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Studies involving the immune response in Chagas disease suggest an imbalance in the immune response of symptomatic patients, with an inflammatory profile dominating in Chagas heart disease, mainly by tumour necrosis factor (TNF). TNF is considered a key cytokine in immunopathology in chronic carriers in several processes during the immune response. Our work aimed to evaluate regulatory (interleukin [IL]-4 and IL-10) and inflammatory (TNF, interferon-gamma [IFN-γ], IL-2 and IL-6) cytokines in peripheral blood mononuclear cells culture supernatants. of affected patients with undetermined clinical forms-IND (n = 13) mild heart form-CARD1 (n = 13) and severe cardiac form-CARD2 (n = 16), treated in vitro with two TNF blockers, Adalimumab (ADA) and Etanercept (ETA) alone or in association with Benznidazole (BZ). The results indicate that ADA was more competent in blocking TNF (compared to ETA) in all groups but with much lower levels in the CARD2 group. ETA statistically decreased TNF levels only in the CARD2 group. IFN-γ increased in the CARD2 group after treatment with ETA relative to ADA. IL-4 had its levels decreased when treated by both drugs. IL-2 was detected in cells from CARD2 carriers compared to the NEG group after treatment with both drugs. The association with BZ decreased levels of IL-2/TNF and increased IL-4. These data reinforce the participation of TNF in severe Chagas heart disease and bring perspectives on using these blockers in the immunological treatment of Chagas disease since the use of BZ is extremely limited in these patients.
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Doença de Chagas , Cardiopatias , Nitroimidazóis , Humanos , Doença de Chagas/tratamento farmacológico , Citocinas , Cardiopatias/tratamento farmacológico , Cardiopatias/parasitologia , Interferon gama , Interleucina-2 , Interleucina-4 , Leucócitos Mononucleares , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Fator de Necrose Tumoral alfaRESUMO
PURPOSE: Data on short courses of antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients are limited. The aim of the study was to describe and compare the frequency of bacteremia relapse, 30-day overall and infection-related mortality, Clostridiodes difficile infection and length of hospital stay since bacteremia among those who received antibiotic therapy for 7 or 14 days. METHODS: This is a multicenter, prospective, observational cohort study in adult high-risk neutropenic patients with hematologic malignancies or hematopoietic stem cell transplant and monomicrobial Enterobacterales bacteremia. They received appropriate empirical antibiotic therapy, had a clinical response within 7 days, and infection source control. Clinical, epidemiological and outcomes variables were compared based on 7 or 14 days of AT. RESULTS: Two hundred patients were included (100, 7-day antibiotic therapy; 100, 14-day antibiotic therapy). Escherichia coli was the pathogen most frequently isolated (47.5%), followed by Klebsiella sp. (40.5%). Among those patients that received 7-day vs. 14-day antibiotic course, a clinical source of bacteremia was found in 54% vs. 57% (p = 0.66), multidrug-resistant Enterobacterales isolates in 28% vs. 30% (p = 0.75), and 40% vs. 47% (p = 0.31) received combined empirical antibiotic therapy. Overall mortality was 3% vs. 1% (p = 0.62), in no case related to infection; bacteremia relapse was 7% vs. 2% (p = 0.17), and length of hospital stay since bacteremia had a median of 9 days (IQR: 7-15) vs. 14 days (IQR: 13-22) (p = < 0.001). CONCLUSIONS: These data suggest that seven-day antibiotic therapy might be adequate for patients with high-risk neutropenia and Enterobacterales bacteremia, who receive appropriate empirical therapy, with clinical response and infection source control.
