOR]

Considering the emergence of antifungal resistance on Sporothrix brasiliensis, we aimed to assess new benzylidene‐carbonyl compounds against feline‐borne S. brasiliensis isolates. The compounds were designed as bioisosteres from previously reported benzylidene‐ketones generating the p‐coumaric (1), cinnamic (2), p‐methoxycinnamic (3) and caffeic acid (4) analogues. The corresponding compounds were tested against feline isolates of S. brasiliensis with sensitivity (n = 4) and resistance (n = 5) to itraconazole (ITZ), following the M38‐A2 protocol (CLSI, Reference method for broth dilution antifungal susceptibility testing of filamentous fungi M38–A2 Guideline, 2008). Eleven analogues showed activity against all fungal strains with minimum inhibitory concentrations (MIC) ≤1 mg/ml (1a‐d, 2e, 3b, 3e, 4, 4a and 5e) and fungicidal concentrations (MFC) ≤1 mg/ml (1b, 1d, 3e and 4a), whereas 3 was the less active with both MIC and MFC values above 1 mg/ml. Compound 3e (4‐methoxy‐N‐butylcinnamamide) was the most potent (MICrange 0.08–0.16 mg/ml; MFCrange 0.32–0.64 mg/ml) from the set, suggesting a different role of the substituents in ester and amide derivatives. The designed compounds proved to be important prototypes with improved drug‐likeness to achieve compounds with higher activity against ITZ‐resistant S. brasiliensis. [ABSTRACT FROM AUTHOR]

We designed a systematic literature review to identify available evidence on adherence to and persistence with antidiabetic medication in people with type 2 diabetes (T2D). Electronic screening and congress searches identified real‐world noninterventional studies (published between 2010 and October 2020) reporting estimates of adherence to and persistence with antidiabetic medication in adults with T2D, and associations with glycaemic control, microvascular and/or macrovascular complications, hospitalizations and healthcare costs. Ninety‐two relevant studies were identified, the majority of which were retrospective and reported US data. The proportions of patients considered adherent (median [range] 51.2% [9.4%‐84.3%]) or persistent (median [range] 47.7% [16.9%‐94.0%]) varied widely across studies. Multiple studies reported an association between greater adherence/persistence and greater reductions in glycated haemoglobin levels. Better adherence/persistence was associated with fewer microvascular and/or macrovascular outcomes, although there was little consistency across studies in terms of which outcomes were improved. More adherent and more persistent patients were typically less likely to be hospitalized or to have emergency department visits/admissions and spent fewer days in hospital annually than less adherent/persistent patients. Greater adherence and persistence were generally associated with lower hospitalization costs, higher pharmacy costs and lower or budget‐neutral total healthcare costs compared with lower adherence/persistence. In conclusion, better adherence and persistence in people with T2D is associated with lower rates of microvascular and/or macrovascular outcomes and inpatient hospitalization, and lower or budget‐neutral total healthcare expenditure. Education and treatment strategies to address suboptimal adherence and persistence are needed to improve clinical and economic outcomes. [ABSTRACT FROM AUTHOR]

In the last years, organizations and companies in general have found the true potential value of collecting and using data for supporting decision‐making. As a consequence, data are being collected at an unprecedented rate. This poses several challenges, including, for example, regarding the storage and processing of these data. Machine Learning (ML) is also not an exception, in the sense that algorithms must now deal with novel challenges, such as learn from streaming data or deal with concept drift. ML engineers also have a harder task when it comes to selecting the most appropriate model, given the wealth of algorithms and possible configurations that exist nowadays. At the same time, training time is a stronger restriction as the computational complexity of the training model increases. In this paper we propose a framework for dealing with these challenges, based on meta‐learning. Specifically, we tackle two well‐defined problems: automatic algorithm selection and continuous algorithm updates that do not require the retraining of the whole algorithm to adapt to new data. Results show that the proposed framework can contribute to ameliorate the identified issues. [ABSTRACT FROM AUTHOR]

The role of histamine and acetylcholine in cognitive functions suggests that compounds able to increase both histaminergic and cholinergic neurotransmissions in the brain should be considered as promising therapeutic options. For this purpose, dual inhibitors of histamine H3 receptors (H3R) and cholinesterases (ChEs) have been designed and assessed. In this context, this paper reviews the strategies used to obtain dual H3R/ChEs ligands using multitarget design approaches. Hybrid compounds designed by linking tacrine or flavonoid motifs to H3R antagonists were obtained with high affinity for both targets, and compounds designed by merging the H3R antagonist pharmacophore with known anticholinesterase molecules were also reported. These reports strongly suggest that key modifications in the lipophilic region (including a second basic group) seem to be a strategy to reach novel compounds, allied with longer linker groups to a basic region. Some compounds have already demonstrated efficacy in memory models, although the pharmacokinetic and toxicity profile should be considered when designing further compounds. In conclusion, the key features to be considered when designing novel H3R/ChEs inhibitors with improved pharmacological profile were herein summarized. [ABSTRACT FROM AUTHOR]

