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1.
Sensors (Basel) ; 24(6)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38544276

RESUMO

The increase in life expectancy, and the consequent growth of the elderly population, represents a major challenge to guarantee adequate health and social care. The proposed system aims to provide a tool that automates the evaluation of gait and balance, essential to prevent falls in older people. Through an RGB-D camera, it is possible to capture and digitally represent certain parameters that describe how users carry out certain human motions and poses. Such individual motions and poses are actually related to items included in many well-known gait and balance evaluation tests. According to that information, therapists, who would not need to be present during the execution of the exercises, evaluate the results of such tests and could issue a diagnosis by storing and analyzing the sequences provided by the developed system. The system was validated in a laboratory scenario, and subsequently a trial was carried out in a nursing home with six residents. Results demonstrate the usefulness of the proposed system and the ease of objectively evaluating the main items of clinical tests by using the parameters calculated from information acquired with the RGB-D sensor. In addition, it lays the future foundations for creating a Cloud-based platform for remote fall risk assessment and its integration with a mobile assistant robot, and for designing Artificial Intelligence models that can detect patterns and identify pathologies for enabling therapists to prevent falls in users under risk.


Assuntos
Inteligência Artificial , Terapia por Exercício , Humanos , Idoso , Medição de Risco/métodos , Computadores
2.
Eur J Intern Med ; 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37858442

RESUMO

INTRODUCTION: The burden of metabolic syndrome (MetS) and its components has been increasing mainly amongst male individuals. Nevertheless, clinical outcomes related to MetS (i.e., cardiovascular diseases), are worse among female individuals. Whether these sex differences in the components and sequalae of MetS are influenced by gender (i.e., psycho-socio-cultural factors)) is a matter of debate.  Therefore, the purpose of this study was to determine the association between gender-related factors and the development of MetS, and to assess if the magnitude of the associations vary by sex. METHOD: Data from the Colaus/PsyColaus study, a prospective population-based cohort of 6,734 middle-aged participants in Lausanne (Switzerland) (2003-2006) were used. The primary endpoint was the development of MetS as defined by the Adult Treatment Panel III of the National Cholesterol Education Program. Multivariable models were estimated using logistic regression to assess the association between gender-related factors and the development of MetS. Two-way interactions between sex,  age and gender-related factors were also tested. RESULTS: Among 5,195 participants without MetS (mean age=51.3 ± 10.6, 56.1 % females), 27.9 % developed MetS during a mean follow-up of 10.9 years. Female sex (OR:0.48, 95 %CI:0.41-0.55) was associated with decreased risk of developing MetS. Conversely, older age, educational attainment less than university, and low income were associated with an increased risk of developing MetS. Statistically significant interaction between sex and strata of age, education, income, smoking, and employment were identified showing that the reduced risk of MetS in female individuals was attenuated in the lowest education, income, and advanced age strata. However, females who smoke and reported being employed demonstrated increased risk of MetS. Conversely smoking and unemployment were significant risk factors for MetS development among male adults. CONCLUSIONS: Gender-related factors such as income level and educational attainment play a greater role in the development of MetS in female than individuals. These factors represent novel modifiable targets for implementation of sex- and gender-specific strategies to achieve health equity for all people.

