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1.
Diabetes Obes Metab ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39054936

RESUMO

AIM: To provide guidance for follow-up and monitoring of children and adolescents identified as positive to islet autoantibodies (IA) in the general population screening for type 1 diabetes (T1D) in Italy. METHODS: Detection of IA helps to diagnose pre-symptomatic T1D, prevent diabetic ketoacidosis (DKA) and identify persons for new therapies to delay symptomatic diabetes. Italy recently became the first country to approve by law a general autoantibody screening program for T1D and celiac disease in all children and adolescents (age 1-17yr). A pilot study is currently underway in four Italian regions addressing feasibility issues to be used in the scale up to nationwide screening. Meanwhile, a group of experts developed guidance recommendations for follow-up and monitoring of identified IA positive persons. RESULTS: Ten key components have been identified: establishment of a registry for children and adolescents at risk; close collaboration with the national network of family paediatricians; creation of T1D centers with expertise in follow-up and monitoring; educational measures; assurance of solid IA tests; identification of appropriate metabolic tests; feed-back feasibility and acceptability questionnaires; potential access to available therapeutic interventions; valuable outcome measures including DKA incidence; costs monitoring. Distinctive features of this program include single (in addition to multiple) IA antibody-positive persons in follow-up and the use of CGM to assess risk progression, rather than the cumbersome OGTT. CONCLUSION: It is expected that the proposed follow-up and monitoring program will be effective, affordable and acceptable to children and families identified in general T1D screening in Italy.

2.
Eur J Public Health ; 34(3): 592-599, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38243748

RESUMO

BACKGROUND: A significant proportion of individuals reports persistent clinical manifestations following SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) acute infection. Nevertheless, knowledge of the burden of this condition-often referred to as 'Long COVID'-on the health care system remains limited. This study aimed to evaluate healthcare utilization potentially related to Long COVID. METHODS: Population-based, retrospective, multi-center cohort study that analyzed hospital admissions and utilization of outpatient visits and diagnostic tests between adults aged 40 years and older recovered from SARS-CoV-2 infection occurred between February 2020 and December 2021 and matched unexposed individuals during a 6-month observation period. Healthcare utilization was analyzed by considering the setting of care for acute SARS-CoV-2 infection [non-hospitalized, hospitalized and intensive care unit (ICU)-admitted] as a proxy for the severity of acute infection and epidemic phases characterized by different SARS-CoV-2 variants. Data were retrieved from regional health administrative databases of three Italian Regions. RESULTS: The final cohort consisted of 307 994 previously SARS-CoV-2 infected matched with 307 994 uninfected individuals. Among exposed individuals, 92.2% were not hospitalized during the acute infection, 7.3% were hospitalized in a non-ICU ward and 0.5% were admitted to ICU. Individuals previously infected with SARS-CoV-2 (vs. unexposed), especially those hospitalized or admitted to ICU, reported higher utilization of outpatient visits (range of pooled Incidence Rate Ratios across phases; non-hospitalized: 1.11-1.33, hospitalized: 1.93-2.19, ICU-admitted: 3.01-3.40), diagnostic tests (non-hospitalized: 1.35-1.84, hospitalized: 2.86-3.43, ICU-admitted: 4.72-7.03) and hospitalizations (non-hospitalized: 1.00-1.52, hospitalized: 1.87-2.36, ICU-admitted: 4.69-5.38). CONCLUSIONS: This study found that SARS-CoV-2 infection was associated with increased use of health care in the 6 months following infection, and association was mainly driven by acute infection severity.


Assuntos
COVID-19 , Hospitalização , Aceitação pelo Paciente de Cuidados de Saúde , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Hospitalização/estatística & dados numéricos , Itália/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Síndrome de COVID-19 Pós-Aguda , Estudos de Coortes , Recursos em Saúde/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos
3.
BMC Endocr Disord ; 22(1): 52, 2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241041

