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BACKGROUND: Obsessive-Compulsive Disorder (OCD) is a common and chronic psychiatric disorder with significant morbidity characterized by intrusive, uncontrollable and reoccurring thoughts (i.e., obsessions) and/or ritualistic behaviours (i.e., compulsions). Conradi-Hünerman-Happle Syndrome (CHHS) is a rare inherited X-linked dominant variant of chondrodysplasia punctata, a heterogeneous group of rare bone dysplasias characterized by punctate epiphyseal calcifications of complex etiology and pathophysiology that remain to be defined. Available literature reveals a lacuna in regards to the coexistence of the entities with no clinical reports described. CASE PRESENTATION: A 12 year old female patient with diagnosis of CHHS, presents to psychiatric consultation due to aggravation of her OCD clinical picture, with aggravation of hand-washing frequency during the Covid-19 pandemic with significant functional impact. Psychopharmacological treatment aimed at OCD with Selective Serotonin Reuptake Inhibitor (SSRI) and antipsychotic was instituted with favourable, albeit partial response. CONCLUSIONS: The authors aim to describe a clinical case in which the patient presents with Conradi-Hünerman-Happle Syndrome and Obsessive-Compulsive Disorder. Clinical descriptions of CHHS and OCD are not available in the literature. Through this case description the authors aim to present a rare case as well as discuss an eventual association between etiology and/or pathophysiology of the two disorders.
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COVID-19 , Condrodisplasia Punctata , Transtorno Obsessivo-Compulsivo , Humanos , Feminino , Criança , Pandemias , Transtorno Obsessivo-Compulsivo/complicações , Transtorno Obsessivo-Compulsivo/diagnóstico , Transtorno Obsessivo-Compulsivo/epidemiologia , Comportamento Compulsivo/psicologiaRESUMO
Newly emerging data suggest that several neutrophil defense mechanisms may play a role in both aggravating and protecting against malaria. These exciting findings suggest that the balance of these cells in the host body may have an impact on the pathogenesis of malaria. To fully understand the role of neutrophils in severe forms of malaria, such as cerebral malaria (CM), it is critical to gain a comprehensive understanding of their behavior and functions. This study investigated the dynamics of neutrophil and T cell responses in C57BL/6 and BALB/c mice infected with Plasmodium berghei ANKA, murine models of experimental cerebral malaria (ECM) and non-cerebral experimental malaria, respectively. The results demonstrated an increase in neutrophil percentage and neutrophil-T cell ratios in the spleen and blood before the development of clinical signs of ECM, which is a phenomenon not observed in the non-susceptible model of cerebral malaria. Furthermore, despite the development of distinct forms of malaria in the two strains of infected animals, parasitemia levels showed equivalent increases throughout the infection period evaluated. These findings suggest that the neutrophil percentage and neutrophil-T cell ratios may be valuable predictive tools for assessing the dynamics and composition of immune responses involved in the determinism of ECM development, thus contributing to the advancing of our understanding of its pathogenesis.
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Malária Cerebral , Animais , Camundongos , Neutrófilos/patologia , Camundongos Endogâmicos C57BL , Plasmodium berghei , Linfócitos T CD8-Positivos , Modelos Animais de DoençasRESUMO
In 2022, the European Society of Enteral and Parenteral Nutrition (ESPEN) has released several relevant updates and guidelines. This review will highlight the key messages of three guidelines focusing on nutritional management in the geriatric population, micronutrient disorders, and sarcopenic obesity. Special emphasis will be directed towards recommendations impacting ambulatory clinical practice.
L'année 2022 a été riche en nouvelles recommandations émises par la Société européenne de nutrition clinique (ESPEN). De la prise en charge nutritionnelle en gériatrie aux micronutriments, tout en abordant le spectre de l'obésité sarcopénique, cette mise à jour a pour objet de synthétiser les messages clés de ces recommandations et de discuter leur impact sur la pratique clinique ambulatoire.
