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Fanny Helena Martins Salles,1 Pedro San Martin Soares,1 Carolina David Wiener,1 Thaise Campos Mondin,1 Paula Moraes da Silva,1 Karen Jansen,1–3 Luciano Dias de Mattos Souza,1 Ricardo Azevedo da Silva,1 Jean Pierre Oses1–3 1Translational Science on Brain Disorders, Department of Health and Behavior, Catholic University of Pelotas, Pelotas, Rio Grande do Sul, Brazil; 2Translational Psychiatry Program, 3Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston (UTHealth) Medical School, Houston, TX, USA Abstract: Nerve growth factor (NGF) is an important member of the neurotrophin family and its alteration has been associated with psychiatric disorders. Functionality consists of the activities that an individual can perform, as well as their social participation, which is an important factor in analyzing the carrier living conditions of subjects with psychiatric suffering. Several studies have evaluated functionality in bipolar disorder; however, no studies have evaluated the functionality in other mental disorders. There are also few studies investigating the association between functionality and the biological bases of mental disorders. This study aimed to evaluate the serum NGF levels in psychiatric patients and to verify a possible association between the serum neurotrophic levels and functionality. This was a cross-sectional study with a convenient sample obtained from the Public Mental Health Service from the south of Brazil. The final sample was composed of 286 patients enrolled from July 2013 to October 2014. Data was collected using a sociodemographic questionnaire, and the diagnosis was confirmed using the Mini International Neuropsychiatric Interview (M.I.N.I) and a Functioning Assessment Short Test. The serum NGF levels were determined using the enzyme-linked immunosorbent assay method. Statistical analyses were performed using IBM SPSS Statistic 21.0 software. NGF serum levels were increased significantly in patients with obsessive–compulsive disorder compared with patients with no obsessive–compulsive disorder (P=0.015). An increase in serum NGF levels in generalized anxiety disorder patients was observed compared with patients with no generalized anxiety disorder (P=0.047). NGF was negatively associated with autonomy (P=0.024, r=–0.136), work (P=0.040, r=–0.124), and cognition (P=0.024, r=–0.137), thereby showing that changes in serum levels of NGF are associated with functionality in mental disorders. Keywords: NGF, mental disorders, functional impairment

Aim: To evaluate the relationship of different levels of social capital with oral health-related adolescents' quality of life (OHRQoL)., Methods: This is a cross-sectional study nested in a cohort study started in 2010 with a sample of children 1 to 5 years old from Brazil. Individuals were followed after 10 years, data which was considered in this study (11 to 15 years old). OHRQoL was evaluated by the short version of CPQ11-14. Individual social capital (ISC) was assessed through the presence of individual social networks and social trust. Community social capital (CSC) was assessed through the presence of voluntary institutions, community cultural centers or residents' associations. For both ISC and CSC, the participants were classified as with high social capital (at least one source) or low social capital (absence of any source). Adjusted Poisson Regression analysis was performed to verify the interaction of different levels of social capital and OHRQoL. Results are present in Rate Ratio (RR) and 95 % confidence interval (95 % CI)., Results: A total of 429 adolescents were evaluated. Adolescents with low CSC and low ISC presented CPQ11-14 scores 36 % higher (RR 1.36 95 %CI 1.15-1.62) than counterparts who presented higher social capital levels. The interaction among high and low levels of social capital was not associated with CPQ11-14 scores, indicating that no level stands out over the other., Conclusion: Only the total absence of both levels of social capital negatively related with OHRQoL, indicating the importance of the presence of at least one source of social capital., Clinical Relevance: The findings show that social capital affects OHRQoL, a crucial psychosocial aspect considering the clinical practice., Competing Interests: Declaration of competing interest The authors have no conflicts of interest in relation to the products or methods mentioned herein., (Published by Elsevier Ltd.)

This study investigated the morphology of Rhinella crucifer cutaneous glands, as well as the protein/peptide profiles and bioactivities of body gland secretions (BGS) and parotoid macrogland secretions (PS). The parotoid as well as dorsal and ventral skin fragments of male and female individuals were processed for histological analysis. The protein and peptide profiles of male and female gland secretions were evaluated. Male secretions were also assessed for proteolytic, trypsin inhibiting, hemagglutinating, hemolytic, antimicrobial, and anticoagulant activities. The R. crucifer skin structure presented protuberances that are clearly visible and formed by the integument, which has cutaneous glands throughout the body. An average of 438 and 333 glands were identified in males in females, respectively. No significant differences were observed in the distribution of glands across the body as well as for area and perimeter of glands. Differences were observed in protein composition between the PS and BGS from males and females, and secretions from animals collected from undisturbed and anthropogenically disturbed areas. Proteins with similarities to catalase and elongation factor 1-alpha were detected in the PS. Zymography revealed proteolytic activity in both male BGS and PS. Male BGS showed antibacterial activity against Enterococcus faecalis and Escherichia coli and anticoagulant activity, being able to prolong prothrombin time by 6.34-fold and activated partial thromboplastin time by 2.17-fold. Finally, male PS and BGS caused a maximum hemolysis degree of 1.4%. The data showed that the cutaneous secretions of R. crucifer are potentially promising for biotechnological prospecting., 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 © 2024 Elsevier Inc. All rights reserved.)

This study investigates the potential and applicability of a novel solid magnetic catalyst constructed by incorporating molybdenum oxide (MoO 3 ) into zinc ferrite (ZnFe 2 O 4 ) to biodiesel production using Waste Frying Oil (WFO) as the residual raw material. The molybdenum amounts (5, 15, 25, 35 and 45%) present in the catalyst were studied and the catalyst demonstrated great characteristics and high acid properties, as well as superior magnetic and catalytic attributes. The one variable at time (OVAT) optimization method revealed that the application of the MoO 3 /ZnFe 2 O 4 catalyst resulted in obtaining a biodiesel with 97.6% ± 0.727 conversion to fatty acid methyl esters (FAME) under the following optimized reaction conditions: temperature of 165 °C, methanol : WFO molar ratio of 40 : 1, catalyst amount of 6 wt% and reaction time of 3 h. In addition, the catalyst showed high reusability after six reaction cycles, with conversion to esters above 90%. Besides, the activation energy ( E a ) calculated in the kinetic study was 25.3 kJ mol -1 . Moreover, the properties of the synthesized biodiesel met the standards set by the ASTM D6751 and EN 14214, which indicates the high MoO 3 /ZnFe 2 O 4 potential for industrial application with low energy consumption as well as minimal negative environmental impact., Competing Interests: Authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Asthma is a disease characterized by chronic inflammation and hyper responsiveness of airways. We aimed to assess the relaxant potential of phosphodiesterase-4 (PDE4) inhibitors N-sulfonilhidrazonic derivatives on non-asthmatic and asthmatic guinea pig trachea. Firstly, guinea pigs were sensitized and challenged with ovalbumin, and then morphological, and contractile changes were evaluated resulting from asthma, followed by evaluation of relaxant effect of derivatives on guinea pig trachea and the cAMP levels measurement by ELISA. It has been evidenced hypertrophy of airway smooth muscle, inflammatory infiltrate, and vascular abnormalities. Moreover, only sensitized tracheal rings were responsive to OVA. Contractile response to histamine, but not to carbachol, was greater in sensitized animals, however the relaxant response to aminophylline and isoprenaline were the same in non-asthmatics and asthmatics. N-sulfonilhidrazonic derivatives presented equipotent relaxant action independent of epithelium, with exception of LASSBio-1850 that presented a low efficacy (< 50%) and LASSBio-1847 with a 4-fold higher potency on asthmatics. LASSBio-1847 relaxant curve was impaired in the presence of propranolol and potentiated by isoprenaline in both groups. Furthermore, relaxation was potentiated 54- and 4-fold by forskolin in non-asthmatics and asthmatics, respectively. Likewise, LASSBio-1847 potentiated relaxant curve of aminophylline 147- and 4-fold in both groups. The PKA inhibitor H-89 impaired the relaxant potency of the derivative. Finally, LASSBio-1847 increased tracheal intracellular cAMP levels similarly to rolipram, selective PDE4 inhibitor, in both animals. LASSBio-1847 showed to be promising to relax guinea pig trachea from non-sensitized and sensitized guinea pigs by activation of β 2 -adrenergic receptors/AC/cAMP pathway., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders of hematopoietic progenitor cells related to ineffective hematopoiesis and an increased risk of transformation to acute myelogenous leukemia. MDS is divided into categories, namely lineage dysplasia (MDS-SLD), MDS with ring sideroblasts (MDS-RS), MDS with multilineage dysplasia (MDS-MLD), MDS with excess blasts (MDS-EB). The International Prognostic Classification System (IPSS) ranks the patients as very low, low, intermediate, high, and very high based on disease evolution and survival rates. Evidence points to toll-like receptor (TLR) abnormal signaling as an underlying mechanism of this disease, providing a link between MDS and immune dysfunction. Microbial signals, such as lipopolysaccharides from gram-negative bacteria, can activate or suppress TLRs. Therefore, we hypothesized that MDS patients present gut microbiota alterations associated with disease subtypes and prognosis. To test this hypothesis, we sequenced the 16S rRNA gene from fecal samples of 30 MDS patients and 16 healthy elderly controls. We observed a negative correlation between Prevotella spp. and Akkermansia spp. in MDS patients compared with the control group. High-risk patients presented a significant increase in the genus Prevotella spp. compared to the other risk categories. There was a significant reduction in the abundance of the genus Akkermansia spp. in high-risk patients compared with low- and intermediate-risk. There was a significant decrease in the genus Ruminococcus spp. in MDS-EB patients compared with controls. Our findings show a new association between gut dysbiosis and higher-risk MDS, with a predominance of gram-negative bacteria., Competing Interests: The authors declare no conflict of interests. The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Tehran University of Medical Sciences.)

