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Mouse models for the study of pancreatic ductal adenocarcinoma (PDAC) are well-established and representative of many key features observed in human PDAC. To monitor tumor growth, cancer cells that are implanted in mice are often transfected with reporter genes, such as firefly luciferase (Luc), enabling in vivo optical imaging over time. Since Luc can induce an immune response, we aimed to evaluate whether the expression of Luc could affect the growth of KPC tumors in mice by inducing immunogenicity. Although both cell lines, KPC and Luc transduced KPC (KPC-Luc), had the same proliferation rate, KPC-Luc tumors had significantly smaller sizes or were absent 13 days after orthotopic cell implantation, compared to KPC tumors. This coincided with the loss of bioluminescence signal over the tumor region. Immunophenotyping of blood and spleen from KPC-Luc tumor-bearing mice showed a decreased number of macrophages and CD4+ T cells, and an increased accumulation of natural killer (NK) cells in comparison to KPC tumor mice. Higher infiltration of CD8+ T cells was found in KPC-Luc tumors than in their controls. Moreover, the immune response against Luc peptide was stronger in splenocytes from mice implanted with KPC-Luc cells compared to those isolated from KPC wild-type mice, indicating increased immunogenicity elicited by the presence of Luc in the PDAC tumor cells. These results must be considered when evaluating the efficacy of anti-cancer therapies including immunotherapies in immunocompetent PDAC or other cancer mouse models that use Luc as a reporter for bioluminescence imaging.
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Carcinoma Ductal Pancreático , Modelos Animais de Doenças , Neoplasias Pancreáticas , Animais , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/genética , Camundongos , Linhagem Celular Tumoral , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/genética , Humanos , Linfócitos T CD8-Positivos/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Luciferases de Vaga-Lume/genética , Luciferases/metabolismo , Luciferases/genéticaRESUMO
PURPOSE: Pancreatic Ductal Adenocarcinoma (PDAC) remains a challenging disease due to its complex biology and aggressive behavior with an urgent need for efficient therapeutic strategies. To assess therapy response, pre-clinical PDAC organoid-based models in combination with accurate real-time monitoring are required. METHODS: We established stable live-imaging organoid/peripheral blood mononuclear cells (PBMCs) co-cultures and introduced OrganoIDNet, a deep-learning-based algorithm, capable of analyzing bright-field images of murine and human patient-derived PDAC organoids acquired with live-cell imaging. We investigated the response to the chemotherapy gemcitabine in PDAC organoids and the PD-L1 inhibitor Atezolizumab, cultured with or without HLA-matched PBMCs over time. Results obtained with OrganoIDNet were validated with the endpoint proliferation assay CellTiter-Glo. RESULTS: Live cell imaging in combination with OrganoIDNet accurately detected size-specific drug responses of organoids to gemcitabine over time, showing that large organoids were more prone to cytotoxic effects. This approach also allowed distinguishing between healthy and unhealthy status and measuring eccentricity as organoids' reaction to therapy. Furthermore, imaging of a new organoids/PBMCs sandwich-based co-culture enabled longitudinal analysis of organoid responses to Atezolizumab, showing an increased potency of PBMCs tumor-killing in an organoid-individual manner when Atezolizumab was added. CONCLUSION: Optimized PDAC organoid imaging analyzed by OrganoIDNet represents a platform capable of accurately detecting organoid responses to standard PDAC chemotherapy over time. Moreover, organoid/immune cell co-cultures allow monitoring of organoid responses to immunotherapy, offering dynamic insights into treatment behavior within a co-culture setting with PBMCs. This setup holds promise for real-time assessment of immunotherapeutic effects in individual patient-derived PDAC organoids.