3.
NPJ Parkinsons Dis ; 9(1): 135, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37726343

RESUMO

Aggregation of α-synuclein (α-syn) is the cornerstone of neurodegenerative diseases termed synucleinopathies, which include Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), and Multiple System Atrophy (MSA). These synucleinopathies are characterized by the deposit of aggregated α-syn in intracellular inclusions observable in neurons and glial cells. In PD and DLB, these aggregates, predominantly located in neurons, are called Lewy Bodies (LBs). These LBs are one of the pathological hallmarks of PD and DLB, alongside dopaminergic neuron loss in the substantia nigra. Previous studies have demonstrated the ability of PD patient-derived LB fractions to induce nigrostriatal neurodegeneration and α-syn pathology when injected into the striatum or the enteric nervous system of non-human primates. Here, we report the pathological consequences of injecting these LB fractions into the cortex of non-human primates. To this end, we inoculated mesencephalic PD patient-derived LB fractions into the prefrontal cortex of baboon monkeys terminated one year later. Extensive analyses were performed to evaluate pathological markers known to be affected in LB pathologies. We first assessed the hypothesized presence of phosphorylated α-syn at S129 (pSyn) in the prefrontal cortices. Second, we quantified the neuronal, microglial, and astrocytic cell survival in the same cortices. Third, we characterized these cortical LB injections' putative impact on the integrity of the nigrostriatal system. Overall, we observed pSyn accumulation around the injection site in the dorsal prefrontal cortex, in connected cortical regions, and further towards the striatum, suggesting α-syn pathological propagation. The pathology was also accompanied by neuronal loss in these prefrontal cortical regions and the caudate nucleus, without, however, loss of nigral dopamine neurons. In conclusion, this pilot study provides novel data demonstrating the toxicity of patient-derived extracts, their potential to propagate from the cortex to the striatum in non-human primates, and a possible primate model of DLB.

4.
Sci Rep ; 13(1): 11540, 2023 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-37460705

RESUMO

Sharing health data for research purposes across international jurisdictions has been a challenge due to privacy concerns. Two privacy enhancing technologies that can enable such sharing are synthetic data generation (SDG) and federated analysis, but their relative strengths and weaknesses have not been evaluated thus far. In this study we compared SDG with federated analysis to enable such international comparative studies. The objective of the analysis was to assess country-level differences in the role of sex on cardiovascular health (CVH) using a pooled dataset of Canadian and Austrian individuals. The Canadian data was synthesized and sent to the Austrian team for analysis. The utility of the pooled (synthetic Canadian + real Austrian) dataset was evaluated by comparing the regression results from the two approaches. The privacy of the Canadian synthetic data was assessed using a membership disclosure test which showed an F1 score of 0.001, indicating low privacy risk. The outcome variable of interest was CVH, calculated through a modified CANHEART index. The main and interaction effect parameter estimates of the federated and pooled analyses were consistent and directionally the same. It took approximately one month to set up the synthetic data generation platform and generate the synthetic data, whereas it took over 1.5 years to set up the federated analysis system. Synthetic data generation can be an efficient and effective tool for enabling multi-jurisdictional studies while addressing privacy concerns.


Assuntos
Sistema Cardiovascular , Humanos , Canadá , Áustria , Revelação , Privacidade
5.
J Neurochem ; 166(3): 427-452, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37161795

RESUMO

Brain aging is a naturally occurring process resulting in the decline of cognitive functions and increased vulnerability to develop age-associated disorders. Fluctuation in lipid species is crucial for normal brain development and function. However, impaired lipid metabolism and changes in lipid composition in the brain have been increasingly recognized to play a crucial role in physiological aging, as well as in several neurodegenerative diseases. In the last decades, the role of sexual dimorphism in the vulnerability to develop age-related neurodegeneration has increased. However, further studies are warranted for detailed assessment of how age, sex, and additional non-biological factors may influence the lipid changes in brains. The aim of this work is to address the presence of sex differences in the brain lipid changes that occur along aging, and in the two most common age-related neurodegenerative disorders (Alzheimer's and Parkinson's diseases). We included the studies that assessed lipid-related alterations in the brain of both humans and experimental models. Additionally, we explored the influence of sex on lipid-lowering therapies. We conclude that sex exerts a notable effect on lipid modifications occurring with age and neurodegeneration, and in lipid-reducing interventions. Therefore, the application of sex as an experimental variable is strongly encouraged for future research in the field of precision medicine approach.


