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1.
Ann Ig ; 34(1): 84-96, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34698764

RESUMO

Background: Law no. 38 of 15 March 2010 ensures and governs the access to the palliative care and pain management network for patients who require it. The professional roles involved in the project have been identified by the law, with the specific experience and expertise in the field of palliative care and pain management, by allocating a meaningful role to general practitioners (GPs). For this reason, an important direct training plan has been drawn up that GPs can count on for dedicated refresher courses to increase and deepen their knowledge in this specific clinical field. If the role of the GPs in the pain management and palliative care network was well-defined by the law, we cannot say the same for the Continuing Care Physician (CCP), a role that only partially overlaps that of the GP. The study observed the response of a Continuing Care Service (CCS) to the demand for services from patients with pain-related problems. The role of the CCP is, therefore, outlined in the pain therapy care network by observing the services provided to patients experiencing pain that is understood as being a non-deferrable problem. Methods: A survey was conducted at the CCSs site in Aquila, AS-01 Abruzzo. For this reason, the attending physician records the data of patients who consult the CCSs for pain-related problems on an appropriate questionnaire. The survey period covered a total of 68 days (1 January - 8 March 2020). Results. One hundred sixty five sheets were completed; females were more represented than males (57.6% v 42.4%) and the 36-65 age group appears most greatly represented (47.9%). One of the most frequent reasons for consulting the service is "musculoskeletal pain" (58.2%), followed by abdominal pain (15.8%). In the majority of patients, pain lasted from days (53.9%), with an average of approximately 3 days (3.1± 2.9), or hours in 40% of cases, with an average of over 6 hours (6.54±3.1). 88.5% of patients defined the level of pain experienced as "severe" (NRS=7-10), and the intensity of the pain associated with its repetitiveness (80.3% vs 92.6%) as "severe", with a statistically significant difference in relation to nonrepetitiveness cases (p=0.02). 66.1% of patients said that they had taken analgesics independently, with nonsteroidal anti-inflammatory drugs (NSAIDs) the most frequently taken (53.5%). Patients who turned to the CCS received a pharmacological prescription in almost all cases. NSAIDs, specifically, were the most prescribed medicines (64.8%), followed by muscle relaxants (29.7%). Tramadol was the most represented among opioids, which was prescribed in 7.9% of cases. Just 6.1% of patients were entered into the regional pain management network. Conclusions: The results of the survey show that a large number of patients turn to the CCS to resolve painful symptoms of various natures. The study offers some food for thought concerning the role of CCPs and the importance of providing for their inclusion in the pain therapy clinical and training pathways provided for by Law 38/2010. This would ensure its more effective implementation and, therefore, better care for patients experiencing painful pathologies.


Assuntos
Clínicos Gerais , Dor , Analgésicos Opioides , Feminino , Humanos , Itália , Masculino , Inquéritos e Questionários
3.
Diabetes Res Clin Pract ; 144: 102-110, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30142362

RESUMO

AIMS: ZnT8 Arg325Trp polymorphism has been associated with type 2 diabetes (T2DM) susceptibility. The Arg-325 risk variant shows accelerated zinc (Zn) transport kinetic and reduced glucose-stimulated insulin secretion in pancreatic cells. However, it remains unexplored the role of Znt8 polymorphism in the regulation of Zn homeostasis and inflammatory response in peripheral blood mononuclear cells (PBMCs) from T2DM patients. METHODS AND RESULTS: A total of 556 healthy controls and 413 T2DM patients were genotyped for ZnT8 Arg325Trp polymorphism confirming the association of Arg-325 variant with an increased T2DM risk (OR = 1.35 95% C.I: 1.10-1.66; p = 0.0044). Moreover, PBMCs from Arg/Arg T2DM subjects showed increased intracellular free Zn, higher gene expression of Metallothioneins, Znt1, Znt8, Zip2 genes, and reduced Znt4 and Znt7. Higher release of IL-1α, IL-1ß, IFN-γ, IL-12p70 and TNF-α and a reduced IL-10 secretion after lipopolysaccharide (LPS) stimulation were observed in PBMCs from Arg/Arg T2DM carriers as compared to subjects with the Trp variant. CONCLUSIONS: Our data provide evidence of a substantial different Zn homeostasis regulation between Znt8 Arg-325 and Trp-325 carriers in PBMCs from T2DM patients. Moreover, Znt8 Arg-325 risk variant shows an enhanced inflammatory response upon LPS stimulation that might aggravate insulin resistance and the progression of diabetes cardiovascular complications.


