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1.
Int J Mol Sci ; 22(12)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207143

RESUMO

Epidemiological studies have emphasized the association between a diet rich in fruits and vegetables and a lower frequency of occurrence of inflammatory-related disorders. Black chokeberry (Aronia melanocarpa L.) is a valuable source of biologically active compounds that have been widely investigated for their role in health promotion and cardiovascular disease prevention. Many in vitro and in vivo studies have demonstrated that consumption of these fruits is associated with significant improvements in hypertension, LDL oxidation, lipid peroxidation, total plasma antioxidant capacity and dyslipidemia. The mechanisms for these beneficial effects include upregulation of endothelial nitric oxide synthase, decreased oxidative stress, and inhibition of inflammatory gene expression. Collected findings support the recommendation of such berries as an essential fruit group in a heart-healthy diet. The aim of this review was to summarize the reports on the impact of black chokeberry fruits and extracts against several cardiovascular diseases, e.g., hyperlipidemia, hypercholesterolemia, hypertension, as well as to provide an analysis of the antioxidant and anti-inflammatory effect of these fruits in the abovementioned disorders.


Assuntos
Frutas/química , Photinia/química , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Humanos , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/etiologia , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Polifenóis/química , Polifenóis/farmacologia
2.
Prim Care Diabetes ; 15(4): 653-681, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34083122

RESUMO

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic has led to a dramatic crisis in health care systems worldwide. These may have significant implications for the management of cardiometabolic diseases. We conducted a systematic review of published evidence to assess the indirect impact of the COVID-19 pandemic on hospitalisations for cardiovascular diseases and their management. METHODS: Studies that evaluated volume of hospitalisations for cardiometabolic conditions and their management with comparisons between the COVID-19 and pre-COVID periods were identified from MEDLINE, Embase and the reference list of relevant studies from January 2020 to 25 February 2021. RESULTS: We identified 103 observational studies, with most studies assessing hospitalisations for acute cardiovascular conditions such as acute coronary syndrome, ischemic strokes and heart failure. About 89% of studies reported a decline in hospitalisations during the pandemic compared to pre-pandemic times, with reductions ranging from 20.2 to 73%. Severe presentation, less utilization of cardiovascular procedures, and longer patient- and healthcare-related delays were common during the pandemic. Most studies reported shorter length of hospital stay during the pandemic than before the pandemic (1-8 vs 2-12 days) or no difference in length of stay. Most studies reported no change in in-hospital mortality among hospitalised patients. CONCLUSION: Clinical care of patients for acute cardiovascular conditions, their management and outcomes have been adversely impacted by the COVID-19 pandemic. Patients should be educated via population-wide approaches on the need for timely medical contact and health systems should put strategies in place to provide timely care to patients at high risk. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2021: CRD42021236102.


Assuntos
COVID-19 , Doenças Cardiovasculares/terapia , Acesso aos Serviços de Saúde/tendências , Hospitalização/tendências , Doenças Metabólicas/terapia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Mortalidade Hospitalar/tendências , Humanos , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/mortalidade , Estudos Observacionais como Assunto , Prognóstico , Índice de Gravidade de Doença , Fatores de Tempo
3.
Int J Paleopathol ; 33: 220-233, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34004547

RESUMO

OBJECTIVE: This research attempts a differential diagnosis of skeletal lesions in a commingled sample from Hisban, Jordan, focusing on non-adults in the assemblage. MATERIALS: 2,883 well-preserved skeletal elements and 9 relatively complete skulls representing an MNI of 32 non-adults (<18 years old). METHODS: All skeletal elements were observed macroscopically and pathophysiological processes underlying any lesions or other anomalies were assessed, followed by a comparative approach to rule out potential diagnoses. RESULTS: The skeletal lesions observed were caused by inflammation due to chronic hemorrhaging, marrow hyperplasia due to an increase in hemopoiesis, rapid bone growth, and the impact of biomechanical strain on poorly mineralized elements. Rickets, scurvy, and acquired anemias best fit this pattern of lesions, although inflammation from other sources such as trauma or infection could not be definitively ruled out. CONCLUSIONS: The in utero and postnatal environments at Hisban were conducive to the development of vitamin C and D deficiencies from birth until 2 years of age. The analysis of commingled remains requires an ontological shift in the importance of the individual to the population in paleopathology. SIGNIFICANCE: This investigation demonstrates the efficacy of a combined biological and comparative approach in differential diagnosis in complicated commingled collections. In addition, it emphasizes the importance of the mother-infant dyad in understanding metabolic disease. LIMITATIONS: Histological and radiographic analyses were not included in this diagnostic study due to COVID-19 travel restrictions. SUGGESTIONS FOR FURTHER RESEARCH: Isotopic analysis to investigate childhood diet and histological and radiographic analyses to assess survival of deficiencies.