Assuntos
Doença de Alzheimer , Neuroquímica , Humanos , Feminino , Masculino , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Envelhecimento/metabolismo , Metabolismo dos Lipídeos , Lipídeos
6.
Biology (Basel) ; 12(5)2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37237559

RESUMO

Cardiovascular diseases represent the leading cause of mortality and morbidity worldwide, and age is an important risk factor. Preclinical models provide supportive evidence toward age-related cardiac changes, as well as allow for the study of pathological aspects of the disease. In the present work, we evaluated the electrocardiogram (ECG) recording in the O. degus during the aging process in both females and males. Taking into account the age and sex, our study provides the normal ranges for the heart rate, duration and voltage of the ECG waves and intervals, as well as electrical axis deviation. We found that the QRS complex duration and QTc significantly increased with age, whereas the heart rate significantly decreased. On the other hand, the P wave, PR and QTc segments durations, S wave voltage and electrical axis were found to be significantly different between males and females. The heart rhythm was also altered in aged animals, resulting in an increased incidence of arrhythmias, especially in males. Based on these results, we suggest that this rodent model could be useful for cardiovascular research, including impacts of aging and biological sex.

7.
Nutrients ; 15(7)2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37049550

RESUMO

Magnesium (Mg) has a vital role in the human body, and the kidney is a key organ in the metabolism and excretion of this cation. The objective of this work is to compile the available evidence regarding the role that Mg plays in health and disease, with a special focus on the elderly population with chronic kidney disease (CKD) and the eventual sex differences. A narrative review was carried out by executing an exhaustive search in the PubMed, Scopus, and Cochrane databases. Ten studies were found in which the role of Mg and sex was evaluated in elderly patients with CKD in the last 10 years (2012-2022). The progression of CKD leads to alterations in mineral metabolism, which worsen as the disease progresses. Mg can be used as a coadjuvant in the treatment of CKD patients to improve glomerular filtration, but its use in clinical applications needs to be further characterized. In conclusion, there's a need for well-designed prospective clinical trials to advise and standardize Mg supplementation in daily clinical practice, taking age and sex into consideration.


Assuntos
Magnésio , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Idoso , Progressão da Doença , Estudos Prospectivos , Rim , Envelhecimento , Taxa de Filtração Glomerular
8.
Neurotox Res ; 41(3): 224-241, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36723781

RESUMO

Causes of dopaminergic neuronal loss in Parkinson's disease (PD) are subject of investigation and the common use of models of acute neurodegeneration induced by neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 6-hydroxydopamine, and rotenone contributed to advances in the study of PD. However, the use of study models more similar to the pathophysiology of PD is required for advances in early diagnosis and translational pharmacology. Aminochrome (AMI), a compound derived from dopamine oxidation and a precursor of neuromelanin, is able to induce all the mechanisms associated with neurodegeneration. Previously, we showed AMI is cytotoxic in primary culture of mesencephalic cells (PCMC) and induces in vitro and in vivo neuroinflammation. On the other hand, the effect of rutin in central nervous system cells has revealed anti-inflammatory, antioxidative, and neuroprotective potential. However, there have been no data studies on the effect of rutin against aminochrome neurotoxicity. Here, we show that rutin prevents lysosomal dysfunction and aminochrome-induced cell death in SHSY-5Y cells, protects PCMC against aminochrome cytotoxicity, and prevents in vivo loss of dopaminergic neurons in substantia nigra pars compacta (SNPc), as well as microgliosis and astrogliosis. Additionally, we show that rutin decreases levels of interleukin-1ß (IL-1ß) mRNA and increases levels of glia-derived neurotrophic factor (GDNF) and nerve-derived neurotrophic factor (NGF) mRNA. We evidence for the first time the protective effect of rutin on PD aminochrome-induced models and suggest the potential role of the anti-inflammatory activity and upregulation of NGF and GDNF in the mechanism of rutin action against aminochrome neurotoxicity.


Assuntos
Fármacos Neuroprotetores , Síndromes Neurotóxicas , Doença de Parkinson , Animais , Camundongos , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Flavonoides/farmacologia , Rutina/farmacologia , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/prevenção & controle , Síndromes Neurotóxicas/metabolismo , Dopamina/metabolismo , Doença de Parkinson/metabolismo , Neurônios Dopaminérgicos , Anti-Inflamatórios/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia
9.
Front Public Health ; 11: 1090541, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36817907