Assuntos
Proteínas de Transporte/metabolismo , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Leucócitos Mononucleares/metabolismo , Polimorfismo Genético , Transportador 8 de Zinco/genética , Zinco/metabolismo , Idoso , Idoso de 80 Anos ou mais , Proteínas de Transporte/genética , Estudos de Casos e Controles , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade
4.
J Thromb Haemost ; 16(5): 842-848, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29532628

RESUMO

Essentials Direct oral anticoagulants (DOACs) do not require laboratory monitoring currently. DOAC specific measurements were performed at trough in patients with atrial fibrillation. Patients who developed thromboembolic events showed lower DOAC plasma levels. This study supports the concept of measuring DOAC levels at steady state. SUMMARY: Background Direct oral anticoagulants (DOACs) are administered at fixed doses without the need for dose adjustment according to laboratory testing. High interindividual variability in drug blood levels has been shown with all DOACs. To evaluate a possible relationship between DOAC C-trough anticoagulant levels and thromboembolic events, 565 consecutive naive patients with atrial fibrillation (AF) were enrolled in this study performed within the START Laboratory Registry. Methods DOAC-specific measurements (diluted thrombin time or anti-activated factor II calibrated for dabigatran; anti-activated FX calibrated for rivaroxaban or apixaban) at C-trough were performed locally at steady state within 15-25 days after the start of treatment. For each DOAC, the interval of C-trough levels, from the limit of quantification to the highest value, was subdivided into four equal classes, and results were attributed to these classes; the median values of results were also calculated. Thromboembolic complications occurring during 1 year of follow-up were recorded. Results Thromboembolic events (1.8%) occurred in 10 patients who had baseline C-trough levels in the lowest class of drug levels. The incidence of thromboembolic events among patients with DOAC C-trough levels in the lowest level class was 2.4%, and that in the remaining groups was 0%. The patients with thrombotic complications also had a higher mean CHA2 DS2 -VASc score than that of the total patient population: 5.3 (95% confidence interval [CI] 4.3-6.3 versus 3.0 (95% CI 2.9-3.1). Conclusion In this study cohort, thrombotic complications occurred only in DOAC-treated AF patients who had very low C-trough levels, with a relatively high CHA2 DS2 -VASc score. Larger studies are warranted to confirm these preliminary observations.


Assuntos
Antitrombinas/administração & dosagem , Antitrombinas/sangue , Fibrilação Atrial/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/sangue , Tromboembolia/prevenção & controle , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/efeitos adversos , Fibrilação Atrial/sangue , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Testes de Coagulação Sanguínea , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Dabigatrana/sangue , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Dados Preliminares , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirazóis/sangue , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Piridonas/sangue , Sistema de Registros , Medição de Risco , Fatores de Risco , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Rivaroxabana/sangue , Tromboembolia/sangue , Tromboembolia/diagnóstico , Tromboembolia/etiologia , Fatores de Tempo , Resultado do Tratamento
5.
Muscle Nerve ; 57(2): 222-228, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28561920

RESUMO

INTRODUCTION: Few data exist on the feasibility and reliability of measuring muscular atrophy in 2 dimensions (2D) by ultrasonography (US) and elasticity with shear wave elastography (SWE) in spastic muscles. METHODS: Fourteen patients with chronic stroke took part in 2 intersession reliability experiments performed with 1-week intervals between sessions. Pennation angle (PA), muscle thickness (MT), and shear elastic modulus (µ) were measured in spastic gastrocnemius medialis (GM) muscles at rest and at maximal passive stretching in paretic and nonparetic legs. RESULTS: On the paretic side, the coefficient of variation (CV) in GM was 6.30% for MT and 6.40% for PA at rest and was 7.53% and 8.26% for MT and PA, respectively, at maximal passive stretching. The reliability of the µ measurement was good only for GM at rest on the paretic side (CV = 9.86%). DISCUSSION: 2D US associated with SWE shows promise for assessing structural changes in muscles. With some methodological adaptations, this approach could help guide spasticity treatment. Muscle Nerve 57: 222-228, 2018.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Espasticidade Muscular/diagnóstico por imagem , Espasticidade Muscular/diagnóstico , Adolescente , Adulto , Idoso , Atrofia , Módulo de Elasticidade , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/fisiopatologia , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/fisiopatologia , Variações Dependentes do Observador , Paresia/diagnóstico , Paresia/etiologia , Paresia/fisiopatologia , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/complicações , Ultrassonografia , Adulto Jovem
6.
Nutr Metab Cardiovasc Dis ; 26(10): 893-8, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27480449