Assuntos
Anemia/história , Doenças Metabólicas/história , Paleopatologia/história , Raquitismo/história , Escorbuto/história , Adolescente , Anemia/diagnóstico , Criança , Diagnóstico Diferencial , História do Século XIX , Humanos , Jordânia , Doenças Metabólicas/diagnóstico , Raquitismo/diagnóstico , Escorbuto/diagnóstico , Crânio/patologia
4.
Int J Mol Sci ; 22(6)2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33809321

RESUMO

The revolutionary evolution in science and technology over the last few decades has made it possible to face more adequately three main challenges of modern medicine: changes in old diseases, the appearance of new diseases, and diseases that are unknown (mostly genetic), despite research efforts. In this paper we review the road travelled by pathologists in search of a method based upon the use of routine instruments and techniques which once were available for research only. The application to tissue studies of techniques from immunology, molecular biology, and genetics has allowed dynamic interpretations of biological phenomena with special regard to gene regulation and expression. That implies stepwise investigations, including light microscopy, immunohistochemistry, in situ hybridization, electron microscopy, molecular histopathology, protein crystallography, and gene sequencing, in order to progress from suggestive features detectable in routinely stained preparations to more characteristic, specific, and finally, pathognomonic features. Hematoxylin and Eosin (H&E)-stained preparations and appropriate immunohistochemical stains have enabled the recognition of phenotypic changes which may reflect genotypic alterations. That has been the case with hepatocytic inclusions detected in H&E-stained preparations, which appeared to correspond to secretory proteins that, due to genetic mutations, were retained within the rough endoplasmic reticulum (RER) and were deficient in plasma. The identification of this phenomenon affecting the molecules alpha-1-antitrypsin and fibrinogen has led to the discovery of a new field of cell organelle pathology, endoplasmic reticulum storage disease(s) (ERSD). Over fifty years, pathologists have wandered through a dark forest of complicated molecules with strange conformations, and by detailed observations in simple histopathological sections, accompanied by a growing background of molecular techniques and revelations, have been able to recognize and identify arrays of grotesque polypeptide arrangements.


Assuntos
Retículo Endoplasmático/genética , Imuno-Histoquímica , Doenças Metabólicas/patologia , alfa 1-Antitripsina/genética , Retículo Endoplasmático/patologia , Regulação da Expressão Gênica/genética , Genótipo , Humanos , Doenças Metabólicas/classificação , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/genética , Mutação/genética
5.
Isr Med Assoc J ; 23(4): 245-250, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33899358

RESUMO

BACKGROUND: Hypomagnesemia (serum magnesium level < 1.7 mg/dl) occurs more frequently in patients with type 2 diabetes mellitus (T2DM).Serum magnesium levels are not routinely tested in hospitalized patients, including in hospitalized patients with T2DM. OBJECTIVES: To evaluate the prevalence of hypomagnesemia among hospitalized T2DM patients treated with proton pump inhibitors (PPIs) and/or diuretics. METHODS: A total of 263 T2DM patients hospitalized in general departments were included in the study and were further divided into four groups: group 1 (patients not treated with PPIs or diuretics), group 2 (patients treated with PPIs), group 3 (patients treated with diuretics), and group 4 (patients treated with both PPIs and diuretics).  Blood and urine samples were taken during the first 24 hours of admission. Electrocardiogram was performed on admission. RESULTS: Of the 263 T2DM patients, 58 (22.1%) had hypomagnesemia (serum magnesium level < 1.7 mg/dl). Patients in group 2 had the lowest mean serum magnesium level (1.79 mg/dl ± 0.27). Relatively more patients with hypomagnesemia were found in group 2 compared to the other groups, although a statistically significant difference was not observed. Significantly more patients in group 3 and 4 had chronic renal failure. Patients with hypomagnesemia had significantly lower serum calcium levels. CONCLUSIONS: Hospitalized T2DM patients under PPI therapy are at risk for hypomagnesemia and hypocalcemia.