Oral dysfunctions are common in the elderly but the literature lacks a multidisciplinary approach on the relationship between polypharmacy, saliva flow, xerostomia, taste, and swallowing complaints. This cross‐sectional study included 204 non‐institutionalized elderly (>60 years; 123 women/81 men), free of severe disabilities and non‐alcohol/tobacco consumers, from whom specific pharmacological therapies were evaluated, as well xerostomia (Xerostomia Inventory‐XI) and swallowing complaints (EAT‐10 questionnaire), salivary flow rate and gustatory sensitivity. Statistical analysis included Chi‐square, Mann–Whitney, Two‐way ANCOVA, and linear multiple regression. Polypharmacy (≥5 drugs daily), hyposalivation, and severe taste dysfunction were found in 18, 46, and 10% of the participants, respectively. Polypharmacy was related with xerostomia (p =.041) and swallowing complaints (p <.001; power = 94%), but not with taste dysfunction. Dry mouth complaint and higher risk of swallowing disorders were found in 50 and 12% of the elderly, respectively, and angiotensin‐converting enzyme (ACE) inhibitors users (n = 36) showed higher EAT‐10 scores (p =.038). Regression models showed that stimulated salivary flow rate was dependent on gender and diuretic use, while xerostomia scores were dependent on the number of medications and unstimulated saliva flow (p <.001). In conclusion, the results draw attention to the high frequency of oral and maxillofacial dysfunctions found in non‐institutionalized elderly, especially polypharmacy, xerostomia and swallowing complaints, and the side effects of drugs that can disturb the oral functions, the acceptance of food, and the adherence to oral therapies. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the ideal ratios of digestible essential amino acids (EAAs) for pacu (Piaractus mesopotamicus) juveniles by the amino acid (AA) deletion method. A completely randomized design which consisted of 11 treatments and three replicates each was used. The treatments included a control diet (CD) containing 55% of nonpurified natural ingredients and 45% of purified synthetic amino acids and ingredients, and other ten isonitrogenous and isoenergetic EAA limiting diets (LDs), each being deficient in 44.4 ± 0.02% of the respective EAA. Pacu juveniles with initial average body weight of 6.22 ± 0.09 g were distributed among 33 fiber glass tanks. Fish were fed with semipurified and extruded diets for 113 days two times a day until apparent satiation. The ideal ratio of each dietary EAA was calculated on the basis of the relationship between body N retention and amount of EAA deleted from the respective EAA LD. Based on the AA deletion method, the ideal ratios of digestible EAAs for pacu juveniles, relative to lysine requirement of 100% were estimated as: methionine 14.6%, threonine 35.0%, tryptophan 6.6%, arginine 62.8%, histidine 13.6%, isoleucine 26.3%, leucine 43.7%, phenylalanine 27.2%, and valine 35.8%. [ABSTRACT FROM AUTHOR]

Peritonitis is a major peritoneal dialysis complication. Despite a high cure rate, relapsing and repeat peritonitis is associated with Tenckhoff catheter biofilm and multiple episodes of peritoneal damage. In relapsing peritonitis, prompt catheter removal is mandatory; otherwise, in repeat peritonitis, there is not a clear indication for catheter removal. It is questionable if the approach to removal should be different. There are few recent data on repeat and relapsing peritonitis microbiology and clinical outcomes since most studies are from the past decade. This study evaluates the microbiology, clinical outcomes, and impact of relapsing and repeat peritonitis on technique survival and the impact of catheter removal in development of further peritonitis episodes by the same microorganism. We developed a single-center retrospective study from 1998 to 2019 that compared repeat and relapsing peritonitis with a control group in terms of causative microorganisms, cure rate, catheter removal, and permanent and temporary transfer to hemodialysis. We also compared repeat and relapsing peritonitis clinical outcomes when Tenckhoff catheter was not removed. Comparing to the control group, the repeat/relapsing group had a higher cure rate (80.4% versus 74.5%, p = 0.01) and lower rate of hospitalization (10.9% versus 27.7%, p = 0.01). Technique survival was superior in the repeat/relapsing group (log rank = 4.5, p = 0.03). Gram-positive peritonitis was more common in the repeat/relapsing group especially Streptococci viridans (43.5% versus 21.3%, p = 0.01) and Gram-negatives in the control group (26.6% vs 9.0%, p = 0.02). When the Tenckhoff catheter was not removed after a repeat episode, 58.6% developed a new repeat/relapsing episode versus 60.0% in the relapsing group. Although repeat and relapsing peritonitis have a higher cure rate, it leads to further episodes of peritonitis and consequent morbidity. When Tenckhoff catheter was not removed, the probability of another peritonitis episode by the same microorganism is similar in repeat and relapsing peritonitis. [ABSTRACT FROM AUTHOR]

Boronic acid‐derived salicylidenehydrazone complex (BASHY) dyes with a polymethine backbone were designed to yield efficient red‐emitting and two‐photon absorbing fluorophores that can be used as markers for astrocytes. The dyes are chemically stable in aqueous solution and do not undergo photodecomposition. Their photophysical properties can be electronically fine‐tuned and thereby adapted to potentially different imaging situations and requirements. [ABSTRACT FROM AUTHOR]