RESUMO

BACKGROUND AND AIMS: Literature data suggest an association between Helicobacter pylori infection and glucose homeostasis. However, a causative link between them has not been demonstrated yet. The aim of this study is to investigate the effect of H. pylori eradication on glucose homeostasis in patients with type 2 diabetes. METHODS AND RESULTS: A randomized, double-blind, placebo-controlled trial was conducted to investigate the effect of H. pylori eradication on glucose homeostasis in 154 patients with type 2 diabetes and who tested positive for H. pylori infection (mean age (SD), 63.1 (8.1) years). Subjects were assigned to H. pylori eradication treatment or placebo. Metabolic and inflammatory parameters were measured in all subjects at baseline and 4 weeks after the treatment. H. pylori eradication led to an improvement in glucose homeostasis, measured by HOMA-IR (p < 0.001) and KITT (0 = 0.041), due to the decrease in fasting insulin levels (p = 0.004). The results also showed that lower levels of inflammatory parameters were present after eradication. CONCLUSION: To our knowledge this is the first randomized, double blind, controlled study where the effect of H. pylori eradication on glucose homeostasis in subjects with type 2 diabetes has been investigated. Our findings demonstrate that H. pylori eradication improves glucose homeostasis in patients with type 2 diabetes through a decrease in pro-inflammatory factors. TRIAL REGISTRATION NUMBER: ACTRN12609000255280 (https://www.anzctr.org.au/).


Assuntos
Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Glicemia/metabolismo , Claritromicina/administração & dosagem , Diabetes Mellitus Tipo 2/sangue , Esomeprazol/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/administração & dosagem , Idoso , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Biomarcadores/sangue , Claritromicina/efeitos adversos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/microbiologia , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Esomeprazol/efeitos adversos , Feminino , Infecções por Helicobacter/sangue , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Homeostase , Interações Hospedeiro-Patógeno , Humanos , Mediadores da Inflamação/sangue , Insulina/sangue , Resistência à Insulina , Itália , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
7.
Diabetes Obes Metab ; 18(9): 855-67, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27161301

RESUMO

Type 2 diabetes mellitus (T2DM) is a major cause of cardiovascular (CV) disease. Several large clinical trials have shown that the risk for patients with diabetes of developing CV complications is only partially reduced by early, intensive glycaemic control and lifestyle interventions, and that such complications result from changes in complex, not fully explored networks that contribute to the maintenance of endothelial function. The accumulation of senescent cells and the low-grade, systemic, inflammatory status that accompanies aging (inflammaging) are involved in the development of endothelial dysfunction. Such phenomena are modulated by epigenetic mechanisms, including microRNAs (miRNAs). MiRNAs can modulate virtually all gene transcripts. They can be secreted by living cells and taken up in active form by recipient cells, providing a new communication tool between tissues and organs. MiRNA deregulation has been associated with the development and progression of a number of age-related diseases, including the enduring gene expression changes seen in patients with diabetes. We review recent evidence on miRNA changes in T2DM, focusing on the ability of diabetes-associated miRNAs to modulate endothelial function, inflammaging and cellular senescence. We also discuss the hypothesis that miRNA-containing extracellular vesicles (i.e. exosomes and microvesicles) could be harnessed to restore a 'physiological' signature capable of preventing or delaying the harmful systemic effects of T2DM.


Assuntos
Envelhecimento/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Angiopatias Diabéticas/metabolismo , Endotélio Vascular/metabolismo , Vesículas Extracelulares/metabolismo , MicroRNAs/metabolismo , Senescência Celular , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/fisiopatologia , Endotélio Vascular/fisiopatologia , Epigênese Genética , Humanos , Hiperglicemia/metabolismo , Hipoglicemiantes/uso terapêutico , Inflamação
8.
Nutr Metab Cardiovasc Dis ; 26(4): 285-92, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27036849