Assuntos
Cálcio/sangue , Diabetes Mellitus Tipo 2 , Falência Renal Crônica , Magnésio/sangue , Doenças Metabólicas , Idoso , Comorbidade , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diuréticos/administração & dosagem , Diuréticos/efeitos adversos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Israel/epidemiologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Masculino , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Pessoa de Meia-Idade , Prevalência , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos
6.
Sci Data ; 8(1): 114, 2021 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-33883556

RESUMO

Every year individuals experience symptoms that remain undiagnosed by healthcare providers. In the United States, these rare diseases are defined as a condition that affects fewer than 200,000 individuals. However, there are an estimated 7000 rare diseases, and there are an estimated 25-30 million Americans in total (7.6-9.2% of the population as of 2018) affected by such disorders. The NIH Common Fund Undiagnosed Diseases Network (UDN) seeks to provide diagnoses for individuals with undiagnosed disease. Mass spectrometry-based metabolomics and lipidomics analyses could advance the collective understanding of individual symptoms and advance diagnoses for individuals with heretofore undiagnosed disease. Here, we report the mass spectrometry-based metabolomics and lipidomics analyses of blood plasma, urine, and cerebrospinal fluid from 148 patients within the UDN and their families, as well as from a reference population of over 100 individuals with no known metabolic diseases. The raw and processed data are available to the research community so that they might be useful in the diagnoses of current or future patients suffering from undiagnosed disorders.


Assuntos
Lipidômica , Doenças Metabólicas/diagnóstico , Metabolômica , Doenças não Diagnosticadas/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Conjuntos de Dados como Assunto , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Espectrometria de Massas , Doenças Metabólicas/sangue , Doenças Metabólicas/líquido cefalorraquidiano , Doenças Metabólicas/urina , Pessoa de Meia-Idade , Doenças não Diagnosticadas/sangue , Doenças não Diagnosticadas/líquido cefalorraquidiano , Doenças não Diagnosticadas/urina , Adulto Jovem
7.
Front Immunol ; 12: 614429, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717101

RESUMO

The worldwide epidemic of metabolic diseases, especially obesity and other diseases caused by it, has shown a dramatic increase in incidence. A great deal of attention has been focused on the underlying mechanisms of these pathological processes and potential strategies to solve these problems. Chronic inflammation initiated by abdominal adipose tissues and immune cell activation in obesity is the major cause of the consequent development of complications. In addition to adipocytes, macrophages and monocytes, natural killer (NK) cells have been verified to be vital components involved in shaping the inflammatory microenvironment, thereby leading to various obesity-related metabolic diseases. Here, we provide an overview of the roles of NK cells and the interactions of these cells with other immune and nonimmune cells in the pathological processes of metabolic diseases. Finally, we also discuss potential therapeutic strategies targeting NK cells to treat metabolic diseases.


Assuntos
Suscetibilidade a Doenças , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Doenças Metabólicas/etiologia , Doenças Metabólicas/metabolismo , Animais , Biomarcadores , Gerenciamento Clínico , Regulação da Expressão Gênica , Humanos , Imunomodulação , Resistência à Insulina , Células Matadoras Naturais/efeitos dos fármacos , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/terapia , Terapia de Alvo Molecular , Especificidade de Órgãos , Transdução de Sinais
8.
Nat Commun ; 12(1): 1487, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674561

RESUMO

Hyocholic acid (HCA) is a major bile acid (BA) species in the BA pool of pigs, a species known for its exceptional resistance to spontaneous development of diabetic phenotypes. HCA and its derivatives are also present in human blood and urine. We investigate whether human HCA profiles can predict the development of metabolic disorders. We find in the first cohort (n = 1107) that both obesity and diabetes are associated with lower serum concentrations of HCA species. A separate cohort study (n = 91) validates this finding and further reveals that individuals with pre-diabetes are associated with lower levels of HCA species in feces. Serum HCA levels increase in the patients after gastric bypass surgery (n = 38) and can predict the remission of diabetes two years after surgery. The results are replicated in two independent, prospective cohorts (n = 132 and n = 207), where serum HCA species are found to be strong predictors for metabolic disorders in 5 and 10 years, respectively. These findings underscore the association of HCA species with diabetes, and demonstrate the feasibility of using HCA profiles to assess the future risk of developing metabolic abnormalities.


