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1.
Eur J Neurol ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36694382

RESUMO

BACKGROUND: Cardiovascular autonomic dysfunction may reportedly occur after a coronavirus-disease-2019 (COVID-19) infection, but the available evidence is scattered. Here we sought to understand the acute and mid-term effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on cardiovascular autonomic function. METHODS: We performed a systematic PubMed, Embase, Web of Science, medRxiv, and bioRxiv search for cases of cardiovascular autonomic dysfunction during an acute SARS-CoV-2 infection, post-COVID-19 condition. The clinical-demographic characteristics of people in the acute versus post-COVID-19 phase were compared. RESULTS: We screened 6470 titles and abstracts. Fifty-four full-length articles were included in the data synthesis. One-hundred thirty-four cases were identified: 81 during the acute SARS-CoV-2 infection (24 thereof diagnosed by history), 53 in the post-COVID-19 phase. Post-COVID-19 cases were younger than those with cardiovascular autonomic disturbances in the acute SARS-CoV-2 phase (42 vs. 51-year-old, p=0.002) and were more frequently women (68% vs. 49%, p=0.034). Reflex syncope was the most common cardiovascular autonomic disorder in the acute phase (p=0.008), postural orthostatic tachycardia syndrome (POTS) the most frequent diagnosis in people with post-COVID-19 orthostatic complaints (p<0.001). Full recovery was more frequent in people with acute versus post-COVID-19 onset of cardiovascular autonomic disturbances (43% vs. 15%, p=0.002). CONCLUSIONS: There is evidence from the scientific literature about different types of cardiovascular autonomic dysfunction developing during and after COVID-19. More data about the prevalence of autonomic disorders associated with a SARS-CoV-2 infection are needed to quantify its impact on human health.

2.
J Sleep Res ; : e13705, 2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36054586

RESUMO

Insomnia and sleep-disordered breathing (SDB) are prevalent sleep disorders. These disorders can therefore be concurrently present - comorbid insomnia and sleep apnea (COMISA). The prevalence of COMISA in the paediatric age range is unclear. As such, phenotypic constructs should help better define this comorbid condition if it exists in children and improve both diagnostic sensitivity and ultimately clinical care outcomes. We aimed to evaluate the frequency of insomnia in children and adolescents referred for evaluation of sleep symptoms suggestive of SDB in one initial (Cohort#1) and verify such findings in an independent cohort (Cohort#2) using a retrospective cross-sectional approach in patients aged 9-19 years presenting at a sleep centre to be evaluated for symptoms of SDB. Cohort #1 comprised 50 consecutive children (58% males; mean [SD] age 13.6 [3.3] years; median [interquartile range, IQR] Epworth Sleepiness Scale score 10 [6-12]) who were evaluated using validated SDB and insomnia questionnaires. Cohort#2 was extracted from electronic medical records and included 384 polysomnographically evaluated children (mean [SD] age 12.9 [3.6] years; mean [SD] body mass index z score 1.27 [0.28]; median Epworth Sleepiness Scale score 9.7 [4-17]). In Cohort #1, 56% were at high risk of SDB, 36% had insomnia alone, and 18% were at high risk of COMISA. The prevalence of COMISA in Cohort #2 was 16%, 72% had SDB alone, and 12% had insomnia alone. In both cohorts, COMISA manifested as increased propensity for sleepiness and fatigue during both waking and daytime. Thus, the presence of COMISA is frequent in the paediatric age range and accompanied by a more prominent symptomatic phenotype.

