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1.
BMJ Open ; 14(3): e079685, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38531579

RESUMO

INTRODUCTION: Multimodal pain control following cardiothoracic surgery remains a focus in international guidelines. We hypothesise that non-depolarising skeletal muscle relaxants can prove to be a useful adjunct for this population. METHODS/ANALYSIS: This systematic review will focus on human adult studies of pain control using muscle relaxants within 1 week following cardiac and thoracic surgery available in PubMed, Cochrane Central, Web of Science and EMBASE. Target studies will have a primary focus on measured effects on quality of pain control and reduction in opioid usage. Studies that include non-depolarising skeletal muscle relaxants given during cardiothoracic surgery or in the week after will be included. Study selection will be in keeping with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Procedures and agents used will be analysed together, and a meta-analysis will be conducted then compared with current therapies recommended in international practice guidelines. ETHICS AND DISSEMINATION: Formal ethical approval will not be required as primary data will not be collected. The results will be disseminated through peer-reviewed publication, conference presentation and lay press. PROSPERO REGISTRATION NUMBER: CRD42023397917.


Assuntos
Fármacos Neuromusculares , Manejo da Dor , Adulto , Humanos , Revisões Sistemáticas como Assunto , Dor , Projetos de Pesquisa , Metanálise como Assunto
2.
Obes Rev ; 25(6): e13720, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38346847

RESUMO

Food accessibility was considerably impacted by restrictions during the coronavirus disease 2019 (COVID-19) pandemic, leading to growth in the online food retail sector, which offered contact-free delivery. This systematic review aimed to assess the change in use of online food retail platforms during COVID-19. The secondary aim was to identify diet-related chronic disease risk factors including dietary intake, eating behaviors, and/or weight status associated with the use of online food retail platforms during the pandemic. The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022320498) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Nine electronic databases were searched between January 2020 and October 2023. Studies that reported the frequency or change in use of online groceries, meal delivery applications, and/or meal-kit delivery services before and during the pandemic were included. A total of 53 studies were identified, including 46 cross-sectional studies, 4 qualitative studies, 2 longitudinal cohort studies, and 1 mixed-methods study. Overall, 96% (43/45) of outcomes showed an increase in the use of online groceries during COVID-19, while 55% (22/40) of outcomes showed a decrease in meal delivery applications. Eight of nine outcomes associated the use of online food retail with weight gain and emotional eating. Further research is needed to investigate the links between online food retail and obesity.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Fatores de Risco , Doença Crônica/epidemiologia , SARS-CoV-2 , Comportamento Alimentar , Dieta , Abastecimento de Alimentos , Internet , Pandemias , Comércio , Obesidade/epidemiologia
3.
Mar Environ Res ; 193: 106288, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38043169

RESUMO

At the regional scale, upwelling conditions are known to influence ecosystems and communities and their primary and secondary productivity. However, the influence of upwelling on local herbivore-algae interactions is less well understood. We address this question by cross-examining herbivores and seaweeds from sites associated with upwelling and downwelling conditions along the Humboldt Current System. Specifically, we quantified the feeding and benefits attained by the black sea urchin (Tetrapygus niger) and the black sea snail (Tegula atra) while consuming a widespread kelp species (Lessonia spicata). We hypothesized that food quality drives herbivores' preference, consumption, and growth rates, regardless of the origin or "prior" conditions of the consumers. Laboratory trials measured algal consumption rates with (preference) and without a choice, and consumer's growth rates, to assess the influence of food quality (algae from upwelling vs downwelling sites) and the site of origin of the consumers. Our results showed that algal quality was a prevailing factor for both herbivores: they chose, consumed more, and grew faster on high quality (upwelling) algae. By comparison, the origin of the consumer was only significant for sea snails: those coming from an upwelling site, consumed significantly more and grew faster than those from downwelling. The bulk of our results provided strong support to our hypothesis and suggest that the high nutritional quality of algae associated with upwelling centers has a strong influence on consumers' preferences, consumption, and performance (growth). The fact that origin was found to be relevant for one of the herbivores suggests that the conditions in which species grow may dictate some of their efficiency as consumers.