This study investigated the impact of a support matrix and active group on the support to the nutritional properties of orange juice after juice clarification. Pectinase was immobilized on chitosan and aminated silica supports, activated with genipin or glutaraldehyde, and applied for juice clarification. The effects on various juice properties, including reducing sugars, total soluble solids, vitamin C, and phenolic compounds, juice color, and pH, were evaluated. The results revealed that the immobilization on chitosan activated using genipin resulted in the highest biocatalyst activity (1211.21 U·g -1 ). The juice treatments using the biocatalysts led to turbidity reduction in the juice (up to 90%), with the highest reductions observed in treatments involving immobilized enzyme on chitosan. Importantly, the enzymatic treatments preserved the natural sugar content, total soluble solids, and pH of the juice. Color differences between treated and raw juice samples were especially relevant for those treated using enzymes, with significant differences in L* and b* , showing loss of yellow vivid color. Analysis of phenolic compounds and vitamin C showed no significant alterations after the enzymatic treatment of the raw juice. According to our results, the clarification of orange juice using immobilized enzymes can be a compromise in turbidity reduction and color reduction to maintain juice quality.

Aims: We investigated the putative fungistatic and fungicidal activities of pomegranate sarcotesta lectin (PgTeL) against Cryptococcus neoformans B3501 (serotype D), specifically the ability of PgTeL to inhibit yeast capsule and biofilm formation in this strain., Methods and Results: PgTeL showed a minimum inhibitory concentration of 172.0 μg ml-1, at which it did not exhibit a fungicidal effect. PgTeL concentrations of 4.0-256.0 μg ml-1 reduced biofilm biomass by 31.0%-64.0%. Furthermore, 32.0-256.0 μg ml-1 PgTeL decreased the metabolic activity of the biofilm by 32.0%-93.0%. Scanning electron microscopy images clearly revealed disruption of the biofilm matrix. Moreover, PgTeL disrupted preformed biofilms. At concentrations of 8.0-256.0 μg ml-1, PgTeL reduced metabolic activity in C. neoformans by 36.0%-92.0%. However, PgTeL did not inhibit the ability of B3501 cells to form capsules under stress conditions., Conclusions: PgTeL inhibited biofilm formation and disrupted preformed biofilms, demonstrating its potential for use as an anticryptococcal agent., (© The Author(s) 2023. Published by Oxford University Press on behalf of Applied Microbiology International.)

Lectins are carbohydrate-binding proteins with several bioactivities, including antimicrobial properties. Portulaca elatior is a species found at Brazilian Caatinga and data on the biochemical composition of this plant are scarce. The present work describes the purification of P. elatior leaf lectin (PeLL) as well as the assessment of its antimicrobial activity and toxicity. PeLL, isolated by chromatography on a chitin column, had native liquid charge and subunit composition evaluated by electrophoresis. Hemagglutinating activity (HA) of PeLL was determined in the presence of carbohydrates or divalent cations, as well as after heating and incubation at different pH values. Changes in the lectin conformation were monitored by evaluating intrinsic tryptophan fluorescence and using the extrinsic probe bis-ANS. Antimicrobial activity was evaluated against Pectobacterium strains and Candida species. The minimal inhibitory (MIC), bactericidal (MBC), and fungicidal (MFC) concentrations were determined. Finally, PeLL was evaluated for in vitro hemolytic activity in human erythrocytes and in vivo acute toxicity in mice (5 and 10 mg/kg b.w. per os). PeLL (pI 5.4; 20 kDa) had its HA was inhibited by mannose, galactose, Ca 2+ , Mg 2+ , and Mn 2+ . PeLL HA was resistant to heating at 100 °C, although conformational changes were detected. PeLL was more active in the acidic pH range, in which no conformational changes were observed. The lectin presented MIC and MBC of 0.185 and 0.74 μg/mL for all Pectobacterium strains, respectively; MIC of 1.48 μg/mL for C. albicans, C. tropicalis, and C. krusei; MIC and MFC of 0.74 and 2.96 μg/mL for C. parapsilosis. No hemolytic activity or signs of acute toxicity were observed in the mice. In conclusion, a new, low-toxic, and thermostable lectin was isolated from P. elatior leaves, being the first plant compound to show antibacterial activity against Pectobacterium., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hemocytes are the circulating cells of the hemolymph of oysters and are responsible for numerous physiological functions, including immune defense. The oyster Crassostrea gasar is a native species inhabiting mangrove habitat and is of great commercial interest, cultured throughout the Brazilian coast, mainly in the north and northeast. Despite its commercial importance, little is known about its immunological aspects and defense cells, the hemocytes. This work aimed to morphologically characterize hemocytes of the oyster C. gasar and to study one of the main cellular defense response, phagocytosis, using light microscopy and flow cytometry. The results showed the presence of six hemocyte populations in C. gasar hemolymph. These comprise of large and small granulocytes, large and small hyalinocytes, blast-like cells and a rare type classified as vesicular or serous hemocytes. Hyalinocytes were highly abundant and the most heterogeneous cell population, while small granulocytes, along with vesicular hemocytes were the less abundant population. Hemocytes of C. gasar oysters demonstrated capabilities to phagocytose three different types of particles tested: zymosan A, latex particles and Escherichia coli , indicating a broad defense capacity. The zymosan A were the most engulfed particles, followed by beads, mainly phagocytized by granulocytes, the most phagocytic cells, and finally E. coli , which were the least phagocytized. This study is the first characterization of C. gasar oyster hemocytes and will support future studies that aim to understand the participation of different hemocyte types in defense responses against pathogens and/or environmental changes., Competing Interests: 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., (© 2023 The Authors. Published by Elsevier Ltd.)

Teneurin C-terminal associated peptide (TCAP) is an ancient bioactive peptide that is highly conserved in metazoans. TCAP administration reduces cellular and behavioural stress in vertebrate and urochordate models, yet despite numerous studies in higher animals, there is limited knowledge of its role in invertebrates. In particular, there are no studies on TCAP's effects on the heart of any metazoan, which is a critical organ in the stress response. We used the Sydney rock oyster (SRO) as an invertebrate model to investigate a potential role for sroTCAP in regulating cardiac activity, including during stress. sroTCAP is localized to the neural innervation network of the SRO heart, and suggested binding with various heart proteins related to metabolism and stress, including SOD, GAPDH and metabotropic glutamate receptor. Intramuscular injection of sroTCAP (10 pmol) significantly altered the expression of heart genes that are known to regulate remodelling processes under different conditions, and modulated several gene families responsible for stress mitigation. sroTCAP (1 and 10 pmol) was shown to cause transient bradycardia (heart rate was reduced by up to 63% and for up to 40 min post-administration), indicative of an unstressed state. In summary, this study has established a role for a TCAP in the regulation of cardiac activity through modulation of physiological and molecular components associated with energy conservation, stress and adaptation. This represents a novel function for TCAP and may have implications for higher-order metazoans., 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., (Copyright © 2023 Abramov, Suwansa-ard, da Silva, Wang, Dove, O’Connor, Parker, Russell, Lovejoy, Cummins and Elizur.)

