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This study aims to assess the musculoskeletal risk of military personnel on a Leopard 2 A6 main battle tank crew and to identify associated factors for future prevention and mitigation strategies. A sample of 57 Portuguese military personnel, who are or were part of the Leopard 2 A6 main battle tank crew, answered a questionnaire on their perception of task performance, considering muscle demands, comfort, posture, movements, and associated symptoms. A subsample of four soldiers from the Armoured Squadron of the Portuguese Mechanized Brigade were assessed using an inertial measurement unit system and underwent a whole-body kinematic analysis coupled with a Rapid Entire Body Assessment during a simulated two-hour mission. The results indicate that soldiers accurately perceive their roles within the crew and that, overall, there is a high risk of musculoskeletal injuries in all tasks. However, tasks directly related to the crew's primary duties carry consistently high risk when considering the time spent on their tasks. This study highlights the need for targeted preventive measures to reduce the incidence and severity of injuries among the crew of the Leopard 2 A6 main battle tank.
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Personal Militar , Movimiento , Humanos , Factores de Riesgo , Proyectos Piloto , Masculino , Adulto , Movimiento/fisiología , Fenómenos Biomecánicos , Enfermedades Musculoesqueléticas/fisiopatología , Enfermedades Musculoesqueléticas/epidemiología , Femenino , Adulto Joven , Encuestas y Cuestionarios , Análisis y Desempeño de TareasRESUMEN
Proteoglycans (PGs), consisting of glycosaminoglycans (GAGs) linked with the core protein through a tetrasaccharide linkage region, play roles in many important biological events. The chemical synthesis of PG glycopeptides is extremely challenging. In this work, the enzymes required for synthesis of chondroitin sulfate (CS) PG (CSPG) have been expressed and the suitable sequence of enzymatic reactions has been established. To expedite CSPG synthesis, the peptide acceptor was immobilized on solid phase and the glycan units were directly installed enzymatically onto the peptide. Subsequent enzymatic chain elongation and sulfation led to the successful synthesis of CSPG glycopeptides. The CS dodecasaccharide glycopeptide was the longest homogeneous CS glycopeptide synthesized to date. The enzymatic synthesis was much more efficient than the chemical synthesis of the corresponding CS glycopeptides, which could reduce the total number of synthetic steps by 80 %. The structures of the CS glycopeptides were confirmed by mass spectrometry analysis and NMR studies. In addition, the interactions between the CS glycopeptides and cathepsin G were studied. The sulfation of glycan chain was found to be important for binding with cathepsin G. This efficient chemoenzymatic strategy opens new avenues to investigate the structures and functions of PGs.
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Sulfatos de Condroitina , Glicopéptidos , Glicopéptidos/química , Glicopéptidos/síntesis química , Glicopéptidos/metabolismo , Sulfatos de Condroitina/química , Sulfatos de Condroitina/síntesis química , Técnicas de Síntesis en Fase Sólida , Proteoglicanos/químicaRESUMEN
Introduction: According to the guideline published by ESGE/UEG, a high-quality esophagogastroduodenoscopy (EGD) implies the application of some criteria that enable better healthcare outcomes. Although intra-procedural performance measures are dependent on patient factors, there is no reference to sedation practices in the guideline mentioned above. Objective: This study aimed to evaluate whether deep sedation influences EGD performance measures established by ESGE/UEG. Methods: This was a cross-sectional study, with a prospective enrollment, that considered for inclusion consecutive patients referred for EGD. Two questionnaires were used to assess performance measures and patient satisfaction after EGD. Results: Sedation had a statistically significant impact on most quality indicators, including complete examination (77.2% without sedation vs. 97.8% with sedation), inspection time (6.17 ± 3.45 vs. 8.39 ± 2.67 min), photodocumentation (78% vs. 97.8%), biopsies (39.3% vs. 60.7%), and patient satisfaction (5.42 ± 2.93 vs. 9.1 ± 1.19). The main reason for an incomplete procedure was patient intolerance (82.6%). Discussion: Deep sedation of patients submitted to EGD proved to be a determinant in the applicability of the ESGE/UEG quality indicators. Patient intolerance was eliminated in the group with sedation, enhancing procedure completeness, adequate pathology identification, management, and consequently, the effectiveness of the exam. Conclusion: Sedation administration should be considered in patients undergoing EGD since it ensures a high-quality procedure.