The presence of vegetation on the floodplains of compound channels affects the structure of mean flow, increases flow resistance and turbulence intensity, and impacts sediment transport. In prismatic compound channels, the shear stress at the interface between the flows in the main channel and lateral floodplains has a strong influence in the cross sectional velocity distribution and thus conveyance of the channel. Due to mass transfer between subsections, these effects are enhanced in non‐prismatic channels. In the present study, the three‐dimensional turbulent flow structure in a vegetated non‐prismatic convergent compound channel is experimentally investigated. The main purpose is to clarify the explicit influence of the combination of two factors (floodplain vegetation and convergent floodplains) on mean flow and large‐scale turbulence. The experiments were conducted for relative depths (i.e., the ratio between floodplain and main channel flow depths) equal to 0.21 and 0.31 and floodplain convergence angles equal to 7.25° and 11.3°. The results obtained in straight compound channel with vegetated floodplains were used as a reference. The analysis of the Acoustic Doppler Velocimeter measurements shows that due to convergent floodplains, a transverse current is directed from the floodplains to the main channel from both sides, generating two helical secondary currents. Investigations of the vegetation influence on Reynolds stresses shows that there is a significant vertical and lateral spreading of the shear region towards the main channel side slope. As the convergence angle increases, the floodplain flow proportion decreases. In this case, the presence of vegetation in the floodplain leads to a suppression of the momentum exchange between main channel and floodplains causing the discharge distribution between sub‐sections to be significantly different from what would be without floodplain vegetation. [ABSTRACT FROM AUTHOR]

This study aimed to estimate the ideal profile of essential amino acids (EAAs) for Nile tilapia (Oreochromis niloticus) in the finishing growth phase. A total of 264 fish (initial average weight of 625 g) were distributed among randomly arranged 33 fibre tanks of 1000‐L water capacity each, connected to a water recirculation system. The 60‐day experiment consisted of 11 treatments with three replicates each and fish were fed three times a day. The treatments consisted of a control diet (CD), 45% of which was composed of crystalline amino acids along with purified ingredients and the remaining 55% was contributed by the conventional ingredients meeting the nutritional requirements, and other 10 EAA‐deficient test diets (DD) which were deficient from 33%–41% in each evaluated AA. The essential amino acid ratios were calculated from the relationship between body nitrogen retention and the amount of amino acid deleted from the test diet. This study found the following ideal profile of essential amino acids expressed in relation to lysine (100%); arginine (80.73%), phenylalanine (69.73%), histidine (34.15%), isoleucine (51.24%), leucine (66.01%), methionine (41.49%), threonine (88.96%), tryptophan (23.07%) and valine (72.63%). [ABSTRACT FROM AUTHOR]

This 45‐day work aimed to determine the response of juvenile pacu (Piaractus mesopotamicus) to balanced digestible protein (BDP) and to use these responses to determine whether the optimum economic levels of BDP would differ depending on the form in which the fish is sold. Six isoenergetic diets containing 163, 201, 238, 272, 315 and 348 g/kg BDP (dry‐matter basis) were prepared through the serial dilutions of a high‐protein diet with the low‐protein diet. Fish (initial average body weight, 10.82 ± 0.14 g) were fed with respective experimental diets three times a day until apparent satiation. The optimum biological level of BDP was calculated as 326 g/kg (dry‐matter basis) by the quadratic regression model for maximum body weight gain of juvenile pacu. To maximize economic returns (US$/kg) for different end products, the optimum economic levels of BDP were calculated as 311, 317 and 319 g/kg (dry‐matter basis) by an economic model for whole‐body, eviscerated and sliced juvenile pacu respectively. This finding revealed that obtaining maximum biological performance of fish in the case of high feed costs or low prices of the end product in consumer market would substantially reduce the economic returns. [ABSTRACT FROM AUTHOR]

Rationale: Xylella fastidiosa causes citrus variegated chlorosis (CVC) in sweet orange trees. A diagnostic method for detecting CVC before the symptoms appear, which would inform citrus producers in advance about when the plant should be removed from the orchard, is essential for reducing pesticide application costs. Methods: Chemometrics was applied to high‐performance liquid chromatography diode array detector (HPLC‐DAD) data to evaluate the similarities and differences between the chromatographic profiles. A liquid chromatography/atmospheric pressure chemical ionization mass spectrometry selected reaction monitoring (LC/APCI‐MS‐SRM) method was developed to identify the major compounds and to determine their amounts in all samples. Results: We evaluated the effect of this bacterium on the variation in the chemical profile in citrus plants. The organs of C. sinensis grafted on C. limonia were analyzed. Chemometrics was applied to the obtained data, and two major groups were differentiated. Flavonoids were observed in one group (leaves) and coumarins in the second (roots), both at higher concentrations in the plants with CVC symptoms than in those without the symptoms and those in the negative control. The rootstocks also interfered in the metabolism of the scion. Conclusions: The developed LC/APCI‐MS‐SRM method for detecting CVC before the symptoms appear is simple and accurate. It is inexpensive, and many samples can be screened per hour using 1 mg of leaves. Knowledge of the influence of the rootstock on the chemical profile of the graft is limited. This study demonstrates the effect of the rootstock in synthesizing flavonoids and increasing its content in all parts of the graft. [ABSTRACT FROM AUTHOR]