Resynchronization protocols have been proposed as a way of shortening females' unproductive time in the flock, with good results in cattle and sheep. In goats, initial studies have shown that a second progestogen device inserted before luteolysis and pregnancy diagnosis does not interfere with the corpus luteum lifespan or functionality. This study aimed to evaluate the follicular growth, ovulation pattern and pregnancy rate after insertion of a second and new progestogen device for resynchronizing, with or without equine Chorionic Gonadotrophin (eCG), submitted to natural mating (NM) or artificial insemination (AI) to propose a viable resynchronization protocol for dairy goats. A total of 38 multiparous Saanen goats underwent a short-term progesterone protocol [six days exposed to medroxyprogesterone acetate (MAP) intravaginal sponges + 200 IU eCG and 0.12 mg of cloprostenol sodium on the 5 th day + 0.025 mg of lecirelin 34 hours after sponge withdrawal] and, on day 16th after the ovulation, received a new MAP device which was retained until day 21. At this moment females were split into four groups: G eCG+NM - 100 IU eCG with NM; G Sal+NM - saline solution with NM; G eCG+AI - 100 IU eCG with AI; and G Sal+AI - saline solution with AI. Ultrasound scans were performed every 12 h from sponge withdrawal (day 21) until 108 h after sponge withdrawal (day 25) for follicular dynamics evaluation, at 240 h (day 31) for assessing the presence of active corpus luteum, and on day 60 for pregnancy diagnosis. No differences were found regarding ovulation time, synchronization and follicle size. However, G eCG+NM presented a greater estrus manifestation rate (100%) and pregnancy rate (62.5%) when compared to G Sal+AI . In conclusion, resynchronization protocols in dairy goats may present satisfactory results., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare.

Knowing the reproductive biology and population dynamics of invasive species are essential for environmental conservation and protection of native species. The success of these invasive species is directly linked to their reproductive strategy. Therefore, this study aimed to describe the reproductive cycles and evaluate population parameters of the invasive bivalves Mytilopsis sallei and Isognomon bicolor, and to estimate if those characteristics would favor their population growths in the northeast coast of Brazil. The bivalves were sampled monthly from June 2016 to May 2017, respectively from the Sanhauá River estuary and Jacarapé beach, State of Paraíba, Northeast Brazil. Through histological analyses, reproductive parameters were determined in order to identify sex, gonadal development, minimum size at maturity, and mean gonadal index. The asymptotic growth (L∞) and growth rate (K) parameters were estimated using the von Bertalanffy growth curve, and recruitment patterns and cohorts were projected based on shell length frequency distributions. Mytilopsis sallei presented more than 50% spawning individuals in most months, while animals showing gametogenic gonads were predominant during the season of greatest precipitation. Isognomon bicolor had ripe gonads (about 30%) and spawning individuals (more than 40%) in all months of the year, but unlike M. sallei, it had the highest concentration of ripe individuals in the months of greatest precipitation. Both species showed equal and high growth rates (K = 1.1 yr-¹) and analysis of the cohorts indicated that these populations are established and expanding. The results confirmed the great invasive potential of the two species in their local environments (estuary and marine) in Northeast Brazil and, therefore, their harmful potential for the conservation of native species and the environment in the invaded areas., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Teneurin C-terminal associated peptide (TCAP) is an ancient bioactive peptide that is highly conserved in metazoans. TCAP administration reduces cellular and behavioral stress in vertebrate and urochordate models. There is little information for invertebrates regarding the existence or function of a TCAP. This study used the Sydney rock oyster (SRO) as a molluscan model to characterize an invertebrate TCAP, from molecular gene analysis to its physiological effects associated with hemocyte phagocytosis. We report a single teneurin gene (and 4 teneurin splice variants), which encodes a precursor with TCAP that shares a vertebrate-like motif, and is similar to that of other molluscan classes (gastropod, cephalopod), arthropods and echinoderms. TCAP was identified in all SRO tissues using western blotting at 1-2 different molecular weights (~22 kDa and ~37kDa), supporting precursor cleavage variation. In SRO hemolymph, TCAP was spatially localized to the cytosol of hemocytes, and with particularly high density immunoreactivity in granules. Based on 'pull-down' assays, the SRO TCAP binds to GAPDH, suggesting that TCAP may protect cells from apoptosis under oxidative stress. Compared to sham injection, the intramuscular administration of TCAP (5 pmol) into oysters modulated their immune system by significantly reducing hemocyte phagocytosis under stress conditions (low salinity and high temperature). TCAP administration also significantly reduced hemocyte reactive oxygen species production at ambient conditions and after 48 h stress, compared to sham injection. Transcriptomic hemocyte analysis of stressed oysters administered with TCAP demonstrated significant changes in expression of genes associated with key metabolic, protective and immune functions. In summary, this study established a role for TCAP in oysters through modulation of physiological and molecular functions associated with energy conservation, stress and cellular defense., 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., (Copyright © 2022 Abramov, Suwansa-ard, da Silva, Wang, Dove, O’Connor, Parker, Lovejoy, Cummins and Elizur.)

Background: Acridine compounds have been described as promising anticancer agents. Previous studies showed that (E)-1'-((4-chlorobenzylidene)amino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-06), a spiro-acridine compound, has antitumor activity on Ehrlich tumor and low toxicity. Herein, we investigated its antitumor effect against human cells in vitro., Methods: MTT assay was used to assess cytotoxicity of AMTAC-06 (3.125-200 µM) against tumor and non-tumor cells, and the half-maximal inhibitory concentration (IC 50 ) and the selectivity index (SI) were calculated. The effects on the cell cycle (propidium iodide-PI-staining), apoptosis (Annexin V-FITC/PI double staining by flow cytometry), and production of reactive oxygen species, ROS (DCFH assay) were also evaluated. Statistical analysis was achieved using ANOVA followed by Tukey's post-test., Results: AMTAC-06 showed higher cytotoxicity against colorectal carcinoma HCT-116 cells (IC 50 : 12.62 µM). The SI showed that AMTAC-06 was more selective for HCT-116 cells (HaCaT SI: 1.41; PBMC SI: 0.62) than doxorubicin (HaCaT SI: 0.10; PBMC SI: 0.01). AMTAC-06 (15 and 30 µM) induced an increase in the sub-G1 peak (p < 0.000001) and cell cycle arrest in S phase (p = 0.003547). Moreover, treatment with this compound (15 and 30 µM) resulted in increased early (p < 0.000001) and late apoptotic cells (p < 0.000001). In addition, there was a reduction on ROS production (p < 0.000001)., Conclusions: AMTAC-06 presents anticancer activity against HCT-116 cells by regulating the cell cycle, inducing apoptosis and an antioxidant action., (© 2022. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

Introduction: Type 2 diabetes can lead to gait abnormalities, including a longer stance phase, shorter steps and improper foot pressure distribution. Quantitative data from objective methods for evaluating gait patterns are accurate and cost-effective. In addition, it can also help predictive methods to forecast complications and develop early strategies to guide treatments. To date, no research has systematically summarised the predictive methods used to assess type 2 diabetic gait. Therefore, this protocol aims to identify which predictive methods have been employed to assess the diabetic gait., Methods and Analysis: This protocol will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) statement. Electronic searches of articles from inception to January 2022 will be performed, from May 2021 to 31 January 2022, in the Web of Science, MEDLINE, Embase, IEEE Xplore Digital Library, Scopus, CINAHL, Google Scholar, APA PsycInfo, the Cochrane Library and in references of key articles and grey literature without language restrictions. We will include studies that examined the development and/or validation of predictive methods to assess type 2 diabetic gait in adults aged >18 years without amputations, use of assistive devices, ulcers or neuropathic pain. Two independent reviewers will screen the included studies and extract the data using a customised charting form. A third reviewer will resolve any disagreements. A narrative synthesis will be performed for the included studies. Risk of bias and quality of evidence will be assessed using the Prediction Model Risk of Bias Assessment Tool and the Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis., Ethics and Dissemination: Ethical approval is not required because only available secondary published data will be analysed. The findings will be disseminated through peer-reviewed journals and/or presentations at relevant conferences and other media platforms., Prospero Registration Number: CDR42020199495., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Complete spinal cord injury (SCI) is characterized by permanent loss of nerve impulse propagation through the injury level leading to complete loss of voluntary muscle contraction. However, clinically undetectable top-down modulation of lower limbs might be present and can be evidenced using surface electromyography (sEMG)., Case Report: A subject with complete chronic SCI and no spasticity presents voluntary modulation of sEMG signal during a task-specific activity associated with sensory input., Clinical Rehabilitation Impact: We present for the first time the spectral characterization of sEMG signal in response to orthostatic training associated with voluntary movement attempts in complete SCI. Behavior of sEMG signal varied according to kinematic properties of movement, reinforcing the voluntary influence of efferent pathways on motor output. Our findings will contribute to elaborate evaluation protocols to investigate the preservation of corticospinal activities, and to evolve more accessible strategies in a clinical setting.

