RESUMO
PURPOSE: To assess the effects of testosterone (T)-based gender affirming hormone therapy (GAHT) on liver blood tests (LBTs) in assigned female at birth adults, using a meta-analytic approach. METHODS: Prospective and retrospective studies were selected that reported the prevalence of biochemical liver damage (BLD) and LBTs changes during T therapy. Data collected included pre-and-during therapy alanine-aminotransferase (ALT), aspartate-aminotransferase (AST), gamma-glutamyl-transferase (GGT), and alkaline phosphatase (ALP) mean concentration values. RESULTS: The prevalence of BLD in 14 studies on 1698 subjects was 1% (95% CI 0.00-3.00; I2 = 14.1%; p = 0.82). In 17 studies on 2758 subjects, GAHT was associated with a statistically (but not clinically) significant increase in AST, GGT and ALP at 12 months and ALT at 3-7 (MD: 1.19 IU/l; 95% CI 0.31, 2.08; I2: 0%), at 12 (MD: 2.31 IU/l; 95% CI 1.41, 3.21; I2: 29%), but with no more significant increase at 24 months (MD: 1.71 IU/l; 95% CI -0.02, 3.44; I2: 0%). CONCLUSIONS: Analysis of aggregate estimates confirms a low risk of BLD and abnormalities in LBTs, transient in most cases, during T-based GAHT, thus suggesting a limited need for careful liver monitoring in AFAB people.
RESUMO
PURPOSE: We aimed at identifying clinical risk factors or early markers of metabolic syndrome (MetS) in people with spinal cord injury (SCI) that would facilitate a timely diagnosis and implementation of preventive/therapeutic strategies. METHODS: One hundred sixty-eight individuals with chronic (> 1 year) SCI underwent clinical and biochemical evaluations. MetS was diagnosed according to modified criteria of the International Diabetes Federation validated in people with SCI. Wilcoxon rank-sum test and χ2 test were used to compare variables between groups with and without MetS. Multiple logistic regression analysis was performed to reveal independent associations with MetS among variables selected by univariate linear regression analyses. RESULTS: MetS was diagnosed in 56 of 132 men (42.4%) and 17 of 36 women (47.2%). At univariate regression analyses, putative predictors of MetS were an older age, a higher number of comorbidities, a lower insulin-sensitivity, the presence and intensity of pain, a shorter injury duration, a poorer leisure time physical activity (LTPA) and an incomplete motor injury. At the multiple logistic regression analysis, a significant independent association with MetS only persisted for a poorer LTPA in hours/week (OR: 0.880, 95% CI 0.770, 0.990) and more severe pain symptoms as assessed by the numeral rating scale (OR: 1.353, 95% CI 1.085, 1.793). CONCLUSION: In people with chronic SCI, intense pain symptoms and poor LTPA may indicate a high likelihood of MetS, regardless of age, SCI duration, motor disability degree, insulin-sensitivity and comorbidities.
Assuntos
Síndrome Metabólica , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/epidemiologia , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Fatores de Risco , Doença Crônica , Exercício Físico/fisiologia , Idoso , Estudos TransversaisRESUMO
Dementia, osteoporosis, and fragility fractures are chronic diseases, often co-existing in older adults. These conditions pose severe morbidity, long-term disability, and mortality, with relevant socioeconomic implications. While in the research arena, the discussion remains on whether dementia is the cause or the consequence of fragility fractures, healthcare professionals need a better understanding of the interplay between such conditions from epidemiological and physiological standpoints. With this review, we summarized the available literature surrounding the relationship between cognitive impairment, dementia, and both low bone mineral density (BMD) and fragility fractures. Given the strength of the bi-directional associations and their impact on the quality of life, we shed light on the biological connections between brain and bone systems, presenting the main mediators, including gut microbioma, and pathological pathways leading to the dysregulation of bone and brain metabolism. Ultimately, we synthesized the evidence about the impact of available pharmacological treatments for the prevention of fragility fractures on cognitive functions and individuals' outcomes when dementia coexists. Vice versa, the effects of symptomatic treatments for dementia on the risk of falls and fragility fractures are explored. Combining evidence alongside clinical practice, we discuss challenges and opportunities related to the management of older adults affected by cognitive impairment or dementia and at high risk for fragility fracture prevention, which leads to not only an improvement in patient health-related outcomes and survival but also a reduction in healthcare cost and socio-economic burden.