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OBJECTIVES: The objective of this paper is to evaluate changes in lower urinary tract symptoms (LUTS), severity of pain and urodynamic parameters after minimally invasive nerve-sparing surgery for patients with endometriosis. METHODS: We analyzed 143 patients undergoing minimally invasive nerve-sparing surgery for endometriosis excision (laparoscopy/robot-assisted). The endometriosis was confirmed by preoperative clinical evaluation, magnetic resonance imaging (MRI) showing at least one lesion deeper than 5 mm, and histological confirmation after laparoscopy. We evaluated three points prior and after surgery: LUTS parameters according to the International Urogynecological Association; urodynamic measures of storage and voiding and the severity of the dyspareunia, dyschezia and dysmenorrhea assessed on a self-reported 11-point numeric rating scale. The Wilcoxon signed rank and McNemar tests were used for statistical analyses (p < 0.05). RESULTS: We observed significant improvements in LUTS after the surgery with postoperative symptom-free probabilities in urgency (64.5%), daytime frequency (38.5%), and dysuria (87.1%). However, slow stream prevalence increased significantly postsurgery (p = 0.022), with a 20.5% risk of asymptomatic patients developing this symptom. Urodynamic responses varied; for instance, maximum cystometric capacity improved significantly (p = 0.004), while postvoiding residual worsened (p = 0.006). Significant worsening in postvoiding residual occurred in women with normal preoperative values (p = 0.002), with a 17.7% risk of normal values becoming abnormal. Compliance or maximum cystometric capacity not considered normal preoperatively showed significant improvements (p < 0.001), but the risk of normal values becoming abnormal after surgery was 14.5%. CONCLUSION: The minimally invasive nerve-sparing surgery for endometriosis excision shows improvement in lower urinary tract symptoms, urodynamics parameters and severity of pain. The majority of patients became asymptomatic in the postoperative period. When compared to the benefits of the patients' surgical treatment, particularly when considering the reduction of pain, the risks of the lower urinary tract treatment seem to be acceptable. The surgical intervention seems to be a safe alternative in patients with endometriosis, although studies with larger samples are needed to confirm these findings.
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Endometriose , Laparoscopia , Sintomas do Trato Urinário Inferior , Humanos , Feminino , Endometriose/cirurgia , Bexiga Urinária , Disuria , Laparoscopia/métodos , DorRESUMO
This study was performed to investigate the nitrogen (N) and carbohydrate digestive traits of grazing heifers. The experiment was carried out at the Federal University of Lavras. The treatments were a Marandu palisadegrass (Urochloa brizantha [Syn, Brachiaria brizantha] Stapf. A. Rich. cv. Marandu) monoculture fertilised with 150 kg N/[ha â year] (FP) or Marandu palisadegrass mixed pasture with forage peanut (MP). The pastures were grazed by six rumen-cannulated zebu heifers. A double cross-over design was used in four periods. Nutritive value, intake and apparent digestibility of forage, ruminal traits and kinetics and N balance were evaluated. Apparent total-tract digestibility of dry matter (DM) and neutral detergent fibre (NDF) were greater for FP than for MP. There was no effect in apparent total-tract digestibility of N. The estimated intestinal digestibility of nutrients was greater on MP than FP. Even though N intake and faecal N output were greater on MP than FP, there was no effect in urine N output. The N balance tended to be greater on MP than FP. The forage peanut, which contains condensed tannins, decreased ruminal fibre degradation, apparent digestibility and ruminal protein degradation, increased N flow from the rumen. Inclusion of forage peanut in the mixed pasture decreased the ruminal fibre degradability but increased N retention by the animals.
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Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Dieta , Digestão , Rúmen , Animais , Bovinos/fisiologia , Digestão/fisiologia , Ração Animal/análise , Feminino , Dieta/veterinária , Rúmen/fisiologia , Rúmen/metabolismo , Nitrogênio/metabolismo , Proteínas Alimentares/metabolismo , Estudos Cross-Over , Fertilizantes/análise , Valor Nutritivo , Arachis/química , Carboidratos da Dieta/análise , Carboidratos da Dieta/administração & dosagem , Carboidratos da Dieta/metabolismo , Brachiaria/química , Brachiaria/fisiologia , Poaceae/químicaRESUMO
COVID-19 pandemic has changed several aspects in human behaviour, whereas population mobility patterns have been strongly affected by social distancing. In parallel, changes in solid waste generation patterns have been reported worldwide. This work assessed the influence of the COVID-19 pandemic on waste generation and collection in São Paulo city, Brazil, the largest city of Latin America. Data on nine types of wastes collected between 2013 and 2021 were obtained, and the quantities of wastes collected before and during the pandemic were compared. These data were also discussed in light of data on COVID-19 cases and rates of social distancing and mobility. An increase in the amount of recyclables collected during the first wave of COVID-19 (March to September 2020) was observed. Decreases in the quantities of construction, demolition and bulky wastes (first wave of COVID-19) and farmers market wastes (second wave - October 2020 to February 2021) were also evidenced. The quantities of medical wastes collected during the pandemic significantly increased. The amount of residential wastes was lower than the mean for the pre-pandemic period during the first months of COVID-19. Thus, changes in lifestyle and consumption patterns of the population of São Paulo city seem to have affected solid waste generation during the pandemic, which reinforces the need of implementing solid waste management policies based on a diagnostic that characterise and consider these changes.