RESUMO

Aims: The aim of this study was to elucidate whether sex and gender factors influence access to health care and/or are associated with cardiovascular (CV) outcomes of individuals with diabetes mellitus (DM) across different countries. Methods: Using data from the Canadian Community Health Survey (8.4% of respondent reporting DM) and the European Health Interview Survey (7.3% of respondents reporting DM), were analyzed. Self-reported sex and a composite measure of socio-cultural gender was constructed (range: 0-1; higher score represent participants who reported more characteristics traditionally ascribed to women). For the purposes of analyses the Gender Inequality Index (GII) was used as a country level measure of institutionalized gender. Results: Canadian females with DM were more likely to undergo HbA1c monitoring compared to males (OR = 1.26, 95% CI: 1.01-1.58), while conversely in the European cohort females with DM were less likely to have their blood sugar measured compared to males (OR = 0.88, 95% CI: 0.79-0.99). A higher gender score in both cohorts was associated with less frequent diabetes monitoring. Additionally, independent of sex, higher gender scores were associated with higher prevalence of self-reported heart disease, stroke, and hospitalization in all countries albeit European countries with medium-high GII, conferred a higher risk of all outcomes and hospitalization rates than low GII countries. Conclusion: Regardless of sex, individuals with DM who reported characteristics typically ascribed to women and those living in countries with greater gender inequity for women exhibited poorer diabetes care and greater risk of CV outcomes and hospitalizations.


Assuntos
Diabetes Mellitus , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Canadá , Diabetes Mellitus/epidemiologia , Inquéritos e Questionários , Acesso aos Serviços de Saúde
10.
Sensors (Basel) ; 23(1)2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36617079

RESUMO

This paper describes the main results of the JUNO project, a proof of concept developed in the Region of Murcia in Spain, where a smart assistant robot with capabilities for smart navigation and natural human interaction has been developed and deployed, and it is being validated in an elderly institution with real elderly users. The robot is focused on helping people carry out cognitive stimulation exercises and other entertainment activities since it can detect and recognize people, safely navigate through the residence, and acquire information about attention while users are doing the mentioned exercises. All the information could be shared through the Cloud, if needed, and health professionals, caregivers and relatives could access such information by considering the highest standards of privacy required in these environments. Several tests have been performed to validate the system, which combines classic techniques and new Deep Learning-based methods to carry out the requested tasks, including semantic navigation, face detection and recognition, speech to text and text to speech translation, and natural language processing, working both in a local and Cloud-based environment, obtaining an economically affordable system. The paper also discusses the limitations of the platform and proposes several solutions to the detected drawbacks in this kind of complex environment, where the fragility of users should be also considered.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Idoso , Robótica/métodos , Computação em Nuvem , Processamento de Linguagem Natural , Exercício Físico
11.
Cell Mol Neurobiol ; 43(1): 265-281, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34988761

RESUMO

Studies have suggested aminochrome as an endogenous neurotoxin responsible for the dopaminergic neuron degeneration in Parkinson's disease (PD). However, neuroinflammation, an important alteration in PD pathogenesis, has been strictly induced in vitro by aminochrome. The aim of this study was to characterize the neuroinflammation induced in vivo by aminochrome. Wistar rats (male, 250-270 g) received a unilateral single dose by stereotaxic injection of saline into three sites in the striatum in the negative control group, or 32 nmol 6-hydroxydopamine (6-OHDA) in the positive control, or 6 nmol aminochrome. After 14 days, histological and molecular analyses were performed. We observed by immunofluorescence that aminochrome, as well as 6-OHDA, induced an increase in the number of Iba-1+ cells and in the number of activated (Iba-1+/ CD68+) microglia. An increase in the number of S100b+ cells and in the GFAP expression were also evidenced in the striatum and the SNpc of animals from aminochrome and positive control group. Dopaminergic neuronal loss was marked by reduction of TH+ cells and confirmed with reduction in the number of Nissl-stained neurons in the SNpc of rats from aminochrome and positive control groups. In addition, we observed by qPCR that aminocrhome induced an increase in the levels of IL-1ß, TNF-α, NLRP3, CCL5 and CCR2 mRNA in the SNpc. This work provides the first evidence of microgliosis, astrogliosis and neuroinflammation induced by aminochrome in an in vivo model. Since aminochrome is an endogenous molecule derived from dopamine oxidation present in the targeted neurons in PD, these results reinforce the potential of aminochrome as a useful preclinical model to find anti-inflammatory and neuroprotective drugs for PD. Aminochrome induced dopaminergic neuronal loss, microglial activation, astroglial activation and neuroinflammation marked by an increase in NLRP3, IL1ß, TNF-α, CCL2, CCL5 and CCR2.