Assuntos
Demência , Osteoporose , Fraturas por Osteoporose , Humanos , Idoso , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Qualidade de Vida , Osteoporose/epidemiologia , Osteoporose/tratamento farmacológico , Acidentes por Quedas/prevenção & controle , Demência/epidemiologiaRESUMO
PURPOSE: Non-alcoholic fatty liver disease (NAFLD) and hypovitaminosis D are highly prevalent in people with spinal cord injury (SCI) and could exert an unfavorable influence on cardiovascular profile and rehabilitation outcomes. We aimed to assess the independent association between low 25-hydroxy vitamin D (25(OH)D) levels and NAFLD in people with chronic (> 1 year) SCI. METHODS: One hundred seventy-three consecutive patients with chronic SCI (132 men and 41 women) admitted to a rehabilitation program underwent clinical/biochemical evaluations and liver ultrasonography. RESULTS: NAFLD was found in 105 patients (60.7% of the study population). They were significantly older and exhibited a poorer leisure time physical activity (LTPA) and functional independence in activities of daily living, a greater number of comorbidities and a higher prevalence of metabolic syndrome (MetS) and its correlates, including lower HDL and higher values of body mass index (BMI), systolic blood pressure, HOMA-index of insulin resistance and triglycerides. 25(OH)D levels were significantly lower in NAFLD (median: 10.6 ng/ml, range: 2.0-31.0) than in non-NAFLD group (22.5 ng/ml, 4.2-51.6). When all these variables were included in a multiple logistic regression analysis, a significant independent association with NAFLD only persisted for lower 25(OH)D levels, a greater number of comorbidities and a poorer LTPA. The ROC analysis revealed that 25(OH)D levels < 18.25 ng/ml discriminated patients with NAFLD with a sensitivity of 89.0% and a specificity of 73.0% (AUC: 85.7%; 95%CI: 79.6-91.7%). NAFLD was exhibited by 83.9% of patients with 25(OH)D levels < 18.25 ng/ml and by 18% of those with 25(OH)D levels ≥ 18.25 ng/ml (p < 0.0001). CONCLUSION: In people with chronic SCI, 25(OH)D levels < 18.25 ng/ml may represent a marker of NAFLD independent of MetS-related features. Further studies are warranted to define the cause-effect relationships of this association.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Traumatismos da Medula Espinal , Deficiência de Vitamina D , Masculino , Humanos , Feminino , Hepatopatia Gordurosa não Alcoólica/complicações , Estudos Transversais , Atividades Cotidianas , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , Vitamina D , Traumatismos da Medula Espinal/complicaçõesRESUMO
INTRODUCTION: Hypertension (HTN) is the leading cause of mortality and disability in the world. In Argentina, almost 44% of hypertensives do not know about their condition and this may be due to the low rate of blood pressure (BP) measurements during the office visit. Our hypothesis is that the measurement and electronic recording of BP (BPMR) is not a routine practice in Argentina. OBJECTIVE: To describe the rate of office BP measurement in Argentina. METHODS: This is a retrospective, multicentre, point prevalence study. We analysed all office visits on 9/19/2019 at 9 medical institutions in 6 provinces of Argentina. RESULTS: Two thousand and eighty-two office visits were analysed. The patients' mean age was 52.1 years (18-103), 1790 (59.7%) were female, and 702 (36.1%) were hypertensives. BP was measured in 420 visits (14.1%; 95% CI 12.8-15.4). In a multivariate logistic regression model, history of HTN (OR 1.91, P<.001) and previous cardiovascular event (OR 1.76, P<.001) were associated with more odds of BPMR. The presence of cancer was associated with fewer odds of BPMR (OR .51, P<.01). Cardiology measured BP up to 49.5% (144/291 visits), followed by internal medicine 30% (152/507 visits). CONCLUSION: BPMR during office visits is deficient in Argentina and represents a missed healthcare opportunity. Different strategies are needed to detect hypertensive patients and reduce cardiovascular events.
