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Astyanax bimaculatus are small characids known as piabas or lambaris that form a complex encompassing 18 species, including cryptic species. The present study aimed to use DNA barcode to analyze populations of A. bimaculatus found in Maranhão hydrographic basins, comparing molecular diversity indices between populations from the other Brazilian basins. The results revealed the formation of 32 haplotypes (h = 0.9289; π = 0.0523). Seven haplogroups were formed with intrapopulation genetic distance ranging from 0 to 2%. The Maranhão populations of the Western Northeast Atlantic Region basins separated from the other analyzed basins, corroborating with the groups generated in BAPS and with the Bayesian Inference tree. The occurrence of exclusive OTUs for the Maranhão populations of the Western Northeast Atlantic Region was confirmed through delimitation models. Thus, the data from this study provide information on the genetic diversity of the A. bimaculatus complex with the detection of a different lineage for the State of Maranhão, contributing to the understanding of the group's systematics.

Purpose: To describe the practices of pediatric physical therapists (PTs) working with children and adolescents with cerebral palsy (CP) in Brazil., Methods: PTs working with children and adolescents with CP were invited to participate via social media and email campaigns to complete an online survey containing 46 questions., Results: In total, 373 PTs participated. Most PTs reported searching in scientific databases (96.8%) and on social media (71%). The main barrier to information reported was limited access to full-text articles (44%). Among the PTs, 58.4% and 84% reported using the International Classification of Functioning, Disability and Health (ICF) and family centered practice models, respectively. Regarding tools and interventions, there was little focus on the domains of contextual factors and participation., Conclusions: This survey points to some important advances. However, strategies are still needed to promote knowledge translation and evidence-based practices among pediatric PTs in Brazil., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Academy of Pediatric Physical Therapy of the American Physical Therapy Association.)

Background: Leishmania tarentolae is a non-pathogenic species found in lizards representing an important model for Leishmania biology. However, several aspects of this Sauroleishmania remain unknown to explain its low level of virulence., Objectives: We reported several aspects of L. tarentolae biology including glycoconjugates, proteolytic activities and metabolome composition in comparison to pathogenic species (Leishmania amazonensis, Leishmania braziliensis, Leishmania infantum and Leishmania major)., Methods: Parasites were cultured for extraction and purification of lipophosphoglycan (LPG), immunofluorescence probing with anti-gp63 and resistance against complement. Parasite extracts were also tested for proteases activity and metabolome composition., Findings: Leishmania tarentolae does not express LPG on its surface. It expresses gp63 at lower levels compared to pathogenic species and, is highly sensitive to complement-mediated lysis. This species also lacks intracellular/extracellular activities of proteolytic enzymes. It has metabolic differences with pathogenic species, exhibiting a lower abundance of metabolites including ABC transporters, biosynthesis of unsaturated fatty acids and steroids, TCA cycle, glycine/serine/threonine metabolism, glyoxylate/dicarboxylate metabolism and pentose-phosphate pathways., Main Conclusions: The non-pathogenic phenotype of L. tarentolae is associated with alterations in several biochemical and molecular features. This reinforces the need of comparative studies between pathogenic and non-pathogenic species to elucidate the molecular mechanisms of virulence during host-parasite interactions.

Melasma is an acquired chronic condition characterized by hyperchromic patches in photo-exposed areas. The search for new compounds for the treatment of melasma without side effects is constant. In this context, the aim of this study was to investigate the in vitro cytotoxic and antimelanogenic effects of the trace elements Zinc (Zn) and Selenium (Se). In this study, we evaluated the effects of 30 µM hydroquinone, this concentration did not alter mitochondrial function (MTT assay), but increased the percentage of necrotic cells and levels of reactive species. Furthermore, it showed no influence on tyrosinase activity and melanin content. Unlike hydroquinone, exposure for 48 h to 100 µM Zn and 1 and 5 µM Se had no significant influence on the analysis of reactive species, as well as on the percentage of necrotic cells. Still, specifically in relation to 100 µM Zn, it decreased the melanin content. Given the above, the trace elements Zn and Se did not show toxicity at the concentrations tested and Zn showed a promising effect, however, the mechanism needs to be better explored in order to contribute to new and updated research in the fight against melasma with a perspective of therapeutic use., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The Baixada Maranhense Environmental Protection Area of the Brazilian state of Maranhão encompasses a biologically rich region that includes the basins of four principal rivers, the Mearim, Pericumã, Pindaré, and Turiaçu, which form a complex of wetlands. The present study provides a comprehensive inventory of the fish fauna of the rivers that drain the Baixada Maranhense based on the identification of voucher specimens that were deposited in a scientific collection. Expeditions were conducted between 2014 and 2020. The inventory identified a total of 100 fish species representing 79 genera, 34 families, and 11 orders, which are found in both freshwater and estuarine environments. Six (Potamotrygon orbignyi, Leporinus piau, Moenkhausia loweae, Serrasalmus spilopleura, Pachypops fourcroi and Peckoltia greedoi) of the 100 taxa identified here are considered to be new records for one or more of the basins surveyed during this study, based on the existing data, while four - Colossoma macropomum, Megaleporinus macrocephalus, Cichla sp. and Cichla kelberi - are not native. The most speciose orders were the Siluriformes and Characiformes, while the most diverse families were the Loricariidae, Characidae, Auchenipteridae, Cichlidae, and Serrasalmidae. These data are consistent with the findings of most of the previous studies of freshwater ecosystems in the Neotropical region, in particular those of the rivers of Maranhão. The results of the present study represent an important advance in the understanding of the diversity of the fish fauna of the Mearim, Pericumã, Pindaré, and Turiaçu rivers, which are still poorly studied, and have likely had their diversity underestimated up to now.