This study reports the development of conjugates based on quantum dots (QD)s and lectins from Schinus terebinthifolia leaves (SteLL) and Punica granatum sarcotesta (PgTeL). Cryptococcus neoformans cells were chosen to evaluate the efficiency of the conjugates. Lectins were conjugated to QDs via adsorption, and the optical parameters (emission and absorption) were monitored. Lectin stability in the conjugates towards denaturing agents was investigated via fluorometry. The conjugation was evaluated using fluorescence microplate (FMA) and hemagglutination (HA) assays. The labeling of the C. neoformans cell surface was quantified using flow cytometry and observed via fluorescence microscopy. The QDs-SteLL and QDs-PgTeL conjugates, obtained at pH 7.0 and 8.0, respectively, showed the maintenance of colloidal and optical properties. FMA confirmed the conjugation, and the HA assay indicated that the lectin carbohydrate-binding ability was preserved after conjugation. SteLL and PgTeL showed stability towards high urea concentrations and heating. Conjugates labeled over 90% of C. neoformans cells as observed via flow cytometry and confirmed through fluorescence microscopy. C. neoformans labeling by conjugates was inhibited by glycoproteins, suggesting specific interactions through the lectin carbohydrate-binding site. Thus, an effective protocol for the conjugation of SteLL or PgTeL with QDs was proposed, yielding new nanoprobes useful for glycobiological studies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This article presents a study on the degradation of a residual textile mixture composed of cationic surfactant cetyltrimethylammonium bromide (CTAB) and the remazol yellow gold RNL-150% and reactive blue BF-5G textile dyes. This was carried out by employing the photo-peroxidation and photo-Fenton processes in LED and UV-C photoreactors. The photo-Fenton process was the most efficient as regards the degradation of the CTAB and dye mixture, for both types of radiation. In the kinetic study, degradations of 99% were obtained in 180 min for the chromophore groups using both types of radiation. The degradation of the CTAB and aromatic groups was, meanwhile, an average of 25% when employing LED radiation. The behavior of the degradation reaction was pseudo-first-order. Toxicity tests indicated that the solutions were better able to grow seeds and bacteria after treatment with the photo-Fenton process, using both types of radiation. The photo-Fenton processes carried out by employing LED and UV-C photoreactors were able to degrade the CTAB and dye mixture, thus highlighting the efficiency of LED radiation when its power (three times smaller) is compared to that of UV-C radiation. This process, therefore, represents an alternative for use in textile wastewater treatment systems., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The aim of this study was to compare cell integrity indicators according to the playing position in university indoor football athletes., Methods: The sample consisted of 34 university athletes (20 female and 14 male). Dependent variables were cell integrity indicators: total body water (TBW), intracellular water (ICW), extracellular water (ECW), ECW/ICW ratio, body cell mass (BCM), ECW/BCM ratio, phase angle (PhA), resistance (R), Xc (reactance) and impedance (Z), evaluated by the electrical bioimpedance method. Independent variable was the playing position: goalkeeper (a), defender (a), winger (left and right) and pivot collected through questionnaire. Control variables were age, time of sport practice, participation in competitions per year and training load obtained by applying the anamnesis form, and body fat and fat and bone-free mass were obtained through dual emission X-ray absorptiometry (DXA). Covariance analysis (ANCOVA) was used, with post-hoc Tukey's test, to identify difference between groups, with P<0.05., Results: In the adjusted analysis, female athletes in the defense position had BCM values (31.1±2.1) higher than those in the wing position (25.8±1.1, P<0.01). In males, pivots showed higher ICW values (31.47±0.77) when compared to defenders (25.7±0.8, P=0.02). In addition, goalkeepers had higher TBW values (52.7±2.5) compared to wingers (42.3±1.2) (P=0.03)., Conclusions: Cell integrity indicators may vary according to the playing position in indoor football.

Soils are habitat to a variety of flora and fauna in a linked ecosystem which provides essential ecosystem services. In soil, metals can accumulate at high concentrations, because of anthropogenic activities, leading to toxic effects, threatening the ecosystem and the services it provides. In most real-world contamination scenarios, metals occur as complex mixtures which can interact and produce different toxicity than predicted from individual metal data. Current regulatory guidelines are based on single species responses to individual metals and ignore indirect effects inherent to the inter-linked nature of ecosystems. Also, the evaluation of anthropogenic impacts to the soil communities is usually measured through structural endpoints (e.g. abundance) disregarding functional measurements (e.g. organic matter decomposition rates), which are often seen as tightly related, and thus, similarly affected. In this study we tested three mixture ratios of five metal oxides (lead, copper, nickel, zinc, cobalt) at three dose levels (Low, Med, High) in a terrestrial model ecosystem experiment and measured structural and functional endpoints. Exposure to metal mixtures for 16 weeks did not affect the microarthropod community, but produced severe effects on soil microbial activity (PNR and DHA) reducing activity below 50% compared to control levels, in all dosed treatments. Metal contamination also significantly affected feeding activity and organic matter decomposition, but effects were not as pronounced as on microbial activity. Data suggest that, in the risk assessment of metals and their mixtures, effects on ecosystem structure and functions must be considered to provide adequate environmental protection., 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 © 2021 Elsevier B.V. All rights reserved.)

2,4-Dichlorophenoxyacetic acid (2,4-D) herbicide is the main ingredient in over 1500 commercially available products such as Weedestroy® AM40 and DMA® 4 IVM. Although the liver has been identified as one of the organs that are affected by this herbicide, reports on its hepatotoxic effects available in the literature are restricted to rats. Thus, there is a gap in information on other organisms that may be vulnerable to 2,4-D exposure, such as fish. Therefore, the present work aimed to assess the hepatotoxic potential of 2,4-D in fish using zebrafish (Danio rerio) larvae as a model system. For this purpose, its acute toxicity to zebrafish embryos was assessed, as well as its sublethal effects (< LC 50 ) on the activity of enzymes related to oxidative (GST, CAT and GPX) and metabolic (LDH) stress and liver parameters (AST, ALT and ALP) after 48 h of exposure. Morphological analyses of the liver were also assessed in zebrafish larvae. As a result, 2,4-D reduced larvae survival (LC 50 15.010 mg/L in 96 h of exposure), induced malformations, altered the activity of LDH, GST and CAT enzymes and significantly increased the activity of all biomarkers for liver damage. Although no changes in the color or size of larval liver were observed, histopathological analysis revealed that treatment with 2,4-D caused severe changes in liver tissue, such as vacuolization of the cytosol, eccentric cell nucleus, loss of tissue architecture and cellular boundaries. Thus, the results showed that 2,4-D altered the enzymatic profile related to oxidative stress, and induces liver damage., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The majority of coronavirus disease 2019 (COVID-19) have been confirmed in adults, with only a few reported cases in children. In the pediatric population, COVID-19 infection appears to be often unremarkable or associated with mild respiratory symptoms. Little is known about neurologic complications related to COVID-19 in newborns. We present a case of severe encephalitis with cytotoxic brain edema in a newborn with COVID-19., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Oyster production in Brazil has been highlighted as an important economic activity and is directly impacted by the quality of the environment, which is largely the result of human interference and climate change. Harmful algal blooms occur in aquatic ecosystems worldwide, including coastal marine environments which have been increasing over the last decades as a result of global change and anthropogenic activities. In this study, the native oysters Crassostrea gasar from Northeast of Brazil were exposed to two toxic benthic dinoflagellate species, Prorocentrum lima and Ostreopsis cf. ovata. Their respective effects on C. gasar physiology and defense mechanisms were investigated. Oyster hemocytes were first exposed in vitro to different concentrations of both dinoflagellate species to assess their effects on hemocyte functions, such as phagocytosis, production of reactive oxygen species, as well as mortality. Results highlighted an alteration of hemocyte phagocytosis and viability in presence of O. cf. ovata, whereas P. lima did not affect the measured hemocyte functions. In a second experiment, oysters were exposed for 4 days in vivo to toxic culture of O. cf. ovata to assess its effects on hemocyte parameters, tissues damages and pathogenic Perkinsus spp. infection. An increase in hemocyte mortality was also observed in vivo, associated with a decrease of ROS production. Histopathological analyses demonstrated a thinning of the epithelium of the digestive tubules of the digestive gland, inflammatory reaction and a significant increase in the level of infection by Perkinsus spp. in oysters exposed to O. cf. ovata. These results indicate that oysters C. gasar seem to be pretty resilient to an exposure to P. lima and may be more susceptible to O. cf. ovata. Furthermore, the latter clearly impaired oyster physiology and defense mechanisms, thus highlighting that harmful algal blooms of O. cf. ovata could potentially lead to increased susceptibility of C. gasar oysters to parasite infections., (Copyright © 2021. Published by Elsevier B.V.)

