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Plastic pollution has become a global concern, affecting many species around the world. While well-documented for marine ecosystems, the impact of plastic pollution on terrestrial ecosystems is comparatively limited. In fact, only recently have some studies begun to explore the occurrence, pathways, and impacts of plastic in the atmosphere and on terrestrial species. Here, we assess the presence of synthetic material in nests of three swift species breeding in the Western Palearctic: the common swift (Apus apus), the pallid swift (Apus pallidus), and the alpine swift (Tachymarptis melba). Using data from 487 nests spanning 25 colonies and seven European countries, we show that 36.5 % of the examined nests contained anthropogenic materials, mainly plastic debris. Notably, Pallid swifts' nests, with 85 % of the total nests examined with plastic, rank among birds with the highest plastic content in nests. We also demonstrate that the probability of finding plastic in the nest increased substantially with the human footprint of the landscape. Last, we recorded four cases of swifts entangled in their own nest, a low proportion compared to other species studied previously. Our study provides compelling evidence that plastic pollution may also be considered a concern for other terrestrial species, particularly for birds with highly aerial lifestyles, such as other swifts. The correlation with the human footprint suggests that areas with higher human activity contribute more significantly. Moreover, the entanglement cases, although low, indicate a threat to bird health and welfare. To our knowledge, our study is the first to report a direct interaction between floating plastic debris in the atmosphere and any species. Understanding this interaction is key, not only due to the lack of research on the topic, but also because it highlights that plastic pollution is a multifaceted environmental issue affecting various ecosystem categories, and the broader implications of atmospheric plastic circulation on wildlife and ecosystems health.
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Aves , Monitoramento Ambiental , Plásticos , Animais , Plásticos/análise , Comportamento de Nidação , Resíduos/análise , Poluentes Atmosféricos/análise , Ecossistema , Europa (Continente) , Poluição Ambiental/estatística & dados numéricos , Poluição do Ar/estatística & dados numéricosRESUMO
The Preyssler-type polyoxotungstate ({P5W30}) belongs to the family of polyanionic metal-oxides formed by group V and VI metal ions, such as V, Mo and W, commonly known as polyoxometalates (POMs). POMs have demonstrated inhibitory effect on a significant number of ATP-binding proteins in vitro. Purinergic P2 receptors, widely expressed in eukaryotic cells, contain extracellularly oriented ATP-binding sites and play many biological roles with health implications. In this work, we use the immortalized mouse hippocampal neuronal HT-22 cells in culture to study the effects of {P5W30} on the cytosolic Ca2+ concentration. Changes in cytosolic Ca2+ concentration were monitored using fluorescence microscopy of HT-22 cells loaded with the fluorescent Ca2+ indicator Fluo3. 31P-Nuclear magnetic resonance measurements of {P5W30} indicate its stability in the medium used for cytosolic Ca2+ measurements for over 30 min. The findings reveal that addition of {P5W30} to the extracellular medium induces a sustained increase of the cytosolic Ca2+ concentration within minutes. This Ca2+ increase is triggered by extracellular Ca2+ entry into the cells and is dose-dependent, with a half-of-effect concentration of 0.25 ± 0.05 µM {P5W30}. In addition, after the {P5W30}-induced cytosolic Ca2+ increase, the transient Ca2+ peak induced by extracellular ATP is reduced up to 100% with an apparent half-of-effect concentration of 0.15 ± 0.05 µM {P5W30}. Activation of metabotropic purinergic P2 receptors affords about 80% contribution to the increase of Fluo3 fluorescence elicited by {P5W30} in HT-22 cells, whereas ionotropic receptors contribute, at most, with 20%. These results suggest that {P5W30} could serve as a novel agonist of purinergic P2 receptors.
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Cálcio , Compostos de Tungstênio , Animais , Camundongos , Compostos de Tungstênio/farmacologia , Compostos de Tungstênio/química , Cálcio/metabolismo , Trifosfato de Adenosina/metabolismo , Linhagem Celular , Hipocampo/metabolismo , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Agonistas do Receptor Purinérgico P2/farmacologia , Citosol/metabolismoRESUMO
The following letter presents an answer of a comment of our work titled "Ross procedure: valve function, clinical outcomes and predictors after 25 years' follow-up," recently published in your journal by Rangwala et al.1 As our colleagues point out, the Ross procedure has excellent survival rates but a significant risk of valve dysfunction and therefore reintervention at follow-up. Although the survival advantage with the Ross procedure appears to be consistent compared with mechanical valve substitutes, this benefit is not as clear compared with biological valve substitutes. However, biological valve substitutes also have significant reintervention rates during follow-up. The different surgical modifications of the Ross procedure have not clearly demonstrated better results in follow-up in terms of autograft reintervention. This procedure can be performed in a medium-volume center with good results as long as adequate patient selection and adequate surgical training are carried out.
