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1.
Phys Med ; 89: 80-92, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34352679

RESUMO

MR fingerprinting (MRF) is an innovative approach to quantitative MRI. A typical disadvantage of dictionary-based MRF is the explosive growth of the dictionary as a function of the number of reconstructed parameters, an instance of the curse of dimensionality, which determines an explosion of resource requirements. In this work, we describe a deep learning approach for MRF parameter map reconstruction using a fully connected architecture. Employing simulations, we have investigated how the performance of the Neural Networks (NN) approach scales with the number of parameters to be retrieved, compared to the standard dictionary approach. We have also studied optimal training procedures by comparing different strategies for noise addition and parameter space sampling, to achieve better accuracy and robustness to noise. Four MRF sequences were considered: IR-FISP, bSSFP, IR-FISP-B1, and IR-bSSFP-B1. A comparison between NN and the dictionary approaches in reconstructing parameter maps as a function of the number of parameters to be retrieved was performed using a numerical brain phantom. Results demonstrated that training with random sampling and different levels of noise variance yielded the best performance. NN performance was at least as good as the dictionary-based approach in reconstructing parameter maps using Gaussian noise as a source of artifacts: the difference in performance increased with the number of estimated parameters because the dictionary method suffers from the coarse resolution of the parameter space sampling. The NN proved to be more efficient in memory usage and computational burden, and has great potential for solving large-scale MRF problems.


Assuntos
Aprendizado Profundo , Processamento de Imagem Assistida por Computador , Algoritmos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Imagens de Fantasmas
2.
Cytokine ; 148: 155628, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34411989

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a potentially life-threatening disease, defined as Coronavirus Disease 19 (COVID-19). The most common signs and symptoms of this pathological condition include cough, fever, shortness of breath, and sudden onset of anosmia, ageusia, or dysgeusia. The course of COVID-19 is mild or moderate in more than 80% of cases, but it is severe or critical in about 14% and 5% of infected subjects respectively, with a significant risk of mortality. SARS-CoV-2 related infection is characterized by some pathogenetic events, resembling those detectable in other pathological conditions, such as sepsis and severe acute pancreatitis. All these syndromes are characterized by some similar features, including the coexistence of an exuberant inflammatory- as well as an anti-inflammatory-response with immune depression. Based on current knowledge concerning the onset and the development of acute pancreatitis and sepsis, we have considered these syndromes as a very interesting paradigm for improving our understanding of pathogenetic events detectable in patients with COVID-19. The aim of our review is: 1)to examine the pathogenetic mechanisms acting during the emergence of inflammatory and anti-inflammatory processes in human pathology; 2)to examine inflammatory and anti-inflammatory events in sepsis, acute pancreatitis, and SARS-CoV-2 infection and clinical manifestations detectable in patients suffering from these syndromes also according to the age and gender of these individuals; as well as to analyze the possible common and different features among these pathological conditions; 3)to obtain insights into our knowledge concerning COVID-19 pathogenesis. This approach may improve the management of patients suffering from this disease and it may suggest more effective diagnostic approaches and schedules of therapy, depending on the different phases and/or on the severity of SARS-CoV-2 infection.


Assuntos
Envelhecimento/patologia , COVID-19/patologia , Pancreatite/patologia , Sepse/patologia , Caracteres Sexuais , COVID-19/imunologia , COVID-19/virologia , Feminino , Humanos , Masculino , SARS-CoV-2
3.
Blood Transfus ; 2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34369871

RESUMO

BACKGROUND: We evaluated neurotrophin (NF) levels and their impact on in vitro cell wound healing in eye drops from differently prepared blood sources (cord blood [CB], and peripheral blood [PB]) in the same donor, to avoid intrasubject biological variability. MATERIALS AND METHODS: Twenty healthy adult donor PB samples, and twenty CB samples acquired at the time of delivery were processed to obtain serum (S), platelet-rich plasma (PRP), platelet-poor plasma (PPP), and S retrieved from PRP after activation with Ca-gluconate (PRP-R). The levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), glial-derived neurotrophic factor (GDNF), fibroblast growth factor (FGF), and epidermal growth factor (EGF) were assessed with a Luminex xMAP (Luminex Corporation), and by using multikine kits from R&D system, and were statistically analysed in the eight different preparations. The impact of S, PRP, PPP, PRP-R from both sources on a cell line responding to NF supplementation (MIO-M1, UCL Institute of Ophthalmology, London, UK) was tested with a scratch wound assay, and analysed by IncuCyte S3 equipment. RESULTS: All the preparations from CB showed higher NF levels, except for BDNF where no difference was found as compared to PB. PRP showed higher NF levels with respect to S, PPP and PRP-R in this decreasing order. Younger donors in PB contributed with higher NF levels. The scratch assay showed different cell migration results, with a complete wound closure only recorded with the supplementation of CB-S, and a progressive reduction by using PRP, PRP-R, and PPP from both sources. DISCUSSION: Protocols of preparation and choice of blood source determine different NF levels in the final products. The therapeutic use of a natural neurotrophin pool from blood sources might have a clinical impact in several different settings. Efforts are needed to standardise the manufacturing and the product content in order to establish and modulate the posology of the final supplementation.