With increased interest in cultivation, the study of white-fleshed pitahaya (Selenicereus undatus (Haw.) D.R. Hunt, Cactaceae family) seedling production is of fundamental importance in the search for novel techniques to increase cultivation and guarantee homogeneous and productive orchards. The present study investigated the influence of various gibberellic acid (GA3) concentrations and fruit maturation stages on seed germination and vigor of white-fleshed pitahaya seedlings, considering the physiological quality of seedlings produced to support genetic breeding and conservation programs of the species. White-fleshed pitahaya seeds at two maturation stages (physiologically ripe and maintained at 10 °C in Biochemical Oxygen Demand incubators for three months) were treated with varying GA3 concentrations of 0, 50, 100, and 500 mg/L. We observed the influence of fruit storage on seedling germination, emergence, and growth as a function of GA3 concentration. According to the results, seeds extracted from ripe white-fleshed pitahaya fruits grown under the conditions tested here required GA3 application to increase seedling emergence and vigor, with optimal doses in the 150-300-mg/L range. In the case of pitahaya fruits intended for storage for future seed removal and maintained under the same sowing conditions, the application of higher doses of GA3 was necessary when compared to the previous condition, with a minimum dose of 500 mg/L GA3. The present study shows that the maturation stage of white-fleshed pitahaya fruits intended for seed removal influences the quality of seedlings; therefore, the use of seeds extracted from ripe pitahaya fruits without fermentation is more appropriate for the purpose.

In the Microvascular Outcomes after Metabolic Surgery randomised clinical trial (MOMS RCT, NCT01821508), combined metabolic surgery (gastric bypass) plus medical therapy (CSM) was superior to medical therapy alone (MTA) as a means of achieving albuminuria remission at 2-year follow-up in patients with obesity and early diabetic kidney disease (DKD). In the present study, we assessed the urinary 1 H-NMR metabolome in a subgroup of patients from both arms of the MOMS RCT at baseline and 6-month follow-up. Whilst CSM and MTA both reduced the urinary excretion of sugars, CSM generated a distinctive urinary metabolomic profile characterised by increases in host-microbial co-metabolites (N-phenylacetylglycine, trimethylamine N-oxide, and 4-aminobutyrate (GABA)) and amino acids (arginine and glutamine). Furthermore, reductions in aromatic amino acids (phenylalanine and tyrosine), as well as branched-chain amino acids (BCAAs) and related catabolites (valine, leucine, 3-hydroxyisobutyrate, 3-hydroxyisovalerate, and 3-methyl-2-oxovalerate), were observed following CSM but not MTA. Improvements in BMI did not correlate with improvements in metabolic and renal indices following CSM. Conversely, urinary metabolites changed by CSM at 6 months were moderately to strongly correlated with improvements in blood pressure, glycaemia, triglycerides, and albuminuria up to 24 months following treatment initiation, highlighting the potential involvement of these shifts in the urinary metabolomic profile in the metabolic and renoprotective effects of CSM., Competing Interests: Conflicts of Interest: C.W.l.R. discloses personal fees outside of the submitted work from Novo Nordisk, GI Dynamics, Eli Lilly, Johnson & Johnson Brasil, Keyron, Herbalife, Sanofi, Aventis, AstraZeneca, Janssen, Bristol-Myers Squibb and Boehringer- Ingelheim. The remaining authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Chronic Chagas cardiomyopathy (CCC) is one of the deadliest cardiomyopathies known and the most severe manifestation of Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi . Idiopathic dilated cardiomyopathies (IDC) are a diverse group of inflammatory heart diseases that affect the myocardium and are clinically similar to CCC, often causing heart failure and death. While T-cells are critical for mediating cardiac pathology in CCC and IDC, the mechanisms underlying T-cell function in these cardiomyopathies are not well-defined. In this study, we sought to investigate the phenotypic and functional characteristics of T-cell subpopulations in CCC and IDC, aiming to clarify whether the inflammatory response is similar or distinct in these cardiomyopathies. We evaluated the expression of systemic cytokines, determined the sources of the different cytokines, the expression of their receptors, of cytotoxic molecules, and of molecules associated with recruitment to the heart by circulating CD4 + , CD8 + , and CD4-CD8- T-cells from CCC and IDC patients, using multiparameter flow cytometry combined with conventional and unsupervised machine-learning strategies. We also used an in silico approach to identify the expression of genes that code for key molecules related to T-cell function in hearts of patient with CCC and IDC. Our data demonstrated that CCC patients displayed a more robust systemic inflammatory cytokine production as compared to IDC. While CD8 + T-cells were highly activated in CCC as compared to IDC, CD4 + T-cells were more activated in IDC. In addition to differential expression of functional molecules, these cells also displayed distinct expression of molecules associated with recruitment to the heart. In silico analysis of gene transcripts in the cardiac tissue demonstrated a significant correlation between CD8 and inflammatory, cytotoxic and cardiotropic molecules in CCC transcripts, while no correlation with CD4 was observed. A positive correlation was observed between CD4 and perforin transcripts in hearts from IDC but not CCC, as compared to normal tissue. These data show a clearly distinct systemic and local cellular response in CCC and IDC, despite their similar cardiac impairment, which may contribute to identifying specific immunotherapeutic targets in these diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer JS declared a shared affiliation with one of the authors AT, to the handling editor at time of review., (Copyright © 2022 Neves, Koh, Souza-Silva, Passos, Silva, Velikkakam, Villani, Coelho, Brodskyn, Teixeira, Gollob, Nunes and Dutra.)