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Valva Aórtica , Humanos , Resultado do Tratamento , Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Valva Pulmonar/cirurgia , Valva Pulmonar/transplante , Próteses Valvulares Cardíacas , Seguimentos , Bioprótese , Procedimentos Cirúrgicos Cardíacos/métodos , Reoperação/estatística & dados numéricos , Doenças das Valvas Cardíacas/cirurgiaRESUMO
Kaempferol, a flavonoid present in many food products, has chemical and cellular antioxidant properties that are beneficial for protection against the oxidative stress caused by reactive oxygen and nitrogen species. Kaempferol administration to model experimental animals can provide extensive protection against brain damage of the striatum and proximal cortical areas induced by transient brain cerebral ischemic stroke and by 3-nitropropionic acid. This article is an updated review of the molecular and cellular mechanisms of protection by kaempferol administration against brain damage induced by these insults, integrated with an overview of the contributions of the work performed in our laboratories during the past years. Kaempferol administration at doses that prevent neurological dysfunctions inhibit the critical molecular events that underlie the initial and delayed brain damage induced by ischemic stroke and by 3-nitropropionic acid. It is highlighted that the protection afforded by kaempferol against the initial mitochondrial dysfunction can largely account for its protection against the reported delayed spreading of brain damage, which can develop from many hours to several days. This allows us to conclude that kaempferol administration can be beneficial not only in preventive treatments, but also in post-insult therapeutic treatments.
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Lesões Encefálicas , AVC Isquêmico , Fármacos Neuroprotetores , Nitrocompostos , Propionatos , Acidente Vascular Cerebral , Animais , Quempferóis/farmacologia , Encéfalo , Estresse Oxidativo , Acidente Vascular Cerebral/tratamento farmacológico , Isquemia/tratamento farmacológico , Lesões Encefálicas/tratamento farmacológico , Reperfusão , AVC Isquêmico/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
Immunotherapy has demonstrated a role in the therapeutic landscape of a small subset of patients with colorectal carcinoma (CRC) that harbor a microsatellite instability (MSI-H) status due to a deficient DNA mismatch repair (dMMR) system. The remarkable responses to immune checkpoint inhibitors (ICIs) are now being tested in the neoadjuvant setting in localized CRC, where the dMMR/MSI-H status can be found in up to 15% of patients, with remarkable results obtained in NICHE2 and 3 trials, among others. This case series aims to report our experience at a tertiary center and provide a comprehensive analysis of the possible questions and challenges to overcome if ICIs were established as standard of care in a neoadjuvant setting, as well as the potential role they may have as conversion therapy not only in locoregional advanced CRC but also in oligometastatic disease.
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Neoplasias Colorretais , Instabilidade de Microssatélites , Humanos , Imunoterapia , Pesquisa , Terapia Neoadjuvante , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapiaRESUMO
OBJECTIVE: To describe long-term outcomes of the Ross procedure in a single center and retrospective series after 25 years follow-up. METHODS: From 1997-2019 we included all consecutive patients who underwent Ross procedure at our center. Clinical and echocardiographic evaluations were performed at least yearly. Echocardiographic valvular impairment was defined as at least moderate autograft or homograft dysfunction. Reintervention outcomes included surgical and percutaneous approach. RESULTS: 151 Ross procedures were performed (mean age 28±12years, 21 %<16years, 70 %male). After 25 years follow-up (median 18 years, interquartile range 9-21, only 3 patients lost) 12 patients died (8 %); Autograft, homograft or any valve dysfunction were present in 38(26 %), 48(32 %) and 75(51 %), respectively; and reintervention in 22(15%), 17(11%) and 38(26 %) respectively. At 20 years of follow-up, probabilities of survival free from autograft, homograft or any valve dysfunction were 63 %, 60 % and 35 %; and from reintervention, 80 %, 85 % and 67 %, respectively. The learning curve period (first 12 cases) was independently associated to autograft dysfunction (HR 2.78, 95 %CI:1.18-6.53, p = 0.02) and reintervention (HR 3.76, 95 %CI: 1.46-9.70, p = 0.006). Larger native pulmonary diameter was also an independent predictor of autograft reintervention (HR 1.22, 95 %CI:1.03-1.45, p = 0.03). Homograft dysfunction was associated with younger age (HR 5.35, 95 %CI: 2.13-13.47, p<0.001) and homograft reintervention, with higher left ventricle ejection fraction (HR 1,10, 95 %CI:1.02-1.19, p<0.02). CONCLUSIONS: In this 25 years' experience after the Ross procedure, global survival was high, although autograft and homograft dysfunction and reintervention rates were not negligible. Clinical and echocardiographic variables can identify patients with higher risk of events in follow up.