Introdução: Uma endoscopia digestiva alta (EDA) de qualidade proporciona melhores resultados em termos de saúde e implica a aplicação dos critérios descritos pelas recomendações da ESGE/UEG. Embora os critérios perprocedimento sejam dependentes da colaboração e tolerância do doente, não está explicito o papel da anestesia. Objetivos: Este estudo pretende avaliar se o recurso a anestesia influencia o cumprimento dos critérios de qualidade para a EDA publicados pela ESGE/UEG. Materiais e métodos: Estudo transversal, com recrutamento prospetivo, que incluiu pacientes consecutivamente encaminhados para realização de EDA. Foram utilizados 2 questionários para avaliar medidas de desempenho e satisfação dos pacientes após realização de EDA. Resultados: A anestesia teve um impacto estatisticamente significativo na maioria dos indicadores de qualidade: exame completo (77,2% sem anestesia vs. 97,8% com anestesia); tempo de inspeção (6,17 ± 3,45 vs. 8,39 ± 2,67 minutos); fotodocumentação (78% vs. 97,8%); biópsias (39,3% vs. 60,7%); satisfação do paciente (5,42 ± 2,93 vs. 9,1 ± 1,19). O principal motivo para um procedimento incompleto foi a intolerância do paciente (82,6%). Discussão: A sedação profunda dos doentes submetidos a EDA provou ser determinante na aplicabilidade dos critérios de qualidade da ESGE/UEG. Eliminando por completo a intolerância por parte do doente, proporcionou a realização de exames completos, com correta identificação e gestão de patologias, potenciando assim a efetividade do exame. Conclusão: A administração de anestesia deve ser ponderada, sempre que possível, nos doentes submetidos a EDA, visto que permite garantir a alta qualidade do procedimento.
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Advances in superconductor technology have been pursued for decades, moving towards room temperature models, such as a postulated nitrogen-doped lutetium hydride network. While experimental observations have been contradictory, insight into the building blocks of potential new superconductor materials can be gained theoretically, unravelling the fascinating electronic structure of these compounds at a molecular level. Here, the fundamental building blocks of lutetium materials (LuH, LuN, and LuNH) have been examined. The structures, spectroscopic constants for the ground and excited states, and the potential energy curves have been obtained for these species using complete active self-consistent field (CASSCF) and multireference configuration interaction with Davidson's correction (MRCI+Q) methods. For LuNH, the energetic properties of its isomers are determined. The bond dissociation energies of the three building blocks are calculated with the state-of-the-art f-block ab initio correlation consistent composite approach (f-ccCA) and the high accuracy extrapolated ab initio thermochemistry (HEAT) scheme. As well, an analysis of different formation pathways of LuNH has been provided.
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We present the case of a 72-year-old woman admitted for epigastric pain, elevated inflammatory parameters and liver enzymes, with a total bilirubin of 6mg/dL. Abdominal ultrasound identified cholelithiasis and posteriorly endoscopic ultrasound showed a 5.8mm stone distally in the biliary tract. Due to acute cholangitis, she underwent endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy, successfully removing the stone. Mild self-limited bleeding after sphincterotomy was reported, for which an adrenaline flush of the biliary tract was performed. The following day, she presented melena and hemoglobin dropped 3g/dL, remaining hemodynamically stable. With side-viewing duodenoscopy we identified an adherent clot and an oozing bleed near the pancreatic duct opening. The clot was removed with a snare after adrenalin injection and 3 endoclips of 8mm were positioned in the superior portion of the sphincterotomy. Even then, bleeding persisted. We opted to apply hemostatic powder (Hemospray®) with successful bleeding cessation. Four days later the patient was released without bleeding recurrence or suspected biliary blockage.
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The work environment plays a crucial role in the health and performance of employees. The growing interest in workers' well-being has driven the inclusion of nature in workplaces, despite many employees spending most of their time indoors, away from nature. Studies show that biophilic design in offices can have positive effects and promote workers' well-being. However, research on the beneficial effects of nature exposure in the workplace is limited and scattered. Thus, the aim of this systematic review was to consolidate current knowledge on the restorative effects of nature exposure on workers during work activities. Different types of exposure, both outdoors and indoors, were considered, with a focus on outcomes related to well-being, motivation, job satisfaction, and work performance. Out of the initially identified 1225 articles, only 16 met the criteria for analysis. Although the analysed studies provided compelling evidence regarding the restorative effects of nature exposure in the workplace, the review also points out gaps and limitations concerning the number of specific studies in this area and the need to adequately assess the sensory dimensions involved in these effects. Conducting more comprehensive and multidimensional investigations into the impacts of nature on the work environment could contribute to guiding more effective design strategies and creating healthier and more productive workplaces for employees.