RESUMO

BACKGROUND: In adult population, Growth Hormone Deficiency (GHD) is a complex clinical condition with heterogeneity of causes and duration. Growth Hormone (GH) replacement therapy has beneficial effects entailing a chronic and expensive use. Therefore, entity, appropriateness and standardization of GHD treatment need to be accurately analysed. In Italy, the epidemiological surveillance on somatropin therapy is entrusted to the National Register of Growth Hormone Therapy (Registro Nazionale degli Assuntori dell'Ormone della Crescita-RNAOC) by the Italian Regulation, in accordance of which the RNAOC-database is collecting the notifications of somatropin prescriptions. METHODS: Aim of this study is to analyse data on somatropin-treated adult population communicated to the RNAOC by the specialist centres of 15 Italian regions and 2 autonomous provinces. RESULTS: From 2011 to 2019, the somatropin-treated adults were 970 with 4061 examinations (1.21 ± 0.33 visits/year). The diagnoses were: hypopituitarism (n = 579); hypophysectomy (n = 383); and congenital GHD (n = 3). Five subjects were addressed with diagnoses not included in the regulation. The starting posology of somatropin was 0.320 (± 0.212) mg/day, 0.292 (± 0.167) mg/day in male and 0.360 (± 0.258) in female patients, with 7 administrations/week in 70.31% of the prescriptions. The differences in posology by gender persisted at 10th year of the follow-up. Starting dosage was higher in patients diagnosed with adult GHD before the age of 30 (0.420 ± 0.225 mg/day), with a progressive decrease of the dosage during the follow-up. CONCLUSIONS: This is the first report on adult GH treatment, describing numbers, diagnoses, and pharmaceutical prescriptions associated to somatropin therapy in a large cohort of Italian GHD-adults.


Assuntos
Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Terapia de Reposição Hormonal/métodos , Hormônio do Crescimento Humano/administração & dosagem , Humanos , Hipofisectomia , Hipopituitarismo/diagnóstico , Hipopituitarismo/tratamento farmacológico , Itália , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Sistema de Registros , Adulto Jovem
4.
Am J Med Genet A ; 182(12): 2964-2970, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32918520

RESUMO

BACKGROUND: Persons with Down syndrome (DS) are presumed to be at high risk of severe CoVID-19, due to immune dysregulation and often compromised cardiopulmonary function. Aim of the present study is to assess epidemiological and clinical characteristics of individuals with DS deceased in Italian hospitals with CoVID-19. METHODS: We used a nationwide database of 3,438 patients deceased with RT-PCR-confirmed SARS-CoV-2 infection in Italy (10.4% of all deaths with CoVID-19 in the country at the time of analysis). Data on demographics, pre-existing comorbidities and in-hospital complications leading to death were extracted from medical charts obtained from hospitals. Data on individuals with DS deceased with CoVID-19 were obtained from this sample. RESULTS: Sixteen cases of death in individuals with DS (0.5% of all charts analyzed) were identified. Acute respiratory distress syndrome occurred in all 16 cases. Compared with individuals without DS, those with DS deceased with CoVID-19 were younger (52.3 ± 7.3 vs. 78.1 ± 10.6 years, p < .001) and presented a higher incidence of superinfections (31.2 vs. 13.0%, p = .029). Autoimmune diseases (43.8 vs. 4%, p < .001), obesity (37.5 vs. 11%, p = .009), and dementia (37.5 vs. 16.3%, p = .012) were more prevalent in individuals with DS. ICU admissions was similar in both groups (25 vs. 18.8%, p = .129). CONCLUSIONS: Individuals with DS deceased with CoVID-19 are younger than individuals without DS. Comorbidity burden and increased risk of complications (i.e., bacterial superinfections) can influence CoVID-19 prognosis in individuals with DS. Specific strategies to prevent and mitigate the effects of CoVID-19 in the population with DS are needed.