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Morte , Ecocardiografia , Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Seguimentos , Estudos Retrospectivos , Volume SistólicoRESUMO
Lipid membrane nanodomains or lipid rafts are 10-200 nm diameter size cholesterol- and sphingolipid-enriched domains of the plasma membrane, gathering many proteins with different roles. Isolation and characterization of plasma membrane proteins by differential centrifugation and proteomic studies have revealed a remarkable diversity of proteins in these domains. The limited size of the lipid membrane nanodomain challenges the simple possibility that all of them can coexist within the same lipid membrane domain. As caveolin-1, flotillin isoforms and gangliosides are currently used as neuronal lipid membrane nanodomain markers, we first analyzed the structural features of these components forming nanodomains at the plasma membrane since they are relevant for building supramolecular complexes constituted by these molecular signatures. Among the proteins associated with neuronal lipid membrane nanodomains, there are a large number of proteins that play major roles in calcium signaling, such as ionotropic and metabotropic receptors for neurotransmitters, calcium channels, and calcium pumps. This review highlights a large variation between the calcium signaling proteins that have been reported to be associated with isolated caveolin-1 and flotillin-lipid membrane nanodomains. Since these calcium signaling proteins are scattered in different locations of the neuronal plasma membrane, i.e., in presynapses, postsynapses, axonal or dendritic trees, or in the neuronal soma, our analysis suggests that different lipid membrane-domain subtypes should exist in neurons. Furthermore, we conclude that classification of lipid membrane domains by their content in calcium signaling proteins sheds light on the roles of these domains for neuronal activities that are dependent upon the intracellular calcium concentration. Some examples described in this review include the synaptic and metabolic activity, secretion of neurotransmitters and neuromodulators, neuronal excitability (long-term potentiation and long-term depression), axonal and dendritic growth but also neuronal cell survival and death.
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Sinalização do Cálcio , Caveolina 1 , Caveolina 1/metabolismo , Cálcio/metabolismo , Proteômica , Microdomínios da Membrana/metabolismo , Neurônios/metabolismo , Gangliosídeos , Neurotransmissores/metabolismoRESUMO
Metastatic colorectal cancer (mCRC) with mutated BRAF exhibits distinct biological and molecular features that set it apart from other subtypes of CRC. Current standard treatment for these tumors involves a combination of chemotherapy (CT) and VEGF inhibitors. Recently, targeted therapy against BRAF and immunotherapy (IT) for cases with microsatellite instability (MSI) have been integrated into clinical practice. While targeted therapy has shown promising results, resistance to treatment eventually develops in a significant portion of responsive patients. This article aims to review the available literature on mechanisms of resistance to BRAF inhibitors (BRAFis) and potential therapeutic strategies to overcome them.