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Rendimiento Laboral , Lugar de Trabajo , Humanos , Satisfacción en el Trabajo , MotivaciónRESUMEN
Nuclear receptors are the fundamental building blocks of gene expression regulation and the focus of many drug targets. While binding to DNA, nuclear receptors act as transcription factors, governing a multitude of functions in the human body. Peroxisome proliferator-activator receptor γ (PPARγ) and the retinoid X receptor α (RXRα) form heterodimers with unique properties and have a primordial role in insulin sensitization. This PPARγ/RXRα heterodimer has been shown to be impacted by per- and polyfluoroalkyl substances (PFAS) and linked to a variety of significant health conditions in humans. Herein, a selection of the most common PFAS (legacy and emerging) was studied utilizing molecular dynamics simulations for PPARγ/RXRα. The local and global structural effects of PFAS binding on the known ligand binding pockets of PPARγ and RXRα as well as the DNA binding domain (DBD) of RXRα were inspected. The binding free energies were predicted computationally and were compared between the different binding pockets. In addition, two electronic structure approaches were utilized to model the interaction of PFAS within the DNA binding domain, density functional theory (DFT) and domain-based pair natural orbital coupled cluster with perturbative triples (DLPNO-CCSD(T)) approaches, with implicit solvation. Residue decomposition and hydrogen-bonding analysis were also performed, detailing the role of prominent residues in molecular recognition. The role of l-carnitine is explored as a potential in vivo remediation strategy for PFAS interaction with the PPARγ/RXRα heterodimer. In this work, it was found that PFAS can bind and act as agonists for all of the investigated pockets. For the first time in the literature, PFAS are postulated to bind to the DNA binding domain in a nonspecific manner. In addition, for the PPARγ ligand binding domain, l-carnitine shows promise in replacing smaller PFAS from the pocket.
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Fluorocarburos , PPAR gamma , Humanos , PPAR gamma/metabolismo , Ligandos , Proliferadores de Peroxisomas , Receptor alfa X Retinoide/química , Receptor alfa X Retinoide/metabolismo , ADN/química , CarnitinaRESUMEN
All endoscopic procedures are invasive and carry risk. Accordingly, all endoscopists should involve the patient in the decision-making process about the most appropriate endoscopic procedure for that individual, in keeping with a patient's right to self-determination and autonomy. Recognition of this has led to detailed guidelines on informed consent for endoscopy in some countries, but in many no such guidance exists; this may lead to variations in care and exposure to risk of litigation. In this document, the European Society of Gastrointestinal Endoscopy (ESGE) sets out a series of statements that cover best practice in informed consent for endoscopy. These statements should be seen as a minimum standard of practice, but practitioners must be aware of and adhere to the law in their own country. 1: Patients should give informed consent for all gastrointestinal endoscopic procedures for which they have capacity to do so. 2: The healthcare professional seeking consent for an endoscopic procedure should ensure that the patient has the capacity to consent to that procedure. 3: For patients who lack capacity, healthcare personnel should at all times try to engage with people close to the patient, such as family, friends, or caregivers, to achieve consensus on the appropriateness of performing the procedure. 4: Where a patient lacks capacity to provide informed consent, the best interest decision should be clearly documented in the medical record. This should include information about the capacity assessment, reason(s) that the decision cannot be delayed for capacity recovery (or if recovery is not expected), who has been consulted, and where relevant the form of authority for the decision. 5: There should be a systematic and transparent disclosure of the expected benefits and harms that may reasonably affect patient choice on whether or not to undergo any diagnostic or interventional endoscopic procedure. Information about possible alternatives, as well as the consequences of doing nothing, should also be provided when relevant. 6: The information provided on the benefit and harms of an endoscopic procedure should be adapted to the procedure and patient-specific risk factors, and the preferences of the patient should be central to the consent process. 7: The consent discussion should be undertaken by an individual who is familiar with the procedure and its risks, and is able to discuss these in the context of the individual patient. 8: Patients should confirm consent to an endoscopic procedure in a private, unrushed, and non-coercive environment. 9: If a patient requests that an endoscopic procedure be discontinued, the procedure should be paused and the patient's capacity for decision making assessed. If a competent patient continues to object to the procedure, or if a conclusive determination of capacity is not feasible, the examination should be terminated as soon as it is safe to do so. 10: Informed consent should be sufficiently detailed to cover all findings that can be reasonably anticipated during an endoscopic examination. The scope of this consent should not be expanded, nor a patient's implicit consent for additional interventions assumed, unless failure to proceed with such interventions would result in immediate and predictable harm to the patient.