Prolonged skin exposure to ultraviolet radiation (UVR) induces premature aging in both the epidermis and the dermis. Chronic exposure to UVR induces the activation of mitogen‐activated protein kinase (MAPK) signaling pathway, activating c‐Jun, c‐Fos expression, and transcription factor of AP‐1 activating protein. AP‐1 activation results in the positive induction of matrix metalloproteinase (MMP) synthesis, which degrade skin collagen fibers. Polysaccharides from the fruit of Lycium barbarum (LBP fraction) have a range of activities and have been demonstrate to repair the photodamage. In different approaches, laser application aims to recover the aged skin without destroying the epidermis, promoting a modulation, called photobiomodulation (PBM), which leads to protein synthesis and cell proliferation, favoring tissue repair. Here we developed a topical hydrogel formulation from a polysaccharide‐rich fraction of Lycium barbarum fruits (LBP). This formulation was associated with PBM (red laser) to evaluate whether the isolated and combined treatments would reduce the UVR‐mediated photodamage in mice skin. Hairless mice were photoaged for 6 weeks and then treated singly or in combination with LBP and PBM. Histological, immunohistochemistry, and immunofluorescence analyses were used to investigate the levels of c‐Fos, c‐Jun, MMP‐1, −2, and −9, collagen I, III, and FGF2. The combined regimen inhibited UVR‐induced skin thickening, decreased the expression of c‐Fos and c‐Jun, as well as MMP‐1, −2, and −9 and concomitantly increased the levels of collagen I, III, and FGF2. The PBM in combination with LBP treatment is a promising strategy for the repair of photodamaged skin, presenting potential clinical application in skin rejuvenation. [ABSTRACT FROM AUTHOR]

Metalloporphyrin tapes form in a solvent‐free oxidative chemical vapor deposition process on glass substrates. The metal center (M = NiII, CuII, ZnII, CoII, PdII, FeIIICl, 2H) in the 5,15‐disubstituted porphyrin monomer affects the initial C–C coupling step and consequently the formation of triply or doubly linked porphyrin tapes as well as the interchain interaction in the tape as shown by optical spectroscopy, high resolution mass spectrometry and X‐ray photoelectron spectroscopy. Optical spectroscopy and conductive atomic force microscopy reveal that these factors influence the near‐infrared absorbance and the electrical conductivity of the films. Consequently, the metal ion of the metalloporphyrin allows tuning of the macroscopic properties of the thin films composed of metalloporphyrin tapes. [ABSTRACT FROM AUTHOR]

Radiocystis fernandoi, a microcystin (MC) producer, has been common in cyanobacterial blooms in tropical regions. Microcystin is a hepatotoxin that causes tissue damage and even death in animals, including humans; its detoxification process may involve biotransformation and activation of the antioxidant defense system. We evaluated the detoxification pathway, examined the antioxidant defense system responses, and determined the alterations and the organ histopathological indexes in the liver of the tropical fish Hoplias malabaricus after acute and subchronic intraperitoneal exposure to microcystin. The crude microcystin extract of R. fernandoi had predominantly MC‐RR and MC‐YR. The detoxification process was activated by increasing ethoxyresorufin‐O‐deethylase activity, whereas glutathione S‐transferase was inhibited. The activity of the antioxidant defense enzymes superoxide dismutase (SOD) and glutathione peroxidase decreased after acute exposure; the SOD–catalase system and the glutathione level increased after subchronic exposure. The carbonyl protein level, lipid peroxidation (LPO), and DNA damage were unchanged after acute exposure, whereas protein carbonyl was unchanged, LPO decreased, and DNA damage increased after subchronic exposure. Histopathological alteration indexes differed between acute and subchronic exposure, but the histopathological organ indexes indicate liver dysfunction in both exposure periods. We conclude that MC‐RR and MC‐YR induce different liver responses depending on the time of exposure, and the antioxidant defense responses after subchronic exposure may help to partially restore the liver function. Environ Toxicol Chem 2020;39:1041–1051. © 2020 SETAC [ABSTRACT FROM AUTHOR]

In the present study, juvenile (live body weight, 54.3 ± 8.2 g), preadult (live body weight, 822.5 ± 33.9 g), and adult (live body weight, 1,562.8 ± 41.8 g) pacu, Piaractus mesopotamicus, were used to estimate their dietary essential amino acid (EAA) requirements using the whole‐body amino acid (AA) pattern. The results showed that whole‐body moisture, crude protein, total lipid, and ash contents expressed on a wet weight basis (%) were significantly different among the studied growth phases. No significant differences were observed in the dietary EAA requirements estimated for the three growth phases of pacu. These dietary EAA requirements were found to be different than those previously estimated for the same fish through its muscle AA pattern. Based on whole‐body EAA to total EAA ratios {A/E ratios; [(each EAA/total EAA) × 1,000]}, EAA requirements were estimated to be histidine (0.42%), arginine (1.36%), threonine (0.82%), valine (0.90%), methionine (0.45%), isoleucine (0.83%), leucine (1.29%), phenylalanine (0.74%), lysine (1.64%), and tryptophan (0.14%) for pacu. These estimated requirements may serve as a reference line in the formulation of practical and experimental diets until dose–response‐based optimum EAA requirements are available for pacu. [ABSTRACT FROM AUTHOR]