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Amyloid ß (Aß) oligomers are the most neurotoxic forms of Aß, and Aß(1-42) is the prevalent Aß peptide found in the amyloid plaques of Alzheimer's disease patients. Aß(25-35) is the shortest peptide that retains the toxicity of Aß(1-42). Aß oligomers bind to calmodulin (CaM) and calbindin-D28k with dissociation constants in the nanomolar Aß(1-42) concentration range. Aß and histidine-rich proteins have a high affinity for transition metal ions Cu2+, Fe3+ and Zn2+. In this work, we show that the fluorescence of Aß(1-42) HiLyteTM-Fluor555 can be used to monitor hexa-histidine peptide (His6) interaction with Aß(1-42). The formation of His6/Aß(1-42) complexes is also supported by docking results yielded by the MDockPeP Server. Also, we found that micromolar concentrations of His6 block the increase in the fluorescence of Aß(1-42) HiLyteTM-Fluor555 produced by its interaction with the proteins CaM and calbindin-D28k. In addition, we found that the His6-tag provides a high-affinity site for the binding of Aß(1-42) and Aß(25-35) peptides to the human recombinant cytochrome b5 reductase, and sensitizes this enzyme to inhibition by these peptides. In conclusion, our results suggest that a His6-tag could provide a valuable new tool to experimentally direct the action of neurotoxic Aß peptides toward selected cellular targets.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Humanos , Peptídeos beta-Amiloides/metabolismo , Histidina/química , Hexosaminidase A , Calbindina 1 , Cobre/química , Fragmentos de Peptídeos/química , Doença de Alzheimer/metabolismoRESUMO
Amyloid ß (Aß) oligomers have been linked to Alzheimer's disease (AD) pathogenesis and are the main neurotoxic forms of Aß. This review focuses on the following: (i) the Aß(1-42):calmodulin interface as a model for the design of antagonist Aß peptides and its limitations; (ii) proteolytic degradation as the major source of highly hydrophobic peptides in brain cells; and (iii) brain peptides that have been experimentally demonstrated to bind to Aß monomers or oligomers, Aß fibrils, or Aß plaques. It is highlighted that the hydrophobic amino acid residues of the COOH-terminal segment of Aß(1-42) play a key role in its interaction with intracellular protein partners linked to its neurotoxicity. The major source of highly hydrophobic endogenous peptides of 8-10 amino acids in neurons is the proteasome activity. Many canonical antigen peptides bound to the major histocompatibility complex class 1 are of this type. These highly hydrophobic peptides bind to Aß and are likely to be efficient antagonists of the binding of Aß monomers/oligomers concentrations in the nanomolar range with intracellular proteins. Also, their complexation with Aß will protect them against endopeptidases, suggesting a putative chaperon-like physiological function for Aß that has been overlooked until now. Remarkably, the hydrophobic amino acid residues of Aß responsible for the binding of several neuropeptides partially overlap with those playing a key role in its interaction with intracellular protein partners that mediates its neurotoxicity. Therefore, these latter neuropeptides are also potential candidates to antagonize Aß peptides binding to target proteins. In conclusion, the analysis performed in this review points out that hydrophobic endogenous brain neuropeptides could be valuable biomarkers to evaluate the risk of the onset of sporadic AD, as well as for the prognosis of AD.
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Highly neurotoxic A1-reactive astrocytes have been associated with several human neurodegenerative diseases. Complement protein C3 expression is strongly upregulated in A1 astrocytes, and this protein has been shown to be a specific biomarker of these astrocytes. Several cytokines released in neurodegenerative diseases have been shown to upregulate the production of amyloid ß protein precursor (APP) and neurotoxic amyloid ß (Aß) peptides in reactive astrocytes. Also, aberrant Ca2+ signals have been proposed as a hallmark of astrocyte functional remodeling in Alzheimer's disease mouse models. In this work, we induced the generation of A1-like reactive astrocytes after the co-treatment of U251 human astroglioma cells with a cocktail of the cytokines TNF-α, IL1-α and C1q. These A1-like astrocytes show increased production of APP and Aß peptides compared to untreated U251 cells. Additionally, A1-like astrocytes show a (75 ± 10)% decrease in the Ca2+ stored in the endoplasmic reticulum (ER), (85 ± 10)% attenuation of Ca2+ entry after complete Ca2+ depletion of the ER, and three-fold upregulation of plasma membrane calcium pump expression, with respect to non-treated Control astrocytes. These altered intracellular Ca2+ dynamics allow A1-like astrocytes to efficiently counterbalance the enhanced release of Ca2+ from the ER, preventing a rise in the resting cytosolic Ca2+ concentration.