5.
Entropy (Basel) ; 23(3)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652826

RESUMO

Cellular contacts modify the way cells migrate in a cohesive group with respect to a free single cell. The resulting motion is persistent and correlated, with cells' velocities self-aligning in time. The presence of a dense agglomerate of cells makes the application of single particle tracking techniques to define cells dynamics difficult, especially in the case of phase contrast images. Here, we propose an original pipeline for the analysis of phase contrast images of the wound healing scratch assay acquired in time-lapse, with the aim of extracting single particle trajectories describing the dynamics of the wound closure. In such an approach, the membrane of the cells at the border of the wound is taken as a unicum, i.e., the wound edge, and the dynamics is described by the stochastic motion of an ensemble of points on such a membrane, i.e., pseudo-particles. For each single frame, the pipeline of analysis includes: first, a texture classification for separating the background from the cells and for identifying the wound edge; second, the computation of the coordinates of the ensemble of pseudo-particles, chosen to be uniformly distributed along the length of the wound edge. We show the results of this method applied to a glioma cell line (T98G) performing a wound healing scratch assay without external stimuli. We discuss the efficiency of the method to assess cell motility and possible applications to other experimental layouts, such as single cell motion. The pipeline is developed in the Python language and is available upon request.

6.
Eur J Dermatol ; 31(1): 55-59, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648913

RESUMO

BACKGROUND: Since December 2019, the global population has been experiencing an unprecedented challenge due to Corona virus disease (COVID-19). A pandemic was declared by the World Health Organization on March 11th 2020, with an escalation of new cases worldwide. Dermatology units experienced a reorganization of regular activity, also providing clinical diagnosis and medical assistance to COVID-19-positive patients who developed cutaneous manifestations. OBJECTIVE: To evaluate the impact of the COVID-19 pandemic on Italian dermatologic clinical practice. MATERIALS & METHODS: This was a prospective online survey, consisting of a questionnaire with 35 multiple-choice questions uploaded on the website of the Italian Society of Dermatology and Venereology - SIDeMaST. RESULTS: A total of 136 dermatologists, 78 women (57%) and 58 men (43%), participated in the survey. The mean age was 58 ± 14 years. In total, 60% of participants reported an impact of the pandemic on their practice, in most cases consisting of a remarkable reduction in routine clinical activity (58%). Concern regarding possible infection was evaluated with a score ranging from 0 (no concern) to 5 (extremely concerned): the fear of becoming infected was high (≥3 in 40%), as was the fear of infecting families, colleagues or patients (≥3 points in 45%). CONCLUSION: The COVID-19 pandemic is having a strong impact on dermatology practice in Italy. The identification of critical points may help scientific societies to improve the clinical scenario and create specific strategies to overcome the emergency.


Assuntos
COVID-19/epidemiologia , Dermatologia/organização & administração , Padrões de Prática Médica , COVID-19/transmissão , Dermatologistas/psicologia , Medo , Feminino , Pesquisas sobre Serviços de Saúde , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Prospectivos , Fatores de Risco , SARS-CoV-2 , Dermatopatias Virais/diagnóstico , Dermatopatias Virais/terapia
7.
J Clin Oncol ; 39(11): 1223-1233, 2021 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-33539200