Assuntos
COVID-19/epidemiologia , Síndrome de Down/epidemiologia , Pandemias , Idoso , COVID-19/virologia , Comorbidade , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade
5.
Cell Mol Neurobiol ; 38(6): 1315-1320, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29846839

RESUMO

Curcumin is one of the major compounds contained in turmeric, the powdered rhizome of Curcuma longa. Results obtained in various experimental models indicate that curcumin has the potential to treat a large variety of neuronal diseases. Excitotoxicity, the toxicity due to pathological glutamate receptors stimulation, has been considered to be involved in several ocular pathologies including ischemia, glaucoma, and diabetic retinopathy. The NMDA receptor (NMDAR), a heteromeric ligand-gated ion channel, is composed of GluN1 and GluN2 subunits. There are four GluN2 subunits (GluN2A-D), which are major determinants of the functional properties of NMDARs. It is widely accepted that GluN2B has a pivotal role in excitotoxicity while the role of GluN2A remains controversial. We previously demonstrated that curcumin is neuroprotective against NMDA-induced excitotoxicity with a mechanism involving an increase of GluN2A subunit activity. In this paper, we investigate the mechanisms involved in curcumin-induced GluN2A increase in retinal cultures. Our results show that curcumin treatment activated CaMKII with a time-course that paralleled those of GluN2A increase. Moreover, KN-93, a CaMKII inhibitor, was able to block the effect of curcumin on GluN2A expression. Finally, in our experimental model, curcumin reduced ser/thr phosphatases activity. Using okadaic acid, a specific PP1 and PP2A blocker, we observed an increase in GluN2A levels in cultures. The ability of okadaic acid to mimic the effect of curcumin on GluN2A expression suggests that curcumin might regulate GluN2A expression through a phosphatase-dependent mechanism. In conclusion, our findings indicate curcumin modulation of CaMKII and/or ser/thr phosphatases activities as a mechanism involved in GluN2A expression and neuroprotection against excitotoxicity.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/efeitos dos fármacos , Curcumina/farmacologia , Fosfoproteínas Fosfatases/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/efeitos dos fármacos , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Células Cultivadas , Neurônios/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Ratos Wistar , Receptores de N-Metil-D-Aspartato/metabolismo , Transdução de Sinais/efeitos dos fármacos
6.
Exp Eye Res ; 145: 158-163, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26607807

RESUMO

The effects of the anti-Vascular Endothelial Growth Factor (VEGF) drugs ranibizumab and aflibercept were studied in Müller glia in primary mixed cultures from rat neonatal retina. Treatment with both agents induced activation of Müller glia, demonstrated by increased levels of Glial Fibrillary Acidic Protein. In addition, phosphorylated Extracellular-Regulated Kinase 1/2 (ERK 1/2) showed enhanced immunoreactivity in activated Müller glia. Treatment with aflibercept induced an increase in K(+) channel (Kir) 4.1 levels and both drugs upregulated Aquaporin 4 (AQP4) in activated Müller glia. The results show that VEGF-antagonizing drugs influence the homeostasis of Müller cells in primary retinal cultures, inducing an activated phenotype. Upregulation of Kir4.1 and AQP4 suggests that Müller glia activation following anti-VEGF drugs may not depict a detrimental gliotic reaction. Indeed, it could represent one of the mechanisms able to contribute to the therapeutic effects of these drugs, particularly in the presence of macular edema.


Assuntos
Células Ependimogliais/metabolismo , Proteínas do Olho/metabolismo , Degeneração Macular/tratamento farmacológico , Neuroglia/metabolismo , Ranibizumab/farmacologia , Proteínas Recombinantes de Fusão/farmacologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Inibidores da Angiogênese/farmacologia , Animais , Animais Recém-Nascidos , Western Blotting , Células Cultivadas , Modelos Animais de Doenças , Eletroforese , Células Ependimogliais/patologia , Degeneração Macular/metabolismo , Degeneração Macular/patologia , Neuroglia/patologia , Ratos , Ratos Wistar , Receptores de Fatores de Crescimento do Endotélio Vascular , Regulação para Cima
7.
Exp Eye Res ; 125: 20-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24877742