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Nutrição Enteral , Sarcopenia , Humanos , Idoso , Nutrição Parenteral , Obesidade/terapia , Sarcopenia/terapiaRESUMO
Plastic production has been rising consistently in the last 30 years and with it, the presence of plastic particles in the environment. A decrease in size often increases the bioavailability and reactivity of the particles. In this study the impact of polystyrene (PS; 22 nm) and polymethylmethacrylate (PMMA; 32 nm) nanoparticles on zebrafish embryo-larval stages was assessed by studying mortality, hatching, morphological features, and biochemical endpoints (associated with neurotransmission, antioxidant status and oxidative damage, and energy metabolism) after 96 h exposure, and swimming behavior after 120 h exposure. Organisms exposed to PMMA nanoparticles exhibited higher mortality and pericardial edema than those exposed to PS nanoparticles but displayed less effects on swimming behavior. Biochemical endpoints were altered to a higher degree in organisms exposed to PS nanoparticles (acetylcholinesterase, glutathione S-transferase and catalase activities) but higher peroxidative damage was found after exposure to lower concentrations of PMMA nanoparticles. Both types of nanoparticles affected energy metabolism with higher levels of glycogen found in animals exposed to PS nanoparticles. The use of integrated biomarker response index confirmed that PS nanoparticles had a higher impact on biochemical endpoints of zebrafish.
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Nanopartículas , Poluentes Químicos da Água , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/metabolismo , Larva , Microplásticos/toxicidade , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Plásticos/metabolismo , Polimetil Metacrilato/metabolismo , Polimetil Metacrilato/toxicidade , Poliestirenos/toxicidade , Poluentes Químicos da Água/metabolismo , Peixe-Zebra/metabolismoRESUMO
OBJECTIVES: To develop and validate a clinical model to identify patients admitted to hospital with community-acquired infection (CAI) caused by pathogens resistant to antimicrobials recommended in current CAI treatment guidelines. METHODS: International prospective cohort study of consecutive patients admitted with bacterial infection. Logistic regression was used to associate risk factors with infection by a resistant organism. The final model was validated in an independent cohort. RESULTS: There were 527 patients in the derivation and 89 in the validation cohort. Independent risk factors identified were: atherosclerosis with functional impairment (Karnofsky index <70) [adjusted OR (aOR) (95% CI) = 2.19 (1.41-3.40)]; previous invasive procedures [adjusted OR (95% CI) = 1.98 (1.28-3.05)]; previous colonization with an MDR organism (MDRO) [aOR (95% CI) = 2.67 (1.48-4.81)]; and previous antimicrobial therapy [aOR (95% CI) = 2.81 (1.81-4.38)]. The area under the receiver operating characteristics (AU-ROC) curve (95% CI) for the final model was 0.75 (0.70-0.79). For a predicted probability ≥22% the sensitivity of the model was 82%, with a negative predictive value of 85%. In the validation cohort the sensitivity of the model was 96%. Using this model, unnecessary broad-spectrum therapy would be recommended in 30% of cases whereas undertreatment would occur in only 6% of cases. CONCLUSIONS: For patients hospitalized with CAI and none of the following risk factors: atherosclerosis with functional impairment; previous invasive procedures; antimicrobial therapy; or MDRO colonization, CAI guidelines can safely be applied. Whereas, for those with some of these risk factors, particularly if more than one, alternative antimicrobial regimens should be considered.
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Infecções Comunitárias Adquiridas , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/epidemiologia , Humanos , Estudos Prospectivos , Curva ROC , Fatores de RiscoRESUMO
BACKGROUND: Healthcare-associated infections (HCAI) represent up to 50 % of all infections among patients admitted from the community. The current review intends to provide a systematic review on the microbiological profile involved in HCAI, to compare it with community-acquired (CAI) and hospital-acquired infections (HAI) and to evaluate the definition accuracy to predict infection by potentially drug resistant pathogens. METHODS: We search for HCAI in MEDLINE, SCOPUS and ISI Web of Knowledge with no limitations in regards to publication language, date of publication, study design or study quality. Only studies using the definition by Friedman et al. were included. This review was registered at PROSPERO Systematic Review Registration with the Number CRD42014013648. RESULTS: A total of 21 eligible studies with 12,096 infected patients were reviewed; of these 3497 had HCAI, 2723 were microbiologically documented. Twelve studies were on pneumonia involving 1051 patients with microbiological documented HCAI, the application of the current guidelines for this group of patients would result in an appropriate antibiotic therapy in 95 % of cases at the expense of overtreatment in 73 %; the application of community-acquired pneumonia guidelines would be adequate in only 73-76 % of the cases; an alternative regimen with piperacillin-tazobactam or aztreonam plus azithromycin would increase antibiotic adequacy rate to 90 %. Few studies were found on additional focus of infection: endocarditis, urinary, intra-abdominal and bloodstream infections. All studies included in this review showed an association of the HCAI definition with infection by PDR pathogens when compared to CAI [odds ratio (OR) 4.05, 95 % confidence interval (95 % CI) 2.60-6.31)]. The sensitivity of HCAI to predict infection by a PDR pathogen was 0.69 (0.65-0.72), specificity was 0.67 (0.66-0.68), positive likelihood ratio was 1.9 and the area under the summary ROC curve was 0.71. CONCLUSIONS: This systematic review provides evidence that HCAI represents a separate group of infections in terms of the microbiology profile, including a significant association with infection by PDR pathogens, for the main focus of infection. The results provided can help clinician in the selection of empiric antibiotic therapy and international societies in the development of specific treatment recommendations.