RESUMO

PURPOSE: Recurrently mutated genes and chromosomal abnormalities have been identified in myelodysplastic syndromes (MDS). We aim to integrate these genomic features into disease classification and prognostication. METHODS: We retrospectively enrolled 2,043 patients. Using Bayesian networks and Dirichlet processes, we combined mutations in 47 genes with cytogenetic abnormalities to identify genetic associations and subgroups. Random-effects Cox proportional hazards multistate modeling was used for developing prognostic models. An independent validation on 318 cases was performed. RESULTS: We identify eight MDS groups (clusters) according to specific genomic features. In five groups, dominant genomic features include splicing gene mutations (SF3B1, SRSF2, and U2AF1) that occur early in disease history, determine specific phenotypes, and drive disease evolution. These groups display different prognosis (groups with SF3B1 mutations being associated with better survival). Specific co-mutation patterns account for clinical heterogeneity within SF3B1- and SRSF2-related MDS. MDS with complex karyotype and/or TP53 gene abnormalities and MDS with acute leukemia-like mutations show poorest prognosis. MDS with 5q deletion are clustered into two distinct groups according to the number of mutated genes and/or presence of TP53 mutations. By integrating 63 clinical and genomic variables, we define a novel prognostic model that generates personally tailored predictions of survival. The predicted and observed outcomes correlate well in internal cross-validation and in an independent external cohort. This model substantially improves predictive accuracy of currently available prognostic tools. We have created a Web portal that allows outcome predictions to be generated for user-defined constellations of genomic and clinical features. CONCLUSION: Genomic landscape in MDS reveals distinct subgroups associated with specific clinical features and discrete patterns of evolution, providing a proof of concept for next-generation disease classification and prognosis.


Assuntos
Genômica/métodos , Síndromes Mielodisplásicas/classificação , Feminino , Humanos , Masculino , Síndromes Mielodisplásicas/genética , Prognóstico , Estudos Retrospectivos
8.
BMC Bioinformatics ; 22(1): 60, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33563206

RESUMO

BACKGROUND: Current high-throughput technologies-i.e. whole genome sequencing, RNA-Seq, ChIP-Seq, etc.-generate huge amounts of data and their usage gets more widespread with each passing year. Complex analysis pipelines involving several computationally-intensive steps have to be applied on an increasing number of samples. Workflow management systems allow parallelization and a more efficient usage of computational power. Nevertheless, this mostly happens by assigning the available cores to a single or few samples' pipeline at a time. We refer to this approach as naive parallel strategy (NPS). Here, we discuss an alternative approach, which we refer to as concurrent execution strategy (CES), which equally distributes the available processors across every sample's pipeline. RESULTS: Theoretically, we show that the CES results, under loose conditions, in a substantial speedup, with an ideal gain range spanning from 1 to the number of samples. Also, we observe that the CES yields even faster executions since parallelly computable tasks scale sub-linearly. Practically, we tested both strategies on a whole exome sequencing pipeline applied to three publicly available matched tumour-normal sample pairs of gastrointestinal stromal tumour. The CES achieved speedups in latency up to 2-2.4 compared to the NPS. CONCLUSIONS: Our results hint that if resources distribution is further tailored to fit specific situations, an even greater gain in performance of multiple samples pipelines execution could be achieved. For this to be feasible, a benchmarking of the tools included in the pipeline would be necessary. It is our opinion these benchmarks should be consistently performed by the tools' developers. Finally, these results suggest that concurrent strategies might also lead to energy and cost savings by making feasible the usage of low power machine clusters.


Assuntos
Biologia Computacional , Sequenciamento de Nucleotídeos em Larga Escala , Software , Sequenciamento Completo do Exoma , Sequenciamento de Cromatina por Imunoprecipitação , Biologia Computacional/métodos , Sequenciamento Completo do Exoma/normas , Fluxo de Trabalho
9.
Br J Nutr ; 125(3): 275-293, 2021 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32703328

RESUMO

In December 2019, a novel human-infecting coronavirus, named Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), was recognised to cause a pneumonia epidemic outbreak with different degrees of severity in Wuhan, Hubei Province in China. Since then, this epidemic has spread worldwide; in Europe, Italy has been involved. Effective preventive and therapeutic strategies are absolutely required to block this serious public health concern. Unfortunately, few studies about SARS-CoV-2 concerning its immunopathogenesis and treatment are available. On the basis of the assumption that the SARS-CoV-2 is genetically related to SARS-CoV (about 82 % of genome homology) and that its characteristics, like the modality of transmission or the type of the immune response it may stimulate, are still poorly known, a literature search was performed to identify the reports assessing these elements in patients with SARS-CoV-induced infection. Therefore, we have analysed: (1) the structure of SARS-CoV-2 and SARS-CoV; (2) the clinical signs and symptoms and pathogenic mechanisms observed during the development of acute respiratory syndrome and the cytokine release syndrome; (3) the modification of the cell microRNome and of the immune response in patients with SARS infection; and (4) the possible role of some fat-soluble compounds (such as vitamins A, D and E) in modulating directly or indirectly the replication ability of SARS-CoV-2 and host immune response.