3.
Eur J Neurol ; 29(12): 3633-3646, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36056590

RESUMO

BACKGROUND AND PURPOSE: Disorders of the autonomic nervous system (ANS) are common conditions, but it is unclear whether access to ANS healthcare provision is homogeneous across European countries. The aim of this study was to identify neurology-driven or interdisciplinary clinical ANS laboratories in Europe, describe their characteristics and explore regional differences. METHODS: We contacted the European national ANS and neurological societies, as well as members of our professional network, to identify clinical ANS laboratories in each country and invite them to answer a web-based survey. RESULTS: We identified 84 laboratories in 22 countries and 46 (55%) answered the survey. All laboratories perform cardiovascular autonomic function tests, and 83% also perform sweat tests. Testing for catecholamines and autoantibodies are performed in 63% and 56% of laboratories, and epidermal nerve fiber density analysis in 63%. Each laboratory is staffed by a median of two consultants, one resident, one technician and one nurse. The median (interquartile range [IQR]) number of head-up tilt tests/laboratory/year is 105 (49-251). Reflex syncope and neurogenic orthostatic hypotension are the most frequently diagnosed cardiovascular ANS disorders. Thirty-five centers (76%) have an ANS outpatient clinic, with a median (IQR) of 200 (100-360) outpatient visits/year; 42 centers (91%) also offer inpatient care (median 20 [IQR 4-110] inpatient stays/year). Forty-one laboratories (89%) are involved in research activities. We observed a significant difference in the geographical distribution of ANS services among European regions: 11 out of 12 countries from North/West Europe have at least one ANS laboratory versus 11 out of 21 from South/East/Greater Europe (p = 0.021). CONCLUSIONS: This survey highlights disparities in the availability of healthcare services for people with ANS disorders across European countries, stressing the need for improved access to specialized care in South, East and Greater Europe.


Assuntos
Doenças do Sistema Nervoso Autônomo , Neurologia , Humanos , Laboratórios , Sistema Nervoso Autônomo , Inquéritos e Questionários
4.
Biology (Basel) ; 11(8)2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-36009791

RESUMO

Lead is a heavy metal whose widespread use has resulted in environmental contamination and significant health problems, particularly if the exposure occurs during developmental stages. It is a cumulative toxicant that affects multiple systems of the body, including the cardiovascular and nervous systems. Chronic lead exposure has been defined as a cause of behavioral changes, inflammation, hypertension, and autonomic dysfunction. However, different environmental lead exposure paradigms can occur, and the different effects of these have not been described in a broad comparative study. In the present study, rats of both sexes were exposed to water containing lead acetate (0.2% w/v), from the fetal period until adulthood. Developmental Pb-exposed (DevPb) pups were exposed to lead until 12 weeks of age (n = 13); intermittent Pb exposure (IntPb) pups drank leaded water until 12 weeks of age, tap water until 20 weeks, and leaded water for a second time from 20 to 28 weeks of age (n = 14); and the permanent (PerPb) exposure group were exposed to lead until 28 weeks of age (n = 14). A control group (without exposure, Ctrl), matched in age and sex was used. After exposure protocols, at 28 weeks of age, behavioral tests were performed for assessment of anxiety (elevated plus maze test), locomotor activity (open-field test), and memory (novel object recognition test). Metabolic parameters were evaluated for 24 h, and the acute experiment was carried out. Blood pressure (BP), electrocardiogram, and heart (HR) and respiratory (RF) rates were recorded. Baroreflex gain, chemoreflex sensitivity, and sympathovagal balance were calculated. Immunohistochemistry protocol for NeuN, Syn, Iba-1, and GFAP staining was performed. All Pb-exposed groups showed hypertension, concomitant with a decrease in baroreflex gain and chemoreceptor hypersensitivity, without significant changes in HR and RF. Long-term memory impairment associated with reactive astrogliosis and microgliosis in the dentate gyrus of the hippocampus, indicating the presence of neuroinflammation, was also observed. However, these alterations seemed to reverse after lead abstinence for a certain period (DevPb) and were enhanced when a second exposure occurred (IntPb), along with a synaptic loss. These results suggest that the duration of Pb exposure is more relevant than the timing of exposure, since the PerPb group presented more pronounced effects and a significant increase in the LF and HF bands and anxiety levels. In summary, this is the first study with the characterization and comparison of physiological, autonomic, behavioral, and molecular changes caused by different low-level environmental lead exposures, from the fetal period to adulthood, where the duration of exposure was the main factor for stronger adverse effects. These kinds of studies are of immense importance, showing the importance of the surrounding environment in health from childhood until adulthood, leading to the creation of new policies for toxicant usage control.