Aim: Despite advances in therapies, the prognosis of patients with advanced gastric cancer (GC) remains poor. Several studies have demonstrated the expression of estrogen receptor alpha (ERa); however, its significance in GC remains controversial. The present study aims to report a case series of GC with ERa-positive expression and describe their clinicopathological characteristics and prognosis., Methods: We retrospectively evaluated patients with GC who underwent gastrectomy with curative intent between 2009 and 2019. ERa expression was assessed by immunohistochemistry through tissue microarray construction. Patients with ERa-negative gastric adenocarcinoma served as a comparison group., Results: During the selected period, 6 (1.8%) ERa-positive GC were identified among the 345 GC patients analyzed. All ERa-positive patients were men, aged 34-78 years, and had Lauren diffuse GC and pN+ status. Compared with ERa-negative patients, ERa-positive patients had larger tumor size (p=0.031), total gastrectomy (p=0.012), diffuse/mixed Lauren type (p=0.012), presence of perineural invasion (p=0.030), and lymph node metastasis (p=0.215). The final stage was IIA in one case, IIIA in three cases, and IIIB in two cases. Among the six ERa-positive patients, three had disease recurrence (peritoneal) and died. There was no significant difference in survival between ERa-positive and ERa-negative groups., Conclusions: ERa expression is less common in GC, is associated with diffuse histology and presence of lymph node metastasis, and may be a marker related to tumor progression and worse prognosis. Also, a high rate of peritoneal recurrence was observed in ERa-positive patients.

Background: Social participation has been incorporated by occupational therapists in Brazil, and worldwide, as a professional concept to guide practice. The concept has been studied, defined, and constructed from multiple fields of knowledge and can be defined as the social and political involvement of people in social groups and /or public and community spaces. There are different understandings of social participation in occupational therapy and the objective of this study was to explore how Brazilian occupational therapists define social participation in their fields of knowledge., Method: Through application of the Delphi technique, Brazilian occupational therapy academics and professionals who have worked in the state of São Paulo, Brazil, collaboratively responded to an online questionnaire. In the consultation phase, occupational therapists wrote their conceptions about social participation and, in the consensus phase, expressed their opinions and judgements, in order to, in a collective construction, establish a consensus on the definition of social participation., Results: In the first round of the consensus phase, 38 academics and 27 professionals participated and in the second round, 20 and 14, respectively. Results were analysed quantitatively, through the establishment of degrees of agreement for conceptions arranged in statements. Then, six categories of analysis were built, which identified the multiple ways of understanding social participation: social participation and social interactions, social participation and freedom of movement, social participation as an experience in public and political life, social participation and human activities, social participation and the process of social inclusion, and social participation in the fields of knowledge and practice in occupational therapy., Conclusion: There are theoretical-conceptual differences in the understandings and uses of social participation in occupational therapy that delimit specificity and design the identities of the profession in society. The need to discuss knowledge production, accumulation, and dissemination and practices is debated., (© 2021 Occupational Therapy Australia.)