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Infecção Hospitalar/epidemiologia , Farmacorresistência Bacteriana Múltipla , Antibacterianos/farmacologia , Área Sob a Curva , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Infecções Comunitárias Adquiridas/epidemiologia , Infecção Hospitalar/microbiologia , Bases de Dados Factuais , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Humanos , Razão de Chances , Pneumonia/epidemiologia , Curva ROCRESUMO
BACKGROUND: Ten years after the first proposal, a consensus definition of healthcare-associated infection (HCAI) has not been reached, preventing the development of specific treatment recommendations. A systematic review of all definitions of HCAI used in clinical studies is made. METHODS: The search strategy focused on an HCAI definition. MEDLINE, SCOPUS and ISI Web of Knowledge were searched for articles published from earliest achievable data until November 2012. Abstracts from scientific meetings were searched for relevant abstracts along with a manual search of references from reports, earlier reviews and retrieved studies. RESULTS: The search retrieved 49,405 references: 15,311 were duplicates and 33,828 were excluded based on title and abstract. Of the remaining 266, 43 met the inclusion criteria. The definition more frequently used was the initial proposed in 2002--in infection present at hospital admission or within 48 hours of admission in patients that fulfilled any of the following criteria: received intravenous therapy at home, wound care or specialized nursing care in the previous 30 days; attended a hospital or hemodialysis clinic or received intravenous chemotherapy in the previous 30 days; were hospitalized in an acute care hospital for ≥2 days in the previous 90 days, resided in a nursing home or long-term care facility. Additional criteria founded in other studies were: immunosuppression, active or metastatic cancer, previous radiation therapy, transfer from another care facility, elderly or physically disabled persons who need healthcare, previous submission to invasive procedures, surgery performed in the last 180 days, family member with a multi-drug resistant microorganism and recent treatment with antibiotics. CONCLUSIONS: Based on the evidence gathered we conclude that the definition initially proposed is widely accepted. In a future revision, recent invasive procedures, hospitalization in the last year or previous antibiotic treatment should be considered for inclusion in the definition. The role of immunosuppression in the definition of HCAI still requires ongoing discussion.
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Infecção Hospitalar/classificação , Infecção Hospitalar/epidemiologia , Atenção à Saúde/tendências , Hospitalização/tendências , Casas de Saúde/tendências , Infecção Hospitalar/diagnóstico , HumanosRESUMO
The use of bioplastics (e.g., polyhydroxybutyrate) emerged as a solution to help reduce plastic pollution caused by conventional plastics. Nevertheless, bioplastics share many characteristics with their conventional counterparts, such as degradation to nano-sized particles and the ability to sorb environmental pollutants, like metals. This study aimed to assess the potential impacts of the interaction of metals (cadmium - Cd, copper - Cu, and zinc - Zn) with polyhydroxybutyrate nanoplastics (PHB-NPLs; ~200 nm) on the freshwater cnidarian Hydra viridissima in terms of mortality rates, morphological alterations, and feeding behavior. The metal concentrations selected for the combined exposures corresponded to concentrations causing 20 %, 50 %, and 80 % of mortality (LC20, LC50, and LC80, respectively) and the PHB-NPLs concentrations ranged from 0.01 to 1000 µg/L. H. viridissima sensitivity to the metals, based on the LC50's, can be ordered as: Zn < Cd < Cu. Combined exposure to metals and PHB-NPLs yielded distinct outcomes concerning mortality, morphological changes, and feeding behavior, uncovering metal- and dose-specific responses. The interaction between Cd-LCx and PHB-NPLs progressed from no effect at LC20,96h to an ameliorative effect at Cd-LC50,96h. Cu-LCx revealed potential mitigation effects (LC20,96h and LC50,96h) but at Cu-LC80,96h the response shifts to a potentiating effect. For Zn-LCx, response patterns across the combinations with PHB-NPLs were like those induced by the metal alone. PHB-NPLs emerged as a key factor capable of modulating the toxicity of metals. This study highlights the context-dependent interactions between metals and PHB-NPLs in freshwater environments while supporting the need for further investigation of the underlying mechanisms and ecological consequences in forthcoming research.