Assuntos
Determinação da Pressão Arterial , Hipertensão , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Feminino , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos RetrospectivosRESUMO
PURPOSE: Autoimmunity has been implicated in some patients with idiopathic chronic urticaria (CU). Because of the frequency of autoimmune thyroid diseases, their association with CU deserves special attention. We tested both the existence and the extent of an association between thyroid autoimmunity and CU. METHODS: A thorough search of PubMed, Scopus, Web of Science, and Cochrane databases was performed. Studies reporting the positivity rate for anti-thyroperoxidase antibodies (TPOAbs) in people with (cases) and without CU (controls) were included. Quality of the studies was assessed by the Newcastle-Ottawa Scale. Between-study heterogeneity was assessed by Cochrane Q and I2 tests, and the odds ratio (OR) for TPOAbs positivity was combined using random-effects models. RESULTS: Nineteen studies provided information about TPOAbs positivity on 14,351 patients with CU and 12,404 controls. The pooled estimate indicated a more than fivefold increased risk of exhibiting TPOAbs positivity in the group with CU (pooled OR 5.18, 95% CI 3.27, 8.22; P < 0.00001). Correction for publication bias had a negligible effect on the overall estimate (pooled adjusted OR: 4.42, 95% CI 2.84, 6.87, P < 0.0001). Betweenstudy heterogeneity was established (I2 = 62%, Pfor heterogeneity = 0.0002) and when, according to metaregression models, a sensitivity analysis was restricted to the 16 studies with the highest quality scores, the OR for TPOAbs positivity rose to 6.72 (95% CI 4.56, 9.89; P < 0.00001) with no significant heterogeneity (I2 = 31%, Pfor heterogeneity = 0.11). CONCLUSIONS: Patients with CU have a five-to-nearly sevenfold higher risk of displaying TPOAbs positivity. All patients with CU may well be offered a screening for thyroid autoimmunity.
Assuntos
Urticária Crônica , Urticária , Autoimunidade , Estudos de Casos e Controles , Humanos , Glândula Tireoide , Urticária/etiologiaRESUMO
Epicardial adipose tissue is a novel cardiovascular risk factor. It plays a role in the progression of coronary artery disease, heart failure and atrial fibrillation. Given its rapid metabolism, clinical measurability, and modifiability, epicardial fat works well as therapeutic target of drugs modulating the adipose tissue. Epicardial fat responds to glucagon-like peptide 1 receptor agonists (GLP1A) and sodium glucose co-transporter 2 inhibitors (SGLT2i). GLP-1A and SGLT2i provide weight loss and cardiovascular protective effects beyond diabetes control, as recently demonstrated. The potential of modulating the epicardial fat morphology and genetic profile with targeted pharmacological agents can open new avenues in the pharmacotherapy of diabetes and obesity, with particular focus on cardiovascular risk reduction.