RESUMO

Müller cell activation is an early finding in diabetic retinopathy (DR), but its physiopathologic role in the disease is still unclear, especially in the early phases. We investigated on Müller glial activation in primary rat retinal cultures, exposed to High Glucose (HG), and in retinas from streptozotocin (stz)-induced diabetic rats. First of all, we checked if the presence of Müller glia influenced HG neurotoxicity. In mixed glial/neuronal retinal cultures, a single HG administration (sHG) for 48 h induced activation of Müller glia, in absence of neuronal damage. In contrast, in pure neuronal cultures, a marked neurotoxic effect was detected, suggesting that in this cell model Müller glia protect neurons from HG neurotoxicity. To better mimic the diabetic milieu, where retinal cells are constantly bathed in hyperglycemic fluid, and to further characterize astrocytic neuroprotective ability, mixed retinal cultures were exposed to repeated daily replacement of HG (rHG). In this paradigm, starting from 48 h, increased apoptosis and synaptic loss were observed, even in the presence of Müller cells. Phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), whose activation triggers a prosurvival pathway, was increased by sHG, while it was down-regulated by rHG, suggesting that ERK1/2 activation is involved in neuroprotection. Consistently, in presence of ERK1/2 inhibitor PD98059, sHG exerted a proapoptotic effect also in glial/neuronal retinal cultures. In line with the in vitro data, early changes in diabetic retinas from stz-injected rats included Müller cell activation and increased pERK1/2 levels, but no signs of neuronal damage. These results suggest that, in the early phases of DR, Müller glial activation does not contribute to neurodegeneration, but may indeed have a neuroprotective activity against HG-induced neurotoxicity through a mechanism involving pERK1/2.


Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética/fisiopatologia , Células Ependimogliais/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Retina/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Retinopatia Diabética/induzido quimicamente , Células Ependimogliais/efeitos dos fármacos , Glucose/toxicidade , Masculino , Ratos , Ratos Sprague-Dawley
8.
Int J Mol Sci ; 15(4): 6286-97, 2014 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-24736780

RESUMO

In recent years, citicoline has been the object of remarkable interest as a possible neuroprotectant. The aim of this study was to investigate if citicoline affected cell survival in primary retinal cultures and if it exerted neuroprotective activity in conditions modeling retinal neurodegeneration. Primary retinal cultures, obtained from rat embryos, were first treated with increasing concentrations of citicoline (up to 1000 µM) and analyzed in terms of apoptosis and caspase activation and characterized by immunocytochemistry to identify neuronal and glial cells. Subsequently, excitotoxic concentration of glutamate or High Glucose-containing cell culture medium (HG) was administered as well-known conditions modeling neurodegeneration. Glutamate or HG treatments were performed in the presence or not of citicoline. Neuronal degeneration was evaluated in terms of apoptosis and loss of synapses. The results showed that citicoline did not cause any damage to the retinal neuroglial population up to 1000 µM. At the concentration of 100 µM, it was able to counteract neuronal cell damage both in glutamate- and HG-treated retinal cultures by decreasing proapoptotic effects and contrasting synapse loss. These data confirm that citicoline can efficiently exert a neuroprotective activity. In addition, the results suggest that primary retinal cultures, under conditions inducing neurodegeneration, may represent a useful system to investigate citicoline neuroprotective mechanisms.


Assuntos
Citidina Difosfato Colina/farmacologia , Fármacos Neuroprotetores/farmacologia , Retina/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Glucose/toxicidade , Ácido Glutâmico/toxicidade , Modelos Biológicos , Ratos , Retina/citologia
9.
Front Med (Lausanne) ; 11: 1401602, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39026549

RESUMO

Introduction: SARS-CoV-2 infection has been associated with the onset or persistence of symptoms in the long-term after the acute infection is resolved. This condition known as Post-COVID, might be particularly severe and potentially life-threatening. However, little is known on the impact of post-COVID condition on mortality. Aim of the present study is to assess and quantify Post-COVID deaths in Italy in years 2020 and 2021, based on an analysis of death certificates. Methods: Data from the Italian National Cause of Death Register were analyzed. ICD-10 code U09.9, released by the World Health Organization in September 2020, was used to identify the 'Post-COVID' condition. Numbers of post-COVID deaths from October 2020 to December 2021 were analyzed. Rates of post-COVID deaths were calculated for the year 2021. Results: Between October 2020 and December 2021, 4,752 death certificates reporting post-COVID condition were identified. Of these, 14.9% (n = 706) occurred between October and December 2020 and 85.1% (n = 4,046) in 2021. In 46.0% of post-COVID-related deaths, the underlying cause of death was COVID-19. Other frequent underlying causes were heart disease (14.3% of cases), neoplasms (9.2%), cerebrovascular diseases (6.3%) and Alzheimer's disease and other dementias (5.5%). The mortality rate related to post-COVID conditions in year 2021 was 5.1 deaths per 100 thousand inhabitants and it increased with increasing age. Men showed a higher mortality rate than women (4.3 deaths per 100 thousand in women and 6.0 deaths per 100 thousand in men). Discussion: Post-COVID conditions contributed to a substantial number of deaths in Italy. Strategies to identify the population at risk of severe long-term consequences of SARS-CoV-2 infection and interventions aimed at reducing this risk must be developed.