5.
EClinicalMedicine ; 48: 101423, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35706482

RESUMO

Background: This study assessed the effectiveness of the NEVERMIND e-health system, consisting of a smart shirt and a mobile application with lifestyle behavioural advice, mindfulness-based therapy, and cognitive behavioural therapy, in reducing depressive symptoms among patients diagnosed with severe somatic conditions. Our hypothesis was that the system would significantly decrease the level of depressive symptoms in the intervention group compared to the control group. Methods: This pragmatic, randomised controlled trial included 425 patients diagnosed with myocardial infarction, breast cancer, prostate cancer, kidney failure, or lower limb amputation. Participants were recruited from hospitals in Turin and Pisa (Italy), and Lisbon (Portugal), and were randomly assigned to either the NEVERMIND intervention or to the control group. Clinical interviews and structured questionnaires were administered at baseline, 12 weeks, and 24 weeks. The primary outcome was depressive symptoms at 12 weeks measured by the Beck Depression Inventory II (BDI-II). Intention-to-treat analyses included 425 participants, while the per-protocol analyses included 333 participants. This trial is registered in the German Clinical Trials Register, DRKS00013391. Findings: Patients were recruited between Dec 4, 2017, and Dec 31, 2019, with 213 assigned to the intervention and 212 to the control group. The sample had a mean age of 59·41 years (SD=10·70), with 44·24% women. Those who used the NEVERMIND system had statistically significant lower depressive symptoms at the 12-week follow-up (mean difference=-3·03, p<0·001; 95% CI -4·45 to -1·62) compared with controls, with a clinically relevant effect size (Cohen's d=0·39). Interpretation: The results of this study show that the NEVERMIND system is superior to standard care in reducing and preventing depressive symptoms among patients with the studied somatic conditions. Funding: The NEVERMIND project received funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement No. 689691.

6.
Auton Neurosci ; 241: 102986, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35567917

RESUMO

BACKGROUND AND PURPOSE: Autonomic dysfunction is associated with worse outcome of ischemic stroke patients by mechanisms that are not fully understood. There is evidence of autonomic influence in cerebrovascular control but this has not been studied in acute stroke. Therefore, we examined the relationship between heart rate variability (HRV) and baroreflex sensitivity (BRS) in dynamic cerebral autoregulation in the early hours post ischemia, and its impact in clinical and radiological outcome. METHODS: We prospectively enrolled 26 patients with acute ischemic stroke in middle cerebral artery. Arterial blood pressure (Finometer), cerebral blood flow velocity (transcranial Doppler), and electrocardiogram were recorded within 6 h. HRV was assessed by the standard side deviations of normal inter-beat intervals, spectral analysis and non-linear entropy indexes. Spontaneous BRS was assessed by spectral and sequence methods. Dynamic cerebral autoregulation was assessed by transfer function analysis (coherence, phase and gain). Infarct volume was calculated from computed tomography at 24 h. Clinical outcome was assessed by the modified Rankin scale. RESULTS: Increased BRS and HRV high frequencies power, both reflecting increased vagal modulation, were correlated with higher gain values of cerebral autoregulation (p < 0.05). The higher vagal modulation was also associated with later large infarct volumes (p < 0.05) but not with clinical outcome. CONCLUSIONS: Increased vagal modulation in early hours of acute ischemic stroke, may interfere with cerebrovascular control and is associated with larger infarcts. Understanding the mechanisms that govern this complex interplay can be useful as novel therapeutic targets to improvement of outcome.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Pressão Sanguínea/fisiologia , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Homeostase/fisiologia , Humanos , Infarto/complicações , AVC Isquêmico/diagnóstico por imagem
7.
Nat Ecol Evol ; 6(7): 855-865, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35577982