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COVID-19 , Gerenciamento de Resíduos , Humanos , Brasil/epidemiologia , Resíduos Sólidos , Pandemias , COVID-19/epidemiologia , Países em DesenvolvimentoRESUMO
Numerous Antarctic species are recognized as reservoirs for various pathogens, and their migratory behavior allows them to reach the Brazilian coast, potentially contributing to the emergence and circulation of new infectious diseases. To address the potential zoonotic risks, we conducted surveillance of influenza A virus (IAV) and coronaviruses (CoVs) in the Antarctic Peninsula, specifically focusing on different bird and mammal species in the region. During the summer of 2021/2022, as part of the Brazilian Antarctic Expedition, we collected and examined a total of 315 fecal samples to target these respiratory viruses. Although we did not detect the viruses of interest during this particular expedition, previous research conducted by our team has shown the presence of the H11N2 subtype of influenza A virus in penguin fecal samples from the same region. Given the continuous emergence of new viral strains worldwide, it is crucial to maintain active surveillance in the area, contributing to strengthening integrated One Health surveillance efforts.
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Infecções por Coronavirus , Vírus da Influenza A , Influenza Aviária , Spheniscidae , Animais , Regiões Antárticas , Conduta Expectante , Influenza Aviária/epidemiologia , Filogenia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/veterinária , MamíferosRESUMO
Fixation methods such as formalin are commonly used for the preservation of tissue with the aim of keeping their structure as close as possible to the native condition. However, fixatives chemically interact with tissue molecules, such as collagen in the extracellular matrix (ECM) or myosin, and may thus modify their structure. Taking advantage of the second- and third-harmonic generation (SHG and THG) emission capabilities of such components, we used nonlinear two-photon microscopy (NL2PM) to evaluate the effect that preservation methods, such as chemical fixatives, have on the nonlinear capabilities of protein components within mouse tissues. Our results show that depending on the preservation technique used, the nonlinear capabilities of collagen, lipid droplets and myosin microarchitecture are strongly affected. Parameters of collagen fibers, such as density and branch points, especially in collagen-sparse regions, e.g., in kidneys, were found to be altered upon formalin fixation. Moreover, cryo-freezing drastically reduced SHG signals from myosin. Our findings provide valuable information to select the best tissue fixation method for visualization and quantification of structural proteins, such as collagen and myosin by advanced NL2PM imaging techniques. This may advance the interpretation of the role these proteins play in disease.
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The development of advanced facemasks stands out as a paramount priority in enhancing healthcare preparedness. In this work, different polypropylene non-woven fabrics (NWF) were characterised regarding their structural, physicochemical and comfort-related properties. The selected NWF for the intermediate layer was functionalised with zinc oxide nanoparticles (ZnO NPs) 0.3 and 1.2wt% using three different methods: electrospinning, dip-pad-dry and exhaustion. After the confirmation of ZnO NP content and distribution within the textile fibres by morphological and chemical analysis, the samples were evaluated regarding their antimicrobial properties. The functionalised fabrics obtained via dip-pad-dry unveiled the most promising data, with 0.017 ± 0.013wt% ZnO NPs being mostly located at the fibre's surface and capable of total eradication of Staphylococcus aureus and Escherichia coli colonies within the tested 24 h (ISO 22196 standard), as well as significantly contributing (**** p < 0.0001) to the growth inhibition of the bacteriophage MS2, a surrogate of the SARS-CoV-2 virus (ISO 18184 standard). A three-layered structure was assembled and thermoformed to obtain facemasks combining the previously chosen NWF, and its resulting antimicrobial capacity, filtration efficiency and breathability (NP EN ISO 149) were assessed. The developed three-layered and multiscaled fibrous structures with antimicrobial capacities hold immense potential as active individual protection facemasks.