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Endoscopía Gastrointestinal , Consentimiento Informado , Humanos , Endoscopía Gastrointestinal/métodosRESUMEN
INTRODUCTION: Hybrid therapy (HT) is a non-bismuth quadruple therapy created to surpass Helicobacter pylori's (H. pylori) resistance rates to antibiotics. HT has excellent eradication rates, as well as a very good compliance and safety profile. We aim to compare HT with sequential therapy (ST) and concomitant therapy (CT) for the eradication of H. pylori. METHODS: This systematic review was conducted following the principles of the PRISMA guidelines. Literature was electronically searched on the CENTRAL library, PubMed, Embase, Scopus, LILACS, and ClinicalTrials.gov. Only randomized controlled trials were included. The primary outcome evaluated was eradication rate of H. pylori. The secondary outcomes evaluated were adverse events and compliance rates. Meta-analyses were performed with Cochrane Review Manager 5.4. The Mantel-Haenszel method was used to estimate the pooled relative risk and 95% confidence interval of the eradication rates between HT and other regimens, as well as the secondary outcomes. RESULTS: 10 studies were included, comprising 2993 patients. The mean eradication rates achieved by HT with intention-to-treat (ITT) and per-protocol (PP) analyses were, respectively, 86% (range: 79.2-90.8%) and 91.7% (range: 82.6-96.1%). No statistically significant difference was found in ITT eradication rate between HT and CT (relative risk: 1; 95% CI: 0.96- 1.03) and between HT and ST (relative risk: 1.02; 95% CI: 0.92-1.14). PP analysis revealed similar results. HT was associated with higher compliance rates than CT and slightly lower than ST. As far as adverse events are concerned, this meta-analysis demonstrated a higher occurrence of adverse events on the group of patients treated with CT when compared with HT. HT and ST showed similar results. CONCLUSION: HT has similar eradication, compliance and adverse event rates when compared to ST, but a better safety profile than the CT.
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Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Quimioterapia Combinada , Antibacterianos/uso terapéutico , Resultado del Tratamiento , Amoxicilina/uso terapéuticoRESUMEN
IgG4-related disease is a recently recognized autoimmune systemic disorder that has been described in various organs. The disease is characterized histologically by a dense lymphoplasmacytic infiltrate with IgG4-positive cells, storiform fibrosis, obliterative phlebitis, and can be associated with space-occupying lesions. IgG4-related disease involving the upper gastrointestinal tract is rare. We report the case of a 30-year-old female patient with a long-standing history of severe dysphagia and odynophagia. Symptoms persisted despite anti-acid therapy, and control esophagogastroduodenoscopy revealed endoscopic images consistent with a nontransposable stenosis in the proximal esophagus. An underlying autoimmune process was suspected, and topical immunosuppressants were tried to control her disease. The patient maintained disabling dysphagia secondary to chronic esophageal strictures. A diagnosis of probable IgG4-related disease was made after esophageal biopsies. Treatment attempts with topical corticosteroids was not associated with a significant improvement of the symptoms of dysphagia and odynophagia, possibly because of the chronic nature of the disease associated with a high fibrotic component. This report describes a case of IgG4-related esophageal disease presenting as chronic esophagitis with strictures. We also briefly review the main histopathological features and treatment options in IgG4-related disease.
A doença relacionada com IgG4 é uma doença sistémica, autoimune, que pode acometer vários órgãos. Caracteriza-se histologicamente por um denso infiltrado linfoplasmocítico com células IgG4-positivas, fibrose e flebite obliterante, podendo estar associada a lesões ocupantes de espaço. A doença relacionada com IgG4 envolvendo o trato gastrointestinal superior é rara. Relatamos o caso de uma paciente de 30 anos com história de disfagia e odinofagia com vários anos de evolução, em que apesar da instituição de terapêutica antiácida, os sintomas persistiram. A endoscopia digestiva alta revelou imagens endoscópicas consistentes com uma estenose não transponível no esófago proximal. Suspeitou-se de um processo autoimune subjacente sendo tentada terapêutica imunossupressora tópica para controlo da doença. A paciente manteve disfagia incapacitante secundária a estenose esofágica crónica. O diagnóstico de provável doença relacionada com IgG4 foi feito após biópsias esofágicas. As tentativas de tratamento com corticosteroides tópicos não foram associadas a uma melhora significativa dos sintomas de disfagia e odinofagia, possivelmente devido à natureza crónica da doença associada a um elevado componente fibrótico. Este caso pretende ilustrar uma situação de doença esofágica relacionada com IgG4 apresentando-se como esofagite crónica estenosante. Apresentamos ainda, uma breve revisão das principais características histopatológicas e opções de tratamento em doenças relacionadas com IgG4.
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Complete active space self-consistent field (CASSCF) and multireference configuration interaction with Davidson correction (MRCI+Q) calculations have been carried out for lawrencium fluoride (LrF) and lawrencium oxide (LrO) molecules, detailing 19 and 20 electronic states for LrF and LrO, respectively. For LrF, two dissociation channels were considered, Lr(2P)+F(2P) and Lr(2D)+F(2P). However, due to the more complex electronic manifold of LrO, three dissociation channels were computed: Lr(2P)+O(3P), Lr(2D)+O(3P), and Lr(2P)+O(1D). In addition, equilibrium bond lengths, harmonic vibrational frequencies ωe, anharmonicity constants ωeχe, ΔG1/2 values, and excitation energies Te for the ground and several excited electronic states were calculated for both molecules, for the first time. Bond dissociation energies (BDEs) were calculated for LrF and LrO using several different levels of theory: unrestricted coupled-cluster with single, double, and perturbative triple excitations (UCCSD(T)), density functional theory (B3LYP, TPSS, M06-L, and PBE), and the correlation-consistent composite approach developed for f-elements (f-ccCA).