Objective: Defects/bubbles can occur during the manufacture of bis‐acryl resin provisional restorations, requiring repair or new prosthesis. This study evaluated the color stability of bis‐acryl resin specimens repaired, aging, and immersioned in beverages. Material and methods: Eighty disks were made of bis‐acryl resin. Twenty disks were not repaired (BCR), 20 disks were repaired with the same bis‐acryl resin (BCR‐BCR), 20 disks were repaired with flowable resin (BCR‐FR), and 20 disks received an adhesive layer prior to flowable resin repair (BCR‐AFR). Coordinates L*a*b* were obtained. Ten disks from each group were thermocycled (5000 cycles) and the others were immersed in coffee with sugar (n = 5) and cola‐based soft drinks (n = 5) for 7 days. Color, lightness, chroma, and hue differences were calculated by the CIEDE2000 formula, analyzed by two‐way analysis of variance. Multiple comparisons were made with the Tukey's HSD test (α =.05). Results: BCR‐FR group presented the highest color differences (5.6) between groups repaired (P < .001). BCR‐BCR group showed the smallest color differences (0.9) after aging (P = .003), but the greatest variation between T0 and T1 (about 1 ΔE). BCR‐ARF immersed in coffee showed the greatest color differences (20.6) (P < .001). Conclusions: Aging and immersion altered the colorimetric behavior of repairs, especially after the use of coffee. Clinical implications: Repairs are indicated when defects and bubbles are present in the surface of the bis‐acryl resin provisional restorations after its manufacture. However, they may present noticeable color changes, especially when the use of coffee is frequent. [ABSTRACT FROM AUTHOR]

Experiments were conducted to estimate daily N maintenance requirements (NMRs) and the genetic potential for daily N retention (NRmaxT) of pullets in growth phase. Three nitrogen balance trials were conducted, and a total of 48 Hy‐line W‐36 pullets were used in each trial in age periods (starter: 14–28, grower: 56–70 and developer: 98–112 days). The treatments consisted of six graded levels of nitrogen in the diets (L1 = 8, L2 = 16, L3 = 24, L4 = 32, L5 = 40 and L6 = 48 g N/kg of feed), formulated using the dilution technique. The regression analyses between nitrogen intake and nitrogen excretion were performed to fit the exponential function and to determine the NMR. The daily NMRs that were estimated at 294, 331 and 355 mg/BWkg0.67 for the initial, grower and developer periods, respectively, were applied for further calculation of NRmaxT as the threshold value of the function between N intake and daily N balance. The NRmaxT was estimated by a statistical procedure following several iteration steps by the Levenberg–Marquardt algorithm until the sum of the squares of the residual was minimized. The NRmaxT was estimated at 3,200, 2,633 and 1,826 mg/BWkg0.67 for starter, grower and developer periods respectively. The determined model parameters were the precondition for modelling of the amino acid requirement based on an exponential N‐utilization model and depended on performance and dietary amino acid efficiency. This procedure will be further developed and applied in the subsequent study. [ABSTRACT FROM AUTHOR]

Persistent inflammation in end-stage renal disease (ESRD) patients is known to underlie the progression of chronic kidney disease and to be associated with multiple risk factors including malnutrition, atherosclerosis, and cardiovascular disease (CVD). The acute-phase protein pentraxin 3 (PTX3) has a proven potential as a local inflammatory biomarker, but its clinical utility in ESRD remains unclear. Circulating levels of PTX3 and classical inflammatory mediators, including the clinical prototypical C-reactive protein (CRP), were assessed in 246 ESRD patients on dialysis and analysed in relation to the lipid profile, adipokine levels, and nutritional, cardiac, and renal fibrosis markers. Occurrence of deaths was recorded for the following year. Contrarily to the classical inflammatory markers, PTX3 levels were negatively correlated with nutritional markers and associated with a less atherogenic lipid profile. Levels of the cardiac and renal fibrosis markers and of the oxidized LDL/LDL-C ratio were found to be independent determinants of PTX3 concentration. When comparing inflammatory mediators, the increase in the PTX3 levels was the only predictor of all-cause mortality in dialysis patients in a survival model adjusted to all markers under study, other than the inflammatory ones, besides common confounding factors in dialysis. Data support the clinical applicability of PTX3 as a broader inflammatory biomarker than the classical ones, presenting a close association with inflammation, malnutrition, CVD, and renal fibrosis and a great potential to predict all-cause mortality in dialysis patients. The pleiotropic character of PTX3 may be of clinical relevance, and it could be targeted to ameliorate the high morbidity and mortality associated with ESRD. [ABSTRACT FROM AUTHOR]