Assuntos
Tecido Adiposo , Doenças Cardiovasculares , Diabetes Mellitus/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Obesidade/tratamento farmacológico , Pericárdio/patologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Cardiotônicos/farmacologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/prevenção & controle , Fatores de Risco de Doenças Cardíacas , Humanos , Distribuição TecidualRESUMO
PURPOSE: To investigate the relationship between the single-point insulin sensitivity estimator (SPISE) index, an insulin sensitivity indicator validated in adolescents and adults, and metabolic profile in overweight/obese children, and to evaluate whether basal SPISE is predictive of impaired glucose regulation (IGR) development later in life. METHODS: The SPISE index (= 600 × HDL0.185/Triglycerides0.2 × BMI1.338) was calculated in 909 overweight/obese children undergoing metabolic evaluations at University of Cagliari, Italy, and in 99 normal-weight, age-, sex-comparable children, selected as a reference group, together with other insulin-derived indicators of insulin sensitivity/resistance. 200 overweight/obese children were followed-up for 6.5 [3.5-10] years, data were used for longitudinal retrospective investigations. RESULTS: At baseline, 96/909 (11%) overweight/obese children had IGR; in this subgroup, SPISE was significantly lower than in normo-glycaemic youths (6.3 ± 1.7 vs. 7 ± 1.6, p < 0.001). The SPISE index correlated positively with the insulin sensitivity index (ISI) and the disposition index (DI), negatively with age, blood pressure, HOMA-IR, basal and 120 min blood glucose and insulin (all p values < 0.001). A correlation between SPISE, HOMA-IR and ISI was also reported in normal-weight children. At the 6.5-year follow-up, lower basal SPISE-but not ISI or HOMA-IR-was an independent predictor of IGR development (OR = 3.89(1.65-9.13), p = 0.002; AUROC: 0.82(0.72-0.92), p < 0.001). CONCLUSION: In children, low SPISE index is significantly associated with metabolic abnormalities and predicts the development of IGR in life.
Assuntos
Glicemia/metabolismo , Transtornos do Metabolismo de Glucose , Resistência à Insulina , Metaboloma , Sobrepeso , Obesidade Infantil , Adolescente , Adulto , Fatores Etários , Índice de Massa Corporal , Feminino , Transtornos do Metabolismo de Glucose/sangue , Transtornos do Metabolismo de Glucose/diagnóstico , Transtornos do Metabolismo de Glucose/epidemiologia , Transtornos do Metabolismo de Glucose/metabolismo , Humanos , Secreção de Insulina , Itália/epidemiologia , Masculino , Sobrepeso/diagnóstico , Sobrepeso/epidemiologia , Sobrepeso/metabolismo , Obesidade Infantil/diagnóstico , Obesidade Infantil/epidemiologia , Obesidade Infantil/metabolismo , Valor Preditivo dos Testes , Puberdade/metabolismo , Fatores de Risco , Triglicerídeos/sangueRESUMO
AIMS: Parkinson's disease and related disorders are devastating neurodegenerative pathologies. Since α-synuclein was identified as a main component of Lewy bodies and neurites, efforts have been made to clarify the pathogenic mechanisms of α-synuclein's detrimental effects. α-synuclein oligomers are the most harmful species and may recruit and activate glial cells. Inflammation is emerging as a bridge between genetic susceptibility and environmental factors co-fostering Parkinson's disease. However, direct evidence linking inflammation to the harmful activities of α-synuclein oligomers or to the Parkinson's disease behavioural phenotype is lacking. METHODS: To clarify whether neuroinflammation influences Parkinson's disease pathogenesis, we developed: (i) a 'double-hit' approach in C57BL/6 naive mice where peripherally administered lipopolysaccharides were followed by intracerebroventricular injection of an inactive oligomer dose; (ii) a transgenic 'double-hit' model where lipopolysaccharides were given to A53T α-synuclein transgenic Parkinson's disease mice. RESULTS: Lipopolysaccharides induced a long-lasting neuroinflammatory response which facilitated the detrimental cognitive activities of oligomers. LPS-activated microglia and astrocytes responded differently to the oligomers with microglia activating further and acquiring a pro-inflammatory M1 phenotype, while astrocytes atrophied. In the transgenic 'double-hit' A53T mouse model, lipopolysaccharides aggravated cognitive deficits and increased microgliosis. Again, astrocytes responded differently to the double challenge. These findings indicate that peripherally induced neuroinflammation potentiates the α-synuclein oligomer's actions and aggravates cognitive deficits in A53T mice. CONCLUSIONS: The fine management of both peripheral and central inflammation may offer a promising therapeutic approach to prevent or slow down some behavioural aspects in α-synucleinopathies.