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INTRODUCTION: Helicobacter pylori (H. pylori) infection is highly prevalent in Portugal and its eradication is formally recommended. However, the indiscriminate use of antimicrobials has led to a drastic rise in antibiotic resistance, with the failure of traditional eradication schemes. A single-capsule bismuth-based quadruple therapy became recently available in Portugal. This study aims to evaluate the efficacy and safety of a bismuth-based quadruple therapy as a second-line or rescue therapy. PATIENTS AND METHODS: This was a multicentric study. All consecutive patients that were treated with bismuth-based quadruple therapy, as second-line or salvage treatment between July 2017 and April 2019 were enrolled. Their medical records were reviewed and clinical and laboratorial parameters, as well as data on treatment efficacy and adverse events were retrieved. Patients were also contacted by phone after treatment to confirm compliance, adverse events, and global satisfaction with this specific therapy. RESULTS: A total of 151 subjects were included (female-68.9%; mean age-56 ± 13.5 years). Patients were previously submitted to 212 eradication schemes (Median-1; 1-5; IQR:4): 33.5% triple clarithromycin-based, 25% sequential, 7.5% concomitant, 5.2% others, and in 28.8% it was not possible to know the previous eradication scheme(s) followed by the patient. The PPI of choice was esomeprazole (39.7%), followed by omeprazole (27.8%). Compliance was achieved in 93.4% and the overall eradication rate was 90.1% (95% CI: 84.6-94.2). Treatment-related adverse effects were experienced by 63 patients (41.7%; 95% CI: 34-49.7), being mild in 29, moderate in 19, and severe in 15. The main drawbacks of the treatment, from the patient's perspective, were the high price (47%) and the adverse effects (16.6%). Failure to eradicate H. pylori was correlated with the following: previous rifabutin-based scheme (0 vs. 100%; p = 0.010) and a higher number of previous treatment schemes (1.5 ± 0.7 vs. 2.3 ± 1.2; p < 0.001). CONCLUSION: In this South-European country a single-capsule bismuth-based quadruple therapy is an excellent option as a second-line or rescue therapy, with acceptable compliance and side effects.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Femenino , Bismuto/uso terapéutico , Antibacterianos/efectos adversos , Inhibidores de la Bomba de Protones/efectos adversos , Quimioterapia Combinada , Infecciones por Helicobacter/tratamiento farmacológico , Resultado del Tratamiento , Amoxicilina/uso terapéutico , Metronidazol/uso terapéuticoRESUMEN
BACKGROUND & AIMS: Despite recent approvals, the response to treatment and prognosis of patients with advanced hepatocellular carcinoma (HCC) remain poor. Claudin-1 (CLDN1) is a membrane protein that is expressed at tight junctions, but it can also be exposed non-junctionally, such as on the basolateral membrane of the human hepatocyte. While CLDN1 within tight junctions is well characterized, the role of non-junctional CLDN1 and its role as a therapeutic target in HCC remains unexplored. METHODS: Using humanized monoclonal antibodies (mAbs) specifically targeting the extracellular loop of human non-junctional CLDN1 and a large series of patient-derived cell-based and animal model systems we aimed to investigate the role of CLDN1 as a therapeutic target for HCC. RESULTS: Targeting non-junctional CLDN1 markedly suppressed tumor growth and invasion in cell line-based models of HCC and patient-derived 3D ex vivo models. Moreover, the robust effect on tumor growth was confirmed in vivo in a large series of cell line-derived xenograft and patient-derived xenograft mouse models. Mechanistic studies, including single-cell RNA sequencing of multicellular patient HCC tumorspheres, suggested that CLDN1 regulates tumor stemness, metabolism, oncogenic signaling and perturbs the tumor immune microenvironment. CONCLUSIONS: Our results provide the rationale for targeting CLDN1 in HCC and pave the way for the clinical development of CLDN1-specific mAbs for the treatment of advanced HCC. IMPACT AND IMPLICATIONS: Hepatocellular carcinoma (HCC) is associated with high mortality and unsatisfactory treatment options. Herein, we identified the cell surface protein Claudin-1 as a treatment target for advanced HCC. Monoclonal antibodies targeting Claudin-1 inhibit tumor growth in patient-derived ex vivo and in vivo models by modulating signaling, cell stemness and the tumor immune microenvironment. Given the differentiated mechanism of action, the identification of Claudin-1 as a novel therapeutic target for HCC provides an opportunity to break the plateau of limited treatment response. The results of this preclinical study pave the way for the clinical development of Claudin-1-specific antibodies for the treatment of advanced HCC. It is therefore of key impact for physicians, scientists and drug developers in the field of liver cancer and gastrointestinal oncology.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animales , Ratones , Carcinoma Hepatocelular/genética , Claudina-1/genética , Neoplasias Hepáticas/genética , Carcinógenos , Microambiente Tumoral , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Línea Celular TumoralRESUMEN
Klebsiella pneumoniae is a gram-negative pathogen that is a common cause of severe infections, including pyogenic liver abscess. Dissemination of K. pneumoniae to other organs, including the eye, is associated with significant morbidity and mortality. In the particular case of endogenous endophthalmitis (EE) by K. pneumoniae the prognosis is poor. We report the case of a middle-aged female with K. pneumoniae liver abscess. The patient developed metastatic endophthalmitis that was aggressively treated with systemic antibiotics. The liver abscess resolved with antimicrobials and percutaneous transhepatic drainage, but regarding the endophthalmitis she was discharged from our hospital without recovery of her eyesight. Metastatic spread to the eye should be considered in all patients with liver abscesses who experience ocular signs and symptoms in order to establish a timely diagnosis of EE.