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Chromatin access and epigenetic control over gene expression play important roles in regulating developmental processes. However, little is known about how chromatin access and epigenetic gene silencing influence mature glial cells and retinal regeneration. Herein, we investigate the expression and functions of S-adenosylhomocysteine hydrolase (SAHH; AHCY) and histone methyltransferases (HMTs) during the formation of Müller glia (MG)-derived progenitor cells (MGPCs) in the chick and mouse retinas. In chick, AHCY, AHCYL1 and AHCYL2, and many different HMTs are dynamically expressed by MG and MGPCs in damaged retinas. Inhibition of SAHH reduced levels of H3K27me3 and potently blocks the formation of proliferating MGPCs. By using a combination of single cell RNA-seq and single cell ATAC-seq, we find significant changes in gene expression and chromatin access in MG with SAHH inhibition and NMDA-treatment; many of these genes are associated with glial and neuronal differentiation. A strong correlation across gene expression, chromatin access, and transcription factor motif access in MG was observed for transcription factors known to convey glial identity and promote retinal development. By comparison, in the mouse retina, inhibition of SAHH has no influence on the differentiation of neuron-like cells from Ascl1-overexpressing MG. We conclude that in the chick the activity of SAHH and HMTs are required for the reprogramming of MG into MGPCs by regulating chromatin access to transcription factors associated with glial differentiation and retinal development.
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Cromatina , Transdução de Sinais , Animais , Camundongos , Transdução de Sinais/fisiologia , Cromatina/metabolismo , Células-Tronco/metabolismo , Células Ependimogliais/metabolismo , Retina , Neuroglia/metabolismo , Galinhas/genética , Fatores de Transcrição/metabolismo , Proliferação de Células/fisiologiaRESUMO
Benznidazole (Bz) is the recommended drug for the treatment of Chagas disease; however, its efficacy may vary according to the sensitivity of Trypanosoma cruzi strains to the drug and host immune background. The study evaluated the immune response of peripheral blood mononuclear cells (PBMC) that were infected in vitro with the Colombian strain (Col) and treated with Bz. The co-cultures were incubated for 24 h, 5 and 10 days, where cytokine dosage was performed in the supernatant and evaluation of the cells for CD28+ and CTLA-4+ molecules in CD4+ and CD8+ lymphocytes, and CD80+ , CD86+ and HLA-DR+ in CD14+ cells. The results showed that Col induced a strong inflammatory response, with an increase in IFN-γ and TNF early in the infection (24 h), however, from 5 days of infection on, TNF production declined, and IL-10 production increased, which may be associated with a control mechanism of the exacerbated inflammatory response. The Bz treatment did not significantly alter the frequencies of the phenotypes evaluated both T cell subsets and CD14+ cells. Therefore, this study reinforces the need for typing the patient's strain to guide therapy and promote individualized treatment protocols due to the heterogeneous genetic background among T. cruzi strains.
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Doença de Chagas , Nitroimidazóis , Tripanossomicidas , Trypanosoma cruzi , Humanos , Leucócitos Mononucleares , Colômbia , Nitroimidazóis/farmacologia , Nitroimidazóis/uso terapêutico , Doença de Chagas/tratamento farmacológico , Tripanossomicidas/farmacologia , Tripanossomicidas/uso terapêuticoRESUMO
Chagas disease (CD), caused by the protozoan Trypanosoma cruzi (T. cruzi), affects millions of people worldwide. Polymerase Chain Reaction (PCR) and real-time quantitative PCR (qPCR) have been used as tools to monitor parasitic levels in the bloodstream of individuals exposed to infection, thus enabling the monitoring of relapses and the effectiveness of therapy, for example. The aim of this study was to evaluate the TcSAT-IAM system, developed by our research group, on samples from patients with suspected Chagas disease infection. Initially, primer systems were developed for the detection of the nuclear DNA (SAT-DNA) from T. cruzi (TcSAT-IAM). The Cruzi system, predicted in the literature, and TcSAT-IAM were then evaluated in relation to their analytical sensitivity, specificity and efficiency. Afterwards, the applicability of the qPCR technique using both systems (separately) for the diagnosis of acute CD was evaluated in samples from 77 individuals exposed to the outbreak that occurred in Pernambuco-Brazil, relating the results obtained to those of the classical diagnostic methods recommended for this stage of the infection. TcSAT-IAM and Cruzi had a detection limit of 1 fg of target DNA (0,003 parasites). Thirty-eight cases were recorded, 28 by laboratory criteria and 10 by clinical and epidemiological criteria. Blood samples from 77 subjects were submitted to qPCR by both systems, reaching an agreement of 89.61% between them. After analyzes between systems and diagnostic criteria, the TcSAT-IAM showed sensitivity and specificity of 52.36% (CI 37.26-67.52) and 92.31% (CI 79.68-97.35), respectively, accuracy of 72.73% and moderate agreement. The TcSAT-IAM showed an accuracy of 72.58% and 75% in relation to parasitological and serological tests (IgM anti-T. cruzi), respectively. Therefore, quantitative PCR should be incorporated into the diagnosis of suspected acute cases of Chagas disease.