Assuntos
Fármacos Neuroprotetores , Doença de Parkinson , Ratos , Masculino , Animais , Doença de Parkinson/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/metabolismo , Ratos Wistar , Oxidopamina , Doenças Neuroinflamatórias , Dopamina/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neurônios Dopaminérgicos/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/metabolismo , Modelos Animais de Doenças , Microglia/metabolismo
12.
Aging Clin Exp Res ; 35(1): 1-7, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36287324

RESUMO

BACKGROUND: Centenarians often represent one of the best examples of aging successfully. However, the role of body composition or hydration status assessed with bioelectrical impedance analysis (BIA) is poorly explored in this population. Therefore, the aim of this systematic review was to better understand the use and the role of BIA for evaluating body composition and hydration status in centenarians. METHODS: We conducted a systematic review of the literature up to the 1st of May, 2022 for published articles providing data on BIA to evaluate body composition parameters or hydration status in centenarians. Data were summarized descriptively because a meta-analysis was not possible due to the scarcity of available studies. RESULTS: Among 2222 articles screened, four were eligible including 291 centenarians (mean age: 100.5 years) who were mainly women (88%). In one study, BIA overestimated fat-free mass and underestimated fat mass when compared to deuterium oxide dilution. Another study carried out in Italy including 14 centenarians found a significant correlation between BIA and fat-free mass evaluated using anthropometric tools. In one study, BIA showed a significant agreement with anthropometric measures of fat mass. In the same sample, sarcopenia and dehydration, evaluated with BIA, had a high prevalence. CONCLUSION: BIA may be used for assessing body composition in centenarians, but research is limited to a few studies suggesting the need of future research in this area.


Assuntos
Composição Corporal , Centenários , Idoso de 80 Anos ou mais , Humanos , Feminino , Masculino , Impedância Elétrica , Antropometria , Envelhecimento , Índice de Massa Corporal , Absorciometria de Fóton
13.
Glob Heart ; 17(1): 63, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36199562

RESUMO

Background: There is an upsurge of cardiovascular diseases (CVDs) in sub-Saharan Africa (SSA). Irrespective of biological sex, gender-related factors could be the precursor of these conditions. Objective: To examine the associations between biological sex, gender-related variables, and cardiovascular health (CVH) risk factors in SSA countries. Methods: We used data from the STEPwise approach to surveillance of risk factors for non-communicable disease survey, conducted in adults from Ghana, Gambia, Mali, Guinea, and Botswana. The main outcome was CVH, measured through the health index with values ranging from 0 (worst) to 5 (best or ideal) CVH. Multivariable logistic regression was applied to determine the gender-related factors related to poorer CVH (index less than 4). Results: Data included 15,356 adults (61.4% females, mean age 36.9 years). The prevalence of hypertension (21.6% vs. 13.8%) and overweight/obesity (48.3% vs. 27.5%) was higher among females as compared to males. Females were more likely to be unemployed (17.3% vs. 9.7%) or reported unpaid work (36.8% vs. 15.2%). Overall, females showed worse CVH than males (ORfemale = 0.95, 95% CI:0.91-0.99). Being married was associated with better CVH compared with being single, more so for males (ORmale = 1.09, 95% CI:0.96-1.24, pinteraction < 0.01). Males with unpaid work (ORmale = 1.28, 95% CI:1.12-1.47) had better CVH than their unpaid female counterparts (ORfemale = 1.08, 95% CI:1.01-1.17). Conclusion: In SSA populations, being female was associated with poorer CVH given the disproportionate burden of hypertension and overweight/obesity. Gender-related factors such as marital status and unpaid work were associated with better CVH in males compared to females.