Assuntos
Herbivoria , Alga Marinha , Ecossistema , Comportamento Alimentar
4.
Appl Physiol Nutr Metab ; 49(3): 330-339, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37931241

RESUMO

To improve health outcomes, home cooking has been suggested as a solution to reduce intakes of processed foods. However, little is known about how cooking skills or cooking with processed foods influence health. This cross-sectional study examined associations between diet and health outcomes with cooking skills and cooking with processed foods. The dataset included a nationally representative sample of 18 460 adults from Canadian Community Health Survey (CCHS) annual component rapid response modules on food skills. In the CCHS rapid response modules, diet and health outcomes (fruit and vegetable intake, general health, mental health, and obesity) and data related to cooking skills and cooking with processed foods were collected through self-report. Separate logistic regression models were fitted for each outcome, controlling for age, income, and education, and stratified by sex. Adults with poor cooking skills were less likely to have adequate fruit and vegetable intake (≥5 servings per day) (p < 0.001), very good general health (p < 0.001) or mental health (p < 0.001), and obesity (p = 0.02) compared to advanced cooking skills. Adults who cooked with highly processed foods were less likely to have adequate fruit and vegetable intake (p < 0.001), very good general health (p = 0.002) or mental health (p < 0.001), but more likely to have obesity (p = 0.03) compared to cooking with minimally processed foods. Cooking skills alone appear insufficient to protect against obesity. Results suggest that not only are cooking skills important, but the quality of ingredients also matter. Limiting the use of processed foods in addition to improving cooking skills are potential intervention targets to promote better health and diet outcomes.


Assuntos
Culinária , Alimento Processado , Adulto , Humanos , Estudos Transversais , Canadá , Frutas , Obesidade/epidemiologia , Autorrelato
5.
Mar Environ Res ; 189: 106031, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37271060

RESUMO

Eastern Boundary Upwelling Systems (EBUS) deliver cold, nutrient-rich waters, influencing coastal biota from the molecular to the ecosystem level. Although local upwelling (U) and downwelling (DU) conditions are often known, their influence on body attributes of relevant species has not been systematically compared within and between EBUS (i.e., below and above regional scales). Hence, we compared the physical-chemical characteristics of U and DU sites in the Humboldt Current system (Chile) and the Iberian Current system (Portugal). We then assessed the influence of U and DU upon eight body attributes in purple mussels (Perumytilus purpuratus) and Mediterranean mussels (Mytilus galloprovincialis), from the Humboldt and Iberian systems, respectively. We hypothesized that bivalves from U sites display better fitness, as measured by body attributes, regardless of their origin (EBUS). As expected, waters from U sites in both systems showed lower temperatures and pH, and higher nitrite concentrations. We also found that mussels from U sites showed better fitness than those in DU sites in 12 out of 16 direct U vs DU comparisons. Shell length, shell volume, organic content of soft-tissues, and mechanical properties of the shell averaged consistently higher in mussels from U sites in both Current systems. In addition, total weight, soft-tissue weight, shell weight and shell thickness were all higher in the U site at the Humboldt system but had less consistent differences at the Iberian system. Altogether, most results supported our working hypothesis and indicate that U conditions support better fitted mussels. The few attributes that did not exhibit the expected U vs DU differences in the Iberian system suggest that local and species-specific differences also play a role on the attributes of these species. These results may also serve as a reference point for further studies addressing the influence of upwelling in these productive, critically important systems.


Assuntos
Ecossistema , Mytilus , Animais , Chile , Portugal
6.
An Pediatr (Engl Ed) ; 98(6): 436-445, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37169687

RESUMO

INTRODUCTION: One hundred thirty million Chlamydia trachomatis infections are reported worldwide each year. Nineteen serotypes of this pathogen can cause infection in pregnant women and neonates. The distribution of these genotypes in newborns with respiratory infections in Mexico is unknown. MATERIAL AND METHODS: We tested 1062 bronchial lavage samples from neonates with respiratory distress syndrome for Chlamydia infection. The diagnosis of Chlamydia was made by plasmid detection with an in-house PCR assay, and genotypes were identified using a PCR-RFLP assay for the ompA gene. RESULTS: The genotyping of 40 strains identified 14 as I/Ia (35%), 13 as E (32.5%), 7 as D (17.5%), 5 as F (12.5%), and 1 as L2 (2.5%). The relative risk analysis showed that genotype D was associated with neonatal sepsis (RR, 5.83; 95% confidence interval [CI], 1.51-25.985; P < .02), while the I/Ia genotype was significantly associated with chorioamnionitis in the mother (2.8; 95% CI, 1.4-5.5; P < .05). CONCLUSIONS: Although C. trachomatis genotypes I/Ia and E of were the strains involved most frequently in respiratory infections in Mexican neonates, 80% of patients with genotype F developed respiratory disease. In contrast, genotype D was associated with neonatal sepsis, and genotype I/Ia with chorioamnionitis.