Assuntos
Inflamação/patologia , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , alfa-Sinucleína/metabolismo , Animais , Astrócitos/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microglia/patologia , Degeneração Neural/tratamento farmacológico , Degeneração Neural/patologia , Doenças do Sistema Nervoso/patologia , Substância Negra/efeitos dos fármacos , Substância Negra/patologia , alfa-Sinucleína/farmacologiaRESUMO
The aim of this work was to identify and quantify the bioaccesible phenolic compounds and evaluate their relationship with the antioxidant properties of three different cookies formulated with 10.5% peach pulp incorporation and 50% fat or added-sucrose reduction. Peach pulp and dietary fiber were incorporated in cookie formulation and two levels of fat or sucrose were analyzed. Cookie quality was modified by fruit incorporation and reduction of fat and added-sucrose. Fruit incorporation changed the polyphenol profile and improved antioxidant properties. Most phenolic compounds quantified in both the extracts and the different stages of the simulated digestion were higher in the sucrose/fat reduced samples than in the control samples, which represents a nutritional improvement of the pulp-enriched cookies. Evaluation of the bioaccessibility of polyphenols from cookies showed that a fraction of polyphenol could be absorbed by the small intestine. This fraction ranged between ~21% and ~25%, according to the sample.
Assuntos
Antioxidantes/química , Fibras na Dieta/análise , Análise de Alimentos , Frutas/química , Polifenóis/metabolismo , Digestão , Prunus persica/químicaRESUMO
BACKGROUND AND PURPOSE: The involvement of protein C (PC) pathway components in multiple sclerosis (MS) has scarcely been explored. The aim was to investigate their levels in relation to clinical and neurodegenerative magnetic resonance imaging (MRI) outcomes in patients. METHODS: In all, 138 MS patients and 42 healthy individuals were studied. PC, protein S (PS) and soluble endothelial protein C receptor (sEPCR) were evaluated by multiplex assays and enzyme-linked immunosorbent assay. Regression analyses between 3 T MRI outcomes and PC pathway components were performed. ancova was used to compare MRI volumes based on protein level quartiles. Partial correlation was assessed amongst levels of PC pathway components and hemostasis protein levels, including soluble thrombomodulin (sTM), heparin cofactor II (HCII), plasminogen activator inhibitor 1 (PAI-1) and factor XII (FXII). The variation of PC concentration across four time points was evaluated in 32 additional MS patients. RESULTS: There was an association between PC concentration, mainly reflecting the zymogen PC, and MRI measures for volumes of total gray matter (GM) (P = 0.003), thalamus (P = 0.007), cortex (P = 0.008), deep GM (P = 0.009) and whole brain (P = 0.026). Patients in the highest PC level quartile were characterized by the lowest GM volumes. Correlations of PC-HCII, PC-FXII and sEPCR-sTM values were detectable in MS patients, whilst PC-PS and PS-PAI-1 correlations were present in healthy individuals only. CONCLUSIONS: Protein C plasma concentrations might be associated with neurodegenerative MRI outcomes in MS. Several differences in correlation amongst protein plasma levels suggest dysregulation of PC pathway components in MS patients. The stability of PC concentration over time supports a PC investigation in relation to GM atrophy in MS.