Assuntos
Biomarcadores/sangue , Ácidos Cólicos/sangue , Ácidos Cólicos/urina , Doenças Metabólicas/diagnóstico , Adulto , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/metabolismo , Fezes/química , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Sobrepeso/metabolismo , Estado Pré-Diabético/diagnóstico , Estudos Prospectivos
9.
Clin Biochem ; 90: 66-72, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33539811

RESUMO

BACKGROUND: A small amount of methanol is produced endogenously in the human body but it is efficiently metabolized by alcohol dehydrogenase (ADH) and other enzymes, and the products eliminated without harm. In this study, we present a new entity of inborn error of methanol metabolism due to a mutation in the ADH1C gene coding for the γ subunit that is part of several ADH isoenzymes. RESULTS: This disorder was discovered in an 11.58-year-old boy. During one 9-month hospital admission, he had periods of 1-4 days during which he was comatose, and between these periods he was sometimes verbose and euphoric, and had ataxia, dysarthria. Following hemodialysis treatments, he became conscious and appeared healthy. Organ evaluations and his laboratory tests were normal. Toxicological evaluation of his blood showed a high methanol level [12.2 mg/dL (3.8 mmol/L), normal range up to 3.5 mg/dL (1.09 mmol/L) while the formaldehyde level was undetectable. The finding of liver function tests that were within normal limits, coupled with a normal eye examination and size of the liver, elevated blood methanol levels and an undetectable formaldehyde level, suggested ADH insufficiency. Adding zinc to the drug regimen 15 mg/daily dramatically reduced the patient's methanol level and alleviated the abnormal symptoms. When zinc supplementation was discontinued, the patient relapsed into a coma and hemodialysis was once again required. A homozygous mutation in ADH1C gene located at exon 3 was found, and both parents were heterozygous for this mutation. CONCLUSION: Accumulation of methanol due to mutation in ADH1C gene may result in drunkenness and ataxia, and leads to coma. This condition can be successfully treated with zinc supplementation as the cofactor of ADH.


Assuntos
Álcool Desidrogenase/genética , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/genética , Metanol/sangue , Álcool Desidrogenase/metabolismo , Intoxicação Alcoólica/complicações , Ataxia/complicações , Criança , Coma/etiologia , Éxons/genética , Heterozigoto , Humanos , Fígado/metabolismo , Masculino , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/genética , Erros Inatos do Metabolismo/complicações , Erros Inatos do Metabolismo/terapia , Metanol/metabolismo , Mutação , Diálise Renal/métodos , Resultado do Tratamento , Zinco/administração & dosagem
10.
Bratisl Lek Listy ; 122(3): 190-195, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33618527

RESUMO

AIM: Congenital disorders of glycosylation (CDG) belong to an expanding group of rare genetic metabolic disorders caused by defects in the complex chemical enzymatic process of glycosylation. The study is aimed at presenting a case report of a premature dysmorphic newborn, clinical presentation of the condition, the way it was diagnosed and treated, as well as its comparison with the known cases. RESULTS: The result of glycan analysis supports the assumption of a supposed glycosylation disorder and also specifies a specific subtype: CDG-1, subtype ALG12-CDG (Ig). CONCLUSION: CDG have an extremely wide clinical spectrum and should be considered in any child with unexplained developmental delay, failure to thrive, seizures, and abnormalities in liver enzymes, coagulation and immunologic factors. The treatment of most forms of CDG depends upon numerous factors such as specific symptoms present, severity of the disorder, age and overall health of the patients and tolerance to certain medications or procedures. For these reasons, the treatment is specific for every individual. It is based on the symptoms and requires a coordination of efforts of a team of specialists (Tab. 4, Fig. 3, Ref. 19).


Assuntos
Defeitos Congênitos da Glicosilação , Doenças Metabólicas , Criança , Defeitos Congênitos da Glicosilação/diagnóstico , Defeitos Congênitos da Glicosilação/genética , Glicosilação , Humanos , Recém-Nascido , Programas de Rastreamento , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/genética
11.
Nutr Metab Cardiovasc Dis ; 31(3): 902-910, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33549442