Assuntos
Infecções por Chlamydia , Corioamnionite , Sepse Neonatal , Infecções Respiratórias , Humanos , Recém-Nascido , Feminino , Gravidez , Chlamydia trachomatis/genética , Genótipo , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia
7.
Eur J Philos Sci ; 13(1): 6, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36714209

RESUMO

Philosophers of science typically focus on the epistemic performance of scientific models when evaluating them. Analysing the effects that models may have on the world has typically been the purview of sociologists of science. We argue that the reactive (or "performative") effects of models should also figure in model evaluations by philosophers of science. We provide a detailed analysis of how models in financial economics created the impetus for the growing importance of the phenomenon of "passive investing" in financial markets. Considering this case motivates the position that we call contextualism about model evaluation, or model contextualism for short. Model contextualism encompasses standard analyses of the epistemic performance of the model, but also includes their reactive aspects. It entails identifying the epistemic and contextual import of the model, the ways in which a model can engender change in the world (which we call the channels of transmission), and the interactions between the epistemic and reactive import of a model.

8.
Stud Hist Philos Sci ; 97: 91-100, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36638558

RESUMO

The description of how individual models in families of models are related to each other is crucial for the general philosophical understanding of model-based scientific practice. We focus on the Capital Asset Pricing Models (CAPM) family, a cornerstone in financial economics, to provide a descriptive analysis of model relations within a family. We introduce the concepts of theoretical and empirical complementarity to characterise model relations. Our complementarity analysis of model relations has two types of payoff. Specifically regarding the CAPM, our analysis reveals why this model family, which has been empirically contested, has yet remained popular and important: the different models that have been added over time have made new empirically and theoretically complementary contributions to the model family. More generally, our analysis reveals the dynamic character of model-based scientific practice. Characterising relations between models as theoretically and/or empirically complementary yields three hitherto underappreciated lessons: (i) actual modelling purposes are not always primarily epistemic, (ii) a model's individual import is relative, not absolute, and (iii) there is an important interplay between theory and data models. Faithfully characterising scientific modelling in this way facilitates subsequent analysis of models' epistemic import.


Assuntos
Economia , Custos e Análise de Custo
9.
Rev Esp Patol ; 55 Suppl 1: S7-S10, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36075668

RESUMO

We present a case of a 53-year-old female with an 11 year history of myasthenia gravis (MG) with palpebral ptosis in the left eye which had become more marked over the previous year. Examination revealed a painless left orbital mass causing ptosis. The tumor was surgically removed and histopathology revealed deposits of a hyaline substance which when stained with Congo Red had an apple-green birefringence with polarized light, typical of amyloid. In the absence of amyloid deposits elsewhere in the body, amyloid tumor (AT) was diagnosed. No myelo- or lymphoproliferative syndromes, systemic involvement by amyloidosis or any autoimmune disease were found. The evolution and aesthetic results where satisfactory. Only two cases of orbital AT associated with MG have been described previously; however, in one of the cases, the symptoms of the AT had led to a false diagnosis of MG.


Assuntos
Amiloidose , Miastenia Gravis , Neoplasias Orbitárias , Amiloide , Amiloidose/complicações , Amiloidose/diagnóstico , Amiloidose/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Miastenia Gravis/complicações
10.
Sci Total Environ ; 851(Pt 2): 158307, 2022 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-36055497

RESUMO

Upwelling systems deliver nutrient-rich water into coastal ecosystems, influencing primary productivity and potentially altering seaweed-herbivore interactions. Upwelling bottom-up effects on distinct trophic levels are well-known. However, their influence on seaweed biomolecules and on algae-herbivore interactions and growth are less known. The aim of this study was threefold: i) to compare physical-chemical characteristics and nutrient levels in the water of upwelling (U) and downwelling (DU) zones, ii) to quantify their influence on the content of protein and carbohydrates in seaweed tissues of representative U and DU locations, and iii) to experimentally assess their effect on the feeding behavior and growth of a prominent intertidal herbivore, the sea urchin Loxechinus albus. Waters from U zones showed lower temperatures and pH, and higher phosphate concentrations than those from downwelling zones. Similarly, the tissue of seaweeds from a U location had significantly more proteins and carbohydrates than those from a DU location. The origin location of the sea urchins had a significant influence on consumption and growth rates: in general, those coming from a site with U conditions consumed and grew more than those coming from DU conditions. The quality of the algae was a significant factor on consumption rates, although in the case of preference trials, this factor interacted with sea urchin origin location. Our results show that the availability and quality of the food in upwelling zones has an influence on herbivore-seaweed direct interactions. However, these interactions and the growth of the sea urchins were also related to the coastal site and conditions from which the sea urchins came from. These results are relevant considering the expected impact of climate change on the world's oceans, and the importance of U zones as thermal (cold water) refuges for marine ectotherms.