Assuntos
Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Esclerose Múltipla/diagnóstico por imagem , Proteína C/análise , Adulto , Estudos Transversais , Progressão da Doença , Receptor de Proteína C Endotelial/genética , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Proteína S/análise , Transdução de Sinais , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the association between high uric acid (UA), reduced estimated glomerular filtration rate (eGFR), and non-alcoholic fatty liver disease (NAFLD) in outpatient children and adolescents with overweight (OW) or obesity (OB). METHODS: Anthropometric, biochemical, hepatic ultrasound and eGFR data were available from 2565 young people with OW/OB (age 5-18 years). eGFR was calculated using the Schwartz's bedside formula and reduced eGFR (ReGFR+) was defined by a value < 90 mL/min/1.73 m2. High UA was defined as ≥ 75th percentile by sex in children and adolescents. RESULTS: The population was stratified in four categories: (1) normal eGFR and absence of NAFLD (ReGFR-/NAFLD-) (n = 1,236); (2) ReGFR+ and absence of NAFLD (ReGFR+/NAFLD- (n = 155); (3) normal eGFR and presence of NAFLD (ReGFR-/NAFLD+) (n = 1019); (4) presence of both conditions (ReGFR+/NAFLD+) (n = 155). Proportions of youth with high UA across the four categories were 17%, 30%, 33% and 46%, respectively (P < 0.0001). Young people with high levels of UA had odds ratio (95% CI) of 2.11 (1.43-3.11) for ReGFR+; 2.82 (2.26-3.45) for NAFLD+; and 5.04 (3.45-7.39) for both conditions (P < 0.0001 for all), independently of major confounders. CONCLUSIONS: High levels of UA were independently associated with ReGFR, NAFLD and the combination of both conditions in young people with OW/OB. The strength of this association was the highest in cases presenting both reduced eGFR and NAFLD. UA may serve as marker to identify patients at risk for these conditions.
Assuntos
Taxa de Filtração Glomerular/fisiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/complicações , Insuficiência Renal Crônica/etiologia , Ácido Úrico/sangue , Criança , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/metabolismo , Fígado/fisiopatologia , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/metabolismo , Obesidade/fisiopatologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia , UltrassonografiaRESUMO
OBJECTIVES: to update understanding of the effectiveness of transcranial direct current stimulation (tDCS) on motor dysfunction in Parkinson's disease, since the last review was published in 2016. METHODS: in order to identify suitable publications for inclusion, an online search of the Pubmed, Scopus and Cochrane databases was carried out. Searches of relevant full-text articles were performed through specific keywords. The final database check was performed in July 2019. Papers were restricted to studies investigating motor rehabilitative effects of tDCS in adult patients with Parkinson's disease. Studies involving either single or repeated tDCS sessions with a sham or controlled trial type design (which incorporated outcomes on motor performance measures) were considered. As studies varied widely in terms of methodology, a qualitative analysis of the selected studies was performed using the Newcastle-Ottawa Quality Assessment Scale or the Delphi list (depending on the study design). RESULTS: twenty-nine studies were retained in this systematic review. Of the studies included, fifteen involved single tDCS session (patients = 256) and fourteen involved repeated tDCS sessions (patients = 294). Eight investigations of single tDCS and ten investigations of repeated tDCS demonstrated significant results. Studies involving multi- target stimulation demonstrated significant improvements on mobility (p=0.006), balance (by 50.9%), gait velocity (by 29%), fall reduction (p0.05) compared to mono-target stimulations. CONCLUSIONS: despite increasing evidence that tDCS may improve motor symptoms, the results showed that fully optimized tDCS protocols are not yet established.
