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1.
Ageing Res Rev ; 70: 101391, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34119687

RESUMO

Conformational diseases are caused by the aggregation of misfolded proteins. The risk for such pathologies develops years before clinical symptoms appear, and is higher in people with alpha-1 antitrypsin (AAT) polymorphisms. Thousands of people with alpha-1 antitrypsin deficiency (AATD) are underdiagnosed. Enemy-aggregating proteins may reside in these underdiagnosed AATD patients for many years before a pathology for AATD fully develops. In this perspective review, we hypothesize that the AAT protein could exert a new and previously unconsidered biological effect as an endogenous metal ion chelator that plays a significant role in essential metal ion homeostasis. In this respect, AAT polymorphism may cause an imbalance of metal ions, which could be correlated with the aggregation of amylin, tau, amyloid beta, and alpha synuclein proteins in type 2 diabetes mellitus (T2DM), Alzheimer's and Parkinson's diseases, respectively.

2.
J Public Health Res ; 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34036777

RESUMO

BACKGROUND: Patients at risk of breast cancer are submitted to mammography, resulting in a classification of the lesions following the Breast Imaging Reporting and Data System (BI-RADS®). Due to BI-RADS 3 classification problems and the great uncertainty of the possible evolution of this kind of tumours, the integration of mammographic imaging with other techniques and markers of pathology, as metabolic information, may be advisable. DESIGN AND METHODS: Our study aims to evaluate the possibility to quantify by gas chromatography-mass spectrometry (GC-MS) specific metabolites in the plasma of patients with mammograms classified from BI-RADS 3 to BI-RADS 5, to find similarities or differences in their metabolome. Samples from BI-RADS 3 to 5 patients were compared with samples from a healthy control group. This pilot project aimed at establishing the sensitivity of the metabolomic classification of blood samples of patients undergoing breast radiological analysis and to support a better classification of mammographic cases. RESULTS: Metabolomic analysis revealed a panel of metabolites more abundant in healthy controls, as 3-aminoisobutyric acid, cholesterol, cysteine, stearic, linoleic and palmitic fatty acids. The comparison between samples from BI-RADS 3 and BI-RADS 5 patients, revealed the importance of 4-hydroxyproline, found in higher amount in BI-RADS 3 subjects. CONCLUSION: Although the low sample number did not allow the attainment of high validated statistical models, some interesting data were obtained, revealing the potential of metabolomics for an improvement in the classification of different mammographic lesions.

3.
J Public Health Res ; 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34036778

RESUMO

BACKGROUND: Clot characterization is, to the present days, a multimodal approach: scanning the clot by electron microscopy (SEM) is helpful for the visualization of fibrin structure along with laboratory parameters such as the clot waveform analysis (CWA) and thrombin generation in different settings of clot abnormalities. This study aimed to assess whether the coagulative parameters were consistent with the clot images texture acquired by SEM, and therefore to propose a more generalist and integrative approach to clots classification. DESIGN AND METHODS: In this pilot study, the examined population consists of eight healthy subjects, seven patients affected by Acquired Hemophilia A (AHA) and seven patients treated with Vitamin K Antagonists (VKAs), similar for age and gender. We studied the velocity and acceleration (1st and 2nd derivative of the aPTT) of clot formation (CWA), the thrombin generation, and the clots' scanning by SEM. Images acquired with SEM were then analyzed with the MATLAB software with the "Texture Analysis" methods to perform classification. Among the various texture parameters, we reported Contrast and Energy. RESULTS: Significant differences among healthy subjects, patients with AHA and those treated with VKAs were detected for the coagulative parameters. We found no differences between VKAs and AHA patients. Contrast and energy highlighted a significant difference among the three groups in agreement with the laboratory's parameters. We found no significant differences between VKAs and AHA patients. CONCLUSIONS: The use of SEM, CWA and thrombin generation parameters may be a starting point for studies aimed to demonstrate the general characteristics of clot formation in different clinical conditions with a multiparametric approach.

4.
Eur J Radiol ; 140: 109767, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34000598

RESUMO

Cardiovascular disease (CVD) is associated with high mortality around the world. Prevention and early diagnosis are key targets in reducing the socio-economic burden of CVD. Artificial intelligence (AI) has experienced a steady growth due to technological innovations that have to lead to constant development. Several AI algorithms have been applied to various aspects of CVD in order to improve the quality of image acquisition and reconstruction and, at the same time adding information derived from the images to create strong predictive models. In computed tomography angiography (CTA), AI can offer solutions for several parts of plaque analysis, including an automatic assessment of the degree of stenosis and characterization of plaque morphology. A growing body of evidence demonstrates a correlation between some type of plaques, so-called high-risk plaque or vulnerable plaque, and cardiovascular events, independent of the degree of stenosis. The radiologist must apprehend and participate actively in developing and implementing AI in current clinical practice. In this current overview on the existing AI literature, we describe the strengths, limitations, recent applications, and promising developments of employing AI to plaque characterization with CT.


Assuntos
Doença da Artéria Coronariana , Estenose Coronária , Placa Aterosclerótica , Inteligência Artificial , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Humanos , Placa Aterosclerótica/diagnóstico por imagem , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios X
5.
Comput Biol Med ; 130: 104210, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33550068

RESUMO

COVID-19 has infected 77.4 million people worldwide and has caused 1.7 million fatalities as of December 21, 2020. The primary cause of death due to COVID-19 is Acute Respiratory Distress Syndrome (ARDS). According to the World Health Organization (WHO), people who are at least 60 years old or have comorbidities that have primarily been targeted are at the highest risk from SARS-CoV-2. Medical imaging provides a non-invasive, touch-free, and relatively safer alternative tool for diagnosis during the current ongoing pandemic. Artificial intelligence (AI) scientists are developing several intelligent computer-aided diagnosis (CAD) tools in multiple imaging modalities, i.e., lung computed tomography (CT), chest X-rays, and lung ultrasounds. These AI tools assist the pulmonary and critical care clinicians through (a) faster detection of the presence of a virus, (b) classifying pneumonia types, and (c) measuring the severity of viral damage in COVID-19-infected patients. Thus, it is of the utmost importance to fully understand the requirements of for a fast and successful, and timely lung scans analysis. This narrative review first presents the pathological layout of the lungs in the COVID-19 scenario, followed by understanding and then explains the comorbid statistical distributions in the ARDS framework. The novelty of this review is the approach to classifying the AI models as per the by school of thought (SoTs), exhibiting based on segregation of techniques and their characteristics. The study also discusses the identification of AI models and its extension from non-ARDS lungs (pre-COVID-19) to ARDS lungs (post-COVID-19). Furthermore, it also presents AI workflow considerations of for medical imaging modalities in the COVID-19 framework. Finally, clinical AI design considerations will be discussed. We conclude that the design of the current existing AI models can be improved by considering comorbidity as an independent factor. Furthermore, ARDS post-processing clinical systems must involve include (i) the clinical validation and verification of AI-models, (ii) reliability and stability criteria, and (iii) easily adaptable, and (iv) generalization assessments of AI systems for their use in pulmonary, critical care, and radiological settings.


Assuntos
Inteligência Artificial , Pulmão/diagnóstico por imagem , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Humanos
6.
Drug Dev Res ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33533102

RESUMO

The cytochrome P450 (CYP450) superfamily is responsible for the metabolism of most xenobiotics and pharmacological treatments generally used in clinical settings. Genetic factors as well as environmental determinants acting through fine epigenetic mechanisms modulate the expression of CYP over the lifespan (fetal vs. infancy vs. adult phases) and in diverse organs. In addition, pathological processes might alter the expression of CYP. In this selective review, we sought to summarize the evidence on the expression of CYP focusing on three specific aspects: (a) the anatomical distribution of the expression in body districts relevant in terms of drug pharmacokinetics (liver, gut, and kidney) and pharmacodynamics, focusing for the latter on the brain, since this is the target organ of psychopharmacological agents; (b) the patterns of expression during developmental phases; and (c) the expression of CYP450 enzymes during pathological processes such as cancer. We showed that CYP isoforms show distinct patterns of expression depending on the body district and the specific developmental phases. Of particular relevance for neuropsychopharmacology is the complex regulatory mechanisms that significantly modulate the complexity of the pharmacokinetic regulation, including the concentration of specific CYP isoforms in distinct areas of the brain, where they could greatly affect local substrate and metabolite concentrations of drugs.

7.
Talanta ; 222: 121429, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33167196

RESUMO

To have information on the proteolytic activity of convertases and exo-peptidases on human salivary proteins, this study investigated the relative amounts of the truncated proteoforms in the saliva of preterm newborns and compared them with the relative amounts measured in saliva of at-term newborns, of babies (0-10 years old) and of adults. Results indicated that convertase(s), acting on acidic proline-rich proteins and histatin 3, and carboxypeptidase(s) acting on acidic proline-rich proteins, P-C peptide, histatin 6 and statherin were many folds more active in preterm newborns than in the other groups. Conversely, the aminopeptidase responsible for the removal of the N-terminal Asp residue of statherin was not active in preterm newborns, becoming active only several months after the normal term of delivery. The high activity of convertases determined in preterm newborns suggests that it is required for the molecular events connected to the fetus development, and encourages further studies devoted to the characterization of their specific substrates.


Assuntos
Saliva , Proteínas e Peptídeos Salivares , Adulto , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Exopeptidases , Desenvolvimento Fetal , Humanos , Lactente , Recém-Nascido
8.
Curr Med Chem ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33200694

RESUMO

A significant percentage of costs in pharmaceutical markets is devoted to supplements, due to the confidence of consumers on the beneficial effects of these products. Magnesium is one of the supplements with enduring and increasing popularity. According to what is reported online this metal ion can cure, or prevent, almost all kind of diseases. This review aims at illustrating a series of scientifically demonstrated cases in which magnesium was used in clinical practice. Except for its ordinary use as antacid and laxative, other ascertained uses, reported in scientific literature, consist in helping to treat several diseases such as: nocturnal leg cramps, pre-eclampsia, diabetes, depression, Parkinson's and Alzheimer's disease, hypertension, some types of arrhythmias, asthma, migraine headaches, epilepsy, cerebral haemorrhage, stroke. However, many of these promising uses of magnesium require further studies to define, the involved molecular mechanisms which should help establishing its uses in relation to the prolonged use of supplements.

10.
Cardiovasc Diagn Ther ; 10(4): 1005-1018, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32968657

RESUMO

Carotid artery stenosis (CAS) due to the presence of atherosclerotic plaque (AP) is a frequent medical condition and a known risk factor for stroke, and it is also known from literature that several risk factors promote the AP development, in particular aging, smoke, male sex, hypertension, hyperlipidemia, smoke, diabetes type 1 and 2, and genetic factors. The study of carotid atherosclerosis is continuously evolving: even if the strategies of treatment still depends mainly on the degree of stenosis (DoS) determined by the plaque, in the last years the attention has moved to the study of the plaque components in order to identify the so called "vulnerable" plaque: features like the fibrous cap status and thickness, the volume of the lipid-rich necrotic core and the presence of intraplaque hemorrhage (IPH) are risk factors for plaque rupture, that can be studied with modern imaging techniques. The aim of this review is to give a general overview of the principle histological and imaging features of the subcomponent of carotid AP (CAP), focalizing in particular on the features of CAP of patients affected by hypertension and diabetes (in particular type 2 diabetes mellitus).

11.
Cardiovasc Diagn Ther ; 10(4): 1032-1047, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32968659

RESUMO

The prevention and management of atherosclerosis poses a tough challenge to public health organizations worldwide. Together with myocardial infarction, stroke represents its main manifestation, with up to 25% of all ischemic strokes being caused by thromboembolism arising from the carotid arteries. Therefore, a vast number of publications have focused on the characterization of the culprit lesion, the atherosclerotic plaque. A paradigm shift appears to be taking place at the current state of research, as the attention is gradually moving from the classically defined degree of stenosis to the identification of features of plaque vulnerability, which appear to be more reliable predictors of recurrent cerebrovascular events. The present review will offer a perspective on the present state of research in the field of carotid atherosclerotic disease, focusing on the imaging modalities currently used in the study of the carotid plaque and the impact that such diagnostic means are having in the clinical setting.

12.
Comput Biol Med ; 124: 103960, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32919186

RESUMO

Artificial intelligence (AI) has penetrated the field of medicine, particularly the field of radiology. Since its emergence, the highly virulent coronavirus disease 2019 (COVID-19) has infected over 10 million people, leading to over 500,000 deaths as of July 1st, 2020. Since the outbreak began, almost 28,000 articles about COVID-19 have been published (https://pubmed.ncbi.nlm.nih.gov); however, few have explored the role of imaging and artificial intelligence in COVID-19 patients-specifically, those with comorbidities. This paper begins by presenting the four pathways that can lead to heart and brain injuries following a COVID-19 infection. Our survey also offers insights into the role that imaging can play in the treatment of comorbid patients, based on probabilities derived from COVID-19 symptom statistics. Such symptoms include myocardial injury, hypoxia, plaque rupture, arrhythmias, venous thromboembolism, coronary thrombosis, encephalitis, ischemia, inflammation, and lung injury. At its core, this study considers the role of image-based AI, which can be used to characterize the tissues of a COVID-19 patient and classify the severity of their infection. Image-based AI is more important than ever as the pandemic surges and countries worldwide grapple with limited medical resources for detection and diagnosis.


Assuntos
Betacoronavirus , Lesões Encefálicas/epidemiologia , Infecções por Coronavirus/epidemiologia , Traumatismos Cardíacos/epidemiologia , Pneumonia Viral/epidemiologia , Inteligência Artificial , Betacoronavirus/patogenicidade , Betacoronavirus/fisiologia , Lesões Encefálicas/classificação , Lesões Encefálicas/diagnóstico por imagem , Técnicas de Laboratório Clínico/métodos , Comorbidade , Biologia Computacional , Infecções por Coronavirus/classificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/diagnóstico por imagem , Aprendizado Profundo , Traumatismos Cardíacos/classificação , Traumatismos Cardíacos/diagnóstico por imagem , Humanos , Aprendizado de Máquina , Pandemias/classificação , Pneumonia Viral/classificação , Pneumonia Viral/diagnóstico por imagem , Fatores de Risco , Índice de Gravidade de Doença
13.
Pharmaceuticals (Basel) ; 13(8)2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32806755

RESUMO

In recent years, the spectrum of possible applications of gold in diagnostics and therapeutic approaches in clinical practice has changed significantly, becoming surprisingly broad. Nowadays, gold-based therapeutic agents are used in the therapy of multiple human diseases, ranging from degenerative to infectious diseases and, in particular, to cancer. At the basis of these performances of gold, there is the development of new gold-based nanoparticles, characterized by a promising risk/benefit ratio that favors their introduction in clinical trials. Gold nanoparticles appear as attractive elements in nanomedicine, a branch of modern clinical medicine, which combines high selectivity in targeting tumor cells and low toxicity. Thanks to these peculiar characteristics, gold nanoparticles appear as the starting point for the development of new gold-based therapeutic strategies in oncology. Here, the new gold-based therapeutic agents developed in recent years are described, with particular emphasis on the possible applications in clinical practice as anticancer agents, with the aim that their application will give rise to a new golden age in oncology and a breakthrough in the fight against cancer.

14.
J Cutan Pathol ; 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32789924

RESUMO

Cutaneous clear-cell squamous cell carcinoma (ccSCC) is a rare variant of SCC composed of clear cells that lack cytoplasmic glycogen or evidence of tricholemmal keratinization. We report a previously undescribed variant of ccSCC with psammomatous calcification and intratumoral giant cell granulomas. The differential diagnosis with trichilemmal carcinoma is outlined according to the criteria of the fourth edition of World Health Organization (WHO) classification. Our findings outline that psammomatous calcification may occur inside the keratinous pearls of the neoplastic lobules triggering an intratumoral giant cell granulomatous reaction. The prognostic significance of this histopathological presentation is unknown but the potential for formation of psammoma bodies in cSCC should be considered to avoid diagnostic pitfalls.

15.
Curr Med Chem ; 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32744959

RESUMO

Wilson disease is a congenital disorder of copper metabolism whose pathogenesis remains, al least in part, unknown. Subjects carrying the same genotype may show completely different phenotypes, differing for the age at illness onset or for the hepatic, neurologic or psychiatric clinical presentation. The inhability to find a unequivocal correlation between the type of mutation in the ATPase copper transporting beta (ATP7B) gene and the phenotypic manifestation, induced many authors to look for epigenetic factors interacting with the genetic changes. Here the evidences regarding the ability of copper overload to change the global DNA methylation status are discussed.

16.
J Proteome Res ; 19(1): 300-313, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31638822

RESUMO

Because of the distinctive features of the oral cavity, the determination of the proteins involved in the formation of the "oral protein pellicle" is demanding. The present study investigated the susceptibility of several human basic proline-rich peptides, named P-H, P-D, P-F, P-J, and II-2, as substrates of transglutaminase-2. The reactivity of the P-C peptide and statherin was also investigated. Peptides purified from human whole saliva were incubated with the enzyme in the presence or in the absence of monodansyl-cadaverine. Mass spectrometry analyses of the reaction products highlighted that P-H and P-D (P32 and A32 variants) were active substrates, II-2 was less reactive, and P-F and P-J showed very low reactivity. P-C and statherin were highly reactive. All of the peptides formed cyclo derivatives, and only specific glutamine residues were involved in the cycle formation and reacted with monodansyl-cadaverine: Q29 of P-H, Q37 of P-D, Q21 of II-2, Q41 of P-C, and Q37 of statherin were the principal reactive residues. One or two secondary glutamine residues of only P-H, P-D P32, P-C, and statherin were hierarchically susceptible to the reaction with monodansyl-cadaverine. MS and MS/MS data were deposited to the ProteomeXchange Consortium ( http://www.ebi.ac.uk/pride ) via the PRIDE partner repository with the data set identifier PXD014658.

17.
J Neuroradiol ; 47(3): 203-209, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-30439395

RESUMO

PURPOSE: To explore the association between presence of inflammatory cells in the carotid plaques surgically treated and brain MRI findings. MATERIAL AND METHODS: Forty consecutive patients were prospectively analyzed. Brain MRI was performed with a 1.5 Tesla scanner and infacts (lacuna and non-lacunar) pertinence of the anterior circulation were recorded. All patients underwent carotid endarterectomy "en bloc"; carotid plaques histological sections were prepared and immuno-cytochemical analysis was performed to characterize and quantify the presence of inflammatory cells. ROC curve analysis, Pearson Rho correlation and Mann-Whitney test were applied. RESULTS: The immuno-cytochemical analysis demonstrated that plaques of symptomatic patients (stroke\TIA; n = 25) had more inflammatory cells, mainly macrophages (CD68) compared with plaques of patients without symptoms (Mann-Whitney = P < 0.001, ROC curve area = 0.901). Correlation analysis showed a statistically significant association between the number of brain non-lacunar infarcts and the entity of macrophages (P < 0.001); whereas no association with lacunar infarcts (P = 0.1934) was found. CONCLUSION: Results of this preliminary study suggest that the presence and amount of inflammatory cells within carotid artery plaque is associated with cerebrovascular events and with the number of MRI brain detectable infarct.

18.
Rev Cardiovasc Med ; 21(4): 541-560, 2020 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-33387999

RESUMO

Artificial Intelligence (AI), in general, refers to the machines (or computers) that mimic "cognitive" functions that we associate with our mind, such as "learning" and "solving problem". New biomarkers derived from medical imaging are being discovered and are then fused with non-imaging biomarkers (such as office, laboratory, physiological, genetic, epidemiological, and clinical-based biomarkers) in a big data framework, to develop AI systems. These systems can support risk prediction and monitoring. This perspective narrative shows the powerful methods of AI for tracking cardiovascular risks. We conclude that AI could potentially become an integral part of the COVID-19 disease management system. Countries, large and small, should join hands with the WHO in building biobanks for scientists around the world to build AI-based platforms for tracking the cardiovascular risk assessment during COVID-19 times and long-term follow-up of the survivors.


Assuntos
Inteligência Artificial , Doenças Cardiovasculares/epidemiologia , Atenção à Saúde/métodos , Pandemias , Medição de Risco , Doenças Cardiovasculares/terapia , Comorbidade , Humanos , Fatores de Risco
19.
Ann Med Surg (Lond) ; 46: 17-22, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485327

RESUMO

Background: The incidence of node metastases in papillary thyroid carcinoma (PTC) is high, ranging from 20% to 90%. Prophylactic central lymph node compartment dissection (CLND), suggested from the latest guidelines for high-risk tumors, meets resistance due to the high incidence of postoperative complications. Recently, new molecular biologic techniques, such as One Step Nucleic Acid Amplification (OSNA), have spread widely, allowing to quickly isolate, amplify and quantify mRNA encoding for proteins selectively present in neoplastic cells, as Cytokeratine-19. The aim of this study is to evaluate the application of OSNA to intraoperative diagnosis of node metastases of PTC. Methods: We included in the study patients with preoperative diagnosis of PTC; from each patient one or more lymph nodes were collected. To assess OSNA accuracy, each lymph node was divided into two halves: the first one was analysed with histopathological and immunohistochemical examination, whereas the second was studied with OSNA. Results: Twenty-six lymph nodes from 13 patients were included in the study. Overall, OSNA sensitivity was 87.5%, specificity 94.4%, positive predictive value 87.5%, negative predictive value 94.4% and accuracy 92.8%. Discussion and conclusion: OSNA is effective in detecting lymph node metastases of PTC. Considering the high risk of complications in CLND, and the uncertain prognostic value of lymph node metastases of PTC, OSNA seems to be a promising tool to identify intraoperatively patients who may benefit from CLND.

20.
Am J Perinatol ; 36(S 02): S33-S36, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31238356

RESUMO

In the present article, we discuss the following topics: (1) the fetal programming of adult kidney diseases and (2) the role of neonatologists in the regenerative renal medicine, based on the activation of resident renal SC. Here, we report the most important steps of our collaboration between neonatologists, nephrologists, and pathologists. Nephrologists should be more interested in clinical data regarding the first month of life in the womb of their adult patients, being particularly focused on birth weight and on the weeks of gestation at birth, without forgetting data regarding maternal status during gestation and neonatal asphyxia. Neonatologists should be aware that any preterm or low birthweight infant should be considered as a subject with fewer glomeruli, probably predicted to develop renal disease later in life.


Assuntos
Nefropatias/etiologia , Rim/embriologia , Epigênese Genética , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Nefropatias/genética , Nefropatias/prevenção & controle , Neonatologia , Néfrons/embriologia , Papel do Médico
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