A Klebsiella pneumoniae, bactéria gram-negativa, é causa comum de infeções graves, incluindo abscesso hepático piogénico. A disseminação da K. pneumoniae para outros órgãos, incluindo o olho, está associada a morbimortalidade significativas. A endoftalmite endógena por K. pneumoniae, apresenta um mau prognóstico. Apresentamos o caso de uma mulher de meia-idade com um abscesso hepático por K. pneumoniae. A paciente desenvolveu endoftalmite metastática, tratada agressivamente com antibióticos sistêmicos. O abscesso hepático foi resolvido com antibioterapia e drenagem percutânea. No que diz respeito à endoftalmite a paciente acabou por ter alta clínica sem recuperação da visão. A disseminação metastática para o olho deve ser considerada em todos os pacientes com abscessos hepáticos que apresentam sinais e sintomas oculares, a fim de estabelecer um diagnóstico oportuno de endoftalmite endógena.
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Tissue fibrosis is a key driver of end-stage organ failure and cancer, overall accounting for up to 45% of deaths in developed countries. There is a large unmet medical need for antifibrotic therapies. Claudin-1 (CLDN1) is a member of the tight junction protein family. Although the role of CLDN1 incorporated in tight junctions is well established, the function of nonjunctional CLDN1 (njCLDN1) is largely unknown. Using highly specific monoclonal antibodies targeting a conformation-dependent epitope of exposed njCLDN1, we show in patient-derived liver three-dimensional fibrosis and human liver chimeric mouse models that CLDN1 is a mediator and target for liver fibrosis. Targeting CLDN1 reverted inflammation-induced hepatocyte profibrogenic signaling and cell fate and suppressed the myofibroblast differentiation of hepatic stellate cells. Safety studies of a fully humanized antibody in nonhuman primates did not reveal any serious adverse events even at high steady-state concentrations. Our results provide preclinical proof of concept for CLDN1-specific monoclonal antibodies for the treatment of advanced liver fibrosis and cancer prevention. Antifibrotic effects in lung and kidney fibrosis models further indicate a role of CLDN1 as a therapeutic target for tissue fibrosis across organs. In conclusion, our data pave the way for further therapeutic exploration of CLDN1-targeting therapies for fibrotic diseases in patients.
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Anticuerpos Monoclonales , Plasticidad de la Célula , Animales , Ratones , Humanos , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Claudina-1 , Cirrosis Hepática/tratamiento farmacológicoRESUMEN
Introduction: Clinical practice guidelines (CPG) contain recommendations that aim to guide physicians in the diagnosis of and therapeutic approach toward patients affected by gastrointestinal (GI) pathologies. These CPG systematically combine scientific evidence and clinical judgment, culminating in recommendations that have been shown to improve patient care. Material and Methods: European and North American guidelines published in the area of gastroenterology in 2018 and 2019 were considered for inclusion. To standardize the results, only guidelines that used GRADE as an evidence system were included. Thus, in the end, 1,233 recommendations from 29 guidelines published between 2018 and 2019 were analyzed. Results: Of the 1,233 recommendations collected, 324 (26.3%) had a low level of evidence and 127 (10.3%) had a very low level of evidence, indicating little evidence or expert opinion. Of the 29 publications analyzed, 14 (48.3%) did not present any recommendation with a high level of evidence. Regarding the 1,233 individual recommendations expressed in these 29 publications, only 336 (27.25%) assumed a high level of evidence, with 277 (82.44%) referring to liver pathology. Of the recommendations evaluated, 77 were from North American societies and the remaining 1,156 were European recommendations. In relation to the first group, only 3 (3.9%) had a high level of evidence belonging to the Guidelines for Sedation and Anesthesia in GI Endoscopy. Conclusions: More than 25% of all recommendations currently accepted to guide patients with gastroenterological disorders are based on low-quality evidence or expert opinion. Thus, these documents should guide our performance, but clinical sense and multidisciplinarity must not be overlooked in dubious cases and with weak scientific evidence. Research should focus on the development of randomized controlled trials and systematic reviews to improve the evidence supporting the guidelines that guide clinical practice.