RESUMO

Recent studies have brought forward the critical role of emergent properties in shaping microbial communities and the ecosystems of which they are a part. Emergent properties-patterns or functions that cannot be deduced linearly from the properties of the constituent parts-underlie important ecological characteristics such as resilience, niche expansion and spatial self-organization. While it is clear that emergent properties are a consequence of interactions within the community, their non-linear nature makes mathematical modelling imperative for establishing the quantitative link between community structure and function. As the need for conservation and rational modulation of microbial ecosystems is increasingly apparent, so is the consideration of the benefits and limitations of the approaches to model emergent properties. Here we review ecosystem modelling approaches from the viewpoint of emergent properties. We consider the scope, advantages and limitations of Lotka-Volterra, consumer-resource, trait-based, individual-based and genome-scale metabolic models. Future efforts in this research area would benefit from capitalizing on the complementarity between these approaches towards enabling rational modulation of complex microbial ecosystems.


Assuntos
Microbiota , Modelos Biológicos , Modelos Teóricos
8.
Sleep Sci ; 15(Spec 2): 398-405, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371398

RESUMO

Obstructive sleep apnea (OSA) is the most prevalent sleep-disordered breathing in the adult population and if untreated remains a significant cause of morbidity and mortality. Continuous positive airway pressure (CPAP) therapy is still the gold standard treatment for OSA, but patient acceptance and adherence are often poor due to a multitude of factors, thereby compromising treatment success. Mandibular advancement devices (MADs) have been proposed not only as a first line therapy for symptomatic snoring patients, but also for those suffering from mild to moderate OSA, or those who refuse or do not tolerate CPAP. Yet, improved understanding of MAD regarding design, construction, and mechanisms of action is an important requirement to successfully implement MAD as a therapeutic tool. Therefore, the main focus of this paper is to focus on the general concepts and mechanisms of action of MAD, while highlighting important characteristics in the context of their use as a viable and effective treatment option for OSA patients.

9.
Genes (Basel) ; 13(2)2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-35205348

RESUMO

Candida parapsilosis is an emerging human pathogen whose incidence is rising worldwide, while an increasing number of clinical isolates display resistance to first-line antifungals, demanding alternative therapeutics. Genome-Scale Metabolic Models (GSMMs) have emerged as a powerful in silico tool for understanding pathogenesis due to their systems view of metabolism, but also to their drug target predictive capacity. This study presents the construction of the first validated GSMM for C. parapsilosis-iDC1003-comprising 1003 genes, 1804 reactions, and 1278 metabolites across four compartments and an intercompartment. In silico growth parameters, as well as predicted utilisation of several metabolites as sole carbon or nitrogen sources, were experimentally validated. Finally, iDC1003 was exploited as a platform for predicting 147 essential enzymes in mimicked host conditions, in which 56 are also predicted to be essential in C. albicans and C. glabrata. These promising drug targets include, besides those already used as targets for clinical antifungals, several others that seem to be entirely new and worthy of further scrutiny. The obtained results strengthen the notion that GSMMs are promising platforms for drug target discovery and guide the design of novel antifungal therapies.


Assuntos
Antifúngicos , Candida parapsilosis , Antifúngicos/farmacologia , Candida albicans/genética , Candida parapsilosis/genética , Humanos , Incidência , Testes de Sensibilidade Microbiana
10.
Curr Issues Mol Biol ; 43(3): 2305-2319, 2021 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-34940136