The goal of this study was to incorporate community data into the effect assessment of environmental and regulatory relevant metal mixtures. In this experiment three fixed mixture ratios (Canadian soil quality guideline ratio - CSQG; Agricultural, residential and Loamy ratio - ARL; and Sudbury ratio - SUD) were tested in a natural community microcosm with 11 doses for each mixture ratio. The effect of metal mixtures on the community was measured using the community effect concentration (EC) concept which assumes that as contamination increases, the community similarity between test and control treatments decreases producing a dose response curve allowing the calculation of community effect concentrations. In regulatory mixture ratios (CSQG and ARL) community EC10s were four times higher than regulatory thresholds and current regulation might be overprotective of the microarthropod communities in some soils. For the contaminated site ratio (SUD), the field dose in the contaminated site corresponded to a community EC20 and if metal concentrations were reduced by 1TU, (from 3.1TU to 2.1TU) effects would be below a community EC10. Overall, the community EC concept was successfully applied and has the potential for inclusion in risk assessment schemes as a measure of community response., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The choice of alternative donors for HCT for patients without an HLA-matched related donor depends on several factors. We compared major HCT outcomes in 212 consecutive children transplanted at 11 centers in Brazil for acute leukemia or MDS from an HLA-matched unrelated donor (MUD, n = 95), mismatched unrelated donor (MMUD, n = 47) or unrelated umbilical cord blood (UCB, n = 70). Most had ALL (61%), bone marrow (57%) as the graft source and 95% received a MAC regimen. The 3-year OS probability were 57, 55, and 37% after HCT from MUD, MMUD, and UCB, respectively (HR 1.68, 95%CI 1.07-2.63; P = .02). In comparison with MUD, OS was similar after transplantation of a ≥ 6/8 HLA-matched or a high cell dose (>5 × 10 7 TNC/kg) CB unit (HR 1.41, 95%CI 0.88-2.27; P = .15). NRM was higher for UCB (HR 3.90, 95%CI 1.43-10.7; P = .01) but not for MMUD (HR 1.03, 95%CI 0.53-2.00; P > .20). Advanced disease (HR 2.05, 95%CI 1.26-3.33; P < .001) and UCB with high probability of being < 6/8 HLA-matched (HR 5.34, 95%CI 2.0-13.9; P < .001) were associated with higher mortality. Relapse and acute GVHD were similar among groups, while PGF was higher among UCB transplants (P = .002) and chronic GVHD among MMUD group (HR 2.88, 95% CI 1.05-7.88; P = .04). Our results suggest that in Brazil HCT outcomes performed with MMUD and MUD donors were comparable, while with UCB units < 6/8 HLA-matched were associated with higher NRM for children with acute leukemia or MDS., (© 2020 Wiley Periodicals LLC.)

Background/aim: Studies with acridine compounds have reported anticancer effects. Herein, we evaluated the toxicity and antitumor effect of the (E)-1'-((4-chlorobenzylidene)amino)-5'-oxo-1',5'-dihydro-10H-spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-06), a promising anticancer spiro-acridine compound., Materials and Methods: The toxicity of AMTAC-06 was evaluated on zebrafish and mice. Antitumor activity was assessed in Ehrlich ascites carcinoma model. Effects on angiogenesis, cytokine levels and cell cycle were also investigated., Results: AMTAC-06 did not induce toxicity on zebrafish and mice (LD 50 approximately 5000 mg/kg, intraperitoneally). No genotoxicity was observed on micronucleus assay. AMTAC-06 significantly reduced the total viable Ehrlich tumor cells and increased sub-G 1 peak, suggesting apoptosis was triggered. Moreover, the compound significantly decreased the density of peritumoral microvessels, indicating an anti-angiogenic action, possibly dependent on the cytokine modulation (TNF-α, IL-1β and IFN-γ). No significant toxicological effects were recorded for AMTAC-06 on tumor transplanted animals., Conclusion: AMTAC-06 has low toxicity and a significant antitumor activity., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Bivalves were long thought to be "symptomless carriers" of marine microalgal toxins to human seafood consumers. In the past three decades, science has come to recognize that harmful algae and their toxins can be harmful to grazers, including bivalves. Indeed, studies have shown conclusively that some microalgal toxins function as active grazing deterrents. When responding to marine Harmful Algal Bloom (HAB) events, bivalves can reject toxic cells to minimize toxin and bioactive extracellular compound (BEC) exposure, or ingest and digest cells, incorporating nutritional components and toxins. Several studies have reported modulation of bivalve hemocyte variables in response to HAB exposure. Hemocytes are specialized cells involved in many functions in bivalves, particularly in immunological defense mechanisms. Hemocytes protect tissues by engulfing or encapsulating living pathogens and repair tissue damage caused by injury, poisoning, and infections through inflammatory processes. The effects of HAB exposure observed on bivalve cellular immune variables have raised the question of possible effects on susceptibility to infectious disease. As science has described a previously unrecognized diversity in microalgal bioactive substances, and also found a growing list of infectious diseases in bivalves, episodic reports of interactions between harmful algae and disease in bivalves have been published. Only recently, studies directed to understand the physiological and metabolic bases of these interactions have been undertaken. This review compiles evidence from studies of harmful algal effects upon bivalve shellfish that establishes a framework for recent efforts to understand how harmful algae can alter infectious disease, and particularly the fundamental role of cellular immunity, in modulating these interactions. Experimental studies reviewed here indicate that HABs can modulate bivalve-pathogen interactions in various ways, either by increasing bivalve susceptibility to disease or conversely by lessening infection proliferation or transmission. Alteration of immune defense and global physiological distress caused by HAB exposure have been the most frequent reasons identified for these effects on disease. Only few studies, however, have addressed these effects so far and a general pattern cannot be established. Other mechanisms are likely involved but are under-studied thus far and will need more attention in the future. In particular, the inhibition of bivalve filtration by HABs and direct interaction between HABs and infectious agents in the seawater likely interfere with pathogen transmission. The study of these interactions in the field and at the population level also are needed to establish the ecological and economical significance of the effects of HABs upon bivalve diseases. A more thorough understanding of these interactions will assist in development of more effective management of bivalve shellfisheries and aquaculture in oceans subjected to increasing HAB and disease pressures., Competing Interests: Declaration of competing interest Nothing to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Hepatitis A virus (HAV) infection is highly prevalent in developing countries. In countries experiencing a shift from intermediate/high endemicity to low endemicity, the World Health Organization recommends the incorporation of HAV vaccine into the national vaccination calendar for children aged ≥1 year. Since HAV antibodies wane over time, most HSCT revaccination guidelines advise vaccination as optional, following the country recommendation. However, no study has evaluated the serological response to HAV vaccine in allogeneic HSCT recipients., Methods: We conducted a prospective study in 46 HSCT recipients who received two doses of inactivated HAV vaccine. Blood samples were taken before vaccination to determine HAV prevalence rates, and before and 4-6 weeks after the second dose. Specific anti-HAV antibodies were detected by a competitive commercial enzyme immune assay., Results: Patients received the first dose of vaccine at a median of 332.5 (120-4134) days after HSCT. Median absolute lymphocyte count at vaccination was 1947 (696-12 500)/mm 3 . The seroprevalence rate was 93.5% at inclusion. Although safe and well tolerated, the serological response to HAV vaccine in susceptible patients was poor (33%), and no boost effect was observed in seropositive patients., Conclusions: In areas with intermediate/high seroprevalence of HAV, serology should be recommended prior to referral to vaccination. The mechanisms of antibody interference and how to overcome T-cell function deficiency need to be better understood in transplant populations receiving HAV vaccine. Alternative schedules of HAV vaccination should be evaluated in prospective trials., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The aim of the study was to identify, via headspace solid phase microextraction and gas chromatography-mass spectrometry, volatile compounds in eight no processing Apis mellifera L. honey samples produced in the state of Santa Catarina, Brazil, and monitor their stability over 540 days of storage at 20 ± 4 °C, searching for possible degradation indicators compounds. The result of the initial analysis showed the presence of 32 volatile compounds and 24 were selected for the evaluation of the behavior over the storage. The volatiles cis - and trans -linalool oxide and hotrienol showed increased over 540 days, except for one sample, which showed a decrease in the cis - and trans - linalool oxide contents. Other compounds (ethyl acetate, 1-hexanol. 2-ethyl, benzoic acid. ethyl ester, butanoic acid. 3-methyl, butanoic acid. 2-methyl, and salicylic acid. tert.-butyl ester) were detected in at least one sample from 360 days of storage. Considering the storage system applied, the compounds cis - and trans -linalool oxide and hotrienol, which were found in all samples and times evaluated, can be considered possible indicators compounds of degradation of honey., (© Association of Food Scientists & Technologists (India) 2019.)