Magnetic nanocomposites were synthesized for the targeted delivery of hydrophilic bioactives through guidance generated by a magnetic field. Superparamagnetic iron oxide nanoparticles (SPIONs) were used to generate hydroxyethyl starch magnetic nanocapsules (HES MNCs). This synthesis allowed the co-encapsulation of oncocalyxone A (onco A) and surface-modified magnetite nanoparticles (Fe 3 O 4 @citrate) into the same nanostructure. The synthesized nanocapsules exhibited a core-shell morphology, with an average diameter of 143 nm. This nanocomposite showed potential anticancer activity (IC 50 ) against four human tumor cell lines: glioblastoma SNB-19 (1.010 μgmL -1 ), colon carcinoma HCT-116 (2.675 μgmL -1 ), prostate PC3 (4.868 μgmL -1 ), and leukemia HL-60 (2.166 μgmL -1 ). Additionally, in vivo toxicity and locomotor activity were evaluated in a zebrafish (Danio rerio) model. The nanocomposite exhibited in vitro cytotoxicity, prolonged drug release profile and also responded to an applied magnetic field, representing a versatile compound with perspectives for highest concentration of different hydrophilic bioactives in a target tissue through magnetic vectorization., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Busulfan (BU) is an alkylating agent with a narrow therapeutic index and high intraindividual pharmacokinetic variability used in conditioning therapy for hematopoietic stem cell transplantation. Monitoring BU exposure during high-dose conditioning regimens is recommended and positively impacts outcomes. We aimed to develop, validate, and apply a ultra-high-performance liquid chromatography-mass spectrometry (MS)/MS assay to measure BU concentrations in oral fluid and dried plasma spots (DPS) as alternative matrices to plasma., Methods: We prepared plasma and oral fluid samples by protein precipitation and DPS after liquid extraction. We analyzed extracts using an LC-MS/MS system with an Acquity HSS T3 column in the positive electrospray ionization mode. The method was validated and applied to 79 paired plasma and oral fluid samples from 7 patients on BU conditioning treatment. DPS were prepared by pipetting plasma onto Whatman 903 paper. The correlation between BU in plasma, oral fluid, and DPS samples was evaluated., Results: Run time was 4.0 minutes. The assay was linear at 50-5000 ng mL-1 (r > 0.99), precise (1.9%-5.3% oral fluid and 1.8%-5.9% DPS), and accurate (98.1%-108.9% oral fluid and 93%-103.1% DPS). BU was stable in DPS at 23°C for 24 hours. BU levels in oral fluid (r = 0.927) and DPS (r = 0.982) were significantly correlated with plasma. Despite the good correlation, we found a wide variation between oral fluid and plasma levels. The area under curves (AUCs) calculated with oral fluid concentrations were 79.1%-167.1% of plasma AUCs. Bland-Altman plots found a better agreement for DPS, with AUCs estimated from corrected DPS levels at 83.1%-114.1% of plasma values., Conclusions: We developed and validated a simple and fast ultra-high-performance liquid chromatography-MS/MS assay to measure BU in oral fluid and DPS. The results do not support the use of oral fluid as a matrix for routine therapeutic drug monitoring of BU. The AUC estimated from BU measurements in DPS was comparable to that in plasma, supporting the use of DPS in BU therapeutic drug monitoring as an alternative matrix, with adequate short-term stability and logistic advantages., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 strain, was first identified in late 2019 in China. The outcomes of patients affected by the virus can worsen, developing acute respiratory failure and other serious complications, especially in older individuals and people with obesity and comorbidities. Thus, obese patients tend to have a more severe course of COVID-19. Thus, this review aims to synthesize the evidence in the literature that associates COVID-19 and the severity of clinical outcomes in infected obese patients., Methods: This protocol was designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols Statement. Scientific and gray literature will be systematically selected from PubMed/MEDLINE, Latin American Literature in Health Sciences, Online Scientific Electronic Library, Scopus, ScienceDirect, Web of Science, Embase, and Cochrane. The selection of articles will be limited to studies published in English, Portuguese, and Spanish from December 2019 onwards. The main clinical outcomes will be clinical severity in obese patients with COVID-19 as tachypnea (respiratory rate, ≥ 30 breaths per minute), hypoxemia (oxygen saturation, ≤ 93%), the ratio of the partial pressure of arterial oxygen to fraction of inspired oxygen (< 300), lung infiltrate (> 50% of the lung field involved within 24-48 h), diagnosis of the severe acute respiratory syndrome, need of invasive mechanical ventilation, and mortality. Two reviewers will independently screen all citations, full-text articles, and abstract data. Selection bias will be minimized by excluding studies published before December 2019. Conflicts will be resolved through a third reviewer and consensus-building. Moreover, findings will be reported using narrative synthesis and tabulation of the summaries., Discussion: Given the need for early detection of the possible implications and treatment for patients with obesity diagnosed with COVID-19, the scoping review will be useful to capture the state of the current literature, identify the gaps, and make recommendations for future research for directing the conduct and optimization of therapies in these patients by the multiprofessional teams., Systematic Review Registration: Open Science Framework: https://osf.io/xrkec.

Natural polymer-based hybrid nanocomposites have been proposed as one of the most promising tools for biomedical applications, including disease treatment and diagnosis procedures. Xyloglucan nanocapsules can simultaneously load magnetic iron oxide nanoparticles and bioactive for a specific tissue, reducing the processes of degradation and metabolic inactivation of molecules with biological activity. In this work, magnetic nanocapsules of xyloglucan loaded with hydrophilic sulfated quercetin (MNXQ&#95;SO 3 ) were successfully synthesized by inverse miniemulsion process through interfacial polymerization. The polymeric shell formation of nanocapsules was evidenced by Fourier Transform Infrared spectroscopy and Transmission Electron Microscopy. The ferrofluid (Fe 3 O 4 @PAAS) incorporated into the xyloglucan nanocapsules was synthesized by hydrothermal method, using polyacrylic acid sodium salt as coating. Dynamic Light Scattering technique confirmed the nanomeric dimensions (202.3 nm) and the good colloidal stability (-40.2 mV) of MNXQ&#95;SO 3 . The saturation magnetization analyses pointed out the superparamagnetic behavior of Fe 3 O 4 @PAAS (48 emu/g) and MNXQ&#95;SO 3 (4.2 emu/g). MNXQ&#95;SO 3 was able to modify the release profile of sulfated quercetin (67%) when compared to the free bioactive (100%), exhibiting a release profile compatible with the zero-order kinetic model. The results showed that the development of MNXQ&#95;SO 3 presents a new perspective for biomedical applications, including studies of targeted drug delivery., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This work proposes the development of a starch-based drug carrier for fluoxetine (FLX) delivery and evaluate the improvement of the drug antibacterial activity. The starch nanocapsules were prepared via interfacial polyaddition reaction presenting a core-shell morphology, based on polyurethane linkage, with a particle size in the range 250-300 nm. Furthermore, FLX-loaded nanocapsules were evaluated regarding antibacterial potential against Staphylococcus aureus (ATCC® 6538P ™) and its clinical strains of methicillin-resistant. As expected, the FLX-loaded presented lower minimum inhibitory concentration (MIC) values, in the range of 190-95 μg mL -1 , against all isolated microorganisms in comparison to FLX, 255 μg mL -1 . According to results, the FLX-loaded starch nanocapsules have successfully improved drug antibacterial activity, generating promising perspectives on the field of the hydrophilic drug delivery systems., (Copyright © 2020 Elsevier B.V. All rights reserved.)