RESUMO

AIMS: The possible link between hyperglycaemia-induced oxidative stress (OxS) and diabetic complications is suggested by many in vitro studies. However, not much attention has been paid to the clinical evidence supporting this hypothesis, as well as to their possible therapeutic implications. DATA SYNTHESIS: Some prospective studies show a direct correlation between an increase in OxS biomarkers and the appearance of diabetes complications. This is consistent with the evidence that any acute increase of glycaemia, particularly post-prandial, and hypoglycaemia causes endothelial dysfunction and inflammation, through the generation of an OxS. However, the detection of free radicals is difficult as they are highly reactive molecules with a short half-life. Instead, the metabolites of OxS are measured. Interventional trials with supplemented antioxidants have failed to show any beneficial effects. Conversely, natural foods show very promising results. CONCLUSIONS: The "new antioxidant" approach includes the possibility of controlling free radical production and increasing intracellular antioxidant defence, a concept different from the old one, when antioxidant activities implied scavenging the free radicals already produced. A synergistic action in this respect could convincingly be obtained with a balanced 'Mediterranean Diet' (MedD) type. Early intensive glucose control is still the best strategy to avoid OxS and its associated diabetes complications.


Assuntos
Antioxidantes/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Hipoglicemiantes/farmacologia , Estresse Oxidativo , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Angiopatias Diabéticas/sangue , Dieta Mediterrânea , Sinergismo Farmacológico , Endotélio Vascular/fisiopatologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Espécies Reativas de Oxigênio/metabolismo
10.
Diabet Med ; 32(2): 243-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25307368

RESUMO

AIMS: To investigate the validity and reliability of the Audit of Diabetes-Dependent Quality of Life instrument in older Italians with diabetes and to test the association of diabetes-related quality of life with glycaemic control over time. METHODS: A total of 558 outpatients with Type 2 diabetes from the Diabetic Unit of the Italian National Research Centre on Aging Hospital in Ancona were enrolled to complete questionnaires (Audit of Diabetes-Dependent Quality of Life-19 and the Short-Form-12), and to undergo clinical and biochemical testing at baseline and at 12 months of follow-up. The overall impact of diabetes using the average weighted impact score from the Audit of Diabetes-Dependent Quality of Life questionnaire was calculated. Participants were categorized according to this score as having either less or more negative diabetes-related quality of life. RESULTS: Participants had a mean ± SD age of 67.7 ± 9.2 years and 51.8% were male. Factor analysis and Cronbach's coefficient of internal consistency (Cronbach's α = 0.931) confirmed that the 19 domain-specific Audit of Diabetes-Dependent Quality of Life items could be combined into a single scale in this Italian population. The impact score correlated with the physical (r = 0.275; P < 0.001) and mental components (r = 0.291; P < 0.001) of the Short-Form-12 questionnaire. Significant differences were found according to diabetic complications in specific Audit of Diabetes-Dependent Quality of Life items and impact scores. Insulin use had a greater association with a more negative quality of life compared with other antidiabetic agents. A multivariate linear regression model with restricted linear spline application showed that the relationship between HbA1c and impact score was not linear and that the change in the impact score was associated with improved glycaemic control in those with a less negative diabetes-related quality of life at 12 months. CONCLUSIONS: The Audit of Diabetes-Dependent Quality of Life-19 is a valid tool for measuring the impact of diabetes on quality of life in older Italians. Perception of diabetes-related quality of life is associated with glycaemic control over time.


Assuntos
Envelhecimento , Efeitos Psicossociais da Doença , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Tipo 2/terapia , Avaliação do Impacto na Saúde/métodos , Hiperglicemia/prevenção & controle , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Terapia Combinada/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta para Diabéticos/efeitos adversos , Feminino , Seguimentos , Hospitais Urbanos , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Insulina/efeitos adversos , Insulina/uso terapêutico , Itália , Masculino , Pessoa de Meia-Idade , Ambulatório Hospitalar , Reprodutibilidade dos Testes , Inquéritos e Questionários
11.
J Intellect Disabil Res ; 59(8): 689-702, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25414060

RESUMO

BACKGROUND: Studies on adaptive behaviour and ageing in adults with Down syndrome (DS) (without dementia) have typically analysed age-related change in terms of the total item scores on questionnaires. This research extends the literature by investigating whether the age-related changes in adaptive abilities could be differentially attributed to changes in the number or severity (intensity) of behavioural questionnaire items endorsed. METHODS: The Adaptive Behaviour Assessment System-II Adult (ABAS-II Adult) was completed by parents and caregivers of 53 adults with DS aged between 16 and 56 years. Twenty adults with DS and their parents/caregivers were a part of a longitudinal study, which provided two time points of data. In addition 33 adults with DS and their parents/caregivers from a cross-sectional study were included. Random effects regression analyses were used to examine the patterns in item scores associated with ageing. RESULTS: Increasing age was found to be significantly associated with lower adaptive behaviour abilities for all the adaptive behaviour composite scores, expect for the practical composite. These associations were entirely related to fewer ABAS-II Adult items being selected as present for the older participants, as opposed to the scores being attributable to lower item severity. CONCLUSIONS: This study provides evidence for a differential pattern of age-related change for various adaptive behaviour skills in terms of range, but not severity. Possible reasons for this pattern will be discussed. Overall, these findings suggest that adults with DS may benefit from additional support in terms of their social and conceptual abilities as they age.