Introdução: As diretrizes que orientam a prática clínica contêm recomendações de forma a que os médicos possam determinar os cuidados mais adequados para cada paciente. Estas diretrizes combinam evidências científicas com o julgamento clínico, culminando em recomendações destinadas a otimizar a prestação de cuidados. Material e Métodos: Diretrizes publicadas na área de Gastroenterologia entre 2018 e 2019 foram consideradas para inclusão.Para padronizar os resultados, apenas diretrizes usando o GRADE como um sistema de evidência foram incluídas. Assim, foram analisadas 1,233 recomendações de 29 diretrizes publicadas entre 20182019. Resultados: Das 1,233 recomendações incluídas, 334 (26.3%) apresentavam um nível de evidência baixo e 127 (10.3%) um nível de evidência muito baixo, indicando pouca evidência ou mesmo opinião de especialistas. Das 29 publicações analisadas, 14 (48,3%) não apresentavam nenhuma recomendação com alto nível de evidência. Em relação às 1,233 recomendações incluídas nas 29 publicações, apenas 336 (27.25%) assumiam alto nível de evidência, sendo 277 (82.44%) referentes à patologia hepática. Das recomendações avaliadas, 77 eram de sociedades norteamericanas e as restantes 1,156 recomendações europeias.Em relação ao primeiro grupo, apenas 3 (3,9%) possuíam alto nível de evidência e pertenciam às "Diretrizes para sedação e anestesia em endoscopia gastrointestinal.". Conclusões: Mais de 25% de todas as recomendações atualmente aceites para orientar pacientes com patologias gastrointestinais são baseadas em evidências de baixa qualidade ou opinião de especialistas. Estes documentos devem orientar a nossa forma de atuar, mas o senso clínico e a abordagem multidisciplinar não devem ser esquecidos em casos duvidosos e com evidência científica fraca. A investigação deve concentrar-se no desenvolvimento de ensaios clínicos randomizados e revisões sistemáticas para melhorar as evidências que apoiam as diretrizes que orientam a prática clínica.
RESUMEN
The f-block ab initio correlation consistent composite approach was used to predict the dissociation energies of lanthanide sulfides and selenides. Geometry optimizations were carried out using density functional theory and coupled cluster singles, doubles, and perturbative triples with one- and two-component Hamiltonians. For the two-component calculations, relativistic effects were accounted for by utilizing a third-order Douglas-Kroll-Hess Hamiltonian. Spin-orbit coupling was addressed with the Breit-Pauli Hamiltonian within a multireference configuration interaction approach. The state averaged complete active space self-consistent field wavefunctions obtained for the spin-orbit coupling energies were used to assign the ground states of diatomics, and several diagnostics were used to ascertain the multireference character of the molecules.
RESUMEN
This study aimed to determine the intra-day reliability, individuals performance expectancy, and biomechanical response of nine stretching instructions in assessing the maximal range of motion (mROM) during the passive ankle dorsiflexion test. Twenty healthy young participants were tested in two sessions within the same day. Nine stretching instructions composed by intensity-domain (i.e. minimum, point, and maximum) and sensation-domain (i.e. tolerance, discomfort, and pain) words were used to impose plantar flexors stretching. In the first session, individuals were requested to order the nine stretching instructions in ascending order. The ankle joint torque-angle and medial gastrocnemius, soleus and tibialis anterior electric activity were assessed in both sessions. A moderate to high reliability was observed across instructions (ICC = 0.65-0.87). Most stretching instructions showed high intra-day reliability outcomes, where discomfort and tolerance showed moderate reliability. 70% of individuals performed the stretching maneuvers consistently to stretching instructions performance expectancy. A greater torque-angle response was observed for the instructions involving the word pain (ROM = 40.5 ± 1.6°), compared to discomfort (29.5 ± 1.8°), and tolerance (30.5 ± 2.0°) that produced similar stretching intensities. Instructions involving the terms minimum (29.6 ± 2.0°), point (33.3 ± 7.6°), and maximum (37.6 ± 7.2°) were more discriminative of stretching intensities than sensation-domain terms. In conclusion, stretching instructions targeting the joint maximal range of motion produce different joint torque-angle responses and they may not be understandable by all individuals, although (in general) they can be used reliably.