RESUMO

The increasing consumption of sugar and fat seen over the last decades and the consequent overweight and obesity, were recently linked with a deleterious effect on cognition and synaptic function. A major question, which remains to be clarified, is whether obesity in the elderly is an additional risk factor for cognitive impairment. We aimed at unravelling the impact of a chronic high caloric diet (HCD) on memory performance and synaptic plasticity in aged rats. Male rats were kept on an HCD or a standard diet (control) from 1 to 24 months of age. The results showed that under an HCD, aged rats were obese and displayed significant long-term recognition memory impairment when compared to age-matched controls. Ex vivo synaptic plasticity recorded from hippocampal slices from HCD-fed aged rats revealed a reduction in the magnitude of long-term potentiation, accompanied by a decrease in the levels of the brain-derived neurotrophic factor receptors TrkB full-length (TrkB-FL). No alterations in neurogenesis were observed, as quantified by the density of immature doublecortin-positive neurons in the hippocampal dentate gyrus. This study highlights that obesity induced by a chronic HCD exacerbates age-associated cognitive decline, likely due to impaired synaptic plasticity, which might be associated with deficits in TrkB-FL signaling.


Assuntos
Dieta , Transtornos da Memória/etiologia , Plasticidade Neuronal , Fatores Etários , Animais , Biomarcadores , Encéfalo/metabolismo , Modelos Animais de Doenças , Ingestão de Alimentos , Imuno-Histoquímica , Masculino , Ratos
11.
Bragança; s.n; 20210000. tab..
Tese em Português | BDENF - Enfermagem | ID: biblio-1362560

RESUMO

De acordo com a Direção Geral da Saúde (2004), a osteoartrose é uma das principais doenças que acomete a população, causa elevado impacto na capacidade funcional no mundo ocidental, levando ao absentismo laboral e a reformas antecipadas. Ocorre de forma mais ou menos localizada, afetando as articulações de maior importância para a funcionalidade, especificamente a articulação do joelho. A indicação para a artroplastia total do joelho passa por fazer uma avaliação da dor, da amplitude de movimentos, da força muscular, da marcha, do nível percebido de incapacidade e do nível de função geral. O enfermeiro especialista em enfermagem de reabilitação tem a competência de promover diagnósticos precoces e ações preventivas com a finalidade de melhorar a capacidade funcional da pessoa, prevenir complicações e evitar incapacidades (OE, 2010). Objetivos ­ Avaliar os efeitos de um programa de reabilitação no doente submetido a artroplastia total do joelho. Metodologia ­ Foi realizada uma revisão sistemática da literatura, utilizando a base de dados Pubmed, sendo analisados artigos publicados nos últimos 5 anos e que permitissem responder à questão de investigação: Quais os efeitos de um programa de reabilitação no doente submetido a artroplastia total do joelho? Após aplicação dos critérios de inclusão foram selecionados 9 estudos para análise. Resultados - Os programas de reabilitação dos estudos selecionados revelaram ganhos significativos no que respeita à amplitude de movimento, capacidade funcional e qualidade de vida, dos doentes submetidos a artroplastia total do joelho. Conclusões ­ A presente revisão sistemática de literatura conseguiu determinar que a realização de um programa de reabilitação após a artroplastia total do joelho traz ganhos em saúde para o doente. Dos estudos analisados conseguiu-se observar ganhos na amplitude de movimento, qualidade de vida e capacidade funcional dos doentes submetidos a ATJ.


According to the Directorate-General for Health (2004), osteoarthrosis is one of the main diseases that affects the population, causing a high impact on functional capacity in the Western world, leading to absenteeism from work and early retirement. It occurs in a more or less localized form, affecting the joints that are most important for functionality, specifically the knee joint. The indication for total knee arthroplasty involves an assessment of pain, range of motion, muscle strength, gait, the perceived level of disability and the level of general function. The specialist nurse in rehabilitation nursing has the competence to promote early diagnoses and preventive actions in order to improve the person's functional capacity, prevent complications and avoid disabilities (OE, 2010). Objectives ­ To assess the effects of a rehabilitation program for patients undergoing total knee arthroplasty. Methodology ­ This systematic literature review was carried out, using the Pubmed database, analyzing articles published in the last 5 years and allowing to answer the research question: What are the benefits of a rehabilitation program for patients undergoing total knee arthroplasty? After applying the inclusion criteria, 9 studies were selected for analysis. Results ­ The rehabilitation programs of the selected studies revealed significant gains in terms of range of motion, functional capacity and life quality of patients undergoing total knee arthroplasty. Conclusions ­ The present systematic literature review was able to determine that carrying out a rehabilitation program after total knee arthroplasty brings health gains for the patient. From the analyzed studies, it was possible to observe gains in the range of motion, quality of life and functional capacity of patients undergoing total knee arthroplasty.