Histamine is a transmitter that activates the four receptors H1R to H4R. The H3R is found in the nervous system as an autoreceptor and heteroreceptor, and controls the release of neurotransmitters, making it a potential drug target for neuropsychiatric conditions. We have previously reported that the 1‐(2,3‐dihydro‐1‐benzofuran‐2‐yl)methylpiperazines (LINS01 compounds) have the selectivity for the H3R over the H4R. Here, we describe their pharmacological properties at the human H1R and H2R in parallel with the H3R, thus providing a full analysis of these compounds as histamine receptor ligands through reporter gene assays. Eight of the nine LINS01 compounds inhibited H3R‐induced histamine responses, but no inhibition of H2R‐induced responses was seen. Three compounds were weakly able to inhibit H1R‐induced responses. No agonist responses were seen to any of the compounds at any receptor. SAR analysis shows that the N‐methyl group improves H3R affinity while the N‐phenyl group is detrimental. The methoxy derivative, LINS01009, had the highest affinity. LINS01 compounds have been evaluated as H3R/H4R antagonists, showing very promising anti‐inflammatory activity in murine asthma model. The paper examines their pharmacological properties at the human H1R, H2R, and H3R in parallel, thus completing the pharmacological analysis across all the histamine receptors. [ABSTRACT FROM AUTHOR]

Abstract: This paper analyzes the concept of nature‐based solutions as instruments to turn anthromes more nature compatible, efficient, causing less degradation, and developing new biodiversity hotspots. It is mainly focused on solutions using living organisms (in particular plants and microorganisms) to perform functions such as those of soil‐ and water‐bioengineering interventions in order to ensure the safety of human infrastructures and constructions in contexts of conflict between natural processes and human needs. Further, it handles the problematic of reintroducing natural processes and functions in the built environment (urban, industrial, infrastructures, etc.) in order to recover, recreate, or reinvent nature in humanized landscapes and developing a more creative relation between humans and natural elements, processes, and functions. It presents, furthermore, the contribution of natural solutions to a wide variety of decontamination processes and prevention and recovery of degraded land and natural resources. Finally, we discuss the way these solutions can be implemented and the cultural, organizational, administrative and governance, paradigmatic, and practice changes it implies. Examples are given on the different issues presented as well on the possible implementation solutions. [ABSTRACT FROM AUTHOR]

Alkylphenols isolated from Piper malacophyllum (Piperaceae), gibbilimbols A and B, showed interesting activity against the parasites Trypanosoma cruzi and Leishmania infantum. In continuation to our previous work, a new natural product from the essential oil of the leaves of P. malacophyllum was isolated, the 5-[(3 E)-oct-3-en-1-il]-1,3-benzodioxole, and also a new set of five compounds was prepared. The antiparasitic activity of the natural product was evaluated in vitro against these parasites, indicating potential against the promastigote/trypomastigote/amastigote forms ( IC50 32-83 μ m) of the parasites and low toxicity ( CC50 > 200 μ m) to mammalian cells. The results obtained to the synthetic compounds indicated that the new derivatives maintained the promising antiparasitic activity, but the cytotoxicity was considerably lowered. The amine derivative LINS03011 displayed the most potent IC50 values (13.3 and 16.7 μ m) against amastigotes of T. cruzi and L. infantum, respectively, indicating comparable activity to the phenolic prototype LINS03003, with threefold decreased ( CC50 73.5 μ m) cytotoxicity, leading the selectivity index ( SI) towards the parasites up to 24.5. In counterpart, LINS03011 has not shown membrane disruptor activity in SYTOX Green model. In summary, this new set showed the hydroxyl is not essential for the antiparasitic activity, and its substitution could decrease the toxicity to mammalian cells. [ABSTRACT FROM AUTHOR]

Resistance development in pest insects has guided the advance of cleaner and more effective strategies for pest control. An interesting and promising strategy is the manipulation of insects via their gut microbiota., To evaluate the feasibility of this strategy, Diabrotica speciosa, a highly polyphagous pest insect from South America that causes substantial damage to several important crops, was reared under controlled conditions. Aerobic culturable bacteria were isolated from the gut of D. speciosa and identified using proteomic fingerprints obtained by matrix-assisted laser desorption ionization coupled to time-of-flight mass spectrometry ( MALDI-TOF MS), as well as by genomic methods via partial sequencing of the 16S rRNA gene., Seventy-three strains belonging to 17 genera and up to 29 different species were isolated. γ-Proteobacteria of the orders Pseudomonadales and Enterobacteriales were the predominant. A core gut microbiome for the genus Diabrotica could be inferred when microbiotas from different species from the genus were compared. Molecular and spectrometric techniques indicated complete agreement of genera classification, although cluster analysis revealed distinct taxonomic grouping patterns., MALDI-TOF MS provided reliable identification of culturable gut bacteria, demonstrating similar efficacy, with cheaper and faster results relative to partial 16S rRNA gene sequencing, and also showed an interesting and unexpected phyloproteomic correlation. [ABSTRACT FROM AUTHOR]