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Hydra , Nanopartículas , Poluentes Químicos da Água , Animais , Poluentes Químicos da Água/toxicidade , Nanopartículas/toxicidade , Hydra/efeitos dos fármacos , Hidroxibutiratos/toxicidade , Poliésteres , Metais Pesados/toxicidadeRESUMO
The accumulation of increasingly smaller plastic particles in aquatic ecosystems is a prominent environmental issue and is causing a significant impact on aquatic biota. In response to this challenge, biodegradable plastics have emerged as a potential ecological alternative. Nevertheless, despite recent progress in polymer toxicology, there is still limited understanding of the ecological implications of biodegradable plastics in freshwater ecosystems. This study evaluated the toxicity of polyhydroxybutyrate nano-sized particles (PHB-NPLs) on the freshwater cnidarian Hydra viridissima assessing individual and population-level effects. Data revealed low toxicity of PHB-NPLs to H. viridissima in the short-term, as evidenced by the absence of significant malformations and mortality after the 96-h assays. In addition, hydras exhibited rapid and complete regeneration after 96 h of exposure to PHB-NPLs. Feeding assays revealed no significant alterations in prey consumption behavior in the 96-h mortality and malformations assay and the regeneration assay. However, significantly increased feeding rates were observed after long-term exposure, across all tested concentrations of PHB-NPLs. This increase may be attributed to the organisms' heightened energetic demand, stemming from prolonged activation of detoxification mechanisms. These changes may have a cascading effect within the food web, influencing community dynamics and ecosystem stability. Furthermore, a dose-dependent response on the hydras' populational growth was found, with an estimated 20 % effect concentration (EC20,8d) on this endpoint of 10.9 mg PHB-NPLs/L that suggests potential long-term impacts on the population's reproductive output and potential depression and local extinction upon long-term exposure to PHB-NPLs on H. viridissima. The obtained data emphasizes the importance of evaluating sublethal effects and supports the adoption of long-term assays when assessing the toxicity of novel polymers, providing crucial data for informed regulation to safeguard freshwater ecosystems. Future research should aim to unravel the underlying mechanisms behind these sublethal effects, as well as the impact of the generated degradation products.
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Plásticos Biodegradáveis , Cnidários , Hydra , Poluentes Químicos da Água , Animais , Hydra/fisiologia , Ecossistema , Poli-Hidroxibutiratos , Água Doce , Polímeros , Poluentes Químicos da Água/toxicidade , PlásticosRESUMO
The presence of plastic particles in oceans has been recognized as a major environmental concern. The decrease in particle size increases their ability to directly interact with biota, with particles in the nanometer size range (nanoplastics-NPs) displaying a higher ability to penetrate biological membranes, which increases with the decrease in particle size. This study aimed to evaluate the role of life stages in the effects of poly(methyl)methacrylate (PMMA) NPs on the polychaete Hediste diversicolor, a key species in the marine food web and nutrient cycle. Thus, behavioral (burrowing activity in clean and spiked sediment) and biochemical endpoints (neurotransmission, energy reserves, antioxidant defenses, and oxidative damage) were assessed in juvenile and adult organisms after 10 days of exposure to spiked sediment (between 0.5 and 128 mg PMMA NPs/Kg sediment). Overall, the results show that H. diversicolor is sensitive to the presence of PMMA NPs. In juveniles, exposed organisms took longer to burrow in sediment, with significant differences from the controls being observed at all tested concentrations when the test was performed with clean sediment, whereas in PMMA NP-spiked sediment, effects were only found at the concentrations 8, 32, and 128 mg PMMA NPs/Kg sediment. Adults displayed lower sensitivity, with differences to controls being found, for both sediment types, at 8, 32, and 128 mg PMMA NPs/Kg sediment. In terms of Acetylcholinesterase, used as a marker of effects on neurotransmission, juveniles and adults displayed opposite trends, with exposed juveniles displaying increased activity (suggesting apoptosis), whereas in adults, overall decreased activity was found. Energy-related parameters revealed a generally similar pattern (increase in exposed organisms) and higher sensitivity in juveniles (significant effects even at the lower concentrations). NPs also demonstrated the ability to increase antioxidant defenses (higher in juveniles), with oxidative damage only being found in terms of protein carbonylation (all tested NPs conditions) in juveniles. Overall, the data reveal the potential of PMMA NPs to affect behavior and induce toxic effects in H. diversicolor, with greater effects in juveniles.
