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Herpes simplex virus (HSV) infections can occur throughout life, thereby allowing transmission to new hosts, with an impact on public health. Acyclovir remains the treatment of choice for these infections; however, an increase in resistant strains in recent years has been observed. In this study, the activity of a native Delonix regia galactomannan (NDr) against HSV-1 was investigated in vitro. NDr was characterized using infrared spectroscopy and NMR. Evaluation of cytotoxicity and the antiviral effect was determined, respectively, by MTT and plaque reduction assays. The NDr concentrations that inhibited cell viability (CC 50 ) and viral infection (IC 50 ) by 50% were above 2000 and 64 μg/mL, respectively. Thus, the polysaccharide showed a high selectivity index (> 31.25). When NDr was added at different stages of HSV-1 replication, a strong inhibitory effect was found by direct interaction with the virus (71-67%, virucidal effect) or previously with the cell, 6 h before infection (99.8-68.4%, prophylactic effect) at concentrations from 200 to 50 μg/mL. NDr showed similar effects in prophylactic 1 h (52%) and adsorption inhibition (55%) assays at 200 μg/mL. A reduction in the antiherpetic effect was observed after infection. These results suggest that NDr is effective in the early stages of HSV-1 infection and is a promising agent for controlling herpetic infections., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The Human Respiratory Syncytial Virus (RSV) is the leading cause of acute respiratory infections in children. Currently, no safe, effective, or feasible option for pharmacological management of RSV exists. Hence, plant-derived natural compounds have been explored as promising antiviral agents. Mangifera indica is a globally distributed plant with reported anti-inflammatory, cardioprotective, and antiviral activities. Our study investigated the antiviral potential of a novel pectin from M. indica peels (PMi) and its chemically sulfated derivative (PSMi) against RSV in HEp-2 cells. The compounds were characterized using Fourier-transform infrared spectroscopy and nuclear magnetic resonance (NMR). NMR analysis revealed the presence of ester and carboxylic acid groups in PMi, and sulfation resulted in a sulfation degree of 0.5. PMi and PSMi showed no cytotoxic effects even at concentrations as high as 2000 μg/mL. PSMi completely inhibited RSV infectivity (100-1.56 μg/mL, 50 % inhibitory concentration of viral infectivity = 0.77 ± 0.11 μg/mL). The mechanism of action was investigated using the 50 % tissue culture infectious dose assay . PSMi displayed virucidal activity at concentrations from 100 to 6.25 μg/mL, and a significant reduction in viral infection was observed at all treatment times. Overall, PSMi is antiviral, cell-safe, and exhibits promising potential as an RSV treatment., 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 B.V. All rights reserved.)

We report a 12-month-old boy with a skin eruption that developed 15 days after receiving the measles, mumps, rubella (MMR), pneumococcal, and meningococcal vaccines, consistent with the diagnosis of Wells syndrome. Patch testing showed a positive reaction to gelatin, which is used as a stabilizer for both live and inactivated vaccines. Gelatin was only present in the MMR vaccine., (© 2024 Wiley Periodicals LLC.)

This study aimed to investigate the anti-inflammatory and wound healing effects of the polysaccharide extract from Opuntia ficus-indica cladodes (TPL-Ofi) using a rat cutaneous wound model. After anaesthesia, four 7-mm-diameter dorsal wounds per animal (n = 6/group for each experimental day of evaluation) were created in female Wistar rats using a surgical punch. The animals were treated topically twice daily with TPL-Ofi (0.01-1%; treated group) or sterile saline (control group) for a period of 21 days. Ulcerated tissue was collected for analysis of histological parameters (inflammation score, number of polymorphonuclear, mononuclear, fibroblast/myofibroblasts and blood vessels), immunohistochemical (fibroblast growth factor 2 [FGF-2]) and oxidative stress markers (myeloperoxidase [MPO] and glutathione [GSH]). After 21 days of treatment, body weight, net organ weight and plasma biochemical levels were measured. TPL-Ofi, containing a total carbohydrate content of 65.5% and uronic acid at 2.8%, reduced oedema on the second day and increased the nociceptive threshold on the second and third days. TPL-Ofi reduced mononuclear infiltrate on the second and MPO activity on the fifth day. TPL-Ofi increased GSH levels on the second day, as well as fibroblast/myofibroblasts counts, neoangiogenesis and FGF-2 levels on the fifth and seventh days. No changes were observed in body weight, net organ weight or toxicology assessment. Topical application of TPL-Ofi exhibited anti-inflammatory and antinociceptive effects, ultimately improving wound healing in cutaneous wounds., (© 2023 Company of the International Journal of Experimental Pathology (CIJEP).)

Bacterial pathogens are leading causes of infections with high mortality worldwide having a great impact on healthcare systems and the food industry. Gold standard methods for bacterial detection mainly rely on culture-based technologies and biochemical tests which are laborious and time-consuming. Regardless of several developments in existing methods, the goal of achieving high sensitivity and specificity, as well as a low detection limit, remains unaccomplished. In past years, various biorecognition elements, such as antibodies, enzymes, aptamers, or nucleic acids, have been widely used, being crucial for the pathogens detection in different complex matrices. However, these molecules are usually associated with high detection limits, demand laborious and costly production, and usually present cross-reactivity. (Bacterio)phage-encoded proteins, especially the receptor binding proteins (RBPs) and cell-wall binding domains (CBDs) of endolysins, are responsible for the phage binding to the bacterial surface receptors in different stages of the phage lytic cycle. Due to their remarkable properties, such as high specificity, sensitivity, stability, and ability to be easily engineered, they are appointed as excellent candidates to replace conventional recognition molecules, thereby contributing to the improvement of the detection methods. Moreover, they offer several possibilities of application in a variety of detection systems, such as magnetic, optical, and electrochemical. Herein we provide a review of phage-derived bacterial binding proteins, namely the RBPs and CBDs, with the prospect to be employed as recognition elements for bacteria. Moreover, we summarize and discuss the various existing methods based on these proteins for the detection of nosocomial and foodborne pathogens.