Assuntos
Doença de Parkinson , Estimulação Transcraniana por Corrente Contínua , Adulto , Marcha , Humanos , Doença de Parkinson/terapiaRESUMO
Epilepsy is the most common chronic neurological disorder in dogs. Approximately 20-30% of dogs do not achieve satisfactory seizure control with two or more anti-epileptic drugs at appropriate dosages. This condition, defined as refractory epilepsy, is a multifactorial condition involving both acquired and genetic factors. The P glycoprotein might play and important role in the pathophysiological mechanism and it is encoded by the ABCB1 gene. An association between a single nucleotide variation of the ABCB1 gene (c.-6-180T>G) and phenobarbital resistance has previously been reported in a Border collie population with idiopathic epilepsy. To date, the presence and relevance of this polymorphism has not been assessed in other breeds. A multicentre retrospective, case-control study was conducted to investigate associations between ABCB1 c.-6-180T>G, clinical variables, and refractoriness in a multi-breed population of dogs with refractory idiopathic epilepsy. A secondary aim was to evaluate the possible involvement of the ABCB1 c.-6-180T>G single nucleotide variation this population. Fifty-two refractory and 50 responsive dogs with idiopathic epilepsy were enrolled. Of these, 45 refractory and 50 responsive (control) dogs were genotyped. The G allele was found in several breeds, but there was no evidence of association with refractoriness (P=0.69). The uncertain role of the c.-6-180T>G variation was further suggested by an association between the T/T genotype with both refractoriness and responsiveness in different breeds. Furthermore, high seizure density (cluster seizure) was the main clinical risk factor for refractory idiopathic epilepsy (P=0.003).
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Doenças do Cão/genética , Epilepsia Resistente a Medicamentos/veterinária , Polimorfismo de Nucleotídeo Único , Animais , Estudos de Casos e Controles , Estudos de Coortes , Cães , Epilepsia Resistente a Medicamentos/genética , Feminino , Itália , Masculino , Linhagem , Estudos Retrospectivos , Fatores de RiscoRESUMO
Adipose tissue (AT) is one of the largest endocrine organs contributing to metabolic homeostasis. The functional pleiotropism of AT depends on its ability to secrete a large number of hormones, cytokines, extracellular matrix proteins and growth factors, all influencing many local and systemic physiological and pathophysiological processes. In condition of chronic positive energy balance, adipocyte expansion, hypoxia, apoptosis and stress all lead to AT inflammation and dysfunction, and it has been demonstrated that this sick fat is a main risk factor for many metabolic disorders, such as type 2 diabetes mellitus, fatty liver, cardiovascular disease and cancer. AT dysfunction is tightly associated with aberrant secretion of bioactive peptides, the adipocytokines, and their blood concentrations often reflect the expression in the AT. Despite the existence of an association between AT dysfunction and systemic pro-inflammatory state, most of the circulating molecules detectable in obese and dysmetabolic individuals do not identify specifically the condition of sick fat. Based on this premise, this review provides a concise overview of "classic" and novel promising adipocytokines associated with AT inflammation and discusses possible critical approaches to their interpretation in clinical practice.
Assuntos
Tecido Adiposo/imunologia , Tecido Adiposo/patologia , Biomarcadores/metabolismo , Inflamação/imunologia , Inflamação/patologia , Gordura Intra-Abdominal/imunologia , Gordura Intra-Abdominal/patologia , Tecido Adiposo/metabolismo , Animais , Humanos , Inflamação/metabolismo , Gordura Intra-Abdominal/metabolismoRESUMO
Progresses in multimodal treatments have significantly improved the outcomes for childhood cancer. Nonetheless, for about one-third of patients with Ewing sarcoma, rhabdomyosarcoma, or osteosarcoma steady remission has remained intangible. Thus, new biomarkers to improve early diagnosis and the development of precision-targeted medicine remain imperative. Over the last decade, remarkable progress has been made in the basic understanding of miRNAs function and in interpreting the contribution of their dysregulation to cancer development and progression. On this basis, this review focuses on what has been learned about the pivotal roles of miRNAs in the regulation of key genes implicated in childhood sarcomas.