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Chemical pollution is a major driver for the current worldwide crisis of amphibian decline. The present study aimed to assess the influence of polystyrene nanoplastics (PS-NPLs) on the toxicity of haloperidol to aquatic life stages of amphibians, by using in vivo (tadpoles of Xenopus laevis and Pelophylax perezi) and in vitro (A6 and XTC-2 cell lines of X. laevis) biological models. Tadpoles of both species were exposed, for 96 h, to haloperidol: 0.404 to 2.05 mg l-1 (X. laevis) or 0.404 to 3.07 mg L-1 (P. perezi). The most sensitive species to haloperidol (X. laevis) was exposed to haloperidol's LC50,96h combined with two PS-NPLs concentrations (0.01 mg L-1 or 10 mg L-1); the following endpoints were monitored: mortality, malformations, body lengths and weight. In vitro cytotoxicity was assessed by exposing the two cell lines, for 72 h, to: haloperidol (0.195 to 100 mg L-1) alone and combined with 0.01 mg L-1 or 10 mg L-1 of PS-NPLs. Xenopus laevis tadpoles revealed a higher lethal and sublethal sensitivity to haloperidol than those of P. perezi, with LC50,96h of 1.45 and 2.20 mg L-1. In vitro assays revealed that A6 cell line is more sensitive haloperidol than XTC-2: LC50,72h of 13.2 mg L-1 and 5.92 mg L-1, respectively. Results also suggested a higher sensitivity of in vivo models when compared to in vitro biological. Overall, PS-NPLs did not influence haloperidol's toxicity for in vivo and in vitro biological models, except for a reduction on the incidence of malformations while increasing the lethal toxicity (at the lowest concentration) in tadpoles. These opposite interaction patterns highlight the need for a deeper comprehension of NPLs and pharmaceuticals interactions. Results suggest a low risk of haloperidol for anuran tadpoles, though in the presence of PS-NPLs the risk may be increased.
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The functional conservation of important selective serotonin reuptake inhibitor (SSRI) targets in non-target organisms raises concerns about their potential adverse effects on the ecosystems. Although the environmental levels of SSRIs like paroxetine (PAR) have risen, the knowledge regarding the effects of long-term exposure to PAR is limited. This study investigated the impact of sub-chronic exposure (21 days) to two sub-lethal concentrations of PAR (40 and 400 µg/L) on the behaviour of adult zebrafish in different scenarios: basal activity (under dark and light conditions), stress response (evoked by sudden light transitions) and stress response recovery. A new framework was employed for the integrative study of fish's swimming performance based on their innate ability to respond to light shifts. Several swimming-associated parameters (e.g., total swimming distance, time of inactivity, swimming angles) and thigmotaxis were monitored for an integrated analysis in each scenario. Data revealed reduced swimming activity, impaired behavioural response to stress and alterations in stress recovery of PAR-exposed fish. An anxiolytic effect was particularly noticeable in fish basal swimming activity in the dark at 400 µg/L and in the behavioural response to stress (from dark to light) and stress recovery (from light to dark) for organisms exposed to 40 µg/L. The detected PAR-induced behavioural modifications suggest a disruption of brain glucocorticoid signalling that may have implications at the individual level (e.g., changing behavioural responses to predators), with potential repercussions on the population and community levels. Therefore, the applied protocol proved sensitive in detecting behavioural changes induced by PAR.
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Paroxetina , Poluentes Químicos da Água , Animais , Paroxetina/toxicidade , Peixe-Zebra , Ecossistema , Comportamento Animal , Inibidores Seletivos de Recaptação de Serotonina , Natação , Poluentes Químicos da Água/toxicidadeRESUMO
Biopolymeric nanoparticles (NPs) have gained significant attention in several areas as an alternative to synthetic polymeric NPs due to growing environmental and immunological concerns. Among the most promising biopolymers is poly(lactic acid) (PLA), with a reported high degree of biocompatibility and biodegradability. In this work, PLA NPs were synthesized according to a controlled gelation process using a combination of single-emulsion and nanoprecipitation methods. This study evaluated the influence of several experimental parameters for accurate control of the PLA NPs' size distribution and aggregation. Tip sonication (as the stirring method), a PLA concentration of 10 mg/mL, a PVA concentration of 2.5 mg/mL, and low-molecular-weight PLA (Mw = 5000) were established as the best experimental conditions to obtain monodisperse PLA NPs. After gelification process optimization, flutamide (FLU) was used as a model drug to evaluate the encapsulation capability of the PLA NPs. The results showed an encapsulation efficiency of 44% for this cytostatic compound. Furthermore, preliminary cell viability tests showed that the FLU@PLA NPs allowed cell viabilities above 90% up to a concentration of 20 mg/L. The comprehensive findings showcase that the PLA NPs fabricated using this straightforward gelification method hold promise for encapsulating cytostatic compounds, offering a novel avenue for precise drug delivery in cancer therapy.