The histamine receptors (HRs) are members of G-protein-coupled receptor superfamily and traditional targets of huge therapeutic interests. Recently, H3R and H4R have been explored as targets for drug discovery, including in the search for dual-acting H3R/H4R ligands. The H4R, the most recent histamine receptor, is a promising target for novel anti-inflammatory agents in several conditions such as asthma and other chronic inflammatory diseases. Due to similarity with previously reported ligands of HRs, a set of 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazines were synthesized and evaluated in competitive binding assays as H3R/H4R ligands herein. The results showed the compounds presented affinity ( Ki) for H3R/H4R in micromolar range, and they are more selective to H3R. All the compounds showed no important cytotoxicity to mammalian cells. The phenyl-substituted compound LINS01005 has shown the higher affinity of the set for H4R, but no considerable selectivity toward this receptor over H3R. LINS01005 showed interesting anti-inflammatory activity in murine asthma model, reducing the eosinophil counts in bronchoalveolar lavage fluid, as well as the COX-2 expression. The presented compounds are valuable prototypes for further improvements to achieve better anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

The essential oil was obtained by hydrodistillation and the identification and quantification of components were achieved with the use of GC-MS analysis. The antioxidant activity was evaluated by the method of sequestration of DPPH. Essential oils were used for study the cytotoxic front larvae of Artemia salina. In the evaluation of the antimicrobial activity of essential oils, we employed the disk-diffusion method. The potential larvicide in mosquito larvae of the third stage of development of Aedes aegypti to different concentrations of essential oils was evaluated. The major compounds found in the essential oils of M. piperita were linalool (51.8%) and epoxyocimene (19.3%). The percentage of antioxidant activity was 79.9 ± 1.6%. The essential oil showed LC50 = 414.6 μg/mL front of A. saline and is considered highly toxic. It shows sensitivity and halos significant inhibition against E. coli. The essential possessed partial larvicidal efficiency against A. aegypti. [ABSTRACT FROM AUTHOR]

This study evaluated the effects of the addition of microalgae ( Ankistrodesmus gracilis and Haematococcus pluvialis) to the fish diet in improving the growth and optimal pigmentation (red carotenoid) of Hyphessobrycon eques. The basal mixed diets consisted of a formulated diet, supplemented with dried microalgae biomass of A. gracilis (1.5 g kg−1) and H. pluvialis (1.5 g kg−1). The live food diets contained zooplankton was cultured in open ponds, associated with microalgae. All the microalgae were cultured in the laboratory. No mortality was observed with any experimental diets. Fish performance results showed significant differences ( P < 0.05) between the basal diet ( BD) and the live food diet. The higher weight and total length were observed with mixed diets ( BD + H. pluvialis and BD + A. gracilis). The mixed diets promoted more intense values of chroma (Cab*), lightness (L*) and redness (a*) to H. eques. Diaphanosoma birgei (Cladocera) represented more than 32% of zooplankton ingested by ornamental fish in live food (zooplankton and zooplankton + microalgae), and Argyrodiaptomus furcatus (Copepoda) was the species most ingested by H. eques in live food dietary treatment zooplankton. The feeding behaviour observed in the laboratory as well as the food preferences of H. eques was dependent on the zooplankton composition present in the used open ponds. This study showed that diets with microalgae and zooplankton were able to enhance the pigmentation of H. eques, being a good tool to benefit the culture management of this species. [ABSTRACT FROM AUTHOR]

Hepcidin is the major central regulator of iron metabolism, controlling iron absorption and mobilization. Considering its interaction with several factors that are altered in chronic kidney disease (CKD), particularly in hyporesponsive CKD patients under therapy with high recombinant human erythropoietin (rHuEPO) doses, it was aimed to study the impact of increasing rHuEPO doses on the regulation of iron-hepcidin metabolism. The blood, cellular, and tissue studies, using the remnant kidney rat model of CKD induced by 5/6 nephrectomy, under rHuEPO (100, 200, 400, and 600 IU/Kg body weight [BW]/week) treatment during 3 weeks were performed. It was found that the rHuEPO stimulus triggered a first wave to achieve correction of anemia, by inhibiting hepcidin synthesis, favoring erythropoiesis and iron absorption; this continuous stimulus enhanced iron absorption leading to iron overload, as showed by the hepatic iron deposits found in rats treated with higher rHuEPO dose that seems to trigger the upregulation of hepcidin synthesis through the activation of the BMP6/SMAD pathway. The data suggested that liver iron overload was an important stimuli for hepcidin synthesis, stronger than the inhibitory effect of high rHuEPO doses; moreover, the findings raised the hypothesis that when high inflammation (triggering hepcidin expression) was associated with increased iron stores in hemodialysis patients, hepcidin expression was also upregulated via BMP6, enhancing hepcidin synthesis, leading, therefore, to worsening of anemia and, eventually, to a hyporesponse/resistance to rHuEPO therapy. © 2016 BioFactors, 42(3):296-306, 2016 [ABSTRACT FROM AUTHOR]