For more than three decades, major efforts in sampling and analyzing tree diversity in South America have focused almost exclusively on trees with stems of at least 10 and 2.5 cm diameter, showing highest species diversity in the wetter western and northern Amazon forests. By contrast, little attention has been paid to patterns and drivers of diversity in the largest canopy and emergent trees, which is surprising given these have dominant ecological functions. Here, we use a machine learning approach to quantify the importance of environmental factors and apply it to generate spatial predictions of the species diversity of all trees (dbh ≥ 10 cm) and for very large trees (dbh ≥ 70 cm) using data from 243 forest plots (108,450 trees and 2832 species) distributed across different forest types and biogeographic regions of the Brazilian Amazon. The diversity of large trees and of all trees was significantly associated with three environmental factors, but in contrasting ways across regions and forest types. Environmental variables associated with disturbances, for example, the lightning flash rate and wind speed, as well as the fraction of photosynthetically active radiation, tend to govern the diversity of large trees. Upland rainforests in the Guiana Shield and Roraima regions had a high diversity of large trees. By contrast, variables associated with resources tend to govern tree diversity in general. Places such as the province of Imeri and the northern portion of the province of Madeira stand out for their high diversity of species in general. Climatic and topographic stability and functional adaptation mechanisms promote ideal conditions for species diversity. Finally, we mapped general patterns of tree species diversity in the Brazilian Amazon, which differ substantially depending on size class., (© 2023 John Wiley & Sons Ltd.)

Herein, A microfluidic device is described, produced with a 3D-printed master mould that rapidly separates and concentrates Escherichia coli directly from whole blood samples, enabling a reduction in the turnaround time of bloodstream infections (BSIs) diagnosis. Moreover, it promotes the cleansing of the blood samples whose complexity frequently hampers bacterial detection. The device comprises a serpentine mixing channel with two inlets, one for blood samples (spiked with bacteria) and the other for magnetic nanoparticles (MNPs) functionalized with a (bacterio)phage receptor-binding protein (RBP) with high specificity for E. coli. After the magnetic labelling of bacteria throughout the serpentine, the microchannel ends with a trapping reservoir where bacteria-MNPs conjugates are concentrated using a permanent magnet. The optimized sample preparation device successfully recovered E. coli (on average, 66%) from tenfold diluted blood spiked within a wide range of bacterial load (10 2  CFU to 10 7  CFU mL -1 ). The non-specific trapping, tested with Staphylococcus aureus, was at a negligible level of 12%. The assay was performed in 30 min directly from diluted blood thus presenting an advantage over the conventional enrichment in blood cultures (BCs). The device is simple and cheap to fabricate and can be tailored for multiple bacterial separation from complex clinical samples by using RBPs targeting different species. Moreover, the possibility to integrate a biosensing element to detect bacteria on-site can provide a reliable, fast, and cost-effective point-of-care device., (© 2023. The Author(s).)

During the austral winter (June-August) of 2021, the meteorological services of Brazil, Argentina, Peru, Paraguay, Bolivia, and Chile all issued forecasts for unusually cold conditions. Record-low minimum temperatures and cold spells were documented, including one strong cold wave episode that affected 5 countries. In this study, we define a  cold wave as a period in which daily maximum and minimum air temperatures are below the corresponding climatological 10th percentile for three or more consecutive days. The intense cold wave event in the last week of June, 2021, resulted in record-breaking minimum daily temperatures in several places in central South America and Chile. Several locations had temperatures about 10 °C below average, central South America had freezing conditions, and southern Brazil even saw snow. The cold air surge was characterized by an intense upper-air trough located close to 35° S and 70° W. The southerly flow to the west of this trough brought very cold air northward into subtropical and tropical South America. A northward flow between the lower-level cyclonic and anticyclonic perturbations caused the intense southerly flow between the upper-level ridge and trough. This condition facilitated the inflow of near-surface cold air from southern Argentina into southeastern Brazil and tropical South America east of the Andes. In the city of São Paulo, the cold wave caused the death of 13 homeless people from hypothermia. Frost and snow across southern and southeastern Brazil caused significant damage to coffee, sugarcane, oranges, grapes, and other fruit and vegetable crops. Wine and coffee production fell, the latter by 30%, and prices of food and commodities in the region rose., Supplementary Information: The online version contains supplementary material available at 10.1007/s00382-023-06701-1., Competing Interests: Conflict of interestThe authors declare having no competing interests., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

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Escherichia coli is a problematic pathogen that causes life-threatening diseases, being a frequent causative agent of several nosocomial infections such as urinary tract and bloodstream infections. Proper and rapid bacterial identification is critical for allowing prompt and targeted antimicrobial therapy. (Bacterio)phage receptor-binding proteins (RBPs) display high specificity for bacterial surface epitopes and, therefore, are particularly attractive as biorecognition elements, potentially conferring high sensitivity and specificity in bacterial detection. In this study, we elucidated, for the first time, the potential of a recombinant RBP (Gp17) to recognize E. coli at different viability states, such as viable but not culturable cells, which are not detected by conventional techniques. Moreover, by using a diagnostic method in which we combined magnetic and spectrofluorimetric approaches, we demonstrated the ability of Gp17 to specifically detect E. coli in various human specimens (e.g., whole blood, feces, urine, and saliva) in about 1.5 h, without requiring complex sample processing., 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 Costa, Cunha, Freitas and Carvalho.)

Several large-scale drivers of both anthropogenic and natural environmental changes are interacting nonlinearly in the transition zone between eastern Amazonia and the adjacent Cerrado, considered to be another Brazilian agricultural frontier. Land-use change for agrobusiness expansion together with climate change in the transition zone between eastern Amazonia and the adjacent Cerrado may have induced a worsening of severe drought conditions over the last decade. Here we show that the largest warming and drying trends over tropical South America during the last four decades are observed to be precisely in the eastern Amazonia-Cerrado transition region, where they induce delayed wet-season and worsen severe drought conditions over the last decade. Our results evidence an increase in temperature, vapor pressure deficit, subsidence, dry-day frequency, and a decrease in precipitation, humidity, and evaporation, plus a delay in the onset of the wet season, inducing a higher risk of fire during the dry-to-wet transition season. These findings provide observational evidence of the increasing climatic pressure in this area, which is sensitive for global food security, and the need to reconcile agricultural expansion and protection of natural tropical biomes., (© 2022. The Author(s).)