Assuntos
Adaptação Psicológica , Envelhecimento/psicologia , Síndrome de Down/psicologia , Adolescente , Adulto , Fatores Etários , Cuidadores , Estudos Transversais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pais , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto Jovem
13.
Nutr Metab Cardiovasc Dis ; 24(2): 116-23, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24094827

RESUMO

BACKGROUND AND AIMS: Hypoglycemia produces thrombosis activation, but little attention has been paid to the effects of hyperglycemia following recovery from hypoglycemia on thrombosis activation. METHODS AND RESULTS: In both twenty-two healthy subjects and twenty-one matched persons with type 1 diabetes, recovery from a 2-h induced hypoglycemia was obtained by reaching normo-glycemia or hyperglycemia for another 2 h. After this, normal glycemia was maintained for the following 6 h. Hyperglycemia after hypoglycemia was also repeated with the concomitant infusion of vitamin C. In both controls and people with diabetes, the recovery with normo-glycemia was accompanied by a significant improvement of Von Willebrand factor (vWF), prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III-complexes (TAT), P-selectin, plasminogen activator inhibitor-1 (PAI-1), nitrotyrosine and 8-iso-prostaglandin F2α (8-iso-PGF2α) (p < 0.01 vs hypoglycemia for all the parameters), all directly affected by hypoglycemia itself (p < 0.01 vs baseline for all the parameters). On the contrary, the recovery with hyperglycemia after hypoglycemia worsens all these parameters (p < 0.01 vs normoglycemia for all the parameters), an effect persisting even after the additional 6 h of normo-glycemia. The effect of hyperglycemia following hypoglycemia was partially counterbalanced when vitamin C was infused (p < 0.01 vs hyperglycemia alone for all the parameters), suggesting that hyperglycemia following hypoglycemia may activate thrombosis through the oxidative stress production. CONCLUSION: This study shows that, in type 1 diabetes as well as in controls, the way in which recovery from hypoglycemia takes place could play an important role in favoring the activation of thrombosis and oxidative stress, widely recognized cardiovascular risk factors.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Endotélio Vascular/patologia , Hiperglicemia/tratamento farmacológico , Hipoglicemia/terapia , Trombose/patologia , Adulto , Antitrombina III/metabolismo , Ácido Ascórbico/administração & dosagem , Glicemia/metabolismo , Dinoprosta/análogos & derivados , Dinoprosta/metabolismo , Feminino , Voluntários Saudáveis , Humanos , Hiperglicemia/etiologia , Hipoglicemia/complicações , Masculino , Estresse Oxidativo/fisiologia , Selectina-P/metabolismo , Fragmentos de Peptídeos/metabolismo , Peptídeo Hidrolases/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Precursores de Proteínas/metabolismo , Protrombina/metabolismo , Trombose/etiologia , Adulto Jovem , Fator de von Willebrand/metabolismo
14.
Mol Psychiatry ; 19(4): 504-10, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22965006