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A male neonate was born at 34 weeks due to spontaneous labor with associated fetal distress and meconium-stained amniotic fluid. The neonate presented with septic shock and congenital pneumonia shortly after birth and later neurological symptoms. Listeria monocytogenes was identified in blood samples, but with negative urine and cerebrospinal fluid cultures. The neonate required assisted ventilation for a period of 10 days and received high-dose and long-term antibiotic therapy. Despite the fact that the mother denied an infectious risk for listeriosis infection, she developed mild respiratory symptoms. Her microbiological investigation was negative, although it did not include placental samples. Vertical transmission in this case was presumed but not confirmed. The newborn was discharged asymptomatic at day 26 of life and has presented normal developmental evolution until present, at eight months old. Listeria monocytogenes is a classic but relatively rare cause of neonatal sepsis and meningitis. This case describes a clinically successfully managed case with no possible epidemiological link and illustrates the challenges in managing cases of a public health disease. In neonatal listeriosis, communication between Neonatology and Obstetrics departments, as well as with public health, is vital, and long-term follow-up is crucial to identify possible neurological sequelae.
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Pressure injuries (PIs) are a major public health problem and can be used as quality-of-care indicators. An incipient development in the field of medical devices takes the form of Smart Health Textiles, which can possess innovative properties such as thermoregulation, sensing, and antibacterial control. This protocol aims to describe the process for the development of a new type of smart clothing for individuals with reduced mobility and/or who are bedridden in order to prevent PIs. This paper's main purpose is to present the eight phases of the project, each consisting of tasks in specific phases: (i) product and process requirements and specifications; (ii and iii) study of the fibrous structure technology, textiles, and design; (iv and v) investigation of the sensor technology with respect to pressure, temperature, humidity, and bioactive properties; (vi and vii) production layout and adaptations in the manufacturing process; (viii) clinical trial. This project will introduce a new structural system and design for smart clothing to prevent PIs. New materials and architectures will be studied that provide better pressure relief, thermo-physiological control of the cutaneous microclimate, and personalisation of care.
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We investigated the potential of exogenous hyaluronic acid (HA) associated with corticosteroid injections to improve pain and function for the treatment of post-traumatic subtalar osteoarthritis, in comparison with isolated intra-articular corticosteroid. Twenty-five symptomatic participants (50 ± 8 years) with a minimum follow-up of 1 year after surgery for calcaneus fractures were enrolled. Participants were randomly assigned into a therapeutic group that underwent isolated corticosteroid intra-articular subtalar injection (Corticosteroid Group, nâ¯=â¯12) or a combination of HA plus corticosteroid (HA+C Group, nâ¯=â¯13). All participants underwent three repeated injections with intervals of 1 week. We assessed the visual analog scale of pain (VAS) and the AOFAS scores at 4 moments: before treatment (pre), 4-, 12-, and 24-weeks following the last injection. HA+C Group showed lower VAS at the 12th (pâ¯=â¯.003) and 24th weeks (pâ¯=â¯.003) and greater AOFAS at the 4th (pâ¯=â¯0.040), 12th (pâ¯=â¯.014), and 24th weeks (pâ¯=â¯.021), in comparison to Corticosteroid Group. We observed a reduction in VAS in the Corticosteroid Group only at the 4th week (pâ¯=â¯.007), compared with pretreatment values. In the HA+C Group, VAS presented lower levels at the 4- (p < .001), 12- (p < .001), and 24 weeks (p < .001). In the Corticosteroid Group, participants presented higher AOFAS score only at the 4th week (p < .001), while in the HA+C Group, the AOFAS scores were greater at the 4th, 12th, and 24th weeks compared to baseline (p < .001). The combination of exogenous HA and corticosteroid showed greater and longer analgesic effects and function improvement in comparison with isolated intra-articular corticosteroids.