Assuntos
Alga Marinha , Animais , Ecossistema , Ouriços-do-Mar , Comportamento Alimentar , Nutrientes , Plantas , Água , Carboidratos , Fosfatos
11.
Sci Rep ; 12(1): 5696, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35383257

RESUMO

Cerebral malaria is the most serious manifestation of severe falciparum malaria. Sequestration of infected red blood cells and microvascular dysfunction are key contributing processes. Whether these processes occur in early stage disease prior to clinical manifestations is unknown. To help localize and understand these processes during the early stages of infection, we performed 18-F fluorodeoxyglucose positron emission tomography/magnetic resonance imaging in volunteers with Plasmodium falciparum induced blood stage malaria (IBSM) infection, and compared results to individuals with P. vivax infection, in whom coma is rare. Seven healthy, malaria-naïve participants underwent imaging at baseline, and at early symptom onset a median 9 days following inoculation (n = 4 P. falciparum, n = 3 P. vivax). Participants with P. falciparum infection demonstrated marked lability in radiotracer uptake across all regions of the brain, exceeding expected normal variation (within subject coefficient of variation (wCV): 14.4%) compared to the relatively stable uptake in participants with P. vivax infection (wCV: 3.5%). No consistent imaging changes suggestive of microvascular dysfunction were observed in either group. Neuroimaging in early IBSM studies is safe and technically feasible, with preliminary results suggesting that differences in brain tropism between P. falciparum and P. vivax may occur very early in infection.


Assuntos
Malária Cerebral , Malária Falciparum , Malária Vivax , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Humanos , Imageamento por Ressonância Magnética , Malária Cerebral/diagnóstico por imagem , Malária Falciparum/diagnóstico por imagem , Malária Falciparum/patologia , Malária Vivax/patologia , Plasmodium falciparum , Plasmodium vivax , Tomografia por Emissão de Pósitrons , Estudos Prospectivos
12.
Lancet Infect Dis ; 22(6): 879-890, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35247321

RESUMO

BACKGROUND: New antimalarials with novel mechanisms of action are needed to combat the emergence of drug resistance. Triaminopyrimidines comprise a novel antimalarial class identified in a high-throughput screen against asexual blood-stage Plasmodium falciparum. This first-in-human study aimed to characterise the safety, pharmacokinetics, and antimalarial activity of the triaminopyrimidine ZY-19489 in healthy volunteers. METHODS: A three-part clinical trial was conducted in healthy adults (aged 18-55 years) in Brisbane, QLD, Australia. Part one was a double-blind, randomised, placebo-controlled, single ascending dose study in which participants enrolled into one of six dose groups (25, 75, 150, 450, 900, or 1500 mg) were randomly assigned (3:1) to ZY-19489 or placebo. Part two was an open-label, randomised, two-period cross-over, pilot food-effect study in which participants were randomly assigned (1:1) to a fasted-fed or a fed-fasted sequence. Part three was an open-label, randomised, volunteer infection study using the P falciparum induced blood-stage malaria model in which participants were enrolled into one of two cohorts, with participants in cohort one all receiving the same dose of ZY-19489 and participants in cohort two randomly assigned to receive one of two doses. The primary outcome for all three parts was the incidence, severity, and relationship to ZY-19489 of adverse events. Secondary outcomes were estimation of ZY-19489 pharmacokinetic parameters for all parts; how these parameters were affected by the fed state for part two only; and the parasite reduction ratio, parasite clearance half-life, recrudescent parasitaemia, and pharmacokinetic-pharmacodynamic modelling parameters for part three only. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619000127101, ACTRN12619001466134, and ACTRN12619001215112). FINDINGS: 48 participants were enrolled in part one (eight per cohort for 25-1500 mg cohorts), eight in part two (four in each group, all dosed with 300 mg), and 15 in part three (five dosed with 200 mg, eight with 300 mg, and two with 900 mg). In part one, the incidence of drug-related adverse events was higher in the 1500 mg dose group (occurring in all six participants) than in lower-dose groups and the placebo group (occurring in one of six in the 25 mg group, two of six in the 75 mg group, three of six in the 150 mg group, two of six in the 450 mg group, four of six in the 900 mg group, and four of 12 in the placebo group), due to the occurrence of mild gastrointestinal symptoms. Maximum plasma concentrations occurred 5-9 h post-dosing, and the elimination half-life was 50-97 h across the dose range. In part two, three of seven participants had a treatment-related adverse event in the fed state and four of eight in the fasted state. Dosing in the fed state delayed absorption (maximum plasma concentration occurred a median of 12·0 h [range 7·5-16·0] after dosing in the fed state vs 6·0 h [4·5-9·1] in the fasted state) but had no effect on overall exposure (difference in area under the concentration-time curve from time 0 [dosing] extrapolated to infinity between fed and fasted states was -0·013 [90% CI -0·11 to 0·08]). In part three, drug-related adverse events occurred in four of five participants in the 200 mg group, seven of eight in the 300 mg group, and both participants in the 900 mg group. Rapid initial parasite clearance occurred in all participants following dosing (clearance half-life 6·6 h [95% CI 6·2-6·9] for 200 mg, 6·8 h [95% CI 6·5-7·1] for 300 mg, and 7·1 h [95% CI 6·6-7·6] for 900 mg). Recrudescence occurred in four of five participants in the 200 mg group, five of eight in the 300 mg group, and neither of the two participants in the 900 mg group. Simulations done using a pharmacokinetic-pharmacodynamic model predicted that a single dose of 1100 mg would clear baseline parasitaemia by a factor of 109. INTERPRETATION: The safety, pharmacokinetic profile, and antimalarial activity of ZY-19489 in humans support the further development of the compound as a novel antimalarial therapy. FUNDING: Cadila Healthcare and Medicines for Malaria Venture.