Assuntos
Humanos , Artroplastia do Joelho , Reabilitação
12.
Mol Syst Biol ; 17(7): e10253, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34292675

RESUMO

First-principle metabolic modelling holds potential for designing microbial chassis that are resilient against phenotype reversal due to adaptive mutations. Yet, the theory of model-based chassis design has rarely been put to rigorous experimental test. Here, we report the development of Saccharomyces cerevisiae chassis strains for dicarboxylic acid production using genome-scale metabolic modelling. The chassis strains, albeit geared for higher flux towards succinate, fumarate and malate, do not appreciably secrete these metabolites. As predicted by the model, introducing product-specific TCA cycle disruptions resulted in the secretion of the corresponding acid. Adaptive laboratory evolution further improved production of succinate and fumarate, demonstrating the evolutionary robustness of the engineered cells. In the case of malate, multi-omics analysis revealed a flux bypass at peroxisomal malate dehydrogenase that was missing in the yeast metabolic model. In all three cases, flux balance analysis integrating transcriptomics, proteomics and metabolomics data confirmed the flux re-routing predicted by the model. Taken together, our modelling and experimental results have implications for the computer-aided design of microbial cell factories.


Assuntos
Engenharia Metabólica , Saccharomyces cerevisiae , Ciclo do Ácido Cítrico/genética , Metabolômica , Saccharomyces cerevisiae/genética , Ácido Succínico
13.
PLoS Comput Biol ; 17(6): e1009022, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34115746

RESUMO

Chinese hamster ovary (CHO) cells are the leading platform for the production of biopharmaceuticals with human-like glycosylation. The standard practice for cell line generation relies on trial and error approaches such as adaptive evolution and high-throughput screening, which typically take several months. Metabolic modeling could aid in designing better producer cell lines and thus shorten development times. The genome-scale metabolic model (GSMM) of CHO can accurately predict growth rates. However, in order to predict rational engineering strategies it also needs to accurately predict intracellular fluxes. In this work we evaluated the agreement between the fluxes predicted by parsimonious flux balance analysis (pFBA) using the CHO GSMM and a wide range of 13C metabolic flux data from literature. While glycolytic fluxes were predicted relatively well, the fluxes of tricarboxylic acid (TCA) cycle were vastly underestimated due to too low energy demand. Inclusion of computationally estimated maintenance energy significantly improved the overall accuracy of intracellular flux predictions. Maintenance energy was therefore determined experimentally by running continuous cultures at different growth rates and evaluating their respective energy consumption. The experimentally and computationally determined maintenance energy were in good agreement. Additionally, we compared alternative objective functions (minimization of uptake rates of seven nonessential metabolites) to the biomass objective. While the predictions of the uptake rates were quite inaccurate for most objectives, the predictions of the intracellular fluxes were comparable to the biomass objective function.


Assuntos
Análise do Fluxo Metabólico , Animais , Biomassa , Reatores Biológicos , Células CHO , Isótopos de Carbono/metabolismo , Ciclo do Ácido Cítrico , Biologia Computacional/métodos , Cricetulus , Metabolismo Energético , Glicólise , Modelos Biológicos
14.
Sleep Sci ; 14(1): 55-63, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104338