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Cálcio , Doenças Neurodegenerativas , Camundongos , Animais , Humanos , Cálcio/metabolismo , Regulação para Cima , Astrócitos/metabolismo , Peptídeos beta-Amiloides/metabolismo , Sinalização do Cálcio , Precursor de Proteína beta-Amiloide/genética , Doenças Neurodegenerativas/metabolismo , Membrana Celular/metabolismoRESUMO
Introduction Radiosurgery is a treatment in which a high dose of ionizing radiation is administered to a small field with high-precision techniques, and is a common treatment for tumors and other diagnoses. A typical complication is the development of radiation-induced edema that can progress to radiation necrosis in some cases. The administration of corticosteroids has been used empirically as a prophylaxis in patients who will be treated by stereotactic radiosurgery with intracranial tumors and other pathologies with the intention to prevent radiation-induced edema and or necrosis. Objective The aim of our study is to describe the actual use of corticosteroids in hospitals that perform stereotactic radiosurgery treatments in Latin America and Spain through a survey applied to neurosurgeons and radiation oncologists and expose the implications of the results, as well as to analyze the available literature on it. Methods We designed a questionnaire of 15 items related to the use of corticosteroids as prophylaxis in patients who will be treated with radiosurgery. The questionnaire was answered by 121 Ibero-Latin Americans through Google Drive considering a database from the Iberolatinoamerican Radiosurgery Association. Results We found that the preference for the use of corticosteroids as prophylaxis for radiosurgery is associated with informal training in radiosurgery, and it was more used by radiation oncologists compared to neurosurgeons (p=0.023). Side effects can exceed the benefit of its use. Conclusions There is practically no literature on the use of corticosteroids as prophylaxis for radiation necrosis in stereotactic radiosurgery. This is a controversial inter- and intra-specialty issue, and its empirical use has a relatively high prevalence, making us reconsider the value of experience in a medical environment that should be fundamentally guided by evidence-based medicine.
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Caveolin-2 is a protein suitable for the study of interactions of caveolins with other proteins and lipids present in caveolar lipid rafts. Caveolin-2 has a lower tendency to associate with high molecular weight oligomers than caveolin-1, facilitating the study of its structural modulation upon association with other proteins or lipids. In this paper, we have successfully expressed and purified recombinant human caveolin-2 using E. coli. The structural changes of caveolin-2 upon interaction with a lipid bilayer of liposomes were characterized using bioinformatic prediction models, circular dichroism, differential scanning calorimetry, and fluorescence techniques. Our data support that caveolin-2 binds and alters cholesterol-rich domains in the membranes through a CARC domain, a type of cholesterol-interacting domain in its sequence. The far UV-CD spectra support that the purified protein keeps its folding properties but undergoes a change in its secondary structure in the presence of lipids that correlates with the acquisition of a more stable conformation, as shown by differential scanning calorimetry experiments. Fluorescence experiments using egg yolk lecithin large unilamellar vesicles loaded with 1,6-diphenylhexatriene confirmed that caveolin-2 adsorbs to the membrane but only penetrates the core of the phospholipid bilayer if vesicles are supplemented with 30% of cholesterol. Our study sheds light on the caveolin-2 interaction with lipids. In addition, we propose that purified recombinant caveolin-2 can provide a new tool to study protein-lipid interactions within caveolae.
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Caveolina 1 , Escherichia coli , Humanos , Escherichia coli/metabolismo , Caveolina 1/metabolismo , Caveolina 2/metabolismo , Cavéolas/metabolismo , Colesterol/metabolismo , Microdomínios da Membrana/metabolismo , Bicamadas Lipídicas/metabolismoRESUMO
Detecting and locating victims in emergency scenarios comprise one of the most powerful tools to save lives. Fast actions are crucial for victims because time is running against them. Radio devices are currently omnipresent within the physical proximity of most people and allow locating buried victims in catastrophic scenarios. In this work, we present the benefits of using WiFi Fine Time Measurement (FTM), Ultra-Wide Band (UWB), and fusion technologies to locate victims under rubble. Integrating WiFi FTM and UWB in a drone may cover vast areas in a short time. Moreover, the detection capacity of WiFi and UWB for finding individuals is also compared. These findings are then used to propose a method for detecting and locating victims in disaster scenarios.