RESUMO

BACKGROUND AND AIMS: Neurotensin (NT) is an intestinal peptide released after fat ingestion, which regulates appetite and facilitates lipid absorption. Elevated plasma levels of its stable precursor pro-neurotensin (pro-NT) are associated with type 2 diabetes, obesity and cardiovascular mortality in adult populations; no data on pro-NT and metabolic disease are available in children. Aim of the study was to evaluate plasma pro-NT in relation to the presence of obesity in children, and to test if high pro-NT associates with the development of metabolic impairment later in life. METHODS AND RESULTS: For this longitudinal retrospective study, we studied 151 overweight/obese children undergoing metabolic evaluations at University of Cagliari, Italy. Pro-NT was also assessed in 46 normal-weight, age-, sex-comparable normal-weight children, selected as a reference group. At the baseline, pro-NT was comparable between overweight/obese and normal-weight children and correlated positively with age (p < 0.001), triglycerides (p < 0.001) and inversely with HDL levels (p = 0.008). Plasma pro-NT associated with high triglycerides with OR = 5.9 (95%CI: 1.24-28.1; p = 0.026) after adjustment for multiple confounders. At the 6.5-year follow-up, high basal pro-NT associated with impaired ß-cell function to compensate for insulin-resistance (disposition index: r = -0.19, p = 0.035) and predicted bodyweight increase, as indicated by percentage change of standard deviation score BMI (median(95%CI) = +20.8(+4.9-+27.5)% in the highest tertile), independently from age, sex, triglycerides and insulin-resistance (standardized ß = 0.24; p = 0.036). CONCLUSIONS: Elevated pro-NT levels in children are significantly associated with weight gain later in life and may represent a marker of susceptibility to metabolic impairment in presence of obesity.


Assuntos
Metabolismo Energético , Doenças Metabólicas/sangue , Neurotensina/sangue , Obesidade Pediátrica/sangue , Precursores de Proteínas/sangue , Ganho de Peso , Fatores Etários , Biomarcadores/sangue , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/fisiopatologia , Obesidade Pediátrica/diagnóstico , Obesidade Pediátrica/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Regulação para Cima
12.
Pediatrics ; 147(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33479165

RESUMO

BACKGROUND AND OBJECTIVES: The Child Opportunity Index (ChOI) is a publicly available surveillance tool that incorporates traditional and novel attributes of neighborhood conditions that may promote or inhibit healthy child development. The extent to which ChOI relates to individual-level cardiometabolic risk remains unclear. METHODS: We geocoded residential addresses obtained from 743 participants in midchildhood (mean age 7.9 years) in Project Viva, a prebirth cohort from eastern Massachusetts, and linked each location with census tract-level ChOI data. We measured adiposity and cardiometabolic outcomes in midchildhood and early adolescence (mean age 13.1 years) and analyzed their associations with neighborhood-level ChOI in midchildhood using mixed-effects models, adjusting for individual and family sociodemographics. RESULTS: On the basis of nationwide distributions of ChOI, 11.2% (n = 83) of children resided in areas of very low overall opportunity (ChOI score <20 U) and 55.3% (n = 411) resided in areas of very high (ChOI score ≥80 U) overall opportunity. Children who resided in areas with higher overall opportunity in midchildhood had persistently lower levels of C-reactive protein from midchildhood to early adolescence (per 25-U increase in ChOI score: ß = .14 mg/L; 95% confidence interval, .28 to .00). Additionally, certain ChOI indicators, such as greater number of high-quality childhood education centers, greater access to healthy food, and greater proximity to employment in midchildhood, were associated with persistently lower adiposity, C-reactive protein levels, insulin resistance, and metabolic risk z scores from midchildhood to early adolescence. CONCLUSIONS: Our findings suggest more favorable neighborhood opportunities in midchildhood predict better cardiometabolic health from midchildhood to early adolescence.


Assuntos
Doenças Cardiovasculares/epidemiologia , Planejamento Ambiental/tendências , Doenças Metabólicas/epidemiologia , Vigilância da População/métodos , Características de Residência , Fatores Socioeconômicos , Adiposidade/fisiologia , Adolescente , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Criança , Escolaridade , Planejamento Ambiental/economia , Feminino , Humanos , Masculino , Massachusetts/epidemiologia , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/prevenção & controle , Fatores de Risco
13.
Hum Genet ; 140(6): 897-913, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33409574