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Doença de Chagas , Trypanosoma cruzi , Humanos , Brasil/epidemiologia , Patologia Molecular , DNA de Protozoário/genética , Doença de Chagas/diagnóstico , Doença de Chagas/epidemiologia , Doença de Chagas/tratamento farmacológico , Trypanosoma cruzi/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Surtos de DoençasRESUMO
Previously, functional coatings on 3D-printed titanium implants were developed to improve their biointegration by separately incorporating Ga and Ag on the biomaterial surface. Now, a thermochemical treatment modification is proposed to study the effect of their simultaneous incorporation. Different concentrations of AgNO3 and Ga(NO3)3 are evaluated, and the obtained surfaces are completely characterized. Ion release, cytotoxicity, and bioactivity studies complement the characterization. The provided antibacterial effect of the surfaces is analyzed, and cell response is assessed by the study of SaOS-2 cell adhesion, proliferation, and differentiation. The Ti surface doping is confirmed by the formation of Ga-containing Ca titanates and nanoparticles of metallic Ag within the titanate coating. The surfaces generated with all combinations of AgNO3 and Ga(NO3)3 concentrations show bioactivity. The bacterial assay confirms a strong bactericidal impact achieved by the effect of both Ga and Ag present on the surface, especially for Pseudomonas aeruginosa, one of the main pathogens involved in orthopedic implant failures. SaOS-2 cells adhere and proliferate on the Ga/Ag-doped Ti surfaces, and the presence of gallium favors cell differentiation. The dual effect of both metallic agents doping the titanium surface provides bioactivity while protecting the biomaterial from the most frequent pathogens in implantology.
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Gálio , Titânio , Titânio/farmacologia , Titânio/química , Prata/farmacologia , Prata/química , Osseointegração , Porosidade , Gálio/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/química , Antibacterianos/farmacologia , Antibacterianos/química , Propriedades de SuperfícieRESUMO
BACKGROUND AND PURPOSE: Telemedicine for stroke patients' care (telestroke [TS]) has grown notably in recent decades and may offer advantages during health crisis. Hospital admissions related to stroke have decreased globally during the COVID-19 pandemic, but scarce information is available regarding the effect of COVID-19 in TS. Using a population-based TS registry, we investigated the impact of the first year of the COVID-19 pandemic throughout our TS network in Santiago, Chile. METHODS: Stroke codes evaluated after the onset of COVID-19 restrictions in Chile (defined as March 15, 2020) were compared with those evaluated in 2019. We analyzed differences between number of stroke codes, thrombolysis rate, stroke severity, and time from the stroke onset to hospital admission. RESULTS: We observed that the number of stroke codes and the number of patients undergoing reperfusion therapy did not change significantly (p = 0.669 and 0.415, respectively). No differences were found with respect to the median time from the stroke onset to admission (p = 0.581) or in National Institutes of Health Stroke Scale (NIHSS) scores (p = 0.055). The decision-making-to-needle time was significantly shorter in the COVID-19 period (median 5 min [IQR 3-8], p < 0.016), but no significant changes were found at the other times. CONCLUSIONS: This study demonstrates the potential of adapting TS to extreme situations such as the COVID-19 pandemic, as well as the importance of establishing networks that facilitate patient access to quality treatments.