The objective of the study was to prepare active films based on pectin and polyphenol-rich extracts from Tommy Atkins mango peels. Aqueous and methanolic extracts showed a variety of phenolic compounds that were identified by UPLC-MS analysis, and a high content of total phenolics that were quantified by the Folin-Ciocalteau method. The methanolic extract showed better results in antioxidant tests and was more effective in inhibiting the growth of Gram-positive and Gram-negative bacteria. The pectin extracted from mango peels showed good thermal stability and a degree of methoxylation of 58.3% by 1 H NMR. The films containing the phenolic extracts showed lower water vapor permeability when compared to the control film (without any phenolic extracts). The incorporation of the extracts led to an increase in elongation (ε) and a decrease in tensile strength (σ) and modulus of elasticity (Y). The films with aqueous or methanolic extracts showed higher antioxidant activity in terms of inhibition of the DPPH radical. Therefore, the films developed in this work are presented as a promising alternative for food packaging and/or coating applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Myeloid suppressor cells promote tumor growth by a variety of mechanisms which are not fully characterized. We identified myeloid cells (MCs) expressing the latency-associated peptide (LAP) of TGF-β on their surface and LAP Hi MCs that stimulate Foxp3 + Tregs while inhibiting effector T cell proliferation and function. Blocking TGF-β inhibits the tolerogenic ability of LAP Hi MCs. Furthermore, adoptive transfer of LAP Hi MCs promotes Treg accumulation and tumor growth in vivo . Conversely, anti-LAP antibody, which reduces LAP Hi MCs, slows cancer progression. Single-cell RNA-Seq analysis on tumor-derived immune cells revealed LAP Hi dominated cell subsets with distinct immunosuppressive signatures, including those with high levels of MHCII and PD-L1 genes. Analogous to mice, LAP is expressed on myeloid suppressor cells in humans, and these cells are increased in glioma patients. Thus, our results identify a previously unknown function by which LAP Hi MCs promote tumor growth and offer therapeutic intervention to target these cells in cancer., Competing Interests: A patent for the use of anti-LAP antibodies for cancer treatment has been issued., (© 2021 The Authors.)

Provoked by sterile/nonsterile insults, prolonged monocyte mobilization and uncontrolled monocyte/macrophage activation can pose imminent or impending harm to the affected organs. Curiously, folate receptor beta (FRβ), with subnanomolar affinity for the vitamin folic acid (FA), is upregulated during immune activation in hematopoietic cells of the myeloid lineage. This phenomenon has inspired a strong interest in exploring FRβ-directed diagnostics/therapeutics. Previously, we have reported that FA-targeted aminopterin (AMT) therapy can modulate macrophage function and effectively treat animal models of inflammation. Our current investigation of a lead compound (EC2319) leads to discovery of a highly FR-specific mechanism of action independent of the root causes against inflammatory monocytes. We further show that EC2319 suppresses interleukin-6/interleukin-1β release by FRβ + monocytes in a triple co-culture leukemic model of cytokine release syndrome with anti-CD19 chimeric antigen receptor T cells. Because of its chemical stability and metabolically activated linker, EC2319 demonstrates favorable pharmacokinetic characteristics and cross-species translatability to support future pre-clinical and clinical development., Competing Interests: I.R.V., C.P.L., F.Y., P.J.K., and Y.J.L. hold a patent in Japan (JP 6772186) for the design and synthesis of EC2319. There is a patent pending in the United States., (© 2021 Novartis Pharmaceuticals.)

Nosocomial or hospital-acquired infections (HAIs) have a major impact on mortality worldwide. Enterococcus and Staphylococcus are among the leading causes of HAIs and thus are important pathogens to control mainly due to their increased antibiotic resistance. The gold-standard diagnostic methods for HAIs are time-consuming, which hinders timely and adequate treatment. Therefore, the development of fast and accurate diagnostic tools is an urgent demand. In this study, we combined the sensitivity of magnetoresistive (MR) sensors, the portability of a lab-on-chip platform, and the specificity of phage receptor binding proteins (RBPs) as probes for the rapid and multiplex detection of Enterococcus and Staphylococcus. For this, bacterial cells were firstly labelled with magnetic nanoparticles (MNPs) functionalized with RBPs and then measured on the MR sensors. The results indicate that the RBP-MNPS provided a specific individual and simultaneous capture of more than 70% of Enterococcus and Staphylococcus cells. Moreover, high signals from the MR sensors were obtained for these samples, providing the detection of both pathogens at low concentrations (10 CFU/ml) in less than 2 h. Overall, the lab-on-chip MR platform herein presented holds great potential to be used as a point-of-care for the rapid, sensitive and specific multiplex diagnosis of bacterial infections., (© 2021 Wiley Periodicals LLC.)

Purpose: To reduce false-negative rates (FNR) in sentinel lymph node biopsy (SLNB) of clinically positive (cN+) axilla in patients undergoing neoadjuvant chemotherapy (NAC). The removal of three or more lymph nodes with dual-tracer mapping including a radioisotope was used. However, in the Brazilian Unified Health System, the radioisotope tracer is not feasible in some hospitals. We conducted a cross-sectional study to evaluate the detection rate of sentinel lymph node (SLN) in patients who converted from cN+ to ycN0 after NAC using blue dye as a single-agent mapping tracer., Methods: During the period of March 2018 to September 2019, 34 patients who underwent NAC with cN+ who converted to ycN0 were enrolled in the study. The SLNB was performed using blue dye as a single-agent mapping followed by axillary lymph node dissection (ALND)., Results: The detection rate of sentinel lymph node was of 85.3%, being SLNB not possible for five patients (14.7%), due to fibrosis. The mean number of removed SLN was 2.5., Conclusions: The use of blue dye as a single-agent mapping tracer demonstrated an acceptable detection rate of 85.3%. Although the FNR was possible to be determined, the small sample size might overestimate this rate. The removal of three or more lymph nodes with single-agent mapping tracer might be indicated for breast cancer patients who converted to ycN0 after NAC in the Brazilian health public services, in which radioisotope tracer is not suitable.