Assuntos
Antimaláricos , Malária Falciparum , Adulto , Antimaláricos/efeitos adversos , Austrália , Método Duplo-Cego , Humanos , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Parasitemia , Projetos Piloto , Voluntários
13.
Nutrients ; 13(11)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34836044

RESUMO

For over two decades, digital food retail services have been emerging alongside advances in mobile technology and improved access to wi-fi. Digitalization has driven changes within the food environment, complicating an already complex system that influences food-related behaviors and eating practices. Digital food retail services support an infrastructure that enhances commercial food systems by extending access to and availability of highly processed foods, further escalating poor dietary intakes. However, digital food retail services are heterogeneous-food delivery apps, online groceries, and meal kits-and can be feasibly adapted to nutrition interventions and personalized to individual needs. Although sparse, new evidence indicates great potential for digital food retail services to address food insecurity in urban areas and to support healthy eating by making it easier to select, plan, and prepare meals. Digital food retail services are a product of the digital transformation that reflect consumers' constant need for convenience, which must be addressed in future research and interventions. This paper will discuss public health opportunities that are emerging from the global uptake of digital food retail services, with a focus on online groceries, food delivery apps, and meal kits.


Assuntos
Comércio/métodos , Dieta Saudável/tendências , Tecnologia Digital/tendências , Serviços de Alimentação/tendências , Abastecimento de Alimentos/métodos , Fast Foods , Comportamento Alimentar , Humanos
14.
PLoS Med ; 18(5): e1003567, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34038421

RESUMO

BACKGROUND: Plasmodium vivax has been proposed to infect and replicate in the human spleen and bone marrow. Compared to Plasmodium falciparum, which is known to undergo microvascular tissue sequestration, little is known about the behavior of P. vivax outside of the circulating compartment. This may be due in part to difficulties in studying parasite location and activity in life. METHODS AND FINDINGS: To identify organ-specific changes during the early stages of P. vivax infection, we performed 18-F fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) at baseline and just prior to onset of clinical illness in P. vivax experimentally induced blood-stage malaria (IBSM) and compared findings to P. falciparum IBSM. Seven healthy, malaria-naive participants were enrolled from 3 IBSM trials: NCT02867059, ACTRN12616000174482, and ACTRN12619001085167. Imaging took place between 2016 and 2019 at the Herston Imaging Research Facility, Australia. Postinoculation imaging was performed after a median of 9 days in both species (n = 3 P. vivax; n = 4 P. falciparum). All participants were aged between 19 and 23 years, and 6/7 were male. Splenic volume (P. vivax: +28.8% [confidence interval (CI) +10.3% to +57.3%], P. falciparum: +22.9 [CI -15.3% to +61.1%]) and radiotracer uptake (P. vivax: +15.5% [CI -0.7% to +31.7%], P. falciparum: +5.5% [CI +1.4% to +9.6%]) increased following infection with each species, but more so in P. vivax infection (volume: p = 0.72, radiotracer uptake: p = 0.036). There was no change in FDG uptake in the bone marrow (P. vivax: +4.6% [CI -15.9% to +25.0%], P. falciparum: +3.2% [CI -3.2% to +9.6%]) or liver (P. vivax: +6.2% [CI -8.7% to +21.1%], P. falciparum: -1.4% [CI -4.6% to +1.8%]) following infection with either species. In participants with P. vivax, hemoglobin, hematocrit, and platelet count decreased from baseline at the time of postinoculation imaging. Decrements in hemoglobin and hematocrit were significantly greater in participants with P. vivax infection compared to P. falciparum. The main limitations of this study are the small sample size and the inability of this tracer to differentiate between host and parasite metabolic activity. CONCLUSIONS: PET/MRI indicated greater splenic tropism and metabolic activity in early P. vivax infection compared to P. falciparum, supporting the hypothesis of splenic accumulation of P. vivax very early in infection. The absence of uptake in the bone marrow and liver suggests that, at least in early infection, these tissues do not harbor a large parasite biomass or do not provoke a prominent metabolic response. PET/MRI is a safe and noninvasive method to evaluate infection-associated organ changes in morphology and glucose metabolism.