English is the lingua franca for scientific communication, but some journals, especially in developing countries, still publish non-English studies. A shift towards publishing in English may promote internationalization and more visibility of scientific journals. Here we compared quality indexes between Brazilian journals that have always published in English and journals that have published in languages other than English. We also investigated whether a temporal shift towards publishing in English led to elevated quality measures. Our analyses covered 16 Brazilian biodiversity journals and accounted for 12640 papers published since 2007. The mean impact factor was on average 55% higher in journals that have published consistently in English, compared to the so-called multilanguage journals. The proportion of publications in English increased to nearly three times the original value in multilanguage journals between 2007 and 2016, and the impact factor tripled during this period. At the same time, the Qualis-Capes classifications (B1-B2-B3) tended to fall. Publishing in English can be a first step to increased visibility, and this is particularly important for biodiversity journals, since Brazilian ecosystems are considered of interest to the international scientific community and nature conservation.

Importance: Early-stage chronic kidney disease (CKD) characterized by microalbuminuria is associated with future cardiovascular events, progression toward end-stage renal disease, and early mortality in patients with type 2 diabetes., Objective: To compare the albuminuria-lowering effects of Roux-en-Y gastric bypass (RYGB) surgery vs best medical treatment in patients with early-stage CKD, type 2 diabetes, and obesity., Design, Setting, and Participants: For this randomized clinical trial, patients with established type 2 diabetes and microalbuminuria were recruited from a single center from April 1, 2013, through March 31, 2016, with a 5-year follow-up, including prespecified intermediate analysis at 24-month follow-up., Intervention: A total of 100 patients with type 2 diabetes, obesity (body mass indexes of 30 to 35 [calculated as weight in kilograms divided by height in meters squared]), and stage G1 to G3 and A2 to A3 CKD (urinary albumin-creatinine ratio [uACR] >30 mg/g and estimated glomerular filtration rate >30 mL/min) were randomized 1:1 to receive best medical treatment (n = 49) or RYGB (n = 51)., Main Outcomes and Measures: The primary outcome was remission of albuminuria (uACR <30 mg/g). Secondary outcomes were CKD remission rate, absolute change in uACR, metabolic control, other microvascular complications, quality of life, and safety., Results: A total of 100 patients (mean [SD] age, 51.4 [7.6] years; 55 [55%] male) were randomized: 51 to RYGB and 49 to best medical care. Remission of albuminuria occurred in 55% of patients (95% CI, 39%-70%) after best medical treatment and 82% of patients (95% CI, 72%-93%) after RYGB (P = .006), resulting in CKD remission rates of 48% (95% CI, 32%-64%) after best medical treatment and 82% (95% CI, 72%-92%) after RYGB (P = .002). The geometric mean uACRs were 55% lower after RYGB (10.7 mg/g of creatinine) than after best medical treatment (23.6 mg/g of creatinine) (P < .001). No difference in the rate of serious adverse events was observed., Conclusions and Relevance: After 24 months, RYGB was more effective than best medical treatment for achieving remission of albuminuria and stage G1 to G3 and A2 to A3 CKD in patients with type 2 diabetes and obesity., Trial Registration: ClinicalTrials.gov Identifier: NCT01821508.