Asthma is a chronic inflammatory disease of the airways characterized by immune cell infiltrates, bronchial hyperresponsiveness, and declining lung function. Thus, the possible effects of virgin coconut oil on a chronic allergic lung inflammation model were evaluated. Morphology of lung and airway tissue exhibited peribronchial inflammatory infiltrate, epithelial hyperplasia, and smooth muscle thickening in guinea pigs submitted to ovalbumin sensitization, which were prevented by virgin coconut oil supplementation. Additionally, in animals with lung inflammation, trachea contracted in response to ovalbumin administration, showed a greater contractile response to carbachol (CCh) and histamine, and these responses were prevented by the virgin coconut oil supplementation. Apocynin, a NADPH oxidase inhibitor, did not reduce the potency of CCh, whereas tempol, a superoxide dismutase mimetic, reduced potency only in nonsensitized animals. Catalase reduced the CCh potency in nonsensitized animals and animals sensitized and treated with coconut oil, indicating the participation of superoxide anion and hydrogen peroxide in the hypercontractility, which was prevented by virgin coconut oil. In the presence of L-NAME, a nitric oxide synthase (NOS) inhibitor, the CCh curve remained unchanged in nonsensitized animals but had increased efficacy and potency in sensitized animals, indicating an inhibition of endothelial NOS but ineffective in inhibiting inducible NOS. In animals sensitized and treated with coconut oil, the CCh curve was not altered, indicating a reduction in the release of NO by inducible NOS. These data were confirmed by peribronchiolar expression analysis of iNOS. The antioxidant capacity was reduced in the lungs of animals with chronic allergic lung inflammation, which was reversed by the coconut oil, and confirmed by analysis of peribronchiolar 8-iso-PGF2 α content. Therefore, the virgin coconut oil supplementation reverses peribronchial inflammatory infiltrate, epithelial hyperplasia, smooth muscle thickening, and hypercontractility through oxidative stress and its interactions with the NO pathway., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Luiz Henrique C. Vasconcelos et al.)

Tumor cells have specific features, including angiogenesis induction, cell cycle dysregulation, and immune destruction evasion. By inducing a T helper type 2 (Th2) immune response, tumor cells may favor immune tolerance within the tumor, which allows progression of cancer growth. Drugs with potential antitumor activity are the spiro-acridines, which is a promising new class of acridine compounds. Herein, the novel spiro-acridine ( E )-5'-oxo-1'-((3,4,5-trimethoxybenzylidene)amino)-1',5'-dihydro-10 H -spiro[acridine-9,2'-pyrrole]-4'-carbonitrile (AMTAC-17) was synthesized and tested for antitumor effects. Toxicity evaluation was performed in mice after acute treatment (2000 mg/kg, intraperitoneally, i.p.). The Ehrlich ascites carcinoma model was used to investigate the antitumor activity of AMTAC-17 (12.5, 25, or 50 mg/kg, i.p.) after seven days of treatment. Effects on the cell cycle, angiogenesis, and inflammatory responses were investigated. LD 50 (lethal dose 50%) was estimated to be higher than 5000 mg/kg. AMTAC-17 reduced the Ehrlich tumor's total viable cancer cells count and peritumoral micro-vessels density, and induced an increase in the sub-G1 peak. Additionally, there was an increase of Th1 cytokine profile levels (IL-1β, TNF-α, and IL-12). In conclusion, the spiro-acridine compound AMTAC-17 presents low toxicity, and its in vivo antitumor effect involves modulation of the immune system to a cytotoxic Th1 profile and a reduction of tumor angiogenesis.

The sarcotesta of Punica granatum fruit contains an antimicrobial lectin called PgTeL. In this work, we evaluated the antibacterial activity of PgTeL against five drug-resistant Escherichia coli isolates able to produce β-lactamases. Minimum inhibitory (MIC) and bactericidal (MBC) concentrations were determined by broth dilution. Morphometric and viability analyses were performed by flow cytometry, and ultrastructural changes were evaluated by scanning electron microscopy. Potential synergistic effects of PgTeL with antibiotics and anti-biofilm effect were also evaluated. PgTeL showed antibacterial activity against all isolates with MIC and MBC values ranging from 12.5 to 50.0 μg/mL and from 25.0 to 100.0 μg/mL, respectively. For most isolates, PgTeL postponed the growth start by at least ten hours. At the MIC, the lectin caused alterations in size, shape and structure of bacterial cells. The combination PgTeL-ceftazidime showed a synergistic effect for all isolates. Synergy was also detected with ampicillin (one isolate), carbenicillin (one isolate), cefotaxime (one isolate), cephalexin (four isolates) and cefuroxime (three isolates). PgTeL exhibited anti-biofilm activity against all isolates, causing ≥50% inhibition of biofilms at or above 6.25 μg/mL. The antibacterial effect of PgTeL and its synergy with antibiotics indicate that this fruit-derived molecule may have potential for future treatment of multidrug-resistant infections., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Portugal. Hypercholesterolemia has a causal role in atherosclerotic CVD. Guidelines recommend that cardiovascular (CV) risk reduction should be individualized and treatment goals identified. Low-density lipoprotein cholesterol (LDL-C) is the primary treatment target., Methods: DISGEN-LIPID was a cross-sectional observational study conducted in 24 centers in Portugal in dyslipidemic patients aged ≥40 years, on lipid-lowering therapy (LLT) for at least three months and with an available lipid profile in the previous six months., Results: A total of 368 patients were analyzed: 48.9% men and 51.1% women (93.9% postmenopausal), of whom 73% had a SCORE of high or very high CV risk. One quarter had a family history of premature CVD; 31% had diabetes; 26% coronary heart disease; 9.5% cerebrovascular disease; and 4.1% peripheral arterial disease. Mean baseline lipid values were total cholesterol (TC) 189 mg/dl, LDL-C 116 mg/dl, high-density lipoprotein cholesterol (HDL-C) 53.5 mg/dl, and triglycerides (TG) 135 mg/dl. Women had higher TC (p<0.001), LDL-C (non-significant) and HDL-C (p<0.001), and lower TG (p=0.002); 57% of men and 63% of women had LDL-C>100 mg/dl (p=0.28), and 58% of men and 47% of women had LDL-C>70 mg/dl (p=0.933)., Conclusion: These observational data show that, despite their high-risk profile, more than half of patients under LLT, both men and women, did not achieve the recommended target levels for LDL-C, and a large proportion also had abnormal HDL-C and/or TG. This is a renewed opportunity to improve clinical practice in CV prevention., (Copyright © 2019 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Lectins are carbohydrate-binding proteins broadly distributed in plants and have several biological functions, including antimicrobial action. Portulaca elatior is a Caatinga plant whose chemical composition and biotechnological potential have not been extensively studied. In this work, a lectin was isolated from P. elatior root extract and evaluated for antimicrobial activity. The P. elatior root lectin (PeRoL) showed native molecular mass of 33 kDa, pI 3.8 and is comprised of two subunits of 15 kDa linked by disulfide bonds. No sequence similarities with Viridiplantae proteins were observed. The PeRoL hemagglutinating activity (HA) was not affected by heating and was detected in a pH ranging from 4.0 to 8.0. Trehalose was identified as an endogenous inhibitor of PeRoL present in the roots. Bacteriostatic activity was detected against Enterococcus faecalis, Pseudomonas aeruginosa and Staphylococcus aureus (minimal inhibitory concentration of 8.1, 32.5 and 4.06 μg/mL, respectively). PeRoL induced the death of Candida albicans, Candida parapsilosis, Candida krusei, and Candida tropicalis cells, with a minimal fungicidal concentration of 16 μg/mL. The lectin (100 μg/mL) was not cytotoxic to human peripheral blood mononuclear cells (PBMCs) and did not show hemolytic activity. In conclusion, the roots of P. elatior contain a trehalose-binding, thermostable, and antimicrobial lectin., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Prorocentrum lima is a widely distributed marine benthic dinoflagellate that produces diarrhetic toxins, okadaic acid (OA) and its analogs, that may promote damage on bivalve tissues and cellular responses. Cultivation of the brown mussel Perna perna represents an important economic activity in the tropical and subtropical regions, where mussels may co-occur with P. lima. This study aimed to assess the behavioral, cellular immune responses, and pathological condition of P. perna following a short-term experimental exposure to P. lima. The toxic dinoflagellate treatment was compared to a non-toxic exposure to the chlorophyte Tetraselmis sp. at similar concentrations. The prevalence of pathological conditions and parasites were assessed, and a pathological index was applied by scoring the prevalences into four levels. Reaction time and the number of stimuli necessary for shell-valve closure response significantly increased after 72 h of P. lima exposure. Circulating hemocyte concentration was significantly lower in P. lima exposed mussels than in control mussels at 48- and 96 h of incubation, while hemocyte relative size in exposed mussels was significantly higher than that in control mussels. Comparatively, phagocytic activity and ROS production by hemocytes was significantly higher in mussels exposed to P. lima at 48- and 96 h of incubation, respectively. In addition, exposed mussels significantly presented exacerbated hemocytic infiltration in digestive organs, higher prevalence of moderate to severe atrophy in digestive tubules, and higher pathological index which suggests an impairment of mussel immunologic responses. A lower prevalence of Rickettsia-like organisms (RLOs), trematodes and copepods in P. lima exposed mussels suggests a direct toxic effect of OA on parasites. The exposure of mussels to P. lima is likely to occur frequently and may lead to constraints on mussel behavior, physiology, and pathological condition., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