Assuntos
Medula Óssea/parasitologia , Glucose/metabolismo , Fígado/parasitologia , Malária Falciparum/parasitologia , Malária Vivax/parasitologia , Baço/parasitologia , Medula Óssea/metabolismo , Medula Óssea/patologia , Feminino , Humanos , Fígado/metabolismo , Fígado/patologia , Imageamento por Ressonância Magnética , Malária Falciparum/patologia , Malária Falciparum/fisiopatologia , Malária Vivax/patologia , Malária Vivax/fisiopatologia , Masculino , Plasmodium falciparum , Plasmodium vivax , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Queensland , Coluna Vertebral/metabolismo , Coluna Vertebral/parasitologia , Coluna Vertebral/patologia , Baço/metabolismo , Baço/patologia , Adulto Jovem
15.
Malar J ; 20(1): 93, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33593375

RESUMO

BACKGROUND: New anti-malarial therapeutics are required to counter the threat of increasing drug resistance. Malaria volunteer infection studies (VIS), particularly the induced blood stage malaria (IBSM) model, play a key role in accelerating anti-malarial drug development. Supply of the reference 3D7-V2 Plasmodium falciparum malaria cell bank (MCB) is limited. This study aimed to develop a new MCB, and compare the safety and infectivity of this MCB with the existing 3D7-V2 MCB, in a VIS. A second bank (3D7-V1) developed in 1995 was also evaluated. METHODS: The 3D7-V2 MCB was expanded in vitro using a bioreactor to produce a new MCB designated 3D7-MBE-008. This bank and 3D7-V1 were then evaluated using the IBSM model, where healthy participants were intravenously inoculated with blood-stage parasites. Participants were treated with artemether-lumefantrine when parasitaemia or clinical thresholds were reached. Safety, infectivity and parasite growth and clearance were evaluated. RESULTS: The in vitro expansion of 3D7-V2 produced 200 vials of the 3D7-MBE-008 MCB, with a parasitaemia of 4.3%. This compares to 0.1% in the existing 3D7-V2 MCB, and < 0.01% in the 3D7-V1 MCB. All four participants (two per MCB) developed detectable P. falciparum infection after inoculation with approximately 2800 parasites. For the 3D7-MBE-008 MCB, the parasite multiplication rate of 48 h (PMR48) using non-linear mixed effects modelling was 34.6 (95% CI 18.5-64.6), similar to the parental 3D7-V2 line; parasitaemia in both participants exceeded 10,000/mL by day 8. Growth of the 3D7-V1 was slower (PMR48 of 11.5 [95% CI 8.5-15.6]), with parasitaemia exceeding 10,000 parasites/mL on days 10 and 8.5. Rapid parasite clearance followed artemether-lumefantrine treatment in all four participants, with clearance half-lives of 4.01 and 4.06 (weighted mean 4.04 [95% CI 3.61-4.57]) hours for 3D7-MBE-008 and 4.11 and 4.52 (weighted mean 4.31 [95% CI 4.16-4.47]) hours for 3D7-V1. A total of 59 adverse events occurred; most were of mild severity with three being severe in the 3D7-MBE-008 study. CONCLUSION: The safety, growth and clearance profiles of the expanded 3D7-MBE-008 MCB closely resemble that of its parent, indicating its suitability for future studies. TRIAL REGISTRATION: Australian New Zealand Clinical Trials registry numbers: P3487 (3D7-V1): ACTRN12619001085167. P3491 (3D7-MBE-008): ACTRN12619001079134.