Amikacin (AMI) is an aminoglycoside antibiotic widely used in the treatment of severe infections caused by multi-resistant bacteria, with established exposition targets in therapeutic drug monitoring (TDM). The usual specimen for AMI concentration measurement is plasma or serum. The access to TDM of AMI in Developing Countries is constrained by the limited availability of laboratories performing the quantitation of this drug. In this context, the use of dried microsamples, such as dried plasma spots (DPS) could be an alternative to allow reduced specimen transportation and storage costs in resource-limited settings, increasing the access to TDM of AMI. This study aimed to develop and validate the first report of simultaneous determination of AMI and creatinine (CRE) in DPS, using UHPLC-MS/MS. Precision, accuracy and stability assays showed acceptable results. AMI was stable in DPS for 14 days at 6 °C, 2 days at 22 °C, and one day at 42 °C. CRE was stable during 14 days at all tested temperatures. AMI and CRE concentrations in DPS and plasma were compared by Passing-Bablok regression and Bland and Altmann plots and presented comparable results. Estimates of patient's clearance, volume of distribution and suggested doses of AMI were also similar using DPS or plasma concentrations. The assay provides a useful logistic alternative to allow more widespread access to dose individualization of AMI in limited resources settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The use of hair as a matrix for the evaluation of chronic ethanol drinking behavior presents the advantage of a longer window of detection and higher specificity when compared to classical biochemical markers. The most recent recommendations the Society of Hair Testing (SOHT) indicate that ethyl palmitate (EtP) hair levels can be used to estimate the ethanol drinking behavior, alternatively to the combined measurement of four main fatty acid ethyl esters. In this study, solid-phase microextraction (SPME) conditions for the extraction of EtP from hair were optimized using response surface analysis, after a Box-Behnken experiment. Analyses were performed by GC-MS. The optimized HS-SPME conditions, using a PDMS-DVB (65 μm) fiber, were pre-adsorption time of 6 min, extraction time of 60 min and incubation temperature of 94°C. The linear range was 0.05 to 3 ng mg-1, with accuracy within 95.15-109.91%. Between-assay and within-assay precision were 8.58-12.53 and 6.12-6.82%, respectively. The extraction yield was 61.3-71.9%. The assay was applied to hair specimens obtained from 46 volunteers, all presenting EtP levels within the linear range of the assay. Using a statistically designed experiment, a sensitive SPME-GC-MS assay for the measurement of EtP in hair was developed and validated, requiring only 20 mg of hair., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The determination of cocaine (COC) and its metabolites ecgonine methyl ester (EME), benzoylecgonine (BZE), norcocaine (NCOC) and cocaethylene (CE) in human plasma is relevant in clinical and forensic toxicology. An efficient extraction and clean-up of plasma specimens for the simultaneous determination of BZE along with COC and basic metabolites is challenging due to their widely different polarities and ionization characteristics. Recently, biocompatible SPME LC tips C18 became commercially available. We applied SPME LC tips C18 to the simultaneous extraction of COC, BZE, EME, NCOC, and CE by direct immersion of the fiber in plasma diluted with a buffer at pH 8.0. Analytes were desorbed from the fiber to methanol containing formic acid and injected into a UPLC-MS/MS system. The assay was linear from 5 to 500 ng mL-1. Precision assays presented CV% in the range of 2.22 to 10.54%, and accuracy was in the range of 93.4-108.1%. The assay requires minimal quantities of plasma and organic solvents, allowing multiple extractions in parallel. Biocompatible SPME is a promising alternative for preparing biological samples prior to drug measurement by UPLC-MS/MS., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The presence of Ethyl glucuronide (EtG) in hair provides a strong indication of ethanol consumption and its investigation is of interest in both clinical and forensic contexts because of the wide window of detection. However, due to the possibility of false negative results in cases of small ethanol intake or excessive hair washing, the combined measurement of ethyl palmitate (EtP) with EtG could be useful. In this study, a sensitive UHPLC-MS/MS procedure for the measurement of EtG in hair was developed and validated, using optimized sample preparation and chromatographic separation. Milled hair was extracted with water for 24 h at room temperature, followed by clean-up of the extract by ion-exchange solid phase extraction (SPE). Extraction was highly efficient, with yield of 96.93-101.06%. Chromatographic separation was performed with a Fluoro-Phenyl stationary phase. The assay was linear from 4 to 500pgmg -1 , with accuracy in the range of 100.30-106.16%. Matrix effects (-0.87 to 5.89%) were adequately compensated by the use of deuterated EtG as internal standard. EtG was measured in hair samples of 46 volunteers, and results were compared with hair concentrations of ethyl palmitate (EtP) and the score in the AUDITC questionnaire. EtG hair concentrations were significantly correlated to the AUDIT-C classification (r s =0.365, p<0.05), but not to EtP hair levels. The diagnostic performance of EtG hair concentrations to identify excessive or moderate ethanol use was similar to the capability of AUDIT-C to identify severe and high health risk (Kappa, p=0.013). The developed assay is suitable for clinical use, providing a useful tool to evaluate chronic ethanol consumption., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The objective of this study was to evaluate the weight and body yield of two families of selectively bred tambaqui farmed in different environments. Two families (FA and FB) were reared in the municipalities (environments) of Santo Antônio de Leverger (MT) and Campo Grande (MS) for 431 days. Pre-bleeding weight, body yield, and the interaction effect between families and environments on these traits were investigated. No interaction effect between the evaluated families and environments was detected on the evaluated traits. Pre-bleeding weight did not differ significantly between the families in MT (FA: 2,421.7g; FB: 2,478.0g) or in MS (FA: 1,138.7g; FB: 1,389.8g), but the fish from MT had a higher (P<0.05) pre-bleeding weight than those farmed in MS. The visceral fat yield (considering the two environments) was higher (P<0.05) in FB family (3.8%) than in FA family (3.3%).Fish from MS showed higher (P<0.05) offal yield (10.6%) and visceral fat yield (3.9%) but a lower clean-trunk yield (70.6%) than the tambaqui farmed in MT (offal: 7.7%; visceral fat: 3.1%; and clean trunk: 72.6%). In conclusion, the MT environment provides higher pre-bleeding weight and clean-trunk yield and lower offal and visceral-fat yields than the MS environment.