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COVID-19 , Acidente Vascular Cerebral , Telemedicina , Chile/epidemiologia , Humanos , Pandemias , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/terapia , Terapia TrombolíticaRESUMO
Aging people living with HIV (PLWH), especially postmenopausal women may be at higher risk of comorbidities associated with HIV, antiretroviral therapy (ART), hypogonadism, and at-risk alcohol use. Our studies in simian immunodeficiency virus (SIV)-infected male macaques demonstrated that chronic binge alcohol (CBA) reduced acute insulin response to glucose (AIRG), and at-risk alcohol use decreased HOMA-ß in PLWH. The objective of this study was to examine the impact of ovariectomy (OVX) on glucose-insulin dynamics and integrity of pancreatic endocrine function in CBA/SIV-infected female macaques. Female macaques were administered CBA (12-15 g/kg/wk) or isovolumetric water (VEH) intragastrically. Three months after initiation of CBA/VEH administration, all macaques were infected with SIVmac251, and initiated on antiretroviral therapy (ART) 2.5 mo postinfection. After 1 mo of ART, macaques were randomized to OVX or sham surgeries (n = 7 or 8/group), and euthanized 8 mo post-OVX (study endpoint). Frequently sampled intravenous glucose tolerance tests (FSIVGTT) were performed at selected time points. Pancreatic gene expression and islet morphology were determined at study endpoint. There was a main effect of CBA to decrease AIRG at Pre-SIV and study endpoint. There were no statistically significant OVX effects on AIRG (P = 0.06). CBA and OVX decreased the expression of pancreatic markers of insulin docking and release. OVX increased endoplasmic stress markers. CBA but not OVX impaired glucose-insulin expression dynamics in SIV-infected female macaques. Both CBA and OVX altered integrity of pancreatic endocrine function. These findings suggest increased vulnerability of PLWH to overt metabolic dysfunction that may be exacerbated by alcohol use and ovarian hormone loss.
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Consumo Excessivo de Bebidas Alcoólicas/complicações , Glicemia/metabolismo , Transtornos do Metabolismo de Glucose/etiologia , Resistência à Insulina , Insulina/sangue , Ovariectomia/efeitos adversos , Pâncreas/metabolismo , Síndrome de Imunodeficiência Adquirida dos Símios/complicações , Vírus da Imunodeficiência Símia/patogenicidade , Animais , Antirretrovirais/uso terapêutico , Consumo Excessivo de Bebidas Alcoólicas/sangue , Consumo Excessivo de Bebidas Alcoólicas/fisiopatologia , Biomarcadores/sangue , Modelos Animais de Doenças , Feminino , Transtornos do Metabolismo de Glucose/sangue , Transtornos do Metabolismo de Glucose/fisiopatologia , Macaca mulatta , Pâncreas/fisiopatologia , Fatores de Risco , Síndrome de Imunodeficiência Adquirida dos Símios/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Fatores de TempoRESUMO
A 79-year-old man, who underwent femoropopliteal bypass surgery 1 month prior to admission, presented with fever and fatigue. ECG showed complete atrioventricular block. Transthoracic echocardiography was performed, revealing a round homogeneous right atrial mass and severe mitral regurgitation. Transoesophageal echocardiography revealed involvement the coronary sinus (CS). Computed tomography imaging demonstrated abscess of the atrioventricular sulcus and infiltration of the CS.