10.
Int J Public Health ; 68: 1606491, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38420040

RESUMO

Objectives: As little is known about the burden of type 1 (T1DM) and type 2 diabetes (T2DM) in adolescents in Western Europe (WE), we aimed to explore their epidemiology among 10-24 year-olds. Methods: Estimates were retrieved from the Global Burden of Diseases Study (GBD) 2019. We reported counts, rates per 100,000 population, and percentage changes from 1990 to 2019 for prevalence, incidence and years lived with disability (YLDs) of T1DM and T2DM, and the burden of T2DM in YLDs attributable to high body mass index (HBMI), for 24 WE countries. Results: In 2019, prevalence and disability estimates were higher for T1DM than T2DM among 10-24 years old adolescents in WE. However, T2DM showed a greater increase in prevalence and disability than T1DM in the 30 years observation period in all WE countries. Prevalence increased with age, while only minor differences were observed between sexes. Conclusion: Our findings highlight the substantial burden posed by DM in WE among adolescents. Health system responses are needed for transition services, data collection systems, education, and obesity prevention.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Adolescente , Adulto Jovem , Criança , Adulto , Carga Global da Doença , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Saúde Global , Prevalência , Incidência , Anos de Vida Ajustados por Qualidade de Vida
11.
Front Public Health ; 11: 1122141, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37151592

RESUMO

A significant number of people, following acute SARS-CoV-2 infection, report persistent symptoms or new symptoms that are sustained over time, often affecting different body systems. This condition, commonly referred to as Long-COVID, requires a complex clinical management. In Italy new health facilities specifically dedicated to the diagnosis and care of Long-COVID were implemented. However, the activity of these clinical centers is highly heterogeneous, with wide variation in the type of services provided, specialistic expertise and, ultimately, in the clinical care provided. Recommendations for a uniform management of Long-COVID were therefore needed. Professionals from different disciplines (including general practitioners, specialists in respiratory diseases, infectious diseases, internal medicine, geriatrics, cardiology, neurology, pediatrics, and odontostomatology) were invited to participate, together with a patient representative, in a multidisciplinary Panel appointed to draft Good Practices on clinical management of Long-COVID. The Panel, after extensive literature review, issued recommendations on 3 thematic areas: access to Long-COVID services, clinical evaluation, and organization of the services. The Panel highlighted the importance of providing integrated multidisciplinary care in the management of patients after SARS-CoV-2 infection, and agreed that a multidisciplinary service, one-stop clinic approach could avoid multiple referrals and reduce the number of appointments. In areas where multidisciplinary services are not available, services may be provided through integrated and coordinated primary, community, rehabilitation and mental health services. Management should be adapted according to the patient's needs and should promptly address possible life-threatening complications. The present recommendations could provide guidance and support in standardizing the care provided to Long-COVID patients.


Assuntos
COVID-19 , Geriatria , Humanos , Criança , Síndrome de COVID-19 Pós-Aguda , COVID-19/epidemiologia , COVID-19/terapia , SARS-CoV-2 , Acessibilidade aos Serviços de Saúde
12.
Front Public Health ; 10: 975527, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36062113