RESUMO

Autism spectrum disorder (ASD) depends on a clinical interview with no biomarkers to aid diagnosis. The current investigation interrogated single-nucleotide polymorphisms (SNPs) of individuals with ASD from the Autism Genetic Resource Exchange (AGRE) database. SNPs were mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG)-derived pathways to identify affected cellular processes and develop a diagnostic test. This test was then applied to two independent samples from the Simons Foundation Autism Research Initiative (SFARI) and Wellcome Trust 1958 normal birth cohort (WTBC) for validation. Using AGRE SNP data from a Central European (CEU) cohort, we created a genetic diagnostic classifier consisting of 237 SNPs in 146 genes that correctly predicted ASD diagnosis in 85.6% of CEU cases. This classifier also predicted 84.3% of cases in an ethnically related Tuscan cohort; however, prediction was less accurate (56.4%) in a genetically dissimilar Han Chinese cohort (HAN). Eight SNPs in three genes (KCNMB4, GNAO1, GRM5) had the largest effect in the classifier with some acting as vulnerability SNPs, whereas others were protective. Prediction accuracy diminished as the number of SNPs analyzed in the model was decreased. Our diagnostic classifier correctly predicted ASD diagnosis with an accuracy of 71.7% in CEU individuals from the SFARI (ASD) and WTBC (controls) validation data sets. In conclusion, we have developed an accurate diagnostic test for a genetically homogeneous group to aid in early detection of ASD. While SNPs differ across ethnic groups, our pathway approach identified cellular processes common to ASD across ethnicities. Our results have wide implications for detection, intervention and prevention of ASD.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Transtornos Globais do Desenvolvimento Infantil/genética , Redes Reguladoras de Genes/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Povo Asiático/etnologia , Povo Asiático/genética , Estudos de Coortes , Feminino , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Testes Genéticos , Humanos , Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Masculino , Proteínas do Tecido Nervoso/genética , Receptor de Glutamato Metabotrópico 5/genética , População Branca/genética
15.
Int J Cardiol ; 164(1): 99-105, 2013 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-21737157

RESUMO

BACKGROUND: The functional characteristics of circulating angiogenic cells (CACs) are impaired in congestive heart failure (CHF) patients, suggesting that CAC dysfunction could contribute to CHF pathogenesis. However, the underlying mechanisms are only partly unraveled. No data are currently available regarding telomere/telomerase system in CACs of CHF patients. METHODS: CACs were obtained from 80 subjects: 40 healthy control subjects (CTR) [median age (IQR), 80 (76-85 yrs)] and 40 patients affected by post-ischemic cardiomyopathy CHF [median age (IQR), 82 (77-89)]. CAC and leukocyte telomere length, assessed as T/S ratio, and telomerase (TERT) activity were determined in all the enrolled subjects. Specificity and sensitivity of CAC and leukocyte T/S in discriminating between CHF and CTR were evaluated using Receiver Operator Characteristic (ROC) curve analysis and reported as AUC values. CD34+/VEGFR2+ number and pro-inflammatory cytokines plasma levels, such as IL-6 and TNF-α, were also measured. RESULTS: CAC T/S and TERT activity were significantly reduced in CHF patients compared to CTR subjects. In leukocytes, only a significant T/S reduction was observed. AUC values were higher for CAC T/S with respect to leukocyte T/S (AUC=0.89, and AUC=0.73, P<0.01, respectively). In multivariate analysis, leukocyte T/S, CAC T/S, CAC TERT activity and NT-proBNP levels were confirmed as parameters significantly associated with CHF. CD34+/VEGFR2+ number, IL-6 and TNF-α plasma levels were significantly increased in CHF patients. CONCLUSIONS: CACs from CHF patients are characterized by telomere/telomerase system impairment, providing new insight into the clinical relevance of CACs in CHF pathogenesis.


Assuntos
Células , Insuficiência Cardíaca/sangue , Neovascularização Fisiológica , Telomerase/fisiologia , Telômero/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino
16.
Orthop Traumatol Surg Res ; 98(2): 159-66, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22336486

RESUMO

INTRODUCTION: A knee is typically evaluated passively by a clinician during an office visit, without using dedicated measurement tools. When the knee is evaluated with the patient standing and actively participating in the movement, the results will differ than when the knee is passively moved through its range-of-motion by the surgeon. If a precise measurement system was available, it could provide additional information to the clinician during this evaluation. HYPOTHESIS: The goal of this study was to verify the reproducibility of a fast, flexible optical measurement system to measure rotational knee laxity during weight-bearing. MATERIAL AND METHODS: Two passive reflective targets were placed on the legs of 11 subjects to monitor femur and tibia displacements in three dimensions. Subjects performed internal and external rotation movements with the knee extended or flexed 30°. During each movement, seven variables were measured: internal rotation, external rotation and overall laxity in extension and 30° flexion, along with neutral rotation value in 30° flexion. Measurement accuracy was also assessed and the right and left knees were compared. Reproducibility was assessed over two measurements sessions. RESULTS: The calculated intra-class correlation coefficient (ICC) for reproducibility was above 0.9 for five of the seven variables measured. The calculated ICC for the right/left comparison was above 0.75 for five of the seven variables measured. DISCUSSION: These results confirmed that the proposed system provides reproducible measurements. Our right/left comparison results were consistent with the published literature. This system is fast, reproducible and flexible, which makes it suitable for assessing various weight-bearing movements during clinical evaluations. LEVEL OF EVIDENCE: Level III, experimental study.