Background: Amikacin (AMI) and vancomycin (VAN) are antibiotics largely used in intensive care in the empiric treatment of severe infections by multi-resistant gram-negative and gram-positive bacteria. AMI and VAN are eliminated untransformed by glomerular filtration, showing depuration ratio highly correlated with creatinine (CRE) clearance. AMI, VAN and CRE are highly polar structures, presenting poor retention in reversed-phase liquid chromatography when using conventional stationary phases., Objective: This study aimed to develop and validate a simple UPLC-MS/MS method for simultaneous determination of AMI, VAN, and CRE in human plasma for therapeutic drug monitoring., Results: Samples were prepared by protein precipitation, followed by dilution. Heptafluorobutyric acid (HFBA) was added to the mobile phase at low concentration (0.01%), and separation was performed in an ultra-performance reversed-phase column (particle diameter of 1.8 μm). These conditions allowed retention times of 0.92, 0.93, 2.12, 2.17 and 2.27 min for CRE, CRE-D3, AMI, KAN and VAN, respectively. The assay was linear from 0.5 to 100 mg L -1 for AMI and VAN and 5 to 100 mg L -1 . Precision, accuracy and stability assays were acceptable according to bioanalytical validation guidelines. Suitable results. Matrix effects were in the range of +10.5 to +11.6% for AMI, -4.3 to -4.5% for VAN, and - 1.7 to +0.7 for CRE., Conclusion: The first assay for the simultaneous determination of AMI, VAN and CRE in plasma by liquid chromatography-tandem mass spectrometry was reported. This assay allows the obtention of the necessary analytical data for the clinical application of population pharmacokinetic methods for therapeutic drug monitoring of AMI and VAN., (Copyright © 2019 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Cocaine (COC) is one of the most widely abused drugs in the world and its sensitive and its reliable measurement in blood is of great importance in the field of forensic and clinical toxicology. Additionally, the determination of COC metabolites such as benzoylecgonine (BZE), cocaethylene (CE), ecgonine methyl ester (EME), and norcocaine (NCOC) are also of complementary diagnostic value. The quantification of COC and metabolites in dried blood spots (DBS) may be an alternative to conventional collection methods with several advantages, including easier, on-site, collection, transportation and storage. In this study, we present a simple and comprehensively validated UPLC-MS/MS assay to measured COC, BZE, EME, NCOC and CE in DBS. The evaluated assay was linear from 5-500 ng mL -1 . Precision assays presented CV% of 1.27-6.82, and accuracy in the range of 97-113.78%. Low haematocrit values had a negative impact in the assay accuracy. COC, BE, NCOC and CE measurements can be made reliably in DBS stored for 14 days at room temperature, as well as at -20 °C and 45 °C. All evaluated compounds can be measured in DBS maintained at -20 °C for 14 days. DBS sampling can be used for the clinical evaluation of the exposure to COC, being an alternative for collection, short-term storage and transportation of blood at room and high temperatures., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The brain stores memories by persistently changing the connectivity between neurons. Sleep is known to be critical for these changes to endure. Research on the neurobiology of sleep and the mechanisms of long-term synaptic plasticity has provided data in support of various theories of how brain activity during sleep affects long-term synaptic plasticity. The experimental findings - and therefore the theories - are apparently quite contradictory, with some evidence pointing to a role of sleep in the forgetting of irrelevant memories, whereas other results indicate that sleep supports the reinforcement of the most valuable recollections. A unified theoretical framework is in need. Computational modeling and simulation provide grounds for the quantitative testing and comparison of theoretical predictions and observed data, and might serve as a strategy to organize the rather complicated and diverse pool of data and methodologies used in sleep research. This review article outlines the emerging progress in the computational modeling and simulation of the main theories on the role of sleep in memory consolidation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background & Aims: The liver is the main hematopoietic site in embryos, becoming a crucial organ in both immunity and metabolism in adults. However, how the liver adapts both the immune system and enzymatic profile to challenges in the postnatal period remains elusive. We aimed to identify the mechanisms underlying this adaptation., Methods: We analyzed liver samples from mice on day 0 after birth until adulthood. Human biopsies from newborns and adults were also examined. Liver immune cells were phenotyped using mass cytometry (CyTOF) and expression of several genes belonging to immune and metabolic pathways were measured. Mortality rate, bacteremia and hepatic bacterial retention after E. coli challenge were analyzed using intravital and in vitro approaches. In a set of experiments, mice were prematurely weaned and the impact on gene expression of metabolic pathways was evaluated., Results: Human and mouse newborns have a sharply different hepatic cellular composition and arrangement compared to adults. We also found that myeloid cells and immature B cells primarily compose the neonatal hepatic immune system. Although neonatal mice were more susceptible to infections, a rapid evolution to an efficient immune response was observed. Concomitantly, newborns displayed a reduction of several macronutrient metabolic functions and the normal expression level of enzymes belonging to lipid and carbohydrate metabolism was reached around the weaning period. Interestingly, early weaning profoundly disturbed the expression of several hepatic metabolic pathways, providing novel insights into how dietary schemes affect the metabolic maturation of the liver., Conclusion: In newborns, the immune and metabolic profiles of the liver are dramatically different to those of the adult liver, which can be explained by the differences in the liver cell repertoire and phenotype. Also, dietary and antigen cues may be crucial to guide liver development during the postnatal phase., Lay Summary: Newborns face major challenges in the extra-uterine life. In fact, organs need to modify their cellular composition and gene expression profile in order to adapt to changes in both microbiota and diet throughout life. The liver is interposed between the gastrointestinal system and the systemic circulation, being the destination of all macronutrients and microbial products from the gut. Therefore, it is expected that delicately balanced mechanisms govern the transformation of a neonatal liver to a key organ in adults., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The aim of this study was to compare the vacuum and air cooling of cooked chicken breast samples arranged in stacks with one, two and three layers (1 kg per layer). The cooling rate obtained with vacuum cooling was approximately three times faster than that of air cooling. Moreover, a more homogeneous cooling was obtained with vacuum cooling, with similar temperature reductions for samples at different positions of the stack. On the other hand, vacuum cooling led to mass losses of 11-12%, while air cooling led to losses of 7-8%. The counts of mesophiles and psychrophiles of the vacuum-cooled samples were lower than those observed for air-cooled samples after ten days of product storage. Thus, the results presented in this work illustrate the potential benefits and disadvantages of the vacuum cooling technique as compared to the air cooling, especially for the processing of small meat cuts.