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INTRODUCTION: Higher compliance with Surviving Sepsis Campaign (SSC) recommendations has been associated with lower mortality. The authors evaluate differences in compliance with SSC 6-hour bundle according to hospital entrance time (day versus night) and its impact on hospital mortality. METHODS: Prospective cohort study of all patients with community-acquired severe sepsis admitted to the intensive care unit of a large university tertiary care hospital, over 3.5 years with a follow-up until hospital discharge. Time to compliance with each recommendation of the SSC 6-hour bundle was calculated according to hospital entrance period: day (08:30 to 20:30) versus night (20:30 to 08:30). For the same periods, clinical staff composition and the number of patients attending the emergency department (ED) was also recorded. RESULTS: In this period 300 consecutive patients were included. Compliance rate was (night vs. day): serum lactate measurement 57% vs. 49% (P = 0.171), blood cultures drawn 59% vs. 37% (P < 0.001), antibiotics administration in the first 3 hours 33% vs. 18% (P = 0.003), central venous pressure >8 mmHg 45% vs. 29% (P = 0.021), and central venous oxygen saturation (SvcO2) >70%, 7% vs. 2% (P = 0.082); fluids were administered in all patients with hypotension in both periods and vasopressors were administered in patients with hypotension not responsive to fluids in 100% vs. 99%. Time to get specific actions done was also different (night vs. day): serum lactate measurement (4.5 vs. 7 h, P = 0.018), blood cultures drawn (4 vs. 8 h, P < 0.001), antibiotic administration (5 vs. 8 h, P < 0.001), central venous pressure (8 vs. 11 h, P = 0.01), and SvcO2 monitoring (2.5 vs. 11 h, P = 0.222). The composition of the nursing team was the same around the clock; the medical team was reduced at night with a higher proportion of less differentiated doctors. The number of patients attending the Emergency Department was lower overnight. Hospital mortality rate was 34% in patients entering in the night period vs. 40% in those entering during the day (P = 0.281). CONCLUSION: Compliance with SSC recommendations was higher at night. A possible explanation might be the increased nurse to patient ratio in that period. Adjustment of the clinical team composition to the patients' demand is needed to increase compliance and improve prognosis.
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Fidelidade a Diretrizes/normas , Admissão do Paciente/normas , Equipe de Assistência ao Paciente/normas , Sepse/mortalidade , Sepse/terapia , Adulto , Idoso , Estudos de Coortes , Feminino , Seguimentos , Fidelidade a Diretrizes/tendências , Mortalidade Hospitalar/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente/tendências , Equipe de Assistência ao Paciente/tendências , Estudos Prospectivos , Sepse/diagnóstico , Taxa de Sobrevida/tendências , Fatores de TempoRESUMO
The present study used functional and electrophysiological approaches to investigate the mechanisms by which warifteine, a bisbenzylisoquinoline alkaloid isolated from Cissampelos sympodialis Eichl., causes vasorelaxation of the rat thoracic aorta. Warifteine (1 pmol/L-10 µmol/L) induced concentration-dependent relaxation (pD(2) = 9.40 ± 0.06; n = 5) of endothelium-intact aortic rings precontracted with noradrenaline (10-100 µmol/L). The relaxation effects were not attenuated by removal of the endothelium. Warifteine also induced the relaxation of prostaglandin F(2α) (1-10 mmol/L)-precontracted rings (pD(2) = 9.2 ± 0.2; n = 8). In contrast, the relaxant activity of warifteine was nearly abolished in high K(+) (80 mmol/L)-precontracted aortic rings. In preparations incubated with 20 mmol/L KCl or with the K(+) channel blockers tetraethylammonium (1, 3 and 5 mmol/L), iberiotoxin (20 nmol/L), 4-aminopyridine (1 mmol/L) or glibenclamide (10 µmol/L), the vasorelaxant activity of warifteine was markedly reduced. However, BaCl(2) (1 mmol/L) had no effect on the relaxant effects of warifteine. In vascular myocytes, warifteine (100 nmol/L) significantly increased whole-cell K(+) currents (at 70 mV). Under nominally Ca(2+) -free conditions, warifteine did not reduce extracellular Ca(2+) -induced contractions in rings precontracted with high K(+) or noradrenaline (100 µmol/L). Together, the results of the present study indicate that warifteine induces potent concentration-dependent relaxation in the rat aorta via an endothelium-independent mechanism that involves the activation of K(+) channels.