Clinical studies showed that high doses of recombinant human erythropoietin ( rHuEPO) used to correct anaemia in chronic kidney disease ( CKD) hyporesponsive patients may lead to deleterious effects. The aim of this study was to analyze the effects of rHuEPO in doses usually used to correct CKD-anaemia (100, 200 IU/kg body weight ( BW) per week) and in higher doses used in the treatment of hyporesponsive patients (400, 600 IU/kg BW per week), focusing on renal damage, hypoxia, inflammation and fibrosis. Male Wistar rats with chronic renal failure ( CRF) induced by 5/6 nephrectomy were treated with rHuEPO or with vehicle, over a 3-week period. Haematological, biochemical and renal function analyses were performed. Kidney and liver mRNA levels were evaluated by quantitative real-time polymerase chain reaction ( qPCR) and protein expression by Western blot and immunohistochemistry. Kidney histopathological evaluations were also performed. The CRF group developed anaemia, hypertension and a high score of renal histopathologic lesions. Correction of anaemia was achieved with all rHuEPO doses, with improvement in hypertension, renal function and renal lesions. In addition, the higher rHuEPO doses also improved inflammation. Blood pressure was reduced in all rHuEPO-treated groups, compared to the CRF group, but increased in a dose-dependent manner. The current study showed that rHuEPO treatment corrected anaemia and improved urinary albumin excretion, particularly at lower doses. In addition, it is suggested that a short-term treatment with high doses, used to overcome an episode of hyporesponsiveness to rHuEPO therapy, can present benefits by reducing inflammation, without worsening of renal lesions; however, the pro-hypertensive effect should be considered, and carefully managed to avoid a negative cardiorenal impact. [ABSTRACT FROM AUTHOR]

Phytoremediation is an attractive alternative to conventional treatments of soil due to advantages such as low cost, large application areas, and the possibility of in situ treatment. This study presents the assessment of phytoremediation processes conducted under controlled experimental conditions to evaluate the ability of Ricinus communis L., tropical plant species, to promote the degradation of 15 persistent organic pollutants (POPs), in a 66-day period. The contaminants tested were hexachlorocyclohexane (HCH), DDT, heptachlor, aldrin, and others. Measurements made in rhizosphere soil indicate that the roots of the studied species reduce the concentration of pesticides. Results obtained during this study indicated that the higher the hydrophobicity of the organic compound and its molecular interaction with soil or root matrix the greater its tendency to concentrate in root tissues and the research showed the following trend: HCHs < diclofop-methyl < chlorpyrifos < methoxychlor < heptachlor epoxide < endrin < o,p'-DDE < heptachlor < dieldrin < aldrin < o,p'-DDT < p,p'-DDT by increasing order of log K ow values. The experimental results confirm the importance of vegetation in removing pollutants, obtaining remediation from 25% to 70%, and demonstrated that Ricinus communis L. can be used for the phytoremediation of such compounds. [ABSTRACT FROM AUTHOR]

Histamine is a chemical transmitter found practically in whole organism and exerts its effects through the interaction with H1 to H4 histaminergic receptors. Specifically, H4 receptors are found mainly in immune cells and blood-forming tissues, thus are involved in inflammatory and immune processes, as well as some actions in central nervous system. Therefore, H4 receptor ligands can have applications in the treatment of chronic inflammatory and immune diseases and may be novel therapeutic option in these conditions. Several H4 receptor ligands have been described from early 2000's until nowadays, being imidazole, indolecarboxamide, 2-aminopyrimidine, quinazoline, and quinoxaline scaffolds the most explored and discussed in this review. Moreover, several studies of molecular modeling using homology models of H4 receptor and QSAR data of the ligands are summarized. The increasing and promising therapeutic applications are leading these compounds to clinical trials, which probably will be part of the next generation of blockbuster drugs. [ABSTRACT FROM AUTHOR]

Polyvinyl alcohol hydrogel (PVA) is a synthetic polymer with an increasing application in the biomedical field that can potentially be used for vascular grafting. However, the tissue and blood-material interactions of such gels and membranes are unknown in detail. The objectives of this study were to: (a) assess the biocompatibility and (b) hemocompatibility of PVA-based membranes in order to get some insight into its potential use as a vascular graft. PVA was evaluated isolated or in copolymerization with dextran (DX), a biopolymer with known effects in blood coagulation homeostasis. The effects of the mesenchymal stem cells (MSCs) isolated from the umbilical cord Wharton's jelly in the improvement of PVA biocompatibility and in the vascular regeneration were also assessed. The biocompatibility of PVA was evaluated by the implantation of membranes in subcutaneous tissue using an animal model (sheep). Histological samples were assessed and the biological response parameters such as polymorphonuclear neutrophilic leucocytes and macrophage scoring evaluated in the implant/tissue interface by International Standards Office (ISO) Standard 10993-6 (annex E). According to the scoring system based on those parameters, a total value was obtained for each animal and for each experimental group. The in vitro hemocompatibility studies included the classic hemolysis assay and both human and sheep bloods were used. Relatively to biocompatibility results, PVA was slightly irritant to the surrounding tissues; PVA-DX or PVA plus MSCs groups presented the lowest score according to ISO Standard 10993-6. Also, PVA was considered a nonhemolytic biomaterial, presenting the lowest values for hemolysis when associated to DX. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 4262-4275, 2014. [ABSTRACT FROM AUTHOR]