Assuntos
Antivirais/uso terapêutico , COVID-19/terapia , COVID-19/virologia , Fatores Imunológicos/uso terapêutico , SARS-CoV-2 , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Regulação Viral da Expressão Gênica/fisiologia , Genoma Viral , Humanos , Desnutrição Aguda Grave/tratamento farmacológico , Desnutrição Aguda Grave/etiologia , Índice de Gravidade de Doença , Proteínas Virais , Vitaminas/administração & dosagem , Vitaminas/uso terapêutico
10.
Nutrients ; 12(11)2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33266447

RESUMO

BACKGROUND AND AIM: A state of chronic, subclinical inflammation known as inflammaging is present in elderly people and represents a risk factor for all age-related diseases. Dietary supplementation with ad hoc fortified foods seems an appealing strategy to counteract inflammaging. The purpose of this study was to test the efficacy of elderly-tailored fortified milk on inflammaging and different health parameters. METHODS: A double-blind randomized cross-over study was performed on forty-eight volunteers aged 63-80 years. The fortified milk was enriched with ω-3 polyunsaturated fatty acids (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA), vitamins (25-hydroxyvitamin D, E, C, B6, B9, B12), and trace elements (zinc, selenium). The two intervention periods lasted for 12 weeks, with a 16-week washout intermission. RESULTS: Compared to placebo, the consumption of fortified milk increased the circulating levels of different micronutrients, including vitamins and the ω-3 index of erythrocyte membranes. Conversely, it reduced the amount of arachidonic acid, homocysteine, and ω-6/ω-3 ratio. CONCLUSION: Twelve-week daily consumption of adhoc fortified milk has an overall positive impact on different health parameters related to inflammaging in the elderly.


Assuntos
Ácidos Graxos Ômega-3/administração & dosagem , Alimentos Fortificados , Inflamação/epidemiologia , Leite , Complexo Vitamínico B/administração & dosagem , Vitamina D/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Animais , Estudos Cross-Over , Método Duplo-Cego , Feminino , Nível de Saúde , Humanos , Masculino , Micronutrientes/sangue , Pessoa de Meia-Idade , Placebos , Vitamina D/administração & dosagem
11.
PLoS One ; 15(10): e0237207, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33125392

RESUMO

In this work we propose an index to estimate the gut microbiota biodiversity using a modeling approach with the aim of describing its relationship with health and aging. The gut microbiota, a complex ecosystem that links nutrition and metabolism, has a pervasive effect on all body organs and systems, undergoes profound changes with age and life-style, and substantially contributes to the pathogenesis of age-related diseases. For these reasons, the gut microbiota is a suitable candidate for assessing and quantifying healthy aging, i.e. the capability of individuals to reach an advanced age, avoiding or postponing major age-related diseases. The importance of the gut microbiota in health and aging has been proven to be related not only to its taxonomic composition, but also to its ecological properties, namely its biodiversity. Following an ecological approach, here we intended to characterize the relationship between the gut microbiota biodiversity and healthy aging through the development a parsimonious model of gut microbiota from which biodiversity can be estimated. We analysed publicly available metagenomic data relative to subjects of different ages, countries, nutritional habits and health status and we showed that a hybrid niche-neutral model well describes the observed patterns of bacterial relative abundance. Moreover, starting from such ecological modeling, we derived an estimate of the gut microbiota biodiversity that is consistent with classical indices, while having a higher statistical power. This allowed us to unveil an increase of the gut microbiota biodiversity during aging and to provide a good predictor of health status in old age, dependent on life-style and aging disorders.