This study aimed to isolate, characterize chemical-structurally and evaluate the effects of polysaccharides from Caesalpinia (Libidibia) ferrea stem barks in the haemostatic system. The deproteinated-polysaccharide extract (PE-Cf) after being fractionated by ion exchange chromatography-DEAE-cellulose resulted in three fractions (FI, FII, FIII) containing total carbohydrates (14.3-38%), including uronic acid (5-16%), and polyphenols (0.94-1.7 mg/g GAE). The polysaccharide fractions presented polydisperse profile in polyacrylamide gel electrophoresis (detected by Stains-All) and molecular masses (9.5 × 10 4  Da-1.5 × 10 5  Da) identified by gel permeation chromatography. FT-IR showed absorption bands (1630 cm -1 , 1396-1331 cm -1 ), indicative of uronic acid, and a band at 1071 cm -1 , typical of COO - groups of galacturonic acid. The NMR spectra of C. ferrea polysaccharides revealed a central core composed mainly by 5-linked α-Araf and minority components as α-Rhap and α-GalAp. UV spectra of fractions revealed discrete shoulders at 269-275 nm, characteristic of polyphenolic compounds. In vitro, polysaccharides inhibited the intrinsic and/or common coagulation pathway (aPTT test) (2.0-3.7 fold) and the platelet aggregation induced by 3 μM adenosine diphosphate (25-48%) and 5 μg/mL collagen (24%), but not that induced by arachidonic acid. In vivo, the polysaccharides inhibited (36-69%) venous thrombosis induced by hypercoagulability and stasis, showing discrete hemorrhagic effect. In conclusion, the polysaccharides of C. ferrea barks, containing arabinose, galactose, rhamnose and uronic acid, possess anticoagulant, antiplatelet and antithrombotic properties of low hemorrhagic risk, suggesting potential applicability in thromboembolic disorders., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The herpes simplex virus, also known as HSV, is an important human pathogen. Acyclovir (ACV) is the first-line antiviral for the treatment of HSV infections; nevertheless HSV resistance to ACV has been increasingly reported and, therefore, search for alternative drugs have been encouraged. Herein, the effect of Cucumis melo sulfated pectin (SPCm) was evaluated in the HSV-1 infection. Pectin cytotoxicity and its antiherpetic action were determined by assays of MTT and plaque reduction, respectively. The SPCm concentration that reduced the cell viability by 50% (CC50) was 1440 μg/mL, while the concentration that reduced PFU in 50% (IC50) was 6 μg/mL against ACV-sensitive (KOS) strain and 12 μg/mL for ACV-resistant (AR-29) strain. The pectin showed high selectivity index (SI) for both viral strains. Therefore, we suggest that SPCm has been effective for HSV-1, strenghten by viral protein and DNA syntheses inhibition. In conclusion, we have found that SPCm is a promising alternative compound to control HSV infection., (© The Author(s) 2021. Published by Oxford University Press on behalf of FEMS.)

Objective: To compare the performance, reliability, and validity of functional tests between women with and without patellofemoral pain., Methods: Twenty women with a diagnosis of patellofemoral pain between 18 and 40 years of age and 20 age-matched pain-free controls participated in the study. All participants performed a set of five function tests: sitting-rising test, sit-to-stand in 30 seconds, stair-climb test, stair descent test, and six-minute step test. To investigate reliability, participants were assessed on two different days, seven days apart, by two independent investigators blinded to the results of the other investigator. Validity was evaluated through associations with the results on the Anterior Knee Pain Scale., Results: Performance in the tests was worse in women with patellofemoral pain than in the control group for the sit-to-stand in 30 seconds (mean difference [MD] 3.4reps; 95%CI: 0.4, 6.4), stair-climb test (MD: 0.36s; 95%CI: 0.1, 0.63), and six-minute step test (MD: 45reps; 95%CI: 20, 70). No differences were observed for the sitting-rising and stair descent tests. All tests in both groups showed moderate to excellent intra- and inter-rater reliability (intraclass correlation coefficients: 0.61 to 0.91 and 0.72 to 0.96, respectively). Finally, only the results on the sit-to-stand in 30 seconds test correlated with the Anterior Knee Pain Scale (r=0.44, p=0.047) in the patellofemoral pain group., Conclusion: Women with patellofemoral pain present lower performance on some functional tests. Functional tests are reliable in patients with patellofemoral pain, although they are not associated with the results on the Anterior Knee Pain Scale self-questionnaire., (Copyright © 2020 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: There are distinct differences in the implementation of physiotherapeutic care in nursing homes. Both nationally and internationally staffing levels of physiotherapy differ significantly between and within nursing homes. Since legislation or guidelines that specify the parameters of physiotherapy required in nursing homes are lacking, it is unknown how physiotherapists currently estimate the usefulness and necessity of physiotherapy in individual situations in long-term care. The purpose of this study was to describe how physiotherapists actually work, and how they want to work, in daily practice in Dutch nursing homes., Methods: We performed a qualitative study with an online questionnaire. We asked 72 physiotherapists working in Dutch nursing homes to describe as accurately as possible usual care in nine different cases in long-term care. Furthermore we asked them to describe their role in the prevention and treatment of a number of indicators that measure the quality of care in nursing homes. Two reviewers thematically analysed the answers to the questionnaires., Results: Forty-six physiotherapists returned the questionnaire. Physiotherapy services include active exercise therapy aimed to improve mobility and movement dysfunctions, advising on prevention and management of falls, pressure ulcers, incontinence, malnutrition and sarcopenia, overweight, physical restraints, intertrigo, chronic wounds, behavioural and psychological symptoms in dementia, and physical inactivity, and ergonomic and behavioural training. The way and extent in which physiotherapists are involved in the various care- and functional problems differs and depends on organisational and personal factors such as, organisation's policy, type of ward, time pressure, staffing level, collaboration with other members of the multidisciplinary team, or lack of knowledge., Conclusion: Physiotherapists in nursing homes are involved in the prevention and management of different care situations and functional problems. The way in which they are involved differs between physiotherapist. Aiming for more uniformity seems necessary. A shared vision can help physiotherapists to work more consistently and will strengthen their position in nursing homes.