RESUMO

Background: Despite the growing clinical relevance of Long-COVID, there is minimal information available on the organizational response of health services to this condition. Methods: A national online survey of centers providing assistance for Long-COVID was implemented. Information collected included date of start of activity, target population, mode of assistance and of referral, type and number of specialists available, diagnostic and instrumental tests, use of telemedicine and of specific questionnaires. Results: Between February and May 2022, 124 centers completed the survey. Half of them were situated in northern Italy. Most (88.9%) provided assistance through either outpatient visits or day hospital services. Eleven (8.9%) assisted pediatric patients. Access to centers included scheduled visits for previously hospitalized patients (67.7%), referral from primary care (62.1%), from other specialists (46.8%), and, less commonly, from other services. Almost half of the centers (46.3%) started their activity early in the pandemics (March-September 2020). Almost all (93.5%) communicated with primary care physicians, and 21.8% used telemedicine tools. The mean number of patients followed was 40 per month (median 20, IQR 10-40). In most cases, the center coordinator was a specialist in respiratory diseases (30.6%), infectious diseases (28.2%), or internal medicine (25.0%). At least half of the centers had specialistic support in cardiology, respiratory diseases, radiology, infectious diseases, neurology and psychology, but roughly one quarter of centers had just only one (14.5%) or two (9.7%) specialists available. The clinical assessment was usually supported by a wide range of laboratory and instrumental diagnostics and by multidimensional evaluations. Conclusions: Most of the centers had an articulate and multidisciplinary approach to diagnosis and care of Long-COVID. However, a minority of centers provided only single or dual specialistic support. These findings may be of help in defining common standards, interventions and guidelines that can reduce gaps and heterogeneity in assistance to patients with Long-COVID.


Assuntos
COVID-19 , Telemedicina , COVID-19/complicações , COVID-19/epidemiologia , Criança , Humanos , Pandemias , SARS-CoV-2 , Telemedicina/métodos , Síndrome de COVID-19 Pós-Aguda
13.
Ann Ist Super Sanita ; 58(1): 67-72, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35324476

RESUMO

INTRODUCTION: Aim of this paper is to present a guide for translating to practice an evidence-based set of Quality Criteria and Recommendations (QCR) to promote the implementation of policies and practices in the field of health promotion, disease prevention and care for people with chronic diseases. METHODS: The guide is based on real-world experiences of eight European pilot actions using QCR as a framework for practice design, development, implementation, monitoring and evaluation. All partners implemented their respective practices by following the same agreed process. RESULTS: The implementation method was summarized in seven steps where each of one outline a particular phase of the process. The guide provides a step-by-step tutorial for the implementation of QCR. CONCLUSIONS: Practical experiences from the pilot actions show the potential value of using the QCR in designing and implementing practices to improve the quality of care for people with chronic diseases.


Assuntos
Promoção da Saúde , Políticas , Doença Crônica , Humanos , Qualidade da Assistência à Saúde
14.
J Hepatol ; 54(5): 975-83, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21145823

RESUMO

BACKGROUND & AIMS: Excess fatty acid oxidation and generation of reactive carbonyls with formation of advanced lipoxidation endproducts (ALEs) is involved in nonalcoholic steatohepatitis (NASH) by triggering inflammation, hepatocyte injury, and fibrosis. This study aimed at verifying the hypothesis that ablation of the ALE-receptor galectin-3 prevents experimental NASH by reducing receptor-mediated ALE clearance and downstream events. METHODS: Galectin-3-deficient (Lgals3(-/-)) and wild type (Lgals3(+/+)) mice received an atherogenic diet or standard chow for 8 months. Liver tissue was analyzed for morphology, inflammation, cell and matrix turnover, lipid metabolism, ALEs, and ALE-receptors. RESULTS: Steatosis was significantly less pronounced in Lgals3(-/-) than Lgals3(+/+) animals on atherogenic diet. NASH, invariably detected in Lgals3(+/+) mice, was observed, to a lower extent, only in 3/8 Lgals3(-/-) mice, showing less inflammatory, degenerative, and fibrotic phenomena than Lgals3(+/+) mice. This was associated with higher circulating ALE levels and lower tissue ALE accumulation and expression of other ALE-receptors. Up-regulation of hepatic fatty acid synthesis and oxidation, inflammatory cell infiltration, pro-inflammatory cytokines, endoplasmic reticulum stress, hepatocyte apoptosis, myofibroblast transdifferentiation, and impaired Akt phosphorylation were also significantly attenuated in Lgals3(-/-) animals. Galectin-3 silencing in liver endothelial cells resulted in reduced N(ε)-carboxymethyllysine-modified albumin uptake and ALE-receptor expression. CONCLUSIONS: Galectin-3 ablation protects from diet-induced NASH by decreasing hepatic ALE accumulation, with attenuation of inflammation, hepatocyte injury, and fibrosis. It also reduced up-regulation of lipid synthesis and oxidation causing less fat deposition, oxidative stress, and possibly insulin resistance. These data suggest that galectin-3 is a major receptor involved in ALE uptake by the liver.