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Ácido Hialurônico , Osteoartrite do Joelho , Humanos , Ácido Hialurônico/uso terapêutico , Corticosteroides/uso terapêutico , Injeções Intra-Articulares , Dor , Resultado do TratamentoRESUMO
A simplex-centroid design was used to evaluate the effect of proportions (0 to 100%) of whole wheat flour (WWF), whole mung bean flour (WMF) and whole rice flour (BRF) on the quality of cookies savory. The dough cut in the shape of a disks (37â mm × 2â mm) showed a 13% retraction in diameter when they contained exclusively WWF, it was less intense (5%) with BRF and null (0%) with WMF. The dough expansion occurred only vertically, the thicknesses of the WWF, WMF and BRF biscuits were 5.33, 2.79 and 2.13 times greater than the initial dough height, respectively. This characteristic showed high correlations with volumetric expansion (r = 0.95), specific volume (r = 0.90), hardness (r = 0.92), fracturability (r = 0.93) and spread factor (r = -0.96). BRF increased the value of the color difference of the biscuits up to 17.70, the effect of WMF was smaller (6.51). Only the radial expansion index correlated with the trough (r = 0.76), final viscosity (r = 0.79) and setback (r = 0.77) parameters. Considering the main desirable physical characteristics in savory biscuits, the highest global desirability obtained was for the proportion of 49% WWF, 24% WMF and 27% BRF.
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Fabaceae , Oryza , Vigna , Farinha , Triticum , DurezaRESUMO
During the last decades, livestock and animal feeding operations have been expanded. In parallel, these activities are among the major sources of estrogens in the environment. Thus, considering the environmental and health risks associated with estrogenic compounds, this work reviews the fate, occurrence, and removal of free and conjugated E1, E2, and E3 in livestock wastewaters. A systematic literature review was carried out, and after applying the eligibility criteria, 66 peer-reviewed papers were selected. Results suggest high estrogen concentrations and, consequently, high estrogenic activity, especially in samples from swine farming. E1 and E2 are frequently found in wastewaters from bovine, swine, and other livestock effluents. Aerobic treatment processes were more efficient for estrogen removal, whereas anaerobic systems seem poorly effective. Removal efficiencies of estrogens and estrogenic activity of up to 90% were reported for constructed wetlands, advanced pond systems, trickling filters, membrane bioreactors, aerated and nitrifying reactors, combined air flotation, and vegetable oil capture processes. High concentrations found in wastewaters from livestock allied to the removal efficiencies reported for anaerobic processes (usually used to treat livestock wastewaters) evidence the importance of monitoring these compounds in environmental matrices.
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Águas Residuárias , Poluentes Químicos da Água , Animais , Bovinos , Estrogênios , Estrona/análise , Gado , Suínos , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análiseRESUMO
Children and adolescents with physical disabilities have motor and social-emotional challenges that interfere with their health-related quality of life and put them at greater risk of developing secondary conditions. Moreover, services that provide them therapies are more likely to be restricted, especially for the low-income population. There must be broader actions towards health promotion, offering not only means for physical habilitation and rehabilitation but for social and emotional improvements as well. This goal is attainable by adaptive sports and recreational activities where physical conditioning is accompanied by an improvement in self-esteem and social benefits. With the COVID-19 pandemic and social isolation, children and adolescents with physical disabilities were even further deprived of assistance. Our aim was to report the efforts of a non-governmental sports organization in maintaining physical and psychological care through virtual consultations and to analyze the perceptions of those affected by the process. Level of evidence IV; case series .
Crianças e adolescentes com deficiência física apresentam desafios motores e socioemocionais que interferem na qualidade de vida relacionada à saúde e os colocam em maior risco de desenvolver doenças secundárias. Além disso, estão mais sujeitos a restrições de serviços adequados que ofereçam terapias, principalmente para a população de baixa renda social. Torna-se necessário oferecer ações voltadas para a promoção da saúde em um sentido mais amplo, oferecendo não só meios de habilitação e reabilitação física, mas também de ganhos sociais e emocionais. Este objetivo pode ser atingido com esportes adaptados e atividades recreativas nos quais o condicionamento físico é acompanhado por ganhos em autoestima e benefícios sociais. Com a pandemia de COVID-19 e o isolamento social, crianças e adolescentes com deficiência física ficaram ainda mais privados de assistência. Relatamos aqui o esforço de uma organização não-governamental esportiva em manter o atendimento físico e psicológico por meio de consultas virtuais, e avaliamos as percepções das partes interessadas no processo. Nível de evidência IV; série de casos .