The aim of the study was to produce and characterize chitosan microparticles loaded with essential oils (CMEOs), evaluate the essential oil (EO) release profile and the CMEOs' anti-Candida activity. The chitosan microparticles (CMs) loaded with lemongrass essential oil (LEO) and geranium essential oil (GEO) were produced by the spray-drying method and characterized regarding CMEO morphological and physicochemical parameters and EO encapsulation efficiency (EE) and release profile. The planktonic activity was quantified by broth microdilution, and the activity against biofilm was quantified by biomass formation measurement. The LEO and GEO compositions were analyzed by gas chromatography combined with mass spectrometry (GC/MS), finding the main components citral (83.17%) and citronellol (24.53%). The CMs and CMEOs showed regular distribution and spherical shape (1 to 15 μm), without any morphological and physical modifications after EO incorporation. EE% ranged from 12 to 39%. In vitro release tests demonstrated the EO release rates, after 144 h, were 33% and 55% in PBS and HCl media, respectively. The minimum inhibitory concentration (MIC) values for CMEOs were lower than for CMs and pure EOs (P < 0.05). The higher CMEO biofilm inhibition percentage demonstrates the efficiency of microparticles against Candida biofilm. These results indicate that CMEOs are promising compounds that have antibiofilm activity against C. albicans., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In a single day, six of 150 (4%) asymptomatic visitors were diagnosed with COVID-19 at a hospital with a universal masking policy. Two inpatients (contacts) subsequently developed symptoms. More rigorous protective measures during visitation periods may need to be included in infection control practices to reduce nosocomial transmissions., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Xylan extracted from corn cobs was used to produce mesalamine-loaded xylan microparticles (XMP5-ASA) by cross-linking polymerization using a non-hazardous cross-linking agent. The microparticles were characterized by thermal analysis (DSC/TG), X-ray diffraction (XRD), Infrared spectroscopy (FTIR-ATR) and scanning electron microscopy (SEM). A comparative study of the in vitro drug release from XMP5-ASA and from gastro-resistant capsules filled with XMP5-ASA (XMPCAP5-ASA) or 5-ASA was also performed. NMR, FTIR-ATR, XRD and DSC/TG studies indicated molecularly dispersed drug in the microparticles with increment on drug stability. The release studies showed that XMPCAP5-ASA allowed more efficient drug retention in the simulated gastric fluid and a prolonged drug release lasting up to 24 h. XMPCAP5-ASA retained approximately 48 % of its drug content after 6 h on the drug release assay. Thus, the encapsulation of 5-ASA into xylan microparticles together with gastro-resistant capsules allowed a better release control of the drug during different simulated gastrointestinal medium., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

We combined the chemical and physical methods of papain immobilization through the aldehyde groups available on oxidized bacterial cellulose (OxBC) to provide high proteolytic activity for future applications as bioactive dressing. Bacterial cellulose (BC) was obtained by the fermentation of Komagataeibacter hansenii in Hestrin-Schramm medium for 5 days, followed by purification and oxidation using NaIO 4 . Surface response methodology was used to optimize papain immobilization (2%, w/v) for 24 h. The independent variables: pH (3-7) and temperature (5 to 45 °C) were investigated. The mathematically validated optimal conditions of 45 °C and pH 7 had a statistical effect on the immobilization yield (IY) of papain in OxBC (52.9%). These ideal conditions were also used for papain immobilization in BC (unoxidized). The IY of 9.1% was lower than that of OxBC. OxBC-Papain and BC-Papain were investigated using thermal analysis, confocal microscopy, and diffusion testing. The OxBC support exhibited a more interactive chemical structure than the BC support, and was capable of immobilizing papain by covalent bonds (-C-NHR) and adsorption (ion exchange), with 93.3% recovered activity, 49.4% immobilization efficiency, and better thermal stability. Papain immobilized to OxBC by adsorption displayed 53% widespread papain activity. The results indicate the potential of prolonged bioactivity in debrided chronic wounds., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest and that the manuscript has not been published elsewhere, is not under editorial review for publication elsewhere, and is not being submitted simultaneously to another journal., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Healthcare-associated infections (HCAIs) affect hundreds of millions of patients, representing a significant burden for public health. They are usually associated to multidrug resistant bacteria, which increases their incidence and severity. Bloodstream infections are among the most frequent and life-threatening HCAIs, with Enterococcus and Staphylococcus among the most common isolated pathogens. The correct and fast identification of the etiological agents is crucial for clinical decision-making, allowing to rapidly select the appropriate antimicrobial and to prevent from overuse and misuse of antibiotics and the consequent increase in antimicrobial resistance. Conventional culture methods are still the gold standard to identify these pathogens, however, are time-consuming and may lead to erroneous diagnosis, which compromises an efficient treatment. (Bacterio)phage receptor binding proteins (RBPs) are the structures responsible for the high specificity conferred to phages against bacteria and thus are very attractive biorecognition elements with high potential for specific detection and identification of pathogens. Taking into account all these facts, we have designed and developed a new, fast, accurate, reliable and unskilled diagnostic method based on newly identified phage RBPs and spectrofluorometric techniques that allows the multiplex detection of Enterococcus and Staphylococcus in blood samples in less than 1.5 hr after an enrichment step., (© 2020 Wiley Periodicals LLC.)