Assuntos
Fígado Gorduroso , Galectina 3/genética , Galectina 3/metabolismo , Animais , Apoptose/fisiologia , Antígenos CD36/genética , Antígenos CD36/metabolismo , Dieta Aterogênica , Fígado Gorduroso/genética , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Feminino , Fibroblastos/patologia , Inativação Gênica , Leucócitos/metabolismo , Leucócitos/patologia , Metabolismo dos Lipídeos/fisiologia , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica , Estresse Oxidativo/fisiologia , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Índice de Gravidade de Doença
15.
Arterioscler Thromb Vasc Biol ; 29(6): 831-6, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19359660

RESUMO

OBJECTIVE: Modified lipoproteins, particularly oxidized LDLs, are believed to evoke an inflammatory response which participates in all stages of atherosclerosis. Disposal of these particles is mediated through receptors which may trigger proinflammatory signaling pathways leading to vascular injury. This study was aimed at assessing the role in atherogenesis of one of these receptors, galectin-3. METHODS AND RESULTS: Galectin-3-deficient and wild-type mice were fed an atherogenic diet or standard chow for 8 months. Lesion area and length were higher in galectin-3-deficient versus wild-type mice. At the level of the aortic sinus, wild-type animals showed only fatty streaks, whereas galectin-3-deficient mice developed complex lesions, associated with extensive inflammatory changes. This was indicated by the presence of T lymphocytes with activated Th1-phenotype and by more marked monocyte-macrophage infiltration, inflammatory mediator expression, vascular cell apoptosis, and proinflammatory transcription factor activation. Increased accumulation of oxidixed LDLs and lipoxidation products and upregulation of other receptors for these compounds, including the proinflammatory RAGE, were detected in galectin-3-deficient versus wild-type mice. CONCLUSIONS: These data suggest a unique protective role for galectin-3 in the uptake and effective removal of modified lipoproteins, with concurrent downregulation of proinflammatory pathways responsible for atherosclerosis initiation and progression.


Assuntos
Doenças da Aorta/metabolismo , Aortite/metabolismo , Aterosclerose/metabolismo , Galectina 3/deficiência , Peroxidação de Lipídeos , Transdução de Sinais , Animais , Aorta/imunologia , Aorta/metabolismo , Aorta/patologia , Doenças da Aorta/etiologia , Doenças da Aorta/imunologia , Doenças da Aorta/patologia , Aortite/etiologia , Aortite/imunologia , Aortite/patologia , Apoptose , Aterosclerose/etiologia , Aterosclerose/imunologia , Aterosclerose/patologia , Quimiotaxia de Leucócito , Dieta Aterogênica , Modelos Animais de Doenças , Progressão da Doença , Feminino , Galectina 3/genética , Mediadores da Inflamação/metabolismo , Lipoproteínas LDL/metabolismo , Ativação Linfocitária , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/imunologia , Estresse Oxidativo , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/metabolismo , Receptores Depuradores/metabolismo , Células Th1/imunologia , Fatores de Tempo , Fatores de Transcrição/metabolismo
16.
J Pathol ; 218(3): 360-9, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19334049