Assuntos
Doenças Cardiovasculares , Hipertensão , Adulto , Botsuana/epidemiologia , Doenças Cardiovasculares/epidemiologia , Feminino , Gâmbia , Gana/epidemiologia , Guiné , Nível de Saúde , Humanos , Hipertensão/epidemiologia , Masculino , Mali , Obesidade/epidemiologia , Sobrepeso , Fatores de Risco
14.
Front Cardiovasc Med ; 9: 916194, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003909

RESUMO

Cardio-pulmonary diseases, which were once regarded as a man's illness, have been one of the leading causes of morbidity and mortality for both men and women in many countries in recent years. Both gender and sex influence the functional and structural changes in the human body and therefore play an important role in disease clinical manifestation, treatment choice, and/or response to treatment and prognosis of health outcomes. The gender dimension integrates sex and gender analysis in health sciences and medical research, however, it is still relatively overlooked suggesting the need for empowerment in the medical research community. Latest advances in the field of cardiovascular research have provided supportive evidence that the application of biological variables of sex has led to the understanding that heart disease in females may have different pathophysiology compared to males, particularly in younger adults. It has also resulted in new diagnostic techniques and a better understanding of symptomatology, while gender analysis has informed more appropriate risk stratification and prevention strategies. The existing knowledge in the pulmonary field shows the higher prevalence of pulmonary disorders among females, however, the role of gender as a socio-cultural construct has yet to be explored for the implementation of targeted interventions. The purpose of this review is to introduce the concept of gender dimension and its importance for the cardiopulmonary continuum with a focus on shared pathophysiology and disease presentation in addition to interrelation with chronic kidney disease. The review presents basic knowledge of what gender dimension means, and the application of sex and gender aspects in cardiovascular medicine with a specific focus on early pulmonary development, pulmonary hypertension, and chronic obstructive pulmonary disease (COPD). Early vascular aging and inflammation have been presented as a potential pathophysiological link, with further interactions between the cardiopulmonary continuum and chronic kidney disease. Finally, implications for potential future research have been provided to increase the impact of gender dimension on research excellence that would add value to everybody, foster toward precision medicine and ultimately improve human health.

15.
Cells ; 11(9)2022 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-35563810

RESUMO

Human ageing can be characterized by a profile of circulating microRNAs (miRNAs), which are potentially predictors of biological age. They can be used as a biomarker of risk for age-related inflammatory outcomes, and senescent endothelial cells (ECs) have emerged as a possible source of circulating miRNAs. In this paper, a panel of four circulating miRNAs including miR-146a-5p, miR-126-3p, miR-21-5p, and miR-181a-5p, involved in several pathways related to inflammation, and ECs senescence that seem to be characteristic of the healthy ageing phenotype. The circulating levels of these miRNAs were determined in 78 healthy subjects aged between 22 to 111 years. Contextually, extracellular miR-146a-5p, miR-126-3p, miR-21-5p, and miR-181a-5p levels were measured in human ECs in vitro model, undergoing senescence. We found that the levels of the four miRNAs, using ex vivo and in vitro models, progressively increase with age, apart from ultra-centenarians that showed levels comparable to those measured in young individuals. Our results contribute to the development of knowledge regarding the identification of miRNAs as biomarkers of successful and unsuccessful ageing. Indeed, they might have diagnostic/prognostic relevance for age-related diseases.


Assuntos
MicroRNA Circulante , MicroRNAs , Idoso de 80 Anos ou mais , Envelhecimento/genética , Biomarcadores , Centenários , MicroRNA Circulante/genética , Células Endoteliais , Humanos , Aprendizado de Máquina , MicroRNAs/genética
16.
Food Funct ; 13(11): 6306-6316, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35611932