Mangiferin is found in many plant species as the mango tree (Mangifera indica) with ethnopharmacological applications and scientific evidence. The emergence of resistant herpes simplex virus (HSV) strains to Acyclovir (ACV) has encouraged the search for new drugs. We investigated the in vitro and in vivo activity of mangiferin obtained from M. indica against ACV-resistant HSV-1 (AR-29) and sensitive (KOS) strains. The in vitro activity was performed under varying treatment protocols. The substance showed a CC 50  > 500 μg/mL and IC 50 of 2.9 μg/mL and 3.5 μg/mL, respectively, for the AR-29 and KOS strains. The in vivo activity was performed in Balb/c mice treated with 0.7% topical mangiferin formulation. This formulation inhibited most effectively the AR-29 strain, attenuated the lesions, postponed their appearance or enhanced healing, in comparison to control group. We demonstrated the potentiality of mangiferin from M. indica to control HSV replication with emphasis to ACV-resistant infection., 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 Ltd. All rights reserved.)

Adenanthera pavonina is a native tree of Africa and Asia, introduced in Brazil for reforestation and wood industry. Several pharmacological activities have described scientifically, including antiviral activity. This study evaluated the antiviral effect of sulfated polysaccharide of Adenanthera pavonina (SP Ap ) against acyclovir (ACV)-resistant (AR-29) and sensitive (KOS) herpes simplex virus strains. The 50% cytotoxic concentration (CC 50 ) was determined by MTT method and the 50% inhibitory concentration (IC 50 ) was evaluated by plaque reduction assay. The in vivo SP Ap antiviral activity was performed in Balb/c mice infected by skin scarification and treated with topical 0.5% (w/w) SP Ap formulations. SP Ap showed a CC 50 of 47.81 μg/mL and the IC 50 were 0.49 μg/mL (SI = 97.5) and 0.54 μg/mL (SI = 88.5) for the strains KOS and AR-29, respectively. Our results demonstrated that mice treated with SP Ap presented a delay in the development and progression of skin lesions compared with the control group., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Association of Microbiologists of India 2019.)

Several studies have been conducted on polysaccharides derived from natural sources, and their different biological properties have been reported. Their low toxicity and antiviral effects i.e., their action on several steps of viral replication, have been extensively examined. In this work, pectin isolated from Inga spp. fruit pulp was first characterized and evaluated using HEp-2 cells against the herpes simplex virus type 1 (HSV-1) and the poliovirus (PV). The isolated pectin (denoted as PDTS) was characterized by infrared spectroscopy, NMR and Gel permeation chromatography. The cytotoxicity was analyzed by the MTT method and antiviral activity by plaque reduction assay, immunofluorescence assay (IF) and polymerase chain reaction (PCR). The cytotoxic concentration (CC 50 ) of PDTS was 870 μg.mL -1 and the inhibitory concentrations (IC 50 ) were 179 μg.mL -1 and 58 μg.mL -1 for HSV-1 and PV, respectively. Greater inhibitory effect was observed when the cells were simultaneously treated with PDTS and infected, suggesting that PDTS inhibited the initial viral replication stages, revealing its antiviral potential., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: There is a paucity of information regarding chronic urticaria patients' care in a real-world setting. The objective of this study was to report and evaluate the baseline characteristics of Portuguese chronic urticaria patients refractory to H1-antihistamines included in the AWARE study., Material and Methods: This is a non-interventional cohort study. Adult patients with a diagnosis of chronic urticaria with symptoms for at least two months, refractory to H1-antihistamines, consulting one of the 10 participating urticaria centers throughout Portugal have been included in the study. Baseline sociodemographic data, medical history, clinical parameters, medication, weekly urticaria activity score, and dermatology quality of life index have been collected., Results: Seventy six patients were included, of which 76.3% were women. The majority of patients had a diagnosis of chronic spontaneous urticaria (88.2%) and 39.5% had angioedema. Around 91.0% of patients were medicated with non-sedative H1-antihistamines and 35.4% with a third line therapy. Median dermatology quality of life index was 5.0 and median weekly urticaria activity score was 13.0., Discussion: The baseline results suggest that patients with chronic urticaria refractory to H1-antihistamines are being under-treated in the real-world setting., Conclusion: The AWARE study demonstrates the real impact of chronic urticaria on Portuguese patients refractory to H1-antihistamines treatment, and 30% report a very large or extremely large deleterious effect on their quality of life. The follow-up of these patients will allow evaluating strategies aimed at optimizing disease control.

Extreme droughts have been recurrent in the Amazon over the past decades, causing socio-economic and environmental impacts. Here, we investigate the vulnerability of Amazonian forests, both undisturbed and human-modified, to repeated droughts. We defined vulnerability as a measure of (i) exposure, which is the degree to which these ecosystems were exposed to droughts, and (ii) its sensitivity, measured as the degree to which the drought has affected remote sensing-derived forest greenness. The exposure was calculated by assessing the meteorological drought, using the standardized precipitation index (SPI) and the maximum cumulative water deficit (MCWD), which is related to vegetation water stress, from 1981 to 2016. The sensitivity was assessed based on the enhanced vegetation index anomalies (AEVI), derived from the newly available Moderate Resolution Imaging Spectroradiometer (MODIS)/Multi-Angle Implementation of Atmospheric Correction algorithm (MAIAC) product, from 2003 to 2016, which is indicative of forest's photosynthetic capacity. We estimated that 46% of the Brazilian Amazon biome was under severe to extreme drought in 2015/2016 as measured by the SPI, compared with 16% and 8% for the 2009/2010 and 2004/2005 droughts, respectively. The most recent drought (2015/2016) affected the largest area since the drought of 1981. Droughts tend to increase the variance of the photosynthetic capacity of Amazonian forests as based on the minimum and maximum AEVI analysis. However, the area showing a reduction in photosynthetic capacity prevails in the signal, reaching more than 400 000 km 2 of forests, four orders of magnitude larger than areas with AEVI enhancement. Moreover, the intensity of the negative AEVI steadily increased from 2005 to 2016. These results indicate that during the analysed period drought impacts were being exacerbated through time. Forests in the twenty-first century are becoming more vulnerable to droughts, with larger areas intensively and negatively responding to water shortage in the region.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'., (© 2018 The Author(s).)