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This study aimed to evaluate the effect of regrowth ages and the use of powdered molasses on nutritional characteristics of Zuri grass (Megathyrsus maximus) silages. A completely randomized design was used, in a 3 × 3 factorial scheme: three regrowth ages (65, 80, and 95 days) and three inclusion levels of powdered molasses of sugarcane (0, 20, and 40 g), with four replications. The chemical composition, fermentation parameters, in vitro digestibility, and in vitro degradation kinetics of the silages were evaluated. Greater dry matter (DM) contents were observed in silages with 95 days with 40 g of molasses. The 65 days of regrowth silages with 40 g of molasses had greater in vitro digestibility of dry matter compared to other treatments. However, lower pH values, N-NH3, DM losses, gas losses, and density were observed in silages with 95 days of regrowth with 40 g of molasses. It is recommended to cut the Zuri grass in the range of 80 to 95 days of regrowth with the addition of 40 g/kg of molasses in powders for the production of silages.
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Melaço , Silagem , Animais , Fermentação , Cinética , Valor Nutritivo , Poaceae , Pós , Silagem/análiseRESUMO
The rising threats to worldwide security (affecting the military, first responders, and civilians) urge us to develop efficient and versatile technological solutions to protect human beings. Soldiers, medical personnel, firefighters, and law enforcement officers should be adequately protected, so that their exposure to biological warfare agents (BWAs) is minimized, and infectious microorganisms cannot be spread so easily. Current bioprotective military garments include multilayered fabrics integrating activated carbon as a sorptive agent and a separate filtrating layer for passive protection. However, secondary contaminants emerge following their accumulation within the carbon filler. The clothing becomes too heavy and warm to wear, not breathable even, preventing the wearer from working for extended hours. Hence, a strong need exists to select and/or create selectively permeable layered fibrous structures with bioactive agents that offer an efficient filtering capability and biocidal skills, ensuring lightweightness, comfort, and multifunctionality. This review aims to showcase the main possibilities and trends of bioprotective textiles, focusing on metal-organic frameworks (MOFs), inorganic nanoparticles (e.g., ZnO-based), and organic players such as chitosan (CS)-based small-scale particles and plant-derived compounds as bioactive agents. The textile itself should be further evaluated as the foundation for the barrier effect and in terms of comfort. The outputs of a thorough, standardized characterization should dictate the best elements for each approach.
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Nanomaterials are increasingly used for the diagnosis and treatment of cancer, including lung cancer. For the clinical translation of nano-based theranostics, it is vital to detect and monitor their accumulation in the tumor, as well as their interaction with tumor, immune cells, and the tumor microenvironment (TME). While high resolution microscopy of fixed tumor specimens can provide some of this information from individual thin slices, it cannot capture cellular events over time and lacks 3D information of the tumor tissue. On the other hand, in vivo optical procedures either fall short of providing the necessary cellular resolution, as in the case of epifluorescence optical imaging, or are very demanding, as for instance intravital lung microscopy. We describe an alternative approach to investigate nanoparticle-cell interactions in entire mouse lung lobes, by longitudinal live cell confocal microscopy at nanometer resolution. By filling the lung ex vivo with 1% agarose, we were able to stabilize the lung lobes and visualize the interaction of fluorescent cells and nanoparticles for at least 4 hours post mortem. This high resolution ex vivo live cell imaging approach is an easy 4D tool for assessing several dynamic processes in tumor tissue, such as the traffic of cells, shedding of extracellular vesicles (EVs), and the accumulation of nanoparticles in tumor tissue. Graphic abstract: Schematic of the workflow for live cell imaging in the mouse lung.