RESUMO

Gut microbiota alteration (gut dysbiosis) occurs during the onset and progression of Parkinson's disease. Gut dysbiosis biomarkers could be relevant to prodromal disease. Urolithins, anti-inflammatory metabolites produced from some dietary polyphenols by specific gut microbial ecologies (urolithin metabotypes), have been proposed as biomarkers of gut microbiota composition and functionality. However, this has not been explored in Parkinson's disease patients. The current study aimed to assess associations between urolithin metabotypes, gut dysbiosis and disease severity in Parkinson's disease patients. Participants (52 patients and 117 healthy controls) provided stool samples for microbiota sequencing and urine samples for urolithin profiling before and after consuming 30 g of walnuts for three days. Data on demographics, medication, disease duration and Hoehn and Yahr disease stage were collected. We observed a significant gradual increase of urolithin non-producers (metabotype-0) as the disease severity increased. The gut microbiome of metabotype-0 patients and patients with the greatest severity was characterized by a more altered bacterial composition, i.e., increased pro-inflammatory Enterobacteriaceae and reduced protective bacteria against autoimmune and inflammatory processes, including butyrate and urolithin-producing bacteria (Lachnospiraceae members and Gordonibacter). Besides, their microbiome was characterized by predictive functions of lipopolysaccharide biosynthesis and metabolism of glutathione, cysteine and methionine that could indirectly reflect the gut pro-inflammatory status. Urolithin detection in urine is a feasible, non-invasive and fast approach that can reflect gut microbiome dysbiosis and intestinal inflammation in Parkinson's disease patients. Our current study could provide novel strategies for improving diagnostics, and for preventing and treating disease progression in microbiota-based interventions.


Assuntos
Microbioma Gastrointestinal , Juglans , Doença de Parkinson , Bactérias/genética , Bactérias/metabolismo , Biomarcadores/metabolismo , Disbiose , Humanos , Juglans/metabolismo
17.
J Glob Health ; 12: 04020, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35265330

RESUMO

Background: Sex and gender-based differences in cardiovascular health (CVH) has been explored in the context of high-income countries. However, these relationships have not been examined in low- and middle-income countries. The main aim of this study was to examine how sex and gender-related factors are associated with cardiovascular risk factors of people in South Asian countries. Methods: We conducted a retrospective analysis of the World Health Organization's "STEPwise approach to surveillance of risk factors for non-communicable disease" or "STEPS" from six South Asian countries, surveys conducted between 2014-2019. The main outcomes were CVH as measured by a composite measure of STEPS-HEART health index (smoking, physical activity, fruit and vegetable consumption, overweight/obesity, diabetes and hypertension), values ranging from 0 (worst) to 6 (best or ideal) and self-reported occurrence of cardiovascular disease (ie, heart attack and stroke). Multivariate linear and logistic regression models were performed. Multiple imputation with chained equations was performed. Results: The final analytic sample consisted of 33 106 participants (57.5% females). The mean STEPS-HEART index score in the South Asian population was 3.43 [SD: 0.92]. Female sex (ß: 0.05, 95% confidence interval (CI) = 0.01-0.08, P < 0.05) was significantly associated with better CVH compared to males. Being married (ßmale = -0.30, 95% CI = -0.37, -0.23 vs ßfemale = -0.23, 95% CI = -0.29, -0.17; P < 0.001) and having a household size ≥5 (ßmale = -0.15, 95% CI = -0.24, -0.06 vs ßfemale = -0.11, 95% CI = -0.16, -0.04; P < 0.01) were associated with poorer CVH, more so in males. Being married was also associated with high risk of CVD (ORmale = 2.54, 95% CI = 1.68-3.86, P < 0.001 vs ORfemale = 1.19, 95% CI = 0.84-1.68, P = 0.31), significant in males. Conclusions: Among the South Asian population, being female may be advantageous in having an ideal CVH. However, gender-related factors such as marital status and large household size were associated with poorer CVH and greater risk of CVD, regardless of sex.