Assuntos
Marcha/fisiologia , Articulação do Joelho/anatomia & histologia , Amplitude de Movimento Articular/fisiologia , Suporte de Carga/fisiologia , Adulto , Feminino , Seguimentos , Humanos , Articulação do Joelho/fisiologia , Masculino , Dispositivos Ópticos , Postura , Valores de Referência , Reprodutibilidade dos Testes , Rotação
17.
Knee Surg Sports Traumatol Arthrosc ; 20(4): 762-6, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22258650

RESUMO

PURPOSE: The aim of our study was to evaluate knee rotational laxity and proprioceptive function 2 years after partial anterior cruciate ligament (ACL) reconstruction. According to our hypothesis, partial ACL reconstruction could restore knee laxity and function to the intact level. METHODS: We conducted a study in fifteen consecutive patients undergoing partial ACL reconstruction. Fifteen anteromedial bundle tears were identified intraoperatively. Partial ACL reconstructions were performed by the same senior surgeon using a single-incision technique. A bone-patellar tendon-bone graft was used in 13 cases and a double-stranded semitendinosus graft in 2 cases of chronic patellar tendonitis. The mean age at surgery was 29 years. The time between ACL tear and surgery averaged 7.8 months (range 2.5-29.5 months). We developed an original device designed to assess knee proprioception (passive and active) and measure weight-bearing rotational laxity in full extension and at 30°, 60° and 90° of knee flexion. All measurements were taken on both the reconstructed and healthy knee. RESULTS: The mean follow-up of the study was 3.4 years (range 2.6-4.4). No statistically significant difference in rotational laxity, active or passive proprioception could be observed between the reconstructed and healthy knee. External rotation was significantly greater than internal rotation in full extension and at 30° of flexion in the reconstructed and the healthy knee (P < 0.05). For each knee, active proprioception was found to be significantly different (higher) than passive proprioception (P < 0.05). CONCLUSION: Our study did not detect any difference in rotational laxity and proprioception between the reconstructed and the healthy knee. Therefore, partial ACL reconstruction appears to restore satisfactory knee laxity and function in case of partial ACL tear. LEVEL OF EVIDENCE: IV.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior/métodos , Instabilidade Articular/diagnóstico , Propriocepção/fisiologia , Rotação , Adolescente , Adulto , Ligamento Cruzado Anterior/cirurgia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Instabilidade Articular/prevenção & controle , Traumatismos do Joelho/diagnóstico , Traumatismos do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Exame Físico/métodos , Estudos Prospectivos , Amplitude de Movimento Articular/fisiologia , Valores de Referência , Medição de Risco , Ruptura/cirurgia , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
18.
Knee Surg Sports Traumatol Arthrosc ; 20(2): 331-6, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21748394

RESUMO

PURPOSE: The influence of the medial patellar ligamentous structures on patellar tracking has rarely been studied. Thus the main purpose of this cadaveric biomechanical study was to determine the influence of the medial patellofemoral (MPFL), medial patellomeniscal (MPML) and medial patellotibial (MPTL) ligaments on the three-dimensional patellar tracking during knee flexion. This study was conducted using a validated cadaveric optoelectronic protocol for analysis of patellar kinematics. METHODS: For each cadaveric knee study, four successive acquisitions were performed; first was studied patellar tracking in healthy knees, then the junction between MPFL and vastus medialis obliquus (VMO) was sectioned, the MPFL was released at its patellar attachment and finally was released the insertion of the MPML and MPTL. RESULTS: In this study, the MPFL accounts for 50-60% of the medial stabilization forces of the lateral patellar shift during patellar engagement in the femoral trochlea. This work confirm and clarify the role of the MPFL as the primary stabilizer of the patella during the initial 30° of knee flexion. Moreover, this study shows no significant results regarding the stabilizing action of the VMO on the patella during knee flexion. CONCLUSION: This in vitro study, conducted with an experimental protocol previously validated in the literature, helps quantify the actions of the MPFL, the VMO, and the MPML/MPTL respectively, and identify areas of joint motion where these structures have the most significant influence. This confirms the importance of reconstruction in the treatment of chronic patellar instability. During its reconstruction, care should be taken to adjust the MPFL balance during the initial 20°-30° of flexion.