RESUMO

Disease gene identification is a critical step towards uncovering the molecular mechanisms of diseases and systematically investigating complex disease phenotypes. Despite considerable efforts to develop powerful computing methods, candidate gene identification remains a severe challenge owing to the connectivity of an incomplete interactome network, which hampers the discovery of true novel candidate genes. We developed a network-based machine-learning framework to identify both functional modules and disease candidate genes. In this framework, we designed a semi-supervised non-negative matrix factorization model to obtain the functional modules related to the diseases and genes. Of note, we proposed a disease gene-prioritizing method called MapGene that integrates the correlations from both functional modules and network closeness. Our framework identified a set of functional modules with highly functional homogeneity and close gene interactions. Experiments on a large-scale benchmark dataset showed that MapGene performs significantly better than the state-of-the-art algorithms. Further analysis demonstrates MapGene can effectively relieve the impact of the incompleteness of interactome networks and obtain highly reliable rankings of candidate genes. In addition, disease cases on Parkinson's disease and diabetes mellitus confirmed the generalization of MapGene for novel candidate gene identification. This work proposed, for the first time, an integrated computing framework to predict both functional modules and disease candidate genes. The methodology and results support that our framework has the potential to help discover underlying functional modules and reliable candidate genes in human disease.


Assuntos
Redes Reguladoras de Genes , Redes e Vias Metabólicas/genética , Valor Preditivo dos Testes , Aprendizado de Máquina Supervisionado , Sequência de Aminoácidos , Biologia Computacional/métodos , Gastroenteropatias/diagnóstico , Gastroenteropatias/genética , Gastroenteropatias/patologia , Humanos , Doenças do Sistema Imunitário/diagnóstico , Doenças do Sistema Imunitário/genética , Doenças do Sistema Imunitário/patologia , Transtornos Mentais/diagnóstico , Transtornos Mentais/genética , Transtornos Mentais/patologia , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/genética , Doenças Metabólicas/patologia , Doenças Musculoesqueléticas/diagnóstico , Doenças Musculoesqueléticas/genética , Doenças Musculoesqueléticas/patologia , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/patologia , Doenças Neurodegenerativas/diagnóstico , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/patologia , Mapeamento de Interação de Proteínas , Terminologia como Assunto
14.
PLoS One ; 16(1): e0244106, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33503029

RESUMO

INTRODUCTION: The independent role of serum uric acid (SUA) on kidney disease is controversial due to its association with metabolic syndrome. The objective of this study was to investigate the association of baseline SUA with development of chronic kidney disease and eGFR decline in normotensive, normoglycemic and non-obese individuals during follow up period. MATERIALS AND METHODS: We included non-hypertensitive, non-diabetic, and non-obese 13,133 adults with estimated glomerular filtration rate (eGFR) ≥ 60ml/min/1.73m2 who had a voluntary health check-up during 2004-2017. RESULTS: SUA was positively related to adjusted means of systolic blood pressure (SBP), triglyceride, body mass index, and body fat percent. SUA was inversely associated with high density lipoprotein HDL (P for trend ≤0.001). SUA was an independent risk factor for the development of diabetes, hypertension, and obesity. During 45.0 [24.0-76.0] months of median follow up, the highest quartiles of SUA showed significant risks of 30% eGFR decline compared than the lowest quartile (RR:3.701; 95% CI: 1.504-9.108). The highest quartile had a 2.2 fold (95% CI: 1.182-4.177) increase in risk for incident chronic kidney disease (CKD). CONCLUSIONS: SUA is an independent risk factor for the development of diabetes, hypertension, and obesity in the healthy population. High SUA is associated with increased risk of CKD development and eGFR decline in participants with intact renal function.


Assuntos
Insuficiência Renal Crônica/diagnóstico , Ácido Úrico/sangue , Adulto , Idoso , Pressão Sanguínea , Índice de Massa Corporal , Estudos de Coortes , Diabetes Mellitus/diagnóstico , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/diagnóstico , Incidência , Masculino , Doenças Metabólicas/diagnóstico , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/etiologia , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco
15.
Arterioscler Thromb Vasc Biol ; 41(1): 501-511, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33176448