Irinotecan (IRI) is an antineoplastic drug widely used for the treatment of colorectal and advanced pancreatic cancer. Despite its clinical utility, the clinical use of IRI is associated with potentially severe hematopoietic and gastrointestinal toxicities. The quantification of IRI and its active metabolite SN-38 in dried blood spots (DBS) may be an alternative to individualize the drug dose through a minimally invasive and easy collection method. The aim of this study was to develop and validate a simple and fast HPLC-FL assay for simultaneous IRI and SN-38 measurement in DBS, with adequate analytical performance for clinical use. The method employs liquid extraction of one 8mm disk of whole blood, followed by separation in a reversed phase Eclipse Plus C8 column (150×4.6mm, 5μm). Detection was performed with a fluorescence detector, with excitation wavelength of 370 and emission of 420 for IRI and 540nm for SN-38 and internal standard (camptothecin). Total analytical run time was 17min. Mobile phase was a mixture of 0.1M phosphate buffer pH 4.0 and acetonitrile (80:20, v/v), at 1mLmin -1 . The assay was linear in the range 10-3,000ngmL -1 and from 0.5 to 300ngmL -1 for IRI and SN-38, respectively. Precision assays presented CV% of 2.71-5.65 and 2.15-10.07 for IRI and SN-38, respectively, and accuracy in the range of 94.26-100.93 and 94.24-99.33%. IRI and SN-38 were stable at 25 and 42°C for 14days in DBS samples. The method was applied to DBS samples obtained from fingerpicks from 19 volunteers receiving IRI in single or combined chemotherapy regimens, collected 1 and 24h after beginning of the infusion. The estimated plasma concentration of IRI and SN-38 in sample collected 1h after star of infusion had 16 of 19 values within the ±20% range of the measured plasma concentrations. On the other hand, predictions of IRI and SN-38 plasma concentrations from DBS measurements obtained 24h after the beginning of the infusion were poor. AUC of IRI that was calculated using plasma and DBS-estimated concentrations, with a high correlation (r=0.918). The method presented suitable characteristics for the clinical use. However, translation of IRI and SN-38 DBS to plasma concentrations is challenging due to the compound's variable plasma/blood partition., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Therapeutic drug monitoring (TDM) of the widely prescribed antidepressant fluoxetine (FLU) is recommended in certain situations, such as occurrence of toxicity, inadequate response or suspect of poor adherence. Dried blood spot (DBS) sampling is an increasingly studied alternative for TDM, particularly for outpatients, due to its ease of collection and inherent stability., Objectives: The aim of this study was to develop and validate an LC-MS/MS assay for the simultaneous quantification of FLU and norfluoxetine (NFLU) in DBS., Design and Methods: The assay is based on a liquid extraction of single DBS with 8mm of diameter, using FLU-D6 as the internal standard, followed by reversed phase separation in an Accucore® C18 column (100×2.1mm, 2.6μm). Mobile phase was composed of water and acetonitrile (gradient from 80:20 to 50:50, v/v), both containing formic acid 0.1%. The assay was validated and applied to 30 patients under FLU pharmacotherapy., Results: The assay was linear in the range 10-750ngmL -1 . Precision assays presented CV% of 3.13-9.61 and 3.54-7.99 for FLU and NFLU, respectively, and accuracy in the range of 97.98-110.44% and 100.25-105.8%. FLU and NFLU were stable at 25 and 45°C for 7days. The assay was evaluated in 30 patients under FLU treatment. Concentrations of both compounds were higher in DBS than in plasma, and the use of the multiplying factors 0.71 and 0.68 for FLU and NFLU, respectively, allowed acceptable estimation of plasma concentrations, with median prediction bias of -0.55 to 0.55% and mean differences of 0.4 to 2.2ngmL -1 ., Conclusions: The presented data support the clinical use of DBS for therapeutic drug monitoring of FLU., (Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: This article reviewed very recent papers (2016) discussing or bringing clinical evidences of the possible common pathways leading to diabetic foot syndrome (DFS) and increased mortality rates., Recent Findings: Diabetic patients with diabetic foot syndrome have a mortality rate greater than twofold when compared with non-ulcerated diabetics. In addition, the 5-year mortality rate following amputation is estimated at 39-68%, a life expectancy comparable to aggressive types of cancer or advanced congestive heart failure. The majority of patients with diabetic foot ulcer also present insulin resistance, central obesity, dyslipidemia, and hypertension that characterize the metabolic syndrome that, in turn, is associated with an elevated risk of major cardiovascular events. Sensory neuropathy is the primary cause of more the 60% of diabetic foot ulcer. Diabetic peripheral neuropathy is a microvascular complication of diabetes mellitus and in type 2 diabetes, not only hyperglycemia but also other metabolic alterations and persistent inflammatory status due to adiposity play a major role in axon injury. Elevated triglycerides have been showed to be an independent risk factor for lower extremity amputation in diabetic patients. Also, toxic adiposity, oxidative stress, mitochondrial dysfunction, activation of the polyol pathway, accumulation of advanced glycation end products (AGEs), and elevation of inflammatory markers are also implicated in diabetic vascular disease and neuropathy. The hypotheses that the association between DFS and increased rates of mortality reflects the progression of micro- and macrovascular complications are reinforced by the additional association of DFU to renal failure and retinopathy.

Giardiasis is an intestinal parasitosis that affects millions of people worldwide and is considered a zoonotic disease. Frequently in contact with humans, dogs are the main host involved in this zoonotic transmission. Here, we compared some aspects of Giardia duodenalis biology between two strains: a recently isolated dog strain (BHFC1) and a human reference strain (Portland-1). Growth curve analysis revealed that BHFC1 trophozoites multiply faster than the human isolate Portland-1 in axenic culture, but has a lower rate of cysts formation. Scanning electron microscopy revealed that BHFC1 trophozoites have the same conventional shape and morphological structures expected for G. duodenalis trophozoites, but presented a more prominent flange. For the best of our knowledge, this work is the first description of morphological aspects and encystation process of a G. duodenalis strain isolated from a dog. Since BHFC1 and Portland-1 have been maintained in axenic cultures for different periods of time, differences observed in growth, encystation rates and flange size may be attributed to adaptation of Portland-1 to axenic culture and lack of the environmental pressures. BHFC1 can be useful as tool for better understanding of Giardia duodenalis biology., (Copyright © 2017 Elsevier B.V. All rights reserved.)