Assuntos
Envelhecimento , Microbioma Gastrointestinal , Modelos Biológicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Envelhecimento/fisiologia , Biodiversidade , Criança , Pré-Escolar , Bases de Dados de Ácidos Nucleicos , Feminino , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Nível de Saúde , Envelhecimento Saudável/genética , Envelhecimento Saudável/fisiologia , Humanos , Lactente , Recém-Nascido , Masculino , Metagenoma , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Adulto Jovem
12.
Sci Rep ; 10(1): 15026, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929164

RESUMO

It is important that antibiotics prescriptions are based on antimicrobial susceptibility data to ensure effective treatment outcomes. The increasing availability of next-generation sequencing, bacterial whole genome sequencing (WGS) can facilitate a more reliable and faster alternative to traditional phenotyping for the detection and surveillance of AMR. This work proposes a machine learning approach that can predict the minimum inhibitory concentration (MIC) for a given antibiotic, here ciprofloxacin, on the basis of both genome-wide mutation profiles and profiles of acquired antimicrobial resistance genes. We analysed 704 Escherichia coli genomes combined with their respective MIC measurements for ciprofloxacin originating from different countries. The four most important predictors found by the model, mutations in gyrA residues Ser83 and Asp87, a mutation in parC residue Ser80 and presence of the qnrS1 gene, have been experimentally validated before. Using only these four predictors in a linear regression model, 65% and 93% of the test samples' MIC were correctly predicted within a two- and a four-fold dilution range, respectively. The presented work does not treat machine learning as a black box model concept, but also identifies the genomic features that determine susceptibility. The recent progress in WGS technology in combination with machine learning analysis approaches indicates that in the near future WGS of bacteria might become cheaper and faster than a MIC measurement.


Assuntos
Antibacterianos/toxicidade , Ciprofloxacina/toxicidade , Farmacorresistência Bacteriana , Genes Bacterianos , Aprendizado de Máquina , DNA Girase/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Concentração Inibidora 50 , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação , Testes de Toxicidade/métodos
13.
Aging Clin Exp Res ; 32(10): 2115-2131, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32865757

RESUMO

BACKGROUND: In December 2019, a novel human-infecting coronavirus, SARS-CoV-2, had emerged. The WHO has classified the epidemic as a "public health emergency of international concern". A dramatic situation has unfolded with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a deficiency in fat-soluble and hydrosoluble vitamins. METHODS: We searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We set them as a paradigm with the purpose to uncover common pathogenetic mechanisms between these pathological conditions and SARS-CoV-2 infection. Furthermore, we searched for studies describing the possible efficacy of vitamins A, D, E, and C in improving the immune system function. RESULTS: SARS-CoV-2 infection induces strong immune system dysfunction characterized by the development of an intense proinflammatory response in the host, and the development of a life-threatening condition defined as cytokine release syndrome (CRS). This leads to acute respiratory syndrome (ARDS), mainly in aged people. High mortality and lethality rates have been observed in elderly subjects with CoV-2-related infection. CONCLUSIONS: Vitamins may shift the proinflammatory Th17-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype. This review discusses the possible activity of vitamins A, D, E, and C in restoring normal antiviral immune system function and the potential therapeutic role of these micronutrients as part of a therapeutic strategy against SARS-CoV-2 infection.


Assuntos
Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/dietoterapia , Infecções por Coronavirus/prevenção & controle , Citocinas/imunologia , Pandemias/prevenção & controle , Pneumonia Viral/dietoterapia , Pneumonia Viral/prevenção & controle , Vitaminas/imunologia , Vitaminas/uso terapêutico , Idoso , Ácido Ascórbico/imunologia , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Betacoronavirus/efeitos dos fármacos , COVID-19 , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Humanos , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , SARS-CoV-2 , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Vitamina A/imunologia , Vitamina A/farmacologia , Vitamina A/uso terapêutico , Vitamina D/imunologia , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Vitamina E/imunologia , Vitamina E/farmacologia , Vitamina E/uso terapêutico , Vitaminas/farmacologia
14.
Gut ; 69(7): 1218-1228, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32066625