RESUMO

OBJECTIVE: Transcriptome profiling of human tissues has revealed thousands of long intergenic noncoding RNAs (lincRNAs) at loci identified through large-scale genome-wide studies for complex cardiometabolic traits. This raises the question of whether genetic variation at nonconserved lincRNAs has any systematic association with complex disease, and if so, how different this pattern is from conserved lincRNAs. We evaluated whether the associations between nonconserved lincRNAs and 8 complex cardiometabolic traits resemble or differ from the pattern of association for conserved lincRNAs. Approach and Results: Our investigation of over 7000 lincRNA annotations from GENCODE Release 33-GRCh38.p13 for complex trait genetic associations leveraged several large, established meta-analyses genome-wide association study summary data resources, including GIANT (Genetic Investigation of Anthropometric Traits), UK Biobank, GLGC (Global Lipids Genetics Consortium), Cardiogram (Coronary Artery Disease Genome Wide Replication and Meta-Analysis), and DIAGRAM (Diabetes Genetics Replication and Meta-Analysis)/DIAMANTE (Diabetes Meta-Analysis of Trans-Ethnic Association Studies). These analyses revealed that (1) nonconserved lincRNAs associate with a range of cardiometabolic traits at a rate that is generally consistent with conserved lincRNAs; (2) these findings persist across different definitions of conservation; and (3) overall across all cardiometabolic traits, approximately one-third of genome-wide association study-associated lincRNAs are nonconserved, and this increases to about two-thirds using a more stringent definition of conservation. CONCLUSIONS: These findings suggest that the traditional notion of conservation driving prioritization for functional and translational follow-up of complex cardiometabolic genomic discoveries may need to be revised in the context of the abundance of nonconserved long noncoding RNAs in the human genome and their apparent predilection to associate with complex cardiometabolic traits.


Assuntos
Doenças Cardiovasculares/genética , Doenças Metabólicas/genética , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Sintenia , Fatores de Risco Cardiometabólico , Doenças Cardiovasculares/diagnóstico , Bases de Dados Genéticas , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Hereditariedade , Humanos , Doenças Metabólicas/diagnóstico , Linhagem , Medição de Risco
16.
Pediatr Clin North Am ; 68(1): 81-102, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33228944

RESUMO

Advances in technology, methodology, and deep phenotyping are increasingly driving the understanding of the pathologic basis of disease. Improvements in patient identification and treatment are impacting survival. This is true in endocrinology and inborn errors of metabolism, where disease-modifying therapies are developing. Inherent to this evolution is the increasing awareness of the respiratory manifestations of these rare diseases. This review updates clinicians, stratifying diseases spirometerically; pulmonary hypertension and diseases with a predisposition to recurrent pulmonary infection are discussed. This division is artificial; many diseases have multiple pathologic effects on respiration. This review does not cover the impact of obesity.


Assuntos
Doenças do Sistema Endócrino/complicações , Pneumopatias/etiologia , Doenças Metabólicas/complicações , Criança , Doenças do Sistema Endócrino/diagnóstico , Doenças do Sistema Endócrino/terapia , Humanos , Pneumopatias/diagnóstico , Pneumopatias/terapia , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/terapia , Fenótipo
17.
Diabetes Metab Syndr ; 15(1): 55-62, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33310177

RESUMO

BACKGROUND AND AIMS: The ongoing pandemic of coronavirus disease 2019 (COVID-19) is rapidly evolving, thereby posing a profound challenge to the global healthcare system. Cardiometabolic disorders are associated with poor clinical outcomes in persons with COVID-19. Healthcare challenges during the COVID-19 pandemic are linked to resource constraints including shortage of Personal Protective Equipment's (PPE), laboratory tests and medication. In this context, a group of clinical experts discussed the endocrine and cardiology vigilance required in times of COVID-19. Further, the group proposed certain resource husbandry recommendations to be followed during the pandemic to overcome the constraints. METHOD: The clinical experts discussed and provided their inputs virtually. The expert panel included clinical experts comprising endocrinologists, Consultant Physicians and cardiologists from India. The panel thoroughly reviewed existing literature on the subject and proposed expert opinion. RESULTS: The expert panel put forward clinical practice-based opinion for the management of cardiometabolic conditions including diabetes mellitus and hypertension. As these conditions are associated with poor clinical outcomes, the expert panel recommends that these persons be extra-cautious and take necessary precautions during the ongoing pandemic. Further, experts also provided appropriate, affordable, available and accessible solution to the resource constraint situations in times of COVID-19 pandemic. CONCLUSION: The clinical expert opinion put forward in this article will serve as a reference for clinicians treating diabetes and cardiovascular disease during the COVID-19 pandemic.