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Alcaloides/farmacologia , Células Musculares/efeitos dos fármacos , Canais de Potássio/metabolismo , Vasodilatação/efeitos dos fármacos , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/metabolismo , Cálcio/metabolismo , Dinoprosta/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Masculino , Células Musculares/metabolismo , Norepinefrina/farmacologia , Potássio/farmacologia , Ratos , Ratos Wistar , Vasodilatadores/farmacologiaRESUMO
Cortaderia selloana (pampas grass), native to South America, is a widespread invasive plant in several regions of the World, including the south of the Atlantic Arc (Europe), where it has been used as an ornamental species. Citizens may help to spread it, e.g., planting it in their gardens, but on the other hand, when they are aware of its invasiveness, can contribute to control it and prevent its spread. An online survey was performed to better understand the perception and knowledge of Portuguese and Spanish citizens, regarding pampas grass. The influence of education and occupation, along with age, gender and country of residence, on the knowledge and perceptions of respondents was analysed. The questionnaire was answered by 486 and 839 citizens in Portugal (PT) and Spain (ES), respectively. Most respondents were between 41 and 64 years old, mostly women in Portugal and equally women and men in Spain, with higher education and working mostly in the services sector. The majority of respondents in both countries recognized the plant, knew it is invasive and were able to name it, alerting to a possible bias of the target audience toward citizens already aware of the invasiveness of the pampas grass. Fewer respondents were aware of the legislation that limits its use, and most were unable to identify particular characteristics of the species. The results showed that respondents' occupation in PT and education in ES influenced their knowledge and perception about pampas grass. This study confirms that education and raising awareness regarding invasive species is of utmost importance, as respondents identified academic training and projects with a strong focus on public awareness as the main sources of knowledge regarding pampas grass. Better informed citizens can be part of the solution rather than part of the problem, especially regarding invasive species with such ornamental interest as pampas grass. Supplementary Information: The online version contains supplementary material available at 10.1007/s10530-023-03025-3.
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Plastics, particularly microplastics (MPs) and nanoplastics (NPs), have been regarded as pollutants of emerging concern due to their effects on organisms and ecosystems, especially considering marine environments. However, in terms of NPs, there is still a knowledge gap regarding the effects of size and polymer on marine invertebrates, such as benthic organisms. Therefore, this study aimed to understand, regarding behavioural, physiological, and biochemical endpoints (neurotransmission, energy metabolism, antioxidant status, and oxidative damage), the effects of 50 nm waterborne polymethylmethacrylate (PMMA) NPs (0.5 to 500 µg/L) on the marine benthic polychaete Hediste diversicolor, a key species in estuarine and coastal ecosystems. Results demonstrated that worms exposed to PMMA NPs had a shorter burrowing time than control organisms. Nevertheless, worms exposed to PMMA NPs (0.5 and 500 µg/L) decreased cholinesterase activity. Energy metabolism was decreased at 50 and 500 µg/L, and glycogen content decreased at all concentrations of PMMA NPs. Enzymes related to the antioxidant defence system (superoxide dismutase and glutathione peroxidase) displayed increased activities in H. diversicolor specimens exposed to concentrations between 0.5 and 500 µg/L, which led to no damage at the cell membrane and protein levels. In this study, polychaetes also displayed a lower regenerative capacity when exposed to PMMA NPs. Overall, the data obtained in this study emphasize the potential consequences of PMMA NPs to benthic worms, particularly between 0.5 and 50 µg/L, with polychaetes exposed to 50 µg/L being the most impacted by the analysed NPs. However, since sediments are considered to be sinks and sources of plastics, further studies are needed to better understand the impacts of different sizes and polymers on marine organisms, particularly benthic species.