Assuntos
Articulação do Joelho/fisiologia , Ligamentos Articulares/fisiologia , Patela/fisiologia , Fenômenos Biomecânicos , Humanos , Técnicas In Vitro
19.
J Eur Acad Dermatol Venereol ; 25(12): 1466-70, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22077871

RESUMO

BACKGROUND: Wegener's granulomatosis (WG) is a rare granulomatous necrotizing vasculitis of small and medium vessels which has predilection for upper airways, lungs and kidney. However, any other organ, including the skin and oral cavity, can be involved. Although mucocutaneous lesions are relatively common, they have only rarely been reported as localized manifestation of the disease. OBJECTIVES: Our aim was to evaluate the type and sites of skin and mucosal lesions, clinical course and response to treatment, histologic features and laboratory findings in localized WG. METHODS: The medical records of three patients (two women and one man) with localized WG followed up at our hospitals for a mean time of 10 years were studied. RESULTS: All patients presented with facial plaques infiltrating the nasal and palatal mucosae and cartilages and, in one case, perforating the palatal bone. Anti-neutrophil cytoplasmic antibodies, which are the marker for multisystem WG, were negative. The disease, refractory to various immunosuppressants, responded well, albeit incompletely, to prednisone plus cyclophosphamide. LIMITATIONS: The limited number of patients is counterbalanced by the rarity of the disease. CONCLUSIONS: Our cases may represent a rare distinctive subset of WG limited to the facial region and upper airway mucosa but showing a locally aggressive behaviour leading to cartilage and bony destruction.


Assuntos
Granulomatose com Poliangiite/diagnóstico , Feminino , Granulomatose com Poliangiite/patologia , Granulomatose com Poliangiite/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
20.
Endodoncia (Madr.) ; 29(3): 119-125, jul.-sept. 2011. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-102083

RESUMO

Objetivo: El propósito de este estudio fue evaluar y comparar “ex vivo”, el porcentaje de paredes dentinarias instrumentadas, mediante el uno de instrumentos de niquel-titanio pertenecientes a los sistemas rotatorios ProTaper Universal e Easy RaCe, complementado con S-Apex. Material y métodos: Se utilizaron 20 dientes unirradiculares humanos extraídos e incorporados en un nuevo tipo de modelo experimental para evaluar la eficiencia de la instrumentación. Se dividió la muestra en dos grupos homogéneos de 10 dientes (n=10) cada uno. En el Grupo 1 los conductos se instrumentaron con ProTaper Universaly en el Grupo 2 Easy RaCe/S-Apex, complementado con S-Apex. Se realizaron secciones transversales de cada espécimen a 3,9 y 15 mm de la longitud de trabajo (LT), lo que fueron fotografiados con microscopía óptica. Las imágenes fueron digitalizadas y evaluadas comparando la morfología de los conductos, antes y después de la instrumentación. Los datos obtenidos fueron analizados por medio la las pruebas no paramétricas de Mann-Whitney y Friedman, estableciéndose un nivel de significación de P<0,05. Resultados y conclusiones: A 15 mm de la LT, el sistema Easy RaCe/S-Apex demostró un desempeño significativamente superior (p<0,05) en comparación con ProTaper Universal. No hubo diferencias significativas (p>0,05), entre ambos sistemas a 3 y 9 mm de la LT (AU)


Objetive: The purpose of this ex vivo study was to evaluate and compare, the percentage of instrumented dentine walls in sections made at 3, 9 and 15 mm form the working length, using engine-driven nickel-titanium instrumentation systems. Protaper Universal and EasyRaCe complemented with S-Apex. Materials and methods: Twenty extracted single rooted human teeth were used along with a new type of experimental model. The sample was divided into two homogeneous groups of 10 teeth each (n=10). In group 1 the canals were instrumented with ProTaper Universal while in group 2 canals were instrumented with Easy RaCe/S-Apex. All specimens were standardized at 19 mm. They were then horizontally sectioned at 3,9 and 15 mm form the working length, and photographed using light microcopy. The images were digitalized and evaluated, comparing the morphology of the canals before and after instrumentation. Results and conclusions: the results were analyzed using the Mann-Whitney-U test and Friedman´s non-parametric tests, with a significance level of P<0,05. At 15 mm form the working length, the results revealed a significantly better performance for the Easy RaCe/S-Apex system, compared to the ProTaper Universal system. No significant differences were found between both systems at 3 and 9 mm form the working length (AU)


Assuntos
Humanos , Preparo de Canal Radicular/instrumentação , Instrumentos Odontológicos , Camada de Esfregaço , Dentina/ultraestrutura , Microscopia
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