Assuntos
Doenças Cardiovasculares , Nível de Saúde , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Organização Mundial da Saúde
18.
Brain ; 145(3): 1001-1017, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35285474

RESUMO

Synucleinopathies encompass several neurodegenerative diseases, which include Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. These diseases are characterized by the deposit of α-synuclein aggregates in intracellular inclusions in neurons and glial cells. Unlike Parkinson's disease and dementia with Lewy bodies, where aggregates are predominantly neuronal, multiple system atrophy is associated with α-synuclein cytoplasmic inclusions in oligodendrocytes. Glial cytoplasmic inclusions are the pathological hallmark of multiple system atrophy and are associated with neuroinflammation, modest demyelination and, ultimately, neurodegeneration. To evaluate the possible pathogenic role of glial cytoplasmic inclusions, we inoculated glial cytoplasmic inclusion-containing brain fractions obtained from multiple system atrophy patients into the striatum of non-human primates. After a 2-year in vivo phase, extensive histochemical and biochemical analyses were performed on the whole brain. We found loss of both nigral dopamine neurons and striatal medium spiny neurons, as well as loss of oligodendrocytes in the same regions, which are characteristics of multiple system atrophy. Furthermore, demyelination, neuroinflammation and α-synuclein pathology were also observed. These results show that the α-synuclein species in multiple system atrophy-derived glial cytoplasmic inclusions can induce a pathological process in non-human primates, including nigrostriatal and striatofugal neurodegeneration, oligodendroglial cell loss, synucleinopathy and gliosis. The present data pave the way for using this experimental model for MSA research and therapeutic development.


Assuntos
Doenças Desmielinizantes , Doença por Corpos de Lewy , Atrofia de Múltiplos Sistemas , Doença de Parkinson , Sinucleinopatias , Animais , Encéfalo/patologia , Doenças Desmielinizantes/patologia , Humanos , Corpos de Inclusão/metabolismo , Doença por Corpos de Lewy/patologia , Atrofia de Múltiplos Sistemas/patologia , Doença de Parkinson/patologia , alfa-Sinucleína/metabolismo
19.
Neuroscientist ; 28(6): 530-542, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-33583239

RESUMO

It has been more than 200 years since James Parkinson made the first descriptions of the disease that bears his name. Since then, knowledge about Parkinson's disease has been improved, and its pathophysiology, diagnosis, and treatments are well described in the scientific and medical literature. However, there is no way to prevent the disease from its progressive nature yet and only its symptoms can be minimized. It is known that the process of neurodegeneration begins before the onset of motor signs and symptoms of the disease, when diagnosis is usually made. Therefore, recognizing manifested non-motor symptoms can make an early diagnosis possible and lead to a better understanding of the disease. Autonomic dysfunctions are important non-motor manifestations of Parkinson's disease and affect the majority of patients. Importantly, heart failure is the third leading cause of death in people suffering from Parkinson's disease. Several evidences have shown the correlation between Parkinson's disease and the preexistence of cardiovascular diseases. Therefore, cardiovascular monitoring and identification of its dysfunctions can have a prodromal role for Parkinson's disease. This review presents studies of the literature that can lead to a better understanding of Parkinson's disease with special attention to its relation to heart and cardiovascular parameters.


Assuntos
Doenças do Sistema Nervoso Autônomo , Cardiopatias , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doenças do Sistema Nervoso Autônomo/etiologia , Doenças do Sistema Nervoso Autônomo/diagnóstico , Cardiopatias/complicações
20.
Cell Mol Neurobiol ; 42(5): 1283-1300, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33387119

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder marked primarily by motor symptoms such as rigidity, bradykinesia, postural instability and resting tremor associated with dopaminergic neuronal loss in the Substantia Nigra pars compacta (SNpc) and deficit of dopamine in the basal ganglia. These motor symptoms can be preceded by pre-motor symptoms whose recognition can be useful to apply different strategies to evaluate risk, early diagnosis and prevention of PD progression. Although clinical characteristics of PD are well defined, its pathogenesis is still not completely known, what makes discoveries of therapies capable of curing patients difficult to be reached. Several theories about the cause of idiopathic PD have been investigated and among them, the key role of inflammation, microglia and the inflammasome in the pathogenesis of PD has been considered. In this review, we describe the role and relation of both the inflammasome and microglial activation with the pathogenesis, symptoms, progression and the possibilities for new therapeutic strategies in PD.


Assuntos
Inflamassomos , Doença de Parkinson , Humanos , Inflamação/patologia , Microglia/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Doença de Parkinson/patologia
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