RESUMO

Atherosclerosis and renal disease are related conditions, sharing several risk factors. This includes hyperlipidaemia, which may result in enhanced lipoprotein accumulation and chemical modification, particularly oxidation, with formation of advanced lipoxidation endproducts (ALEs). We investigated whether increased lipid peroxidation plays a major role in the pathogenesis of lipid-induced renal disease, via receptor-mediated mechanisms involving the scavenger and advanced glycation endproduct (AGE) receptors. Mice knocked out for galectin-3 (Gal3(-/-)), an AGE receptor previously shown to protect from AGE-induced renal injury, and the corresponding wild-type (Gal3(+/+)) animals, were fed an atherogenic high-fat diet (HFD; 15% fat, 1.25% cholesterol and 0.5% sodium cholate); mice fed a normal-fat diet (NFD; 4% fat) served as controls. Gal3(+/+) mice fed a HFD developed glomerular disease, as indicated by proteinuria, mesangial expansion and glomerular hypertrophy and sclerosis. Glomerular injury was associated with increased glomerular matrix protein expression, ALE and oxidized LDL content, oxidative stress, AGE and scavenger receptor expression and macrophage infiltration, with only modest renal/glomerular fat accumulation and changes in lipid metabolism. Fibrotic and inflammatory changes, together with accumulation of ALEs, such as 4-hydroxy-2-nonenal adducts and N(epsilon)-carboxymethyllysine, oxidative stress and expression of the receptor of AGEs (RAGE), were significantly more marked in Gal3(-/-) animals, whereas fat deposition and abnormalities in lipid metabolism remained modest. Thus, lipid-induced renal damage is mainly dependent on lipid peroxidation with formation of carbonyl reactive species and ALEs, which accumulate within the kidney tissue, thus triggering receptor-mediated pro-inflammatory signalling pathways, as in atherogenesis. Moreover, galectin-3 exerts a significant role in the uptake and effective removal of modified lipoproteins, with diversion of these products from RAGE-dependent pro-inflammatory pathways associated with downregulation of RAGE expression.


Assuntos
Dieta Aterogênica , Nefropatias/etiologia , Peroxidação de Lipídeos/fisiologia , Animais , Apoptose/fisiologia , Pressão Sanguínea/fisiologia , Matriz Extracelular/metabolismo , Feminino , Galectina 3/deficiência , Galectina 3/genética , Galectina 3/fisiologia , Produtos Finais de Glicação Avançada/metabolismo , Nefropatias/metabolismo , Nefropatias/patologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Metabolismo dos Lipídeos , Macrófagos/fisiologia , Camundongos , Camundongos Knockout , Estresse Oxidativo/fisiologia , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/metabolismo , Receptores Depuradores/metabolismo
17.
Biol Sex Differ ; 11(1): 57, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066823

RESUMO

BACKGROUND: Among the unknowns posed by the coronavirus disease 2019 (COVID-19) outbreak, the role of biological sex to explain disease susceptibility and progression is still a matter of debate, with limited sex-disaggregated data available. METHODS: A retrospective analysis was performed to assess if sex differences exist in the clinical manifestations and transitions of care among hospitalized individuals dying with laboratory-confirmed SARS-CoV-2 infection in Italy (February 27-June 11, 2020). Clinical characteristics and the times from symptoms' onset to admission, nasopharyngeal swab, and death were compared between sexes. Adjusted multivariate analysis was performed to identify the clinical features associated with male sex. RESULTS: Of the 32,938 COVID-19-related deaths that occurred in Italy, 3517 hospitalized and deceased individuals with COVID-19 (mean 78 ± 12 years, 33% women) were analyzed. At admission, men had a higher prevalence of ischemic heart disease (adj-OR = 1.76, 95% CI 1.39-2.23), chronic obstructive pulmonary disease (adj-OR = 1.7, 95% CI 1.29-2.27), and chronic kidney disease (adj-OR = 1.48, 95% CI 1.13-1.96), while women were older and more likely to have dementia (adj-OR = 0.73, 95% CI 0.55-0.95) and autoimmune diseases (adj-OR = 0.40, 95% CI 0.25-0.63), yet both sexes had a high level of multimorbidity. The times from symptoms' onset to admission and nasopharyngeal swab were slightly longer in men despite a typical acute respiratory illness with more frequent fever at the onset. Men received more often experimental therapy (adj-OR = 2.89, 95% CI 1.45-5.74) and experienced more likely acute kidney injury (adj-OR = 1.47, 95% CI 1.13-1.90). CONCLUSIONS: Men and women dying with COVID-19 had different clinical manifestations and transitions of care. Identifying sex-specific features in individuals with COVID-19 and fatal outcome might inform preventive strategies.


Assuntos
Infecções por Coronavirus/terapia , Transferência de Pacientes/estatística & dados numéricos , Pneumonia Viral/terapia , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/isolamento & purificação , COVID-