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BACKGROUND: Subtalar pain following intra-articular calcaneus fractures may be associated with disability, pain, and a negative impact on the quality of life. Salvage procedures as subtalar fusion are associated with further consequences as stiffness, altered ankle biomechanics, and adjacent articular overloading with degenerative changes. The objective of the present study is to evaluate the short-term effects of viscosupplementation with intra-articular hyaluronic acid (HA) on function and pain, in patients with painful subtalar joint after calcaneus fracture. METHODS: We searched for patients who underwent osteosynthesis of intra-articular calcaneus fracture between January 2011 and July 2015 and were diagnosed during the follow-up with pain and subtalar osteoarthritis. Between January and December of 2018, 13 patients (50 ± 10 years) accepted to participate in this study and received intra-articular HA injections. Three consecutive doses of 20 mg of HA were administered within a week interval, through anterolateral injections into the subtalar joint. We prospectively evaluated the function using the ankle/hindfoot American Orthopaedic Foot & Ankle Society score (AOFAS) and level of pain using the visual analog scale (VAS) before the intervention and 4, 12, and 24 weeks after the first injection. RESULTS: Hindfoot function improved with an increase of AOFAS from 55 ± 19 before the intervention to 88 ± 20 at the 24th week (P = .001). Similarly, we observed relief of pain during the 24 weeks following intra-articular hyaluronic acid injection, with a decrease in VAS from 8.3 ± 1.3 before treatment to 2.2 ± 3.0 at the 24th week (P = .001). CONCLUSION: For patients experiencing pain and dysfunction with subtalar osteoarthritis after intra-articular calcaneus fracture, viscosupplementation with intra-articular HA may be associated with improvement in function and pain in the short term. Furthermore, patients with higher grades of osteoarthritis may have limited benefit in pain relief and function improvement. LEVEL OF EVIDENCE: IV, Case series.
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BACKGROUND: Mutations in the genes that encode the human γ-secretase subunits Presenilin-1, Presenilin Enhancer Protein 2, and Nicastrin (NCSTN) are associated with familial hidradenitis suppurativa (HS); and, regarding Presenilin Enhancer Protein 2, also with comorbidity for the hereditary pigmentation disorder Dowling-Degos disease. OBJECTIVE: Here, the consequences of targeted inactivation of ncstn, the zebrafish homologue of human NCSTN, were studied. METHODS: After morpholino (MO)-mediated ncstn-knockdown, the possibilities of phenotype rescue through co-injection of ncstn-MO with wildtype zebrafish ncstn or human NCSTN mRNA were investigated. Further, the effects of the co-injection of a human missense, nonsense, splice-site, and frameshift mutation were studied. RESULTS: MO-mediated ncstn-knockdown resulted in a significant reduction in melanophore morphology, size and number; and alterations in their patterns of migration and distribution. This phenotype was rescued by co-injection of zebrafish ncstn RNA, human NCSTN RNA, or a construct encoding the human NCSTN missense mutation p.P211R. CONCLUSION: Human NCSTN mutations encoding null alleles confer loss-of-function regarding pigmentation homeostasis in zebrafisch. In contrast, the human missense mutation p.P211R was less harmful, asserting sufficient residual ncstn activity to maintain pigmentation in zebrafish. Since fish lack the anatomical structures affected by HS, our data suggest that the zebrafish ncstn gene and the human NCSTN gene have probably acquired different functions during evolution. In fish, one major role of ncstn is the maintenance of pigmentation homeostasis. In contrast, one of the roles of NCSTN in humans is the prevention of inflammatory processes in the adnexal structures of the skin, as seen in familial HS.
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Secretases da Proteína Precursora do Amiloide/metabolismo , Glicoproteínas de Membrana/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Animais , Hidradenite Supurativa/genética , Humanos , Glicoproteínas de Membrana/genética , Peixe-ZebraRESUMO
BACKGROUND: Pressure ulcers (PUs) are injuries resulting from ischaemia caused by prolonged compression or shear forces on the skin, adjacent tissues and bones. Advanced stages of PUs are associated with infectious complications and constitute a major clinical challenge, with high social and economic impacts in health care. GOALS: This study aims to identify and describe the relationship between PU risk factors, stages and anatomical locations, and the relevance of microbial cohabitation and biofilm growth. METHODS: The narrative review method to advocating a critical and objective analysis of the current knowledge on the topic was performed. Indexed databases and direct consultation to specialized and high-impact journals on the subject were used to extract relevant information, guided by co-authors. The Medical Subject Headings of pressure ulcer (or injury), biofilms, infection and other analogues terms were used. RESULTS: Development of PUs and consequent infection depends on several direct and indirect risk factors, including cutaneous/PU microbiome, microclimate and behavioural factors. Infected PUs are polymicrobial and characterized by biofilm-associated infection, phenotypic hypervariability of species and inherent resistance to antimicrobials. The different stages and anatomical locations also play an important role in their colonization. The prevention and monitoring of PUs remain crucial for avoiding the emergence of systemic infections and reducing health care-associated costs, improve the quality of life of patients and reduce the mortality-associated infected PUs.