Background: This study aimed to investigate and characterize the anti-inflammatory and anti-hypernociceptive effects of the total polysaccharides of X. americana (TPL-Xa) bark in a mouse model of acute pancreatitis-induced by caerulein and the potential involvement of cannabinoid receptors., Methods: TPL-Xa was characterized by 1 H and 13 C NMR spectroscopy. Animals received TPL-Xa (10 mg/kg, i.v.) 30 min before and after caerulein (50 μg/kg, 10×, i.p.) administration. To evaluate the involvement of cannabinoid receptors, AM281 (3 mg/kg, s.c.) and AM630 (1 mg/kg, s.c.) were administered 30 min before TPL-Xa. Plasma levels of amylase and lipase, pancreatic myeloperoxidase (MPO), histology, visceral hypernociception and motor coordination were evaluated 11 and 24 h after acute pancreatitis (AP) induction., Results: TPL-Xa, containing a heteropolysaccharide composed of glucose, galactose, arabinose, rhamnose, fucose and galacturonic acid, reduced amylase and lipase levels, MPO activity, acinar cell necrosis, edema and neutrophil infiltration. TPL-Xa increased the threshold of visceral hypernociception, an effect reversed by AM630, an antagonist of cannabinoid receptor type 2 (CB2). In addition, TPL-Xa did not alter the animals' motor coordination., Conclusions: TPL-Xa contains heteropolysaccharides that inhibit inflammation and hypernociception in the experimental model of caerulein-induced AP, by a mechanism involving type CB2 receptors., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

This study discusses the climatological aspects of the most severe drought ever recorded in the semiarid region Northeast Brazil. Droughts are recurrent in the region and while El Nino has driven some of these events others are more dependent on the tropical North Atlantic sea surface temperature fields. The drought affecting this region during the last 5 years shows an intensity and impact not seen in several decades in the regional economy and society. The analysis of this event using drought indicators as well as meteorological fields shows that since the middle 1990s to 2016, 16 out of 25 years experienced rainfall below normal. This suggests that the recent drought may have in fact started in the middle-late 1990s, with the intense droughts of 1993 and 1998, and then the sequence of dry years (interrupted by relatively wet years in 2007, 2008, 2009 and 2011) after that may have affected the levels of reservoirs in the region, leading to a real water crisis that was magnified by the negative rainfall anomalies since 2010.

Background: This study aimed to chemically characterize a polysaccharide-rich extract (PRE) obtained from Genipa americana leaves and evaluate its neuroprotective effect in the brain morphology and oxidative markers using mice behavioral models., Methods: Dry powder (5 g) of G. americana leaves were submitted to depigmentation in methanol. PRE was obtained by extraction in NaOH and precipitation with absolute ethanol and characterized by infrared spectroscopy (FTIR) and nuclear magnetic resonance ( 1 H and 13 C NMR). Swiss mice (25-35 g) received saline (0.9% NaCl) or PRE (1-27 mg/kg) by intraperitoneal (i.p.) route, 30 min before evaluation in behavioral models (open field, elevated plus maze, sleeping time, tail suspension, forced swimming, seizures induced by pentylenetetrazole-PTZ). Animal's brain were dissected and analyzed for histological alterations and oxidative stress., Results: FTIR spectrum showed bands around 3417 cm -1 and 2928 cm -1 , relative to the vibrational stretching of OH and CH, respectively. 1 H NMR spectrum revealed signals at δ 3.85 (methoxyl groups) and δ 2.4 (acetyl) ppm. 13 C NMR spectrum revealed signals at δ 108.0 and δ 61.5 ppm, corresponding to C1 and C5 of α-L-arabinofuranosyl residues. PRE presented central inhibitory effect, increasing the latency for PTZ-induced seizures by 63% (9 mg/kg) and 55% (27 mg/kg), and the latency to death by 73% (9 mg/kg) and 72% (27 mg/kg). Both effects were reversed by the association with flumazenil., Conclusions: PRE, containing a heteropolysaccharide, presents antioxidant and anticonvulsant effect in the model of PTZ-induced seizures via gamma-aminobutyric acid (GABA), decreasing the number of hippocampal black neurons., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Purpose: The concept of tissue-dependent cytokine hierarchy has been demonstrated in a number of diseases, but it has not been investigated in ophthalmic diseases. Here, we evaluated the functional hierarchy of interleukin-1β (IL-1β), IL-6, IL-17A, and tumor necrosis factor (TNF) in the induction of ocular inflammation., Materials and Methods: We delivered adeno-associated virus (AAV) vectors expressing IL-1β, IL-6, IL-17A, or TNF intravitreally in naïve C57/BL6 mice and compared and contrasted the inflammatory effects in the eye 5 weeks after AAV-mediated gene transfer. We also used an in vitro human system to test the effect of cytokines on barrier function., Results: We found that IL-1β had the highest ability to initiate ocular inflammation. The continuous overexpression of IL-1β resulted in a significant upregulation of additional proinflammatory mediators in the eye. Using scanning laser ophthalmoscope and optical coherence tomography imaging techniques, we showed that a low dose of AAVIL-1β was sufficient and was as pathogenic as a high dose of TNF in inducing vascular leakage, retinal degeneration, and cellular infiltration. Furthermore, only a marginal increase in IL-1β was enough to cause cellular infiltration, thus confirming the highly pathogenic nature of IL-1β in the eye. Contrary to our expectation, IL-6 or IL-17A had minimal or no effect in the eye. To examine the clinical relevance of our findings, we used an impedance assay to show that IL-1β alone or TNF alone was able to cause primary human retinal endothelial cell barrier dysfunction in vitro. Again, IL-6 alone or IL-17A alone had no effect on barrier function; however, in the presence of IL-1β or TNF, IL-17A but not IL-6 may provide additive proinflammatory effects., Conclusions: Our studies demonstrate the existence of a functional hierarchy of proinflammatory cytokines in the eye, and we show that IL-1β is the most pathogenic when it is continuously expressed in the eye.