In this work, we evaluated the ability of Punica granatum sarcotesta lectin (PgTeL) to impair the growth and viability of the Staphylococcus aureus clinical isolates 8325-4 (non-resistant) and LAC USA300 (MRSA strain). The effects of this lectin on aggregating, hemolytic activity, biofilm-forming ability, and expression of virulence genes (hla, rnaIII, and spa) were also investigated. PgTeL showed antibacterial activity against 8325-4 and LAC USA300 strains by interfering with both the growth (MIC 50 of 6.25 and 12.5 μg/mL, respectively) and survival (MBC values of 25.0 and 50.0 μg/mL, respectively). Culture growth started only at the ninth (8325-4) and tenth (LAC USA300) hour in the presence of PgTeL at MIC 50 , while growth was detected since the first hour in the control. The lectin caused markedly altered cell morphology in both the strains. Although, at the MIC 50 , PgTeL caused structural alterations, most cells were still viable, while at the MBC it promoted cell injury and death. PgTeL showed anti-aggregation effect and exhibited antibiofilm activity against both the isolates. However, the lectin did not interfere with the hemolytic activity of LAC USA300 and with the expression of hla, rnaIII, and spa genes. In conclusion, PgTeL is a lectin with multiple inhibitory effects on S. aureus clinical isolates., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Asthma is a heterogeneous disease of the airways characterized by chronic inflammation associated with bronchial and smooth muscle hyperresponsiveness. Currently, different murine models for the study of asthma show poor bronchial hyperresponsiveness due to a scarcity of smooth muscle and large airways, resulting in a failure to reproduce smooth muscle hyperreactivity. Thus, we aimed to standardize a guinea pig model of chronic allergic lung inflammation mimicking airway smooth muscle hyperreactivity observed in asthmatics (Asth). Animals were randomly divided into a control group (Ctrl), which received saline (0.9% NaCl), and the Asth group, subjected to in vivo sensitization with ovalbumin (OVA) nebulization. Morphological analysis was performed by hematoxylin-eosin staining. Bronchial hyperresponsiveness was evaluated by nebulization time in the fifth, sixth, and seventh inhalations (NT5-7) and tracheal isometric contractions were assessed by force transducer. Total antioxidant capacity was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method and protein expression by Western blot. Histologically, the Asth group developed peribronchial cellular infiltrate, epithelial hyperplasia and smooth muscle thickening. After the fourth nebulization, the Asth group developed bronchial hyperreactivity. The trachea from the Asth group contracted after in vitro stimulation with OVA, differing from the Ctrl group, which showed no response. Additionally, airway smooth muscle hyperreactivity to carbachol and histamine was observed in the Asth group only in intact epithelium preparations, but not to KCl, and this effect was associated with an augmented production of reactive oxygen species. Moreover, lung inflammation impaired the relaxant potency of isoproterenol only in intact epithelium preparations, without interfering with nifedipine, and it was found to be produced by transforming growth factor-β negative modulation of β adrenergic receptors and, furthermore, big-conductance Ca 2+ -sensitive K + channels. These effects were also associated with increased levels of phosphatidylinositol 3-kinases but not extracellular signal-regulated kinases 1/2 or phosphorylation, and augmented α-actin content as well, explaining the increased smooth muscle mass. Furthermore, pulmonary antioxidant capacity was impaired in the Asth group. Therefore, we developed a standardized and easy-to-use, reproducible guinea pig model of lung inflammation that mimics airway smooth muscle hypercontractility, facilitating the investigation of the mechanisms of bronchial hyperresponsiveness in asthma and new therapeutic alternatives.

Disseminated neoplasia (DN) is a disease that affects bivalves worldwide and can lead to mass mortalities. In the present study, a pathological survey conducted from December 2011 to August 2012 in Crassostrea gasar, an oyster of commercial interest in northeast Brazil, revealed the occurrence of DN in oysters reared in the Mamanguape estuary, Paraíba State, Brazil. The present work describes the pathological and functional aspects of the disease in C. gasar by light microscopy (haemolymph cell monolayer and histological section) and flow cytometry analyses. The prevalence of the disease was low (7.1% of 182 oysters examined). Enlarged (neoplastic) cells showed reniform, ovoid or circular-shaped nuclei, with prominent nucleoli and predominantly short filipodia. They were found in the haemolymph and infiltrated the connective tissues of different organs, including the digestive system, gills and gonads, as well as in the sinuses and vessels. Three levels of progression of DN in tissues were observed, light (61.5%), moderate (15.4%) and advanced (23.1%). The viability of neoplastic cells circulating in the haemolymph (97.4%) was similar to that in the haemocytes (95.7%). The neoplastic cells showed low phagocytic ability (3.9%) compared with that of haemocytes (42.4%). Conversely, reactive oxygen species production (679 A.U.) and the total haemocyte count (3.9 × 10 6  cells mL -1 ) were higher in the affected oysters than in unaffected oysters (268 A.U. and 1.5 × 10 6  cells mL -1 , respectively). The low prevalence and primarily mild intensity found in the sampled oysters does not preclude an impact at the population level. A timely survey of DN is thus recommended in order to assess the severity and impact of this disease in wild and cultured populations of C. gasar oysters., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Few studies have associated the effects of changes in caloric intake and redox disturbances in the gastrointestinal tract. Therefore, the present study aimed at evaluating the hypercaloric diet consumption influence on the contractile reactivity of intestinal smooth muscle, morphology, and oxidative stress of rat ileum. Wistar rats were randomly divided into groups that received a standard diet and fed with a hypercaloric diet for 8 weeks. Animals were euthanized, and the ileum was isolated to isotonic contraction monitoring. Morphology was evaluated by histological staining and oxidative stress by quantification of malondialdehyde levels and total antioxidant activity. Cumulative concentration-response curves to KCl and carbachol were attenuated in rats fed with a hypercaloric diet compared to those that received a standard diet. In addition, an increase in caloric intake promotes a rise in the thickness of the longitudinal smooth muscle layer of rat ileum and tissue malondialdehyde levels, characterizing lipid peroxidation, as well as a decrease in the antioxidant activity. Thus, it was concluded that the consumption of a hypercaloric diet impairs rat intestinal contractility due to mechanisms involving modifications in the intestinal smooth muscle architecture triggered by redox disturbances.