Assuntos
Poliquetos , Poluentes Químicos da Água , Animais , Antioxidantes/metabolismo , Polimetil Metacrilato/toxicidade , Polimetil Metacrilato/metabolismo , Microplásticos/metabolismo , Plásticos , Ecossistema , Poluentes Químicos da Água/toxicidadeRESUMO
Pex11 proteins are involved in membrane remodelling processes of peroxisomes, and are key components of peroxisomal division and proliferation. In mammals, three Pex11 isoforms, Pex11α, Pex11ß, and Pex11γ exist. Here we demonstrate that Pex11ß, but not Pex11α or Pex11γ, is almost exclusively extracted from peroxisomal membranes of paraformaldehyde-fixed cells by permeabilisation with the non-ionic detergent Triton X-100. This results in diminished detection of Myc-Pex11ß in immunofluorescence preparations and appearance of the protein in the Triton X-100 extract. To our knowledge, Pex11ß is the first peroxisomal membrane protein showing such a peculiar behaviour. Loss of Pex11ß can be avoided by permeabilisation with digitonin, the addition of glutaraldehyde to the fixative, or the expression of a Pex11 fusion protein with a larger protein tag (e.g. YFP). Our observations further point to different functions and biochemical properties of the Pex11 isoforms within the peroxisomal membrane and during peroxisome proliferation.
Assuntos
Detergentes/farmacologia , Membranas Intracelulares/metabolismo , Peroxissomos/metabolismo , Animais , Células COS , Proteínas de Membrana/química , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Peroxissomos/químicaRESUMO
The regulation of retinal ganglion cell (RGC) axon growth and patterning in vivo is thought to be largely dependent on interactions with visual pathway and target cells. Here we address the hypothesis that amacrine cells, RGCs' presynaptic partners, regulate RGC axon growth or targeting. We asked whether amacrine cells play a role in RGC axon growth in vivo using Foxn4(-/-) mice, which have fewer amacrine cells, but a normal complement of RGCs. We found that Foxn4(-/-) mice have a similar reduction in most subtypes of amacrine cells examined. Remarkably, spontaneous retinal waves were not affected by the reduction of amacrine cells in the Foxn4(-/-) mice. There was, however, a developmental delay in the distribution of RGC projections to the superior colliculus. Furthermore, RGC axons failed to penetrate into the retinorecipient layers in the Foxn4(-/-) mice. Foxn4 is not expressed by RGCs and was not detectable in the superior colliculus itself. These findings suggest that amacrine cells are critical for proper RGC axon growth in vivo, and support the hypothesis that the amacrine cell-RGC interaction may contribute to the regulation of distal projections and axon patterning.
Assuntos
Axônios/fisiologia , Axônios/ultraestrutura , Proteínas do Olho/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Células Ganglionares da Retina/citologia , Células Ganglionares da Retina/fisiologia , Potenciais de Ação/fisiologia , Células Amácrinas/citologia , Células Amácrinas/fisiologia , Animais , Axônios/metabolismo , Biomarcadores/metabolismo , Células Cultivadas , Proteínas do Olho/genética , Feminino , Fatores de Transcrição Forkhead/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nervo Óptico/citologia , Células Ganglionares da Retina/metabolismo , Colículos Superiores/anatomia & histologia , Colículos Superiores/crescimento & desenvolvimento , Vias Visuais/anatomia & histologia , Vias Visuais/crescimento & desenvolvimentoRESUMO
The rapid spread of invasive Pampas grass (PG) is having not only ecosystems impact, but also significant economic and social effects. The tonnes of bulky waste from the plant disposal require proper treatment to avoid seed dispersal, greenhouse gas emissions and landscape damage. In the pursuit of zero-waste management, hydrothermal treatment (HT) appears as a challenging alternative. The possibility of mobile HT systems offers an alternative to accomplish on-site both the PG waste management and the application of the resulting by-products within a circular framework. As a first step, this research shows that, without a prior drying step, the hydrothermal treatment at 100-230 °C under autogenous water vapor pressure for only 30 min allows safe seeds inertization, while a stable carbon-enriched solid and an aqueous stream are generated. Prolonging the process for 2 h has no profitable effects. As the reaction temperature increases, the PG residue is converted into a material with 49-58 wt% of carbon, 41-32 wt% of oxygen and 3-4 wt% of ash. The pH (~6.3), low electrical conductivity (1.21-0.86 dS/m), high carbon content, open porosity (5-8 m2/g) and improved performance in seed germination and in the early growth test suggest the potential of HT-solids derived at 100-120 °C as amendment to sequester carbon in the soil and improve its physico-biological properties. The phytotoxicity detected in the peat/lignite-like solids obtained at 200-230 °C limits its application in soil, but calorific values of 22-24 MJ/kg indicate their suitability as CO2-neutral fuel. The agrochemical analysis of the liquid by-products indicates poor value on their own, but their use supplemented with compost may be an option.