Assuntos
Antimaláricos/uso terapêutico , Bancos de Espécimes Biológicos , Ensaios Clínicos como Assunto , Voluntários Saudáveis/estatística & dados numéricos , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum
16.
J Virol ; 94(23)2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-32938764

RESUMO

HIV-1 encodes an envelope glycoprotein (Env) that contains a long cytoplasmic tail (CT) harboring trafficking motifs implicated in Env incorporation into virus particles and viral transmission. In most physiologically relevant cell types, the gp41 CT is required for HIV-1 replication, but in the MT-4 T-cell line the gp41 CT is not required for a spreading infection. To help elucidate the role of the gp41 CT in HIV-1 transmission, in this study, we investigated the viral and cellular factors that contribute to the permissivity of MT-4 cells to gp41 CT truncation. We found that the kinetics of HIV-1 production and virus release are faster in MT-4 than in the other T-cell lines tested, but MT-4 cells express equivalent amounts of HIV-1 proteins on a per-cell basis relative to cells not permissive to CT truncation. MT-4 cells express higher levels of plasma-membrane-associated Env than nonpermissive cells, and Env internalization from the plasma membrane is less efficient than that from another T-cell line, SupT1. Paradoxically, despite the high levels of Env on the surface of MT-4 cells, 2-fold less Env is incorporated into virus particles produced from MT-4 than SupT1 cells. Contact-dependent transmission between cocultured 293T and MT-4 cells is higher than in cocultures of 293T with most other T-cell lines tested, indicating that MT-4 cells are highly susceptible to cell-to-cell infection. These data help to clarify the long-standing question of how MT-4 cells overcome the requirement for the HIV-1 gp41 CT and support a role for gp41 CT-dependent trafficking in Env incorporation and cell-to-cell transmission in physiologically relevant cell lines.IMPORTANCE The HIV-1 Env cytoplasmic tail (CT) is required for efficient Env incorporation into nascent particles and viral transmission in primary CD4+ T cells. The MT-4 T-cell line has been reported to support multiple rounds of infection of HIV-1 encoding a gp41 CT truncation. Uncovering the underlying mechanism of MT-4 T-cell line permissivity to gp41 CT truncation would provide key insights into the role of the gp41 CT in HIV-1 transmission. This study reveals that multiple factors contribute to the unique ability of a gp41 CT truncation mutant to spread in cultures of MT-4 cells. The lack of a requirement for the gp41 CT in MT-4 cells is associated with the combined effects of rapid HIV-1 protein production, high levels of cell-surface Env expression, and increased susceptibility to cell-to-cell transmission compared to nonpermissive cells.


Assuntos
Proteína gp41 do Envelope de HIV/genética , Proteína gp41 do Envelope de HIV/metabolismo , HIV-1/fisiologia , Linhagem Celular , Membrana Celular/metabolismo , Expressão Gênica , Células HEK293 , Humanos , Masculino , Transporte Proteico , Linfócitos T/virologia , Vírion/metabolismo , Replicação Viral
17.
Appl Physiol Nutr Metab ; 45(12): 1311-1323, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32459974

RESUMO

The revised version of Canada's Food Guide, released in January 2019, issued new guidance by combining meat and alternatives with milk and alternatives into a single group called "protein foods" and emphasized selecting plant-based foods from this category more often. Though the changes represent a simple depiction of a healthy plate, the new Food Guide has opened knowledge gaps about protein foods and exposed new concerns about the interpretation and implementation of the Food Guide among vulnerable groups, particularly children and the elderly. To address key knowledge and research gaps, nutrition leaders need to reach a consensus on key messages to best inform the development of tools and resources to support practitioners in translating messages to consumers, including foodservice standards. Among consumers, families with young children are a primary target for these resources as they develop their life-long habits to ensure they have the knowledge and skills to select, prepare, and consume nutrient-rich protein foods. The new Food Guide provides an opportunity to address the existing knowledge gaps, develop tools and resources to support health professionals, and design interventions that will help Canadian families choose, prepare, and eat nutrient-rich protein foods. Novelty An updated Canadian regulatory framework is needed for protein labelling and content/health claims. There are knowledge gaps about protein foods consumption and food literacy needed to optimize nutritional health. Mandatory nutrition policies are needed to safeguard the provision of high-quality protein foods across institutions that serve children and older adults.