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Seio Coronário , Endocardite Bacteriana , Endocardite , Idoso , Seio Coronário/diagnóstico por imagem , Ecocardiografia , Ecocardiografia Transesofagiana , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/diagnóstico por imagem , Humanos , MasculinoRESUMO
In this rare case of intrahepatic cholangiocarcinoma (ICC) tumor thrombus with right atrial (RA) invasion, we describe its diagnostic workup based on cardiac magnetic resonance imaging (cMRI). An 85-year-old man underwent transthoracic echocardiography due to dyspnea, revealing a RA mass. Comprehensive cMRI evaluation, including cine bright blood, T1- and T2-weighed, fat-suppressed, and contrast-enhanced imaging, was performed and diagnosis of ICC tumor thrombus with RA invasion was made. This first description of cMRI-guided diagnosis of RA invasion by ICC tumor thrombus points out the usefulness of cMRI for the diagnostic approach of RA masses suggestive of tumor thrombus.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/diagnóstico por imagem , Átrios do Coração/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , MasculinoRESUMO
Human papillomavirus (HPV) DNA integration is a crucial event in cervical carcinogenesis. However, scarce studies have focused on studying HPV integration (HPVint) in early-stage cervical lesions. Using HPV capture followed by sequencing, we investigated HPVint in pre-tumor cervical lesions. Employing a novel pipeline, we analyzed reads containing direct evidence of the integration breakpoint. We observed multiple HPV infections in most of the samples (92%) with a median integration rate of 0.06% relative to HPV mapped reads corresponding to two or more sequence breakages. Unlike cancer studies, most integrations events were unique (supported by one read), consistent with the lack of clonal selection. Congruent to other studies, we found that breakpoints could occur, practically, in any part of the viral genome. We noted that L1 had a higher frequency of rupture integration (25%). Based on host genome integration frequencies, we found previously reported integration sites in cancer for genes like FHIT, CSMD1, and LRP1B and putatively many new ones such as those exemplified in CSMD3, ROBO2, and SETD3. Similar host integrations regions and genes were observed in diverse HPV types within many genes and even equivalent integration positions in different samples and HPV types. Interestingly, we noted an enrichment of integrations in most centromeres, suggesting a possible mechanism where HPV exploits this structural machinery to facilitate integration. Supported by previous findings, overall, our analysis provides novel information and insights about HPVint.
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Papillomaviridae/fisiologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/etiologia , Integração Viral , Transformação Celular Viral , Biologia Computacional/métodos , Feminino , Genoma Viral , Genótipo , Humanos , México/epidemiologia , Papillomaviridae/classificação , Infecções por Papillomavirus/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/patologia , Análise de Sequência de DNA , Displasia do Colo do Útero/patologiaRESUMO
Since the first publications related to microstructured optical fibers (MOFs), the development of optical fiber sensors (OFS) based on them has attracted the interest of many research groups because of the market niches that can take advantage of their specific features. Due to their unique structure based on a certain distribution of air holes, MOFs are especially useful for sensing applications: on one hand, the increased coupling of guided modes into the cladding or the holes enhances significantly the interaction with sensing films deposited there; on the other hand, MOF air holes enhance the direct interaction between the light and the analytes that get into in these cavities. Consequently, the sensitivity when detecting liquids, gasses or volatile organic compounds (VOCs) is significantly improved. This paper is focused on the reported sensors that have been developed with MOFs which are applied to detection of gases and VOCs, highlighting the advantages that this type of fiber offers.
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Large amounts of calcium are required during pregnancy and lactation to support fetal and neonatal bone growth and calcification. An inadequate supply of calcium during these stages can lead to unsuccessful reproduction or impaired offspring fitness. During reproduction, female mammals undergo numerous physiological changes, including adaptations to allow an adequate supply of calcium. The lack of quantitative studies analysing these physiological changes from a comparative perspective limits our ability to explain and understand these adaptations. Herein, we present our meta-analysis of studies reporting changes in bone turnover and calcium homeostasis during pregnancy and lactation in 14 species of mammals. Our meta-analysis of 60 studies showed that all species have a similar pattern of physiological changes during pregnancy and lactation, which include: (1) decreased serum calcium concentrations; (2) bone tissue loss; (3) decreased serum calcitonin and parathyroid hormone concentrations; and (4) increased serum calcitriol concentration, regardless of changes in parathyroid hormone concentrations. In addition, we found a negative relationship between: (1) serum calcium concentrations and the number of teats; and (2) serum parathyroid hormone concentrations and litter mass.
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Remodelação Óssea/fisiologia , Cálcio/sangue , Homeostase/fisiologia , Lactação/fisiologia , Animais , Calcitonina/sangue , Calcitriol/sangue , Feminino , Humanos , Mamíferos , Hormônio Paratireóideo/sangue , GravidezRESUMO
In this paper, different core structures of microstructured optical fibers (MOFs) for low-finesse Fabryâ»Pérot (FP) sensors are experimentally compared to get the highest sensitivity. These devices are designed for volatile organic compounds (VOCs) measurements. Indium tin oxide (ITO) thin films were deposited by sputtering on the MOFs and different optical fast Fourier transform (FFT) phase responses from the FP were measured for saturated atmospheres of ethanol. It has been demonstrated that the sensitivities of the developed sensors depend strongly on the geometry and the dimensions of the MOF-cores. The sensors show recovery times shorter than 100 s and the baselines are fully recovered after every exposure to ethanol vapors.