Perkinsus protozoan parasites have been associated with high mortality of bivalves worldwide, including Brazil. The use of antiproliferative drugs to treat the Perkinsosis is an unusual prophylactic strategy. However, because of their environment impact it could be used to control parasite proliferation in closed system, such as hatchery. This study evaluated the anti-Perkinsus activity potential of synthesized and commercial compounds. Viability of hypnospores of Perkinsus spp. was assessed in vitro. Cells were incubated with three 2-amino-thiophene (6AMD, 6CN, 5CN) and one acylhydrazone derivatives (AMZ-DCL), at the concentrations of 31.25; 62.5; 125; 250 and 500 μM and one commercial chlorinated phenoxy phenol derivative, triclosan (2, 5, 10 and 20 μM), for 24-48 h. Two synthetic molecules (6CN and AMZ-DCL) caused a significant decline (38 and 39%, respectively) in hypnospores viability, at the highest concentration (500 μM), after 48 h. Triclosan was the most cytotoxic compound, causing 100% of mortality at 20 μM after 24 h and at 10 μM after 48 h. Cytotoxic effects of the compounds 6CN, AMZ-DCL, and triclosan were investigated by measuring parasite's zoosporulation, morphological changes and metabolic activities (esterase activity, production of reactive oxygen species and lipid content). Results showed that zoosporulation occurred in few cell. Triclosan caused changes in the morphology of hypnospores. The 6CN and AMZ-DCL did not alter the metabolic activities studied whilst Triclosan significantly increased the production of reactive oxygen species and changed the amount and distribution of lipids in the hypnospores. These results suggest that three compounds had potential to be used as antiprotozoal drugs, although further investigation of their mechanism of action must be enlightened., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Even with the improvement in lifestyle interventions, a better control of cardiovascular (CV) risk factors, and improvements in CV outcomes, cardiovascular disease (CVD) still persists as the leading cause of morbidity and mortality in Portugal and Europe. Atherogenic dyslipidaemias, namely hypercholesterolaemia, have a crucial and causal role in the development of atherosclerotic CVD. The clinical approach of a patient with dyslipidaemia involves a watchful diagnosis, sustained in lipid and lipoprotein laboratory procedures, which must be harmonized and standardized. Standardization of lipid test results and reports, incorporating the total CV risk and the respective target and goals of treatment approach, guarantees that clinical guidelines and good clinical practices are followed and respected, increasing the reliability of lipid disorders screening, producing more accurate diagnoses and CV risk stratification, and improving the CV prevention and the achievement the desirable treatment goals., (Copyright © 2018. Published by Elsevier B.V.)

[This corrects the article DOI: 10.1186/s12959-018-0163-7.].

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are generally safe and well-tolerated drugs that are extensively used for the primary and secondary prevention of atherosclerotic cardiovascular events. Muscle and liver adverse reactions are the best recognized, while cutaneous side effects are exceedingly rare. We present the case of a 65-year-old woman with severe hypercholesterolemia, who developed generalized erythematous cutaneous lesions with pruritus, resembling lichen planus, months after starting treatment with simvastatin. The symptoms disappeared on withdrawal of simvastatin and reappeared within 3 months upon rechallenge with rosuvastatin. In addition to describing a rare adverse effect of statins, the authors also discuss the nutraceutical approach to the management of a statin-intolerant patient., Learning Points: Lichenoid drug eruption is an uncommon cutaneous adverse effect of several drugs, with very few cases associated with statins.A temporal relationship, dechallenge/rechallenge information, and the lack of confounding factors or alternative explanations support the suggestion of causality.Due to the lack of optimized alternative treatment options for statin-intolerant patients, the nutraceutical approach should be considered., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests.

Background: Venous thromboembolism (VTE, including deep vein thrombosis [DVT] and pulmonary embolism [PE]) has an annual incidence rate of 104-183 per 100,000 person-years. After a VTE episode, the two-year recurrence rate is about 17%. Consequently, effective and safe anticoagulation is paramount. Edoxaban is a direct oral anticoagulant (DOAC) approved VTE treatment. Current safety and efficacy data are derived from clinical trials, and information about treatment durations beyond 12 months are not available., Methods: ETNA-VTE-Europe is an 18-month prospective, single-arm, non-interventional, multinational post-authorisation safety study. Approximately 310 sites across eight European countries (Austria, Belgium, Germany, Ireland, Italy, the Netherlands, Switzerland and the United Kingdom) will participate in the study, with the intention to represent the regional distributions of centres, healthcare settings and specialties. An estimated cohort of 2700 patients will be recruited, the only enrolment criteria being acute symptomatic VTE, no participation in an interventional study, and treating physician decision to prescribe edoxaban independently from the registry. Data from patient medical records and/or telephone interviews will be collected at baseline, 1, 3, 6, 12 and 18 months. The primary objective is to evaluate the 18-month rate of symptomatic VTE recurrence in patients with VTE treated with edoxaban outside a clinical trial. The co-primary objective is to evaluate the real-world rates of bleeding and adverse drug reactions. Secondary outcomes include rates of other patient-relevant safety events, adherence to and discontinuation of edoxaban. Furthermore, 12-month ETNA-VTE-Europe data will be considered in the context of those for patients receiving different anticoagulants in the PREFER in VTE registry and Hokusai-VTE clinical trial., Conclusions: ETNA-VTE-Europe will allow the safety and effectiveness of edoxaban to be evaluated over an extended period in acute symptomatic VTE patients encountered in routine clinical practice. Findings will be informative for European practitioners prescribing edoxaban as part of real-world VTE treatment/prevention., Trial Registration: ClinicalTrials.gov Identifier: NCT02943993., Competing Interests: Approval from the responsible ethics committees and institutional review boards will be obtained prior to protocol implementation. Informed consent will be obtained from all patients prior to enrolment and compliance with the Declaration of Helsinki will be ensured throughout the study.Not applicable.The members of the Steering Committee received honoraria for their advice in the planning of the Registry. They also received honoraria and travel reimbursements from Daiichi Sankyo Europe GmbH for their participation in Steering Committee Meetings. Alexander T. Cohen, Hervé Décousus, Pedro Marques da Silva, David Jimenez Castro, Beatrice Amann-Vesti, Bernd Brüggenjürgen, Eric Vicaut and Giancarlo Agnelli have received research support and/or honoraria for lectures from a number of pharmaceutical companies including Daiichi Sankyo, the sponsor of the registry. Cihan Ay received honoraria for lectures from Sanofi, Pfizer/BMS, Daiichi-Sankyo, Boehringer Ingelheim, and Bayer. Advisory board membership for Pfizer/BMS, Daiichi-Sankyo, Boehringer Ingelheim, and Bayer. Philippe Hainaut received honoraria from Daiichi Sankyo Europe GmbH for lectures and advisory board membership. Ulrich Hoffmann received honoraria for lectures from Bayer, Daiichi-Sankyo, Leo Pharma, Pfizer, Bristol-Meyers, Aspen, Sanofi-Aventis, Amgen. Advisory board membership for Bayer, Daiichi-Sankyo, Leo Pharma, Sanofi-Aventis, and Amgen. Sean Gaine received honoraria for lectures from Actelion Pharmaceuticals Ltd., Bayer, GlaxoSmithKline, Merck Sharpe & Dohme, and has received advisory and/or drug safety board fees from Astra Zeneca, Actelion Pharmaceuticals Ltd., Bayer, GlaxoSmithKline, Novartis, Pfizer and Daiichi-Sankyo, Menerini, and United Therapeutics. Michiel Coppens has received research funding and honoraria for consultancy or lecturing from Daiichi Sankyo, Boehringer Ingelheim, Bayer, Bristol-Myers Squibb and Pfizer. Pierre Levy received honoraria for lectures from AbbVie, Amgen, Gilead, GSK, Novo Nordisk, ViiV. Advisory board membership for AbbVie, Actelion, Amgen, Astellas, Bayer, Biogen, Boehringer Ingelheim, Celgène, Daiichi Sankyo, Eli Lilly, EOS, GSK, Janssen, MSD, Mundipharma, Novartis, Pfizer, Roche, Shire, Vertex. Julio Lopez Bastida received honoraria from Daiichi Sankyo. Petra Laeis, Eva-Maria Fronk, Wolfgang Zierhut, and Thomas Malzer are employees of Daiichi Sankyo Europe GmbH. Peter Bramlage received research funding and consultancy honoraria from Daiichi Sankyo Europe GmbH. He further received funding for drafting the manuscript. The members of the Steering Committee received honoraria and travel reimbursements from Daiichi Sankyo Europe GmbH for their participation in Steering Committee Meetings.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.