RESUMO

OBJECTIVE: Ageing is accompanied by deterioration of multiple bodily functions and inflammation, which collectively contribute to frailty. We and others have shown that frailty co-varies with alterations in the gut microbiota in a manner accelerated by consumption of a restricted diversity diet. The Mediterranean diet (MedDiet) is associated with health. In the NU-AGE project, we investigated if a 1-year MedDiet intervention could alter the gut microbiota and reduce frailty. DESIGN: We profiled the gut microbiota in 612 non-frail or pre-frail subjects across five European countries (UK, France, Netherlands, Italy and Poland) before and after the administration of a 12-month long MedDiet intervention tailored to elderly subjects (NU-AGE diet). RESULTS: Adherence to the diet was associated with specific microbiome alterations. Taxa enriched by adherence to the diet were positively associated with several markers of lower frailty and improved cognitive function, and negatively associated with inflammatory markers including C-reactive protein and interleukin-17. Analysis of the inferred microbial metabolite profiles indicated that the diet-modulated microbiome change was associated with an increase in short/branch chained fatty acid production and lower production of secondary bile acids, p-cresols, ethanol and carbon dioxide. Microbiome ecosystem network analysis showed that the bacterial taxa that responded positively to the MedDiet intervention occupy keystone interaction positions, whereas frailty-associated taxa are peripheral in the networks. CONCLUSION: Collectively, our findings support the feasibility of improving the habitual diet to modulate the gut microbiota which in turn has the potential to promote healthier ageing.


Assuntos
Dieta Mediterrânea , Fragilidade/prevenção & controle , Microbioma Gastrointestinal , Idoso , Europa (Continente) , Feminino , Fragilidade/dietoterapia , Microbioma Gastrointestinal/genética , Nível de Saúde , Humanos , Masculino , Cooperação do Paciente , RNA Ribossômico 16S/genética , Método Simples-Cego
15.
Front Neuroinform ; 14: 611762, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33584238

RESUMO

WISDoM (Wishart Distributed Matrices) is a framework for the quantification of deviation of symmetric positive-definite matrices associated with experimental samples, such as covariance or correlation matrices, from expected ones governed by the Wishart distribution. WISDoM can be applied to tasks of supervised learning, like classification, in particular when such matrices are generated by data of different dimensionality (e.g., time series with same number of variables but different time sampling). We show the application of the method in two different scenarios. The first is the ranking of features associated with electro encephalogram (EEG) data with a time series design, providing a theoretically sound approach for this type of studies. The second is the classification of autistic subjects of the Autism Brain Imaging Data Exchange study using brain connectivity measurements.

16.
J Alzheimers Dis ; 72(3): 911-918, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31658056

RESUMO

BACKGROUND: Elevated peripheral levels of different cytokines and chemokines in subjects with Alzheimer's disease (AD), as compared with healthy controls (HC), have emphasized the role of inflammation in such a disease. Considering the cross-talking between the central nervous system and the periphery, the inflammatory analytes may provide utility as biomarkers to identify AD at earlier stages. OBJECTIVE: Using an advanced statistical approach, we can discriminate the interactive network of cytokines/chemokines and propose a useful tool to follow the progression and evolution of AD, also in light of sex differences. METHODS: A cohort of 289 old-age subjects was screened for cytokine and chemokine profiling, measured in plasma, after a thorough clinical and neuropsychological evaluation. A custom algorithm based on Fisher linear discriminant analysis was applied to ascertain a classification signature able to discriminate HC from mild cognitive impairment (MCI) and AD. RESULTS: We observed that a joint expression of three proteins (a "signature" composed by IFN-α2, IL-1α, TNFα) can discriminate HC from AD with an accuracy of 65.24%. Using this signature on MCI samples, 84.93% of them were classified as "non-HC". Stratifying MCI samples by sex, we observed that 87.23% of women were classified as "non-HC", and only 57.69% of males. Indeed, in a scatter plot of IFN-α2 and IL-1α, the HC group was better separated from MCI and AD in women as compared with men. CONCLUSION: These findings suggest that AD is accompanied by a peripheral inflammatory response that can already be present in MCI subjects, thus providing a mean for detecting this at-risk status and allow an anticipated intervention.


Assuntos
Doença de Alzheimer/sangue , Quimiocinas/sangue , Disfunção Cognitiva/sangue , Citocinas/sangue , Caracteres Sexuais , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Doença de Alzheimer/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Disfunção Cognitiva/diagnóstico , Estudos Transversais , Feminino , Humanos , Masculino
17.
Front Physiol ; 10: 149, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30890946