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The measurement of chemical and biomedical parameters can take advantage of the features exclusively offered by optical fibre: passive nature, electromagnetic immunity and chemical stability are some of the most relevant ones. The small dimensions of the fibre generally require that the sensing material be loaded into a supporting matrix whose morphology is adjusted at a nanometric scale. Thanks to the advances in nanotechnology new deposition methods have been developed: they allow reagents from different chemical nature to be embedded into films with a thickness always below a few microns that also show a relevant aspect ratio to ensure a high transduction interface. This review reveals some of the main techniques that are currently been employed to develop this kind of sensors, describing in detail both the resulting supporting matrices as well as the sensing materials used. The main objective is to offer a general view of the state of the art to expose the main challenges and chances that this technology is facing currently.
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Robust nanostructures were obtained from polymers that otherwise do not assemble by using a novel approach based on electrostatic self-assembly. The essence of this strategy involves the use of divalent counterions to temporarily perturb the packing features of the ionic groups in a homopolymer, which results in a vesicle-like structure that is captured inâ situ through a simple crosslinking reaction. The fidelity of the assembly has been tested for molecular transport across the nanomembrane, both for the molecules encapsulated in the lumen and for those trapped in the membrane itself. The membranes are addressable for robust multifunctionalization of their surfaces and for tunable transmembrane molecular transport.
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Nanoestruturas/química , Polímeros/síntese química , Eletricidade Estática , Tamanho da Partícula , Polímeros/química , Propriedades de SuperfícieRESUMO
We use monodisperse dendrons that allow control over functional group presentation to investigate the influence of the location of a ligand on protein-induced disassembly and release of encapsulated small molecules. Based on both experiments and molecular dynamics simulations, we demonstrate that ligand location greatly influences release of guest molecules from the dendron-based supramolecular assembly. We show that a ligand moiety grafted to the dendron periphery is more accessible for the target protein in aqueous solution. On the other hand, the ligand moiety placed at the focal point or at the intermediate layer within the dendritic scaffold is less accessible, since it is surrounded by an environment rich in PEG chains, which hinders binding and even influences nonspecific interactions. We also demonstrate that the specific binding between one ligand and the target protein can destabilize the dendritic assembly. Furthermore, if more ligands are available, multivalent interactions are also possible with extravidin, which speed up disassembly and trigger the release of hydrophobic guests.
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Dendrímeros/química , Substâncias Macromoleculares/química , Proteínas/química , Tensoativos/química , Dendrímeros/síntese química , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Substâncias Macromoleculares/síntese química , Modelos Moleculares , Simulação de Dinâmica Molecular , Estrutura Molecular , Tensoativos/síntese químicaRESUMO
Background: Cytomegalovirus (CMV) infection remains the most common clinically significant infection after allogeneic hematopoietic stem cell transplantation (allo-HCT) and is associated with considerable morbidity and mortality. Objectives: The present study was designed to describe and compare the incidence of untreated CMV reactivation (uCMVr), clinically significant infection (cs-CMVi) and disease (CMVd), as well as CMV-related hospitalization and outcome of allo-HCT patients, either treated with letermovir (LET) primary prophylaxis or managed with preemptive therapy (PET). Methods: This is a prospective observational cohort study of adult CMV seropositive allo-HCT patients who either received primary prophylaxis with LET within the first 100 days after HCT or were managed with PET. Results: The study population comprised 105 patients (28 in the LET group and 77 in the PET group). Compared to the PET group, patients in the LET group received more allo-HCT from alternative donors (54.5% vs. 82.14%, P=0.012). More than half of the patients in both groups were classified as high risk for CMVd. In the LET vs. PET group, cs-CMVi and CMVd developed respectively in 0 vs. 50 (64.94%), P=<0.0001, and 0 vs. 6 (7.79%), P=0.18. In the LET group, uCMVr occurred in 5 (17.8%) and were all considered blips. Hospital admissions related to cs-CMVi or CMVd in the PET group vs. LET group were 47 (61.04%) vs. 0, respectively, P=<0.0001. No differences were observed in 100-day mortality. Conclusions: LET primary prophylaxis proved effective in preventing cs-CMVi and CMVd and reducing hospitalizations in allo-HCT adults. Blips can occur during prophylaxis and do not require LET discontinuation.