Assuntos
Neoplasias Ósseas/metabolismo , MicroRNAs/metabolismo , Osteossarcoma/metabolismo , Rabdomiossarcoma/metabolismo , Sarcoma de Ewing/metabolismo , Neoplasias Ósseas/genética , Criança , Regulação para Baixo , Humanos , Osteossarcoma/genética , Rabdomiossarcoma/genética , Sarcoma de Ewing/genética , Regulação para CimaRESUMO
OBJECTIVE: ANGPTL4 inhibits lipoprotein lipase in adipose tissue, regulating plasma triglycerides levels. In persons with obesity plasma ANGPTL4 levels have been positively correlated with body fat mass, TG levels and low HDL. A loss-of-function E40K mutation in ANGPTL4 prevents LPL inhibition, resulting in lower TGs and higher HDLc in the general population. Since obesity determines metabolic alterations and consequently is a major risk factor for cardiovascular disease, the aim was to explore if obesity-related metabolic abnormalities are modified by the ANGPTL4-E40K mutation. METHODS: ANGPTL4-E40K was screened in 1206 Italian participants, of which 863 (71.5%) with obesity. All subjects without diabetes underwent OGTT with calculation of indices of insulin-sensitivity. RESULTS: Participants with obesity carrying the E40K variant had significantly lower TG (p = 0.001) and higher HDLc levels (p = 0.024). Also in the whole population low TGs and high HDLc were confirmed in E40K carriers. In the obese subpopulation it was observed that almost all E40K carriers were within the lowest quartile of TGs (p = 1.1 × 10-9). E40K had no substantial effect of on glucose metabolism. Finally, none of the obese E40K carriers had T2D, and together with the favourable lipid profile, they resemble a metabolically healthy obese (MHO) phenotype, compared to 38% of E40E wild-type obese that had diabetes and/or dyslipidaemia (p = 0.0106). CONCLUSIONS: In participants with obesity the ANGPTL4-E40K variant protects against dyslipidemia. The phenotype of obese E40K carriers is that of a patient with obesity without metabolic alterations, similar to the phenotype described as metabolic healthy obesity.
RESUMO
Treatment of older adults with hip fracture is a healthcare challenge. Orthogeriatric comanagement that is an integrated model of care with shared responsibility improves time to surgery and reduces the length of hospital stay and mortality compared with orthopedic care with geriatric consultation service and usual orthopedic care, respectively. INTRODUCTION: Treatment of fractures in older adults is a clinical challenge due partly to the presence of comorbidity and polypharmacy. The goal of orthogeriatric models of care is to improve clinical outcomes among older people with hip fractures. We compare clinical outcomes of persons with hip fracture cared according to orthogeriatric comanagement (OGC), orthopedic team with the support of a geriatric consultant service (GCS), and usual orthopedic care (UOC). METHODS: This is a single-center, pre-post intervention observational study with two parallel arms, OGC and GCS, and a retrospective control arm. Hip fracture patients admitted to the trauma ward were assigned by the orthopedic surgeon to the OGC (n = 112) or GCS (n = 108) group. The intervention groups were compared each with others and both with the retrospective control group (n = 210) of older adults with hip fracture. Several clinical indicators are considered, including time to surgery, length of stay, in-hospital, and 1-year mortality. RESULTS: Patients in the OGC (OR 2.62; CI 95% 1.40-4.91) but not those in the GCS (OR 0.74; CI 95% 0.38-1.47) showed a higher probability of undergoing surgery within 48 h compared with those in the UOC. Moreover, the OGC (ß, - 1.08; SE, 0.54, p = 0.045) but not the GCS (ß, - 0.79; SE, 0.53, p = 0.148) was inversely associated with LOS. Ultimately, patients in the OGC (OR 0.31; CI 95 % 0.10-0.96) but not those in the GCS (OR 0.37; CI 95% 0.10-1.38) experienced a significantly lower 1-year mortality rate compared with those in the UOC. All analyses were independent of several confounders. CONCLUSIONS: Older adults with hip fracture taken in care by the OGC showed better clinical indicators, including time to surgery, length of stay and mortality, than those managed by geriatric consultant service or usual orthopedic care.