RESUMO

In this work we present a novel statistical approach to improve the assessment of the adherence to a 1-year nutritional intervention within the framework of the NU-AGE project. This was measured with a single adherence score based on 7-days food records, under limitations on the number of observations per subject and time frame of intervention. The results of the NU-AGE dietary intervention were summarized by variations of the NU-AGE index as described in the NU-AGE protocol. Food and nutrient intake of all participants was assessed by means of 7-days food records at recruitment and after 10 to 14 months of intervention (depending on the subject availability). Sixteen food groups and supplementations covering the dietary goals of the NU-AGE diet have been used to estimate the NU-AGE index before and after the intervention. The 7-days food record is a reliable tool to register food intakes, however, as with other tools used to assess lifestyle dietary compliance, it is affected by uncertainty in this estimation due to the possibility that the observed week is not fully representative of the entire intervention period. Also, due to logistic limitations, the effects of seasonality can never be completely removed. These variabilities, if not accounted for in the index estimation, will reduce the statistical power of the analyses. In this work we discuss a method to assess these uncertainties and thus improve the resulting NU-AGE index. The proposed method is based on Hierarchical Bayesian Models. This model explicitly includes country-specific averages of the NU-AGE index, index variation induced by the dietary intervention, and country based seasonality. This information is used to evaluate the NU-AGE index uncertainty and thus to estimate the "real" NU-AGE index for each subject, both before and after the intervention. These corrections reduce the possibility of misinterpreting measurement variability as real information, improving the power of the statistical tests that are performed with the resulting index. The results suggest that this method is able to reduce the short term and seasonal variability of the measured index in the context of multicenter dietary intervention trials. Using this method to estimate seasonality and variability would allow one to obtain better measurements from the subjects of a study, and be able to simplify the scheduling of diet assessments. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT01754012.

18.
Eur Radiol ; 29(9): 4968-4979, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30715588

RESUMO

OBJECTIVES: The aim of this work was to examine the cross-sectional relationship between body composition (BC) markers for adipose and lean tissue and bone mass, and a wide range of specific inflammatory and adipose-related markers in healthy elderly Europeans. METHODS: A whole-body dual-energy X-ray absorptiometry (DXA) scan was made in 1121 healthy (65-79 years) women and men from five European countries of the "New dietary strategies addressing the specific needs of elderly population for a healthy aging in Europe" project (NCT01754012) cohort to measure markers of adipose and lean tissue and bone mass. Pro-inflammatory (IL-6, IL-6Rα, TNF-α, TNF-R1, TNF-R2, pentraxin 3, CRP, alpha-1-acid glycoprotein, albumin) and anti-inflammatory (IL-10, TGF-ß1) molecules as well as adipose-related markers such as leptin, adiponectin, ghrelin, and resistin were measured by magnetic bead-based multiplex-specific immunoassays and biochemical assays. RESULTS: BC characteristics were different in elderly women and men, and more favorable BC markers were associated with a better adipose-related inflammatory profile, with the exception of skeletal muscle mass index. No correlation was found with the body composition markers and circulating levels of some standard pro- and anti-inflammatory markers like IL-6, pentraxin 3, IL-10, TGF-ß1, TNF-α, IL-6Rα, glycoprotein 130, TNF-α-R1, and TNF-α-R2. CONCLUSIONS: The association between BC and inflammatory and adipose-related biomarkers is crucial in decoding aging and pathophysiological processes, such as sarcopenia. DXA can help in understanding how the measurement of fat and muscle is important, making the way from research to clinical practice. KEY POINTS: • Body composition markers concordantly associated positively or negatively with adipose-related and inflammatory markers, with the exception of skeletal muscle mass index. • No correlation was found with the body composition markers and circulating levels of some standard pro- and anti-inflammatory markers like IL-6, pentraxin 3, IL-10, TGF-ß1, TNF-α, IL-6Rα, gp130, TNF-α-R1, and TNF-α-R2. • Skeletal muscle mass index (SMI) shows a good correlation with inflammatory profile in age-related sarcopenia.