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Desastres , Emergências , HumanosRESUMO
Dysregulation in calcium signaling pathways plays a major role in the initiation of Alzheimer's disease (AD) pathogenesis. Accumulative experimental evidence obtained with cellular and animal models, as well as with AD brain samples, points out the high cytotoxicity of soluble small oligomeric forms of amyloid-ß peptides (Aß) in AD. In recent works, we have proposed that Aß-calmodulin (CaM) complexation may play a major role in neuronal Ca2+ signaling, mediated by CaM-binding proteins (CaMBPs). STIM1, a recognized CaMBP, plays a key role in store-operated calcium entry (SOCE), and it has been shown that the SOCE function is diminished in AD, resulting in the instability of dendric spines and enhanced amyloidogenesis. In this work, we show that 2 and 5 h of incubation with 2 µM Aß(1-42) oligomers of the immortalized mouse hippocampal cell line HT-22 leads to the internalization of 62 ± 11 nM and 135 ± 15 nM of Aß(1-42), respectively. Internalized Aß(1-42) oligomers colocalize with the endoplasmic reticulum (ER) and co-immunoprecipitated with STIM1, unveiling that this protein is a novel target of Aß. Fluorescence resonance energy transfer measurements between STIM1 tagged with a green fluorescent protein (GFP) and Aß(1-42)-HiLyte™-Fluor555 show that STIM1 can bind nanomolar concentrations of Aß(1-42) oligomers at a site located close to the CaM-binding site in STIM1. Internalized Aß(1-42) produced dysregulation of the SOCE in the HT-22 cells before a sustained alteration of cytosolic Ca2+ homeostasis can be detected, and is elicited by only 2 h of incubation with 2 µM Aß(1-42) oligomers. We conclude that Aß(1-42)-induced SOCE dysregulation in HT-22 cells is caused by the inhibitory modulation of STIM1, and the partial activation of ER Ca2+-leak channels.
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Cálcio , Calmodulina , Camundongos , Animais , Cálcio/metabolismo , Calmodulina/metabolismo , Canais de Cálcio/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Membrana/metabolismo , Molécula 1 de Interação Estromal/metabolismo , Sinalização do Cálcio , Proteína ORAI1/metabolismoRESUMO
Plasma membrane calcium ATPases (PMCA) and sarco(endo) reticulum calcium ATPases (SERCA) are key proteins in the maintenance of calcium homeostasis. Herein, we compare for the first time the inhibition of SERCA and PMCA calcium pumps by several polyoxotungstates (POTs), namely by Wells-Dawson phosphotungstate anions [P2W18O62]6- (intact, {P2W18}), [P2W17O61]10- (monolacunary, {P2W17}), [P2W15O56]12- (trilacunary, {P2W15}), [H2P2W12O48]12- (hexalacunary, {P2W12}), [H3P2W15V3O62]6- (trivanadium-substituted, {P2W15V3}) and by Preyssler-type anion [NaP5W30O110]14- ({P5W30}). The speciation in the solutions of tested POTs was investigated by 31P and 51V NMR spectroscopy. The tested POTs inhibited SERCA Ca2+-ATPase activity, whereby the Preyssler POT showed the strongest effect, with an IC50 value of 0.37 µM. For {P2W17} and {P2W15V3} higher IC50 values were determined: 0.72 and 0.95 µM, respectively. The studied POTs showed to be more potent inhibitors of PMCA Ca2+-ATPase activity, with lower IC50 values for {P2W17}, {P5W30} and {P2W15V3}.
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Cálcio , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Cálcio/química , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismoRESUMO
A high-precision location is becoming a necessity in the future Industry 4.0 applications that will come up in the near future. However, the construction sector remains particularly obsolete in the adoption of Industry 4.0 applications. In this work, we study the accuracy and penetration capacity of two technologies that are expected to deal with future high-precision location services, such as ultra-wide band (UWB) and WiFi fine time measurement (FTM). For this, a measurement campaign has been performed in a construction environment, where UWB and WiFi-FTM setups have been deployed. The performance of UWB and WiFi-FTM have been compared with a prior set of indoors measurements. UWB seems to provide better ranging estimation in LOS conditions but it seems cancelled by reinforcement concrete for propagation and WiFi is able to take advantage of holes in the structure to provide location services. Moreover, the impact of fusion of location technologies has been assessed to measure the potential improvements in the construction scenario.