Asunto(s)
Ejercicios de Estiramiento Muscular , Articulación del Tobillo/fisiología , Humanos , Músculo Esquelético/fisiología , Dolor , Rango del Movimiento Articular/fisiología , Reproducibilidad de los Resultados , TorqueRESUMEN
The COVID-19 pandemic has caused many changes that have influenced the lives of people around the world and have left their mark in the world of sports, as well. Numerous restrictions resulted in the cancellation of the organization of many sports events, and the players themselves had restricted access to training. The main goal of the study was to identify the motivation to participate in a triathlon between athletes who have undergone COVID-19, those who have never been infected and those who do not know if they have ever caught the virus and to evaluate the differences between them. The assessment of the motives for participating in a sports event was conducted according to four types of orientation: social, experience, factual and results to check what benefits for well-being and self-improvement are brought about by participation in a triathlon as a mass sports event. The desire to feel unity, to develop passion, to integrate with other people and to get away from everyday life were the most important motives for those who have never been infected. It turns out that 100% of the respondents who had a history of COVID-19 disease indicated the desire to prove themselves. The desire to maintain good physical condition and health was reported by the majority of researched people, but again, all respondents (100%) who had been infected with COVID-19 indicated these motives as the most important.
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COVID-19 , Deportes , COVID-19/epidemiología , Humanos , Incidencia , Motivación , PandemiasRESUMEN
OBJECTIVE: Propolis has been used since antiquity, but recent reports of its biological properties hint that it could be employed as a topical pharmaceutical and cosmetic ingredient. This work aims to probe the action of Portuguese propolis extracts on skin cells, providing mechanistic insights into its mode of action and preliminarily assessing its applicability as a skin repair ingredient. METHODS: The total phenolic content of propolis extracts was measured by the Folin Ciocalteu method. The cytotoxic effect of propolis extracts in human keratinocytes was determined and non-cytotoxic concentrations of the extracts were used to study the impact on collective cell migration, cell cycle and intracellular ROS levels. RESULTS: o significant impact was observed in collective cell migration, but one of the extracts mildly increased G2 phase while reducing the % of sub-G1 at a non-cytotoxic concentration. The two extracts with higher phenolic content strongly prevented intracellular cellular ROS accumulation upon exposure to TBHP. Collectively, these results indicate that the putative beneficial effects of propolis extracts in skin repair may not be attributable to induction of collective cell migration but could be partially ascribed to the protection from oxidative stress, which could act in synergy with its well-known antimicrobial activity. CONCLUSION: These data support the applicability of this material in topical and cosmetic formulations and further in vivo assays should be conducted to fully characterize its efficacy and safety.
OBJECTIF: la propolis est utilisée depuis l'Antiquité, mais des rapports récents sur ses propriétés biologiques suggèrent qu'elle pourrait être utilisée comme ingrédient pharmaceutique et cosmétique topique. Ce travail de recherche vise à explorer l'effet d'extraits de propolis portugaise sur les cellules cutanées, en fournissant des informations sur le plan mécanique relatives à son mode d'action et en évaluant de manière préliminaire son applicabilité en tant qu'ingrédient de réparation cutanée. MÉTHODES: la teneur en substance phénolique totale d'extraits de propolis a été mesurée par la méthode de Folin-Ciocalteu. L'effet cytotoxique d'extraits de propolis dans les kératinocytes humains a été déterminé, et des concentrations non cytotoxiques de ces extraits ont été utilisées pour étudier l'impact sur la migration cellulaire collective, le cycle cellulaire et les taux de ROS intracellulaires. RÉSULTATS: un impact significatif a été observé sur la migration cellulaire collective, mais l'un des extraits a légèrement augmenté la phase G2 tout en réduisant le % de sub-G1 à une concentration non cytotoxique. Les deux extraits présentant une teneur phénolique plus élevée ont fortement prévenu l'accumulation de ROS intracellulaires lors de l'exposition à l'hydroperoxyde de tert-butyle (TBHP). Collectivement, ces résultats indiquent que les effets bénéfiques présumés des extraits de propolis dans la réparation cutanée pourraient ne pas être attribuables à l'induction de la migration cellulaire collective, mais partiellement à la protection contre le stress oxydatif, qui pourrait agir en synergie avec son activité antimicrobienne bien connue. CONCLUSION: ces données étayent l'applicabilité de cette substance dans les formulations topiques et cosmétiques, et des tests in vivo supplémentaires doivent être réalisés afin de caractériser plus précisément son efficacité et sa sécurité d'emploi.