RESUMO

Insomnia remains the most prevalent sleep disorder worldwide, and its pathophysiology suggests an interface with circadian rhythm sleep-wake disorders (CRSWDs). Some epidemiological studies have linked insomnia and circadian misalignment with adverse cardiometabolic outcomes, but the mechanisms underlying this relationship are still unclear. The autonomic nervous system (ANS) has been pointed out as a crucial/key mediator that triggers cardiometabolic risk. Therefore, a critical review of the literature focused on the past ten years was conducted to highlight the relationship between insomnia, circadian misalignment and cardiometabolic risk, with particular emphasis on the influence of the ANS. Shift work, as a model of circadian misalignment, was shown to increase both cardiovascular and metabolic risk and so may integrate a proof of concept on this link. Furthermore, there is good evidence from previous studies supporting that cardiac autonomic dysfunction is indeed a possible mechanism that potentiates cardiometabolic risk in insomniacs and individuals with a misalignment of the circadian timing system (e.g., shift workers), via changes in autonomic variables. Further research is however required in order to definitively establish this interactive relationship.

15.
J Fungi (Basel) ; 6(3)2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32932905

RESUMO

Candida albicans is one of the most impactful fungal pathogens and the most common cause of invasive candidiasis, which is associated with very high mortality rates. With the rise in the frequency of multidrug-resistant clinical isolates, the identification of new drug targets and new drugs is crucial in overcoming the increase in therapeutic failure. In this study, the first validated genome-scale metabolic model for Candida albicans, iRV781, is presented. The model consists of 1221 reactions, 926 metabolites, 781 genes, and four compartments. This model was reconstructed using the open-source software tool merlin 4.0.2. It is provided in the well-established systems biology markup language (SBML) format, thus, being usable in most metabolic engineering platforms, such as OptFlux or COBRA. The model was validated, proving accurate when predicting the capability of utilizing different carbon and nitrogen sources when compared to experimental data. Finally, this genome-scale metabolic reconstruction was tested as a platform for the identification of drug targets, through the comparison between known drug targets and the prediction of gene essentiality in conditions mimicking the human host. Altogether, this model provides a promising platform for global elucidation of the metabolic potential of C. albicans, possibly guiding the identification of new drug targets to tackle human candidiasis.

16.
Biochem Soc Trans ; 48(5): 1889-1903, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-32940659

RESUMO

The current survey aims to describe the main methodologies for extending the reconstruction and analysis of genome-scale metabolic models and phenotype simulation with Flux Balance Analysis mathematical frameworks, via the integration of Transcriptional Regulatory Networks and/or gene expression data. Although the surveyed methods are aimed at improving phenotype simulations obtained from these models, the perspective of reconstructing integrated genome-scale models of metabolism and gene expression for diverse prokaryotes is still an open challenge.


Assuntos
Redes Reguladoras de Genes , Genoma , Transcrição Genética , Algoritmos , Teorema de Bayes , Fenômenos Bioquímicos , Biomassa , Catálise , Gráficos por Computador , Simulação por Computador , Perfilação da Expressão Gênica , Genoma Humano , Humanos , Redes e Vias Metabólicas , Modelos Biológicos , Modelos Teóricos , Fenótipo , Engenharia de Proteínas/métodos , Biologia de Sistemas
17.
F1000Res ; 9: 9, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742638

RESUMO

Pseudoxanthoma elasticum (PXE) is a rare inherited disorder, characterised by a progressive mineralization and fragmentation of elastic fibres of the skin, retina and cardiovascular system. At an initial stage, the skin usually exhibits distinctive lesions and subsequently extra-dermal manifestations. The diagnosis is based on clinical manifestations, histological analysis of the lesions and genetic analysis. This is a case report of a 12-year-old child complaining of painless, mildly itchy yellow papules in the cervical region with 1 year of evolution. PXE is currently an incurable disease and has a favourable prognosis when cardiovascular and retinal complications are prevented and monitored.