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Mercury (Hg) is a globally important pollutant that can negatively impact metabolic, endocrine and immune systems of marine biota. Seabirds are long-lived marine top predators and hence are at risk of bioaccumulating high Hg concentrations from their prey. Here, we measured blood total mercury (THg) concentrations and relationships with physiology and breeding parameters of breeding brown skuas (Stercorarius antarcticus) (n = 49 individuals) at Esperanza/Hope Bay, Antarctic Peninsula. Mean blood THg concentrations were similar in males and females despite the differences in body size and breeding roles, but differed between study years. Immune markers (hematocrit, Immunoglobulin Y [IgY] and albumin) were negatively correlated with blood THg concentrations, which likely indicates a disruptive effect of Hg on immunity. Alanine aminotransferase (GPT) activity, reflecting liver dysfunction, was positively associated with blood THg. Additionally, triacylglycerol and albumin differed between our study years, but did not correlate with Hg levels, and so were more likely to reflect changes in diet and nutritional status rather than Hg contamination. Egg volume correlated negatively with blood THg concentrations. Our study provides new insights into the sublethal effects of Hg contamination on immunity, liver function and breeding parameters in seabirds. In this Antarctic species, exposure to sublethal Hg concentrations reflects the short-term risks which could make individuals more susceptible to environmental stressors, including ongoing climatic changes.
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Charadriiformes , Mercúrio , Humanos , Masculino , Animais , Feminino , Aves/metabolismo , Mercúrio/análise , Regiões Antárticas , Monitoramento Ambiental , Charadriiformes/metabolismo , Fígado/metabolismo , Imunocompetência , Albuminas/metabolismoRESUMO
Background/Introduction: Adipose tissue (AT) has been highlighted as a promising reservoir of infection for viruses, bacteria and parasites. Among them is Trypanosoma cruzi, which causes Chagas disease. The recommended treatment for the disease in Brazil is Benznidazole (BZ). However, its efficacy may vary according to the stage of the disease, geographical origin, age, immune background of the host and sensitivity of the strains to the drug. In this context, AT may act as an ally for the parasite survival and persistence in the host and a barrier for BZ action. Therefore, we investigated the immunomodulation of T. cruzi-infected human AT in the presence of peripheral blood mononuclear cells (PBMC) where BZ treatment was added. Methods: We performed indirect cultivation between T. cruzi-infected adipocytes, PBMC and the addition of BZ. After 72h of treatment, the supernatant was collected for cytokine, chemokine and adipokine assay. Infected adipocytes were removed to quantify T. cruzi DNA, and PBMC were removed for immunophenotyping. Results: Our findings showed elevated secretion of interleukin (IL)-6, IL-2 and monocyte chemoattractant protein-1 (MCP-1/CCL2) in the AT+PBMC condition compared to the other controls. In contrast, there was a decrease in tumor necrosis factor (TNF) and IL-8/CXCL-8 in the groups with AT. We also found high adipsin secretion in PBMC+AT+T compared to the treated condition (PBMC+AT+T+BZ). Likewise, the expression of CD80+ and HLA-DR+ in CD14+ cells decreased in the presence of T. cruzi. Discussion: Thus, our findings indicate that AT promotes up-regulation of inflammatory products such as IL-6, IL-2, and MCP-1/CCL2. However, adipogenic inducers may have triggered the downregulation of TNF and IL-8/CXCL8 through the peroxisome proliferator agonist gamma (PPAR-g) or receptor expression. On the other hand, the administration of BZ only managed to reduce inflammation in the microenvironment by decreasing adipsin in the infected culture conditions. Therefore, given the findings, we can see that AT is an ally of the parasite in evading the host's immune response and the pharmacological action of BZ.