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Background: Chronic use of Angiotensin-converting enzyme (ACE) inhibitors (ACEi) and aldosterone-receptor blockers (ARB) is not associated with worse outcomes in patients with COVID-19. However, evidence on the impact of their discontinuation during hospital admission is scarce. Our aim was to determine whether withdrawal of ACEi, ARB and mineralocorticoid receptor antagonists (MRA) is associated with all-cause mortality in a real-life large cohort of patients with SARS-CoV-2 infection. Methods: Observational cohort study from a large referral center from 1 March 2020 to 20 April 2020. Withdrawal of renin-angiotensin-aldosterone system inhibitors was defined as the absence of any received dose during hospital admission in patients receiving chronic treatment. Prescriptions during admission were confirmed by data from the central pharmacy computerized system. Results: A total of 2042 patients (mean age 68.4±17.6, 57.1% male) with confirmed COVID-19 were included. During a median follow-up of 57 (21-55) days, 583 (28.6%) died. Prior to hospital admission 468 (22.9%), 343 (16.8%) and 83 (4.1%) patients were receiving ACEi, ARB and MRA respectively. During the study period, 216 (46.2%), 193 (56.3%) and 41 (49.4%) were withdrawn from the corresponding drug. After adjusting for age, cardiovascular risk factors, baseline comorbidities and in-hospital COVID-19 dedicated treatment, withdrawal of ACE inhibitors (hazard ration [HR] 1.48 [95% confidence interval -CI- 1.16-1.89]) and MRA (HR 2.01 [95% CI 1.30-3.10]) were shown to be independent predictors of all-cause mortality. No independent relationship between ARB withdrawal and mortality was observed. Conclusion: ACEi and MRA withdrawal were associated with higher mortality. Strong consideration should be given to not discontinuing these medications during hospital admission.
Introdução: O uso crónico de inibidores da ECA (IECA) e de antagonistas dos recetores de aldosterona (ARA) não está associado a resultados piores em doentes com Covid-19. No entanto, a evidência relativa ao impacto da sua retirada durante a admissão hospitalar é escassa. O nosso objetivo foi determinar se a retirada do IECA, ARA e antagonistas dos recetores dos mineralocorticóides (ARM) está associada à mortalidade por todas as causas numa grande coorte real de doentes com infeção por SRA-CoV-2. Métodos: Estudo coorte observacional a partir de um grande centro de referência de 1 de março de 2020 a 20 de abril de 2020. A retirada dos inibidores do sistema RAAS foi definida como a ausência de qualquer dose recebida durante a admissão hospitalar em doentes que recebem tratamento prolongado. As prescrições durante a admissão foram confirmadas por dados do sistema informático da farmácia central. Resultados: Um total de 2042 doentes (idade média de 68,4 ±17,6, 57,1% do sexo masculino) com COVID-19 confirmado foram incluídos. Durante um acompanhamento médio de 57 (21-55) dias, 583 (28,6%) morreram. Conclusão: A retirada do IECA e do ARM foi associada a uma mortalidade mais elevada. Deve ser dada grande atenção para não interromper estes medicamentos durante a admissão hospitalar.
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Tratamento Farmacológico da COVID-19 , Idoso , Idoso de 80 Anos ou mais , Aldosterona , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Angiotensinas , Anti-Hipertensivos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Renina , Estudos Retrospectivos , SARS-CoV-2RESUMO
Tissue degeneration is an event shared by many, if not all, age-related pathologies [...].
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Kaempferol is a natural antioxidant present in vegetables and fruits used in human nutrition. In previous work, we showed that intraperitoneal (i.p.) kaempferol administration strongly protects against striatum neurodegeneration induced by i.p. injections of 3-nitropropionic acid (NPA), an animal model of Huntington's disease. Recently, we have shown that reactive A1 astrocytes generation is an early event in the neurodegeneration induced by NPA i.p. injections. In the present work, we have experimentally evaluated the hypothesis that kaempferol protects both against the activation of complement C3 protein and the generation of reactive A1 astrocytes in rat brain striatum and hippocampus. To this end, we have administered NPA and kaempferol i.p. injections to adult Wistar rats following the protocol described in previous work. Kaempferol administration prevents proteolytic activation of complement C3 protein and generation of reactive A1 astrocytes NPA-induced in the striatum and hippocampus. Also, it blocked the NPA-induced increase of NF-κB expression and enhanced secretion of cytokines IL-1α, TNFα, and C1q, which have been linked to the generation of reactive A1 astrocytes. In addition, kaempferol administration prevented the enhanced production of amyloid ß peptides in the striatum and hippocampus, a novel finding in NPA-induced brain degeneration found in this work.