Assuntos
Adiposidade , Composição Corporal , Densidade Óssea , Mediadores da Inflamação/sangue , Inflamação/fisiopatologia , Absorciometria de Fóton , Idoso , Biomarcadores/sangue , Estudos Transversais , Europa (Continente) , Feminino , Humanos , Masculino , Músculo Esquelético/diagnóstico por imagem , Obesidade/fisiopatologia , Sarcopenia/fisiopatologia , Fatores Sexuais
19.
FASEB J ; 33(4): 5168-5180, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30620616

RESUMO

The Sarcolab pilot study of 2 crewmembers, investigated before and after a 6-mo International Space Station mission, has demonstrated the substantial muscle wasting and weakness, along with disruption of muscle's oxidative metabolism. The present work aimed at evaluating the pro/anti-inflammatory status in the same 2 crewmembers (A, B). Blood circulating (c-)microRNAs (miRs), c-proteasome, c-mitochondrial DNA, and cytokines were assessed by real-time quantitative PCR or ELISA tests. Time series analysis was performed ( i.e., before flight and after landing) at 1 and 15 d of recovery (R+1 and R+15, respectively). C-biomarkers were compared with an age-matched control population and with 2-dimensional proteomic analysis of the 2 crewmembers' muscle biopsies. Striking differences were observed between the 2 crewmembers at R+1, in terms of inflamma-miRs (c-miRs-21-5p, -126-3p, and -146a-5p), muscle specific (myo)-miR-206, c-proteasome, and IL-6/leptin, thus making the 2 astronauts dissimilar to each other. Final recovery levels of c-proteasome, c-inflamma-miRs, and c-myo-miR-206 were not reverted to the baseline values in crewmember A. In both crewmembers, myo-miR-206 changed significantly after recovery. Muscle biopsy of astronaut A showed an impressive 80% increase of α-1-antitrypsin, a target of miR-126-3p. These results point to a strong stress response induced by spaceflight involving muscle tissue and the proinflammatory setting, where inflamma-miRs and myo-miR-206 mediate the systemic recovery phase after landing.-Capri, M., Morsiani, C., Santoro, A., Moriggi, M., Conte, M., Martucci, M., Bellavista, E., Fabbri, C., Giampieri, E., Albracht, K., Flück, M., Ruoss, S., Brocca, L., Canepari, M., Longa, E., Di Giulio, I., Bottinelli, R., Cerretelli, P., Salvioli, S., Gelfi, C., Franceschi, C., Narici, M., Rittweger, J. Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a proinflammatory setting.


Assuntos
Inflamação/metabolismo , Proteínas Musculares/metabolismo , Voo Espacial , Astronautas , Biomarcadores/metabolismo , Citocinas/metabolismo , DNA Mitocondrial/metabolismo , Humanos , Inflamação/imunologia , Leptina/metabolismo , MicroRNAs/metabolismo , Músculo Esquelético/metabolismo , Projetos Piloto , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteômica
20.
Front Physiol ; 9: 1693, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555339

RESUMO

Body composition (BC) is an emerging important factor for the characterization of metabolic status. The assessment of BC has been studied in various populations and diseases such as obesity, diabetes, endocrine diseases as well as physiological and paraphysiological conditions such as growth and aging processes, and physical training. A gold standard technique for the assessment of human BC at molecular level is represented by dual-energy X-ray absorptiometry (DXA), which is able to precisely assess the body mass (and areal bone mineral density-aBMD) on a regional and whole-body basis. For the first time, within the framework of the NU-AGE project, BC has been assessed by means of a whole-body DXA scan in 1121 sex-balanced free-living, apparently healthy older adults aged 65-79 years enrolled in 5 European countries (Italy, France, United Kingdom, Netherlands, and Poland). The aim of this analysis is to provide a complete profile of BC in healthy elderly participants from five European countries and to investigate country- and sex-related differences by state-of-the-art DXA technology. To compare BC data collected in different centers, specific indexes and ratios have been used. Non-parametric statistical tests showed sex-specific significant differences in certain BC parameters. In particular, women have higher fat mass (FM) (Fat/Lean mass ratio: by 67%, p < 2.2e-16) and lower lean mass (Lean Mass index: by -18%, p < 2.2e-16) than men. On the other hand, men have higher android FM than women (Android/gynoid FM ratio: by 56%, p < 2.2e-16). Interesting differences also emerged among countries. Polish elderly have higher FM (Fat/Lean mass ratio: by 52%, p < 2.2e-16) and lower lean mass (Skeletal Mass index: by -23%, p < 2.2e-16) than elderly from the other four countries. At variance, French elderly show lower FM (Fat/Lean mass ratio: by -34%, p < 2.2e-16) and higher lean mass (Skeletal Mass index: by 18%, p < 2.2e-16). Moreover, five BC profiles in women and six in men have been identified by a cluster analysis based on BC parameters. Finally, these data can serve as reference for normative average and variability of BC in the elderly populations across Europe.

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