Assuntos
Proteínas Alimentares/administração & dosagem , Alimentos/classificação , Recomendações Nutricionais , Canadá , Comunicação , Dieta , Rotulagem de Alimentos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Política Nutricional
18.
Can J Diet Pract Res ; 81(2): 86-90, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31736382

RESUMO

This study aimed to measure the influence of the Chefs in Action program (3 cooking workshops) on cooking skills, nutrition knowledge, and attitudes towards healthy eating in children attending summer day camps and compare it with a single cooking workshop. Groups of children (8-12 years) were randomly assigned to the intervention group (n = 25) or to 1 of 3 comparison groups performing a single workshop (group 1, n = 16; group 2, n = 36; group 3, n = 24). Two dietitians evaluated cooking skills during the workshops. Nutrition knowledge and attitudes towards healthy eating were assessed before and after the intervention. No improvement in cooking skills was observed in the intervention group (P = 0.25). The intervention group's cooking skills score was significantly higher than comparison group 1 (P < 0.001). Nutrition knowledge was significantly improved in the intervention group and the comparison group 3 (P < 0.0001) but no effect on attitudes towards healthy eating was observed (Pgroup × time = 0.36). In conclusion, the Chefs in Action program positively impacted nutrition knowledge in children. The results also suggest that the type of recipe may influence nutrition knowledge and cooking skills. Further studies are needed to better assess the degree of difficulty required in cooking workshop recipes to improve cooking skills in children.


Assuntos
Culinária/métodos , Dieta Saudável/métodos , Educação em Saúde/métodos , Conhecimentos, Atitudes e Prática em Saúde , Criança , Feminino , Humanos , Masculino , Ciências da Nutrição/educação , Nutricionistas , Quebeque
19.
Public Health Nutr ; 22(18): 3349-3359, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31663493

RESUMO

OBJECTIVE: To evaluate awareness of the Eat Well Campaign (EWC) among parents and assess perceptions about its effectiveness. DESIGN: Post-campaign evaluation study with a cross-section of parents recruited through random digit dialling. Participants completed an online survey about EWC awareness, its perceived effectiveness among parents and their meal planning practices (attitudes, behaviours and self-efficacy). SETTING: A federal mass-media campaign disseminated by Health Canada (2013-2014) to promote meal planning to Canadian parents. PARTICIPANTS: Parents (n 964) of children aged 2-12 years from all Provinces and Territories. RESULTS: Of respondents, 41 % (390/964) were aware of the campaign; Quebec City and rural Quebec had the highest rates of awareness, whereas Vancouver, Winnipeg and Toronto had the lowest. Awareness was greater among parents with lower income, basic education and French-speakers. Campaign intensity was significantly associated with greater odds of reporting positive attitudes towards the EWC and meal planning (P < 0·05). Campaign awareness was significantly associated with greater odds of believing that meal planning helps maintain a healthy diet (OR = 1·68, 95 % CI 1·03, 2·74) and planning meals (OR = 1·66, 95 % CI 1·03, 2·54), but not self-efficacy, in adjusted models. CONCLUSIONS: The present study is the first to evaluate an initiative that promoted meal planning with mass media. The EWC demonstrated evidence of success in terms of equitable access to a nutrition initiative by reaching lower-income and less-educated parents. Understanding behavioural factors among different segments of the population will be important to target appropriate audiences and develop tailored interventions that support healthy eating practices.


Assuntos
Dieta Saudável/métodos , Promoção da Saúde/métodos , Meios de Comunicação de Massa , Refeições/fisiologia , Pais/psicologia , Adulto , Canadá , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade
20.
J Biol Chem ; 294(44): 16266-16281, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31519756

RESUMO

The endosomal sorting complexes required for transport (ESCRT) machinery drives membrane scission for diverse cellular functions that require budding away from the cytosol, including cell division and transmembrane receptor trafficking and degradation. The ESCRT machinery is also hijacked by retroviruses, such as HIV-1, to release virions from infected cells. The crucial roles of the ESCRTs in cellular physiology and viral disease make it imperative to understand the membrane scission mechanism. Current methodological limitations, namely artifacts caused by overexpression of ESCRT subunits, obstruct our understanding of the spatiotemporal organization of the endogenous human ESCRT machinery. Here, we used CRISPR/Cas9-mediated knock-in to tag the critical ESCRT-I component tumor susceptibility 101 (Tsg101) with GFP at its native locus in two widely used human cell types, HeLa epithelial cells and Jurkat T cells. We validated this approach by assessing the function of these knock-in cell lines in cytokinesis, receptor degradation, and virus budding. Using this probe, we measured the incorporation of endogenous Tsg101 in released HIV-1 particles, supporting the notion that the ESCRT machinery initiates virus abscission by scaffolding early-acting ESCRT-I within the head of the budding virus. We anticipate that these validated cell lines will be a valuable tool for interrogating dynamics of the native human ESCRT machinery.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Fatores de Transcrição/metabolismo , Sistemas CRISPR-Cas , Citocinese/fisiologia , Proteínas de Ligação a DNA/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Genômica/métodos , HIV-1/metabolismo , Células HeLa , Humanos , Células Jurkat , Transporte Proteico , Fatores de Transcrição/genética , Vírion/metabolismo , Liberação de Vírus
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