Background: The increasing use of long-lasting nail aesthetic products has led to a growing number of cases of allergic contact dermatitis (ACD) caused by (meth)acrylates in recent years., Objectives: To provide information on ACD caused by (meth)acrylates related to nail cosmetic products., Methods: We retrospectively reviewed files of patients with ACD caused by (meth)acrylates related to nail cosmetic products, who were patch tested between January 2011 and December 2015 in 13 departments of dermatology in Portugal., Results: Two-hundred and thirty cases of ACD caused by (meth)acrylates (55 technicians, 56 consumers, and 119 with mixed exposure) had been documented, mostly as chronic hand eczema (93%). The most common sensitizers were: 2-hydroxyethyl methacrylate (HEMA), which was positive in 90% of the tested patients, 2-hydroxypropyl methacrylate (HPMA), which was positive in 64.1%, and ethyleneglycol dimethacrylate, which was positive in 54.5%., Conclusion: HEMA and HPMA were the most frequent positive allergens. HEMA, which identified 90% of cases, can be considered to be a good screening allergen. The high number of cases of ACD caused by (meth)acrylates in nail cosmetic products certainly warrants better preventive measures at the occupational level, and specific regulation in the field of consumer safety., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Despite the effective suppression of viremia with antiretroviral therapy, HIV can still replicate in the central nervous system (CNS). This was a longitudinal study of the cerebrospinal fluid (CSF) and serum dynamics of several biomarkers related to inflammation, the blood-brain barrier, neuronal injury, and IgG intrathecal synthesis in serial samples of CSF and serum from a patient infected with HIV-1 subtype C with CNS compartmentalization.The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation sequencing and F-statistics analysis of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples. The CSF biomarker analysis in this patient showed that symptomatic CSF escape is accompanied by CNS inflammation, high levels of cell and humoral immune biomarkers, CNS barrier dysfunction, and an increase in neuronal injury biomarkers with demyelization. Independent and isolated HIV replication can occur in the CNS, even in HIV-1 subtype C, leading to compartmentalization and development of quasispecies distinct from the peripheral plasma. These immunological aspects of the HIV CNS escape have not been described previously. To our knowledge, this is the first report of CNS HIV escape and compartmentalization in HIV-1 subtype C.

Regulatory T cells (T regs ) promote cancer by suppressing antitumor immune responses. We found that anti-LAP antibody, which targets the latency-associated peptide (LAP)/transforming growth factor-β (TGF-β) complex on T regs and other cells, enhances antitumor immune responses and reduces tumor growth in models of melanoma, colorectal carcinoma, and glioblastoma. Anti-LAP decreases LAP + T regs , tolerogenic dendritic cells, and TGF-β secretion and is associated with CD8 + T cell activation. Anti-LAP increases infiltration of tumors by cytotoxic CD8 + T cells and reduces CD103 + CD8 T cells in draining lymph nodes and the spleen. We identified a role for CD103 + CD8 T cells in cancer. Tumor-associated CD103 + CD8 T cells have a tolerogenic phenotype with increased expression of CTLA-4 and interleukin-10 and decreased expression of interferon-γ, tumor necrosis factor-α, and granzymes. Adoptive transfer of CD103 + CD8 T cells promotes tumor growth, whereas CD103 blockade limits tumorigenesis. Thus, anti-LAP targets multiple immunoregulatory pathways and represents a potential approach for cancer immunotherapy., (Copyright © 2017, American Association for the Advancement of Science.)

Wheat straw has been used as a source of hemicelluloses (WSH) and cellulose nanocrystals (CNC) for the elaboration of biodegradable films. Different films have been formed by using WSH as a matrix and different contents of CNC and citric acid. The predominant hemicelluloses were arabinoxylans. CNC reinforced the films, improving tensile strength and modulus, water resistance and water vapor barrier. Citric acid, on the other hand, presented concomitant plasticizing and crosslinking effects (the latter also evidenced by FTIR), probably due to a crosslinking extension by glycerol. The use of 5.9wt% CNC and 30wt% citric acid was defined as optimal conditions, resulting in minimum water sensitivity and permeability, while maintaining a good combination of tensile properties. Under those conditions, the films presented enhanced modulus, elongation, water resistance, and barrier to water vapor when compared to the control WSH film, and might be used for wrapping or coating a variety of foods., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Oral administration of Ag induces regulatory T cells that express latent membrane-bound TGF-β (latency-associated peptide [LAP]) and have been shown to play an important role in the induction of oral tolerance. We developed an in vitro model to study modulation of LAP + on CD4 + T cells. The combination of anti-CD3 mAb, anti-CD28 mAb, and recombinant IL-2 induced expression of LAP on naive CD4 + T cells, independent of Foxp3 or exogenous TGF-β. In vitro generated CD4 + LAP + Foxp3 - T cells were suppressive in vitro, inhibiting proliferation of naive CD4 + T cells and IL-17A secretion by Th17 cells. Assessing the impact of different cytokines and neutralizing Abs against cytokines, we found that LAP induction was decreased in the presence of IL-6 and IL-21, and to a lesser extent by IL-4 and TNF-α. IL-6 abrogated the in vitro induction of CD4 + LAP + T cells by STAT3-dependent inhibition of Lrrc32 (glycoprotein A repetitions predominant [GARP]), the adapter protein that tethers TGF-β to the membrane. Oral tolerance induction was enhanced in mice lacking expression of IL-6R by CD4 + T cells and by treatment of wild-type mice with neutralizing anti-IL-6 mAb. These results suggest that proinflammatory cytokines interfere with oral tolerance induction and that blocking the IL-6 pathway is a potential strategy for enhancing oral tolerance in the setting of autoimmune and inflammatory diseases., (Copyright © 2017 by The American Association of Immunologists, Inc.)

Methods: Series of cases collected from Brazilian centers., Results: We studied 13 cases of patients presenting with progressive histories of neurological dysfunction caused by SS-CNS. The most frequent clinical findings in these patients were progressive gait ataxia, hearing loss, hyperreflexia and cognitive dysfunction. The diagnoses of SS-CNS were made seven months to 30 years after the disease onset., Conclusion: SS-CNS is a rare disease that may remain undiagnosed for long periods. Awareness of this condition is essential for the clinician.