Assuntos
Pseudoxantoma Elástico , Biópsia , Sistema Cardiovascular/patologia , Criança , Feminino , Humanos , Pseudoxantoma Elástico/diagnóstico , Pseudoxantoma Elástico/genética , Retina/patologia , Pele/patologia , Ultrassonografia
18.
Sleep Med ; 74: 132-140, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32858273

RESUMO

Obstructive Sleep Apnea (OSA) is one of the most common sleep disorders, and invokes numerous negative health-related outcomes and physiopathological processes. Understanding the mechanisms by which OSA potentiates cardiometabolic risk of patients remains a current challenge. Sleep disruption is highly prevalent among shift workers and shift work (SW) is an important modulator of circadian rhythms, with health consequences intimately related to cardiometabolic health. Since the circadian timing system (CTS) interacts with the normal functioning of the ANS, CTS impact on OSA patients should be closely assessed. This review raises the question of whether SW-induced circadian misalignment potentiates the cardiometabolic risk of OSA patients, providing a novel perspective on the role of autonomic modulation as a key downstream mechanism linking cardiometabolic risk with both OSA and CTS misalignment.


Assuntos
Doenças Cardiovasculares , Jornada de Trabalho em Turnos , Apneia Obstrutiva do Sono , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Ritmo Circadiano , Humanos , Sono , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia
19.
J Thromb Thrombolysis ; 50(3): 753-761, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32488831

RESUMO

The cerebrovascular effects of a failing heart-pump are largely unknown. Chronic heart failure (HF) might cause pre-conditioning effect on cerebral hemodynamics but not study so far in acute stroke. We aimed to investigate if HF induces effects in dynamic cerebral autoregulation (CA), within 6 h of symptom-onset through chronic stage of ischemic stroke. We enrolled 50 patients with acute ischemic stroke. Groups with (N = 8) and without HF and 20 heathy controls were compared. Arterial blood pressure (Finometer) and cerebral blood flow velocity (transcranial Doppler) were monitored within 6 and at 24 h from symptom-onset and at 3 months. We assessed dynamic CA by transfer function analysis and cardiac disease markers. HF associated with higher phase (better dynamic CA) at ischemic hemisphere within 6 (p = 0.042) and at 24 h (p = 0.006) but this effect was not evident at 3 months (p > 0.05). Gain and coherence trends were similar between groups. We found a positive correlation between phase and admission troponin I levels (Spearman's r = 0.348, p = 0.044). Our findings advances on the knowledge of how brain and heart interact in acute ischemic stroke by showing a sustained dynamic cerebral autoregulation response in HF patients mainly with severe aortic valve disease. Understanding the physiological mechanisms that govern this complex interplay can be useful to find novel therapeutic targets which can improve outcome in ischemic stroke.


Assuntos
Insuficiência Cardíaca/complicações , AVC Isquêmico/complicações , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Encéfalo/irrigação sanguínea , Encéfalo/fisiopatologia , Circulação Cerebrovascular , Feminino , Coração/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Humanos , AVC Isquêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade
20.
Biotechnol Bioeng ; 117(8): 2571-2587, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32374413

RESUMO

The global market of butanol is increasing due to its growing applications as solvent, flavoring agent, and chemical precursor of several other compounds. Recently, the superior properties of n-butanol as a biofuel over ethanol have stimulated even more interest. (Bio)butanol is natively produced together with ethanol and acetone by Clostridium species through acetone-butanol-ethanol fermentation, at noncompetitive, low titers compared to petrochemical production. Different butanol production pathways have been expressed in Escherichia coli, a more accessible host compared to Clostridium species, to improve butanol titers and rates. The bioproduction of butanol is here reviewed from a historical and theoretical perspective. All tested rational metabolic engineering strategies in E. coli to increase butanol titers are reviewed: manipulation of central carbon metabolism, elimination of competing pathways, cofactor balancing, development of new pathways, expression of homologous enzymes, consumption of different substrates, and molecular biology strategies. The progress in the field of metabolic modeling and pathway generation algorithms and their potential application to butanol production are also summarized here. The main goals are to gather all the strategies, evaluate the respective progress obtained, identify, and exploit the outstanding challenges.


Assuntos
Butanóis/metabolismo , Escherichia coli , Engenharia Metabólica/métodos , Biocombustíveis , Escherichia coli/genética , Escherichia coli/metabolismo , Fermentação
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