Assuntos
COVID-19/epidemiologia , Doenças Cardiovasculares/epidemiologia , Prova Pericial/tendências , Recursos em Saúde/tendências , Doenças Metabólicas/epidemiologia , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , COVID-19/diagnóstico , COVID-19/prevenção & controle , Cardiotônicos/uso terapêutico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Índia/epidemiologia , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/tratamento farmacológico
18.
PLoS Med ; 17(12): e1003387, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33290405

RESUMO

BACKGROUND: Individuals with obesity do not represent a homogeneous group in terms of cardiometabolic risk. Using 3 nationally representative British birth cohorts, we investigated whether the duration of obesity was related to heterogeneity in cardiometabolic risk. METHODS AND FINDINGS: We used harmonised body mass index (BMI) and cardiometabolic disease risk factor data from 20,746 participants (49.1% male and 97.2% white British) enrolled in 3 British birth cohort studies: the 1946 National Survey of Health and Development (NSHD), the 1958 National Child Development Study (NCDS), and the 1970 British Cohort Study (BCS70). Within each cohort, individual life course BMI trajectories were created between 10 and 40 years of age, and from these, age of obesity onset, duration spent obese (range 0 to 30 years), and cumulative obesity severity were derived. Obesity duration was examined in relation to a number of cardiometabolic disease risk factors collected in mid-adulthood: systolic (SBP) and diastolic blood pressure (DBP), high-density-lipoprotein cholesterol (HDL-C), and glycated haemoglobin (HbA1c). A greater obesity duration was associated with worse values for all cardiometabolic disease risk factors. The strongest association with obesity duration was for HbA1c: HbA1c levels in those with obesity for <5 years were relatively higher by 5% (95% CI: 4, 6), compared with never obese, increasing to 20% (95% CI: 17, 23) higher in those with obesity for 20 to 30 years. When adjustment was made for obesity severity, the association with obesity duration was largely attenuated for SBP, DBP, and HDL-C. For HbA1c, however, the association with obesity duration persisted, independent of obesity severity. Due to pooling of 3 cohorts and thus the availability of only a limited number harmonised variables across cohorts, our models included adjustment for only a small number of potential confounding variables, meaning there is a possibility of residual confounding. CONCLUSIONS: Given that the obesity epidemic is characterised by a much earlier onset of obesity and consequently a greater lifetime exposure, our findings suggest that health policy recommendations aimed at preventing early obesity onset, and therefore reducing lifetime exposure, may help reduce the risk of diabetes, independently of obesity severity. However, to test the robustness of our observed associations, triangulation of evidence from different epidemiological approaches (e.g., mendelian randomization and negative control studies) should be obtained.


Assuntos
Fatores de Risco Cardiometabólico , Doenças Cardiovasculares/epidemiologia , Doenças Metabólicas/epidemiologia , Obesidade Pediátrica/epidemiologia , Adolescente , Adulto , Idade de Início , Doenças Cardiovasculares/diagnóstico , Criança , Feminino , Humanos , Masculino , Doenças Metabólicas/diagnóstico , Obesidade Pediátrica/diagnóstico , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Reino Unido/epidemiologia , Adulto Jovem
20.
Hematology Am Soc Hematol Educ Program ; 2020(1): 115-122, 2020 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-33275732

RESUMO

The short telomere syndromes encompass a spectrum of clinical manifestations that present from infancy to late adulthood. They are caused by mutations in telomerase and other telomere maintenance genes and have a predominantly degenerative phenotype characterized by organ failure across multiple systems. They are collectively one of the most common inherited bone marrow failure syndromes; however, their most prevalent presentations are extrahematopoietic. This review focuses on these common nonhematologic complications, including pulmonary fibrosis, liver pathology, and immunodeficiency. The short telomere syndrome diagnosis informs clinical care, especially in guiding diagnostic evaluations as well as in the solid organ transplant setting. Early recognition allows an individualized approach to screening and management. This review illustrates a myriad of extrahematopoietic presentations of short telomere syndromes and how they impact clinical decisions.


Assuntos
Transtornos do Crescimento , Hipercalcemia , Doenças Metabólicas , Nefrocalcinose , Telômero , Animais , Feminino , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/genética , Transtornos do Crescimento/metabolismo , Transtornos do Crescimento/patologia , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/genética , Hipercalcemia/metabolismo , Hipercalcemia/patologia , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/genética , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Camundongos , Pessoa de Meia-Idade , Nefrocalcinose/diagnóstico , Nefrocalcinose/genética , Nefrocalcinose/metabolismo , Nefrocalcinose/patologia , Telômero/genética , Telômero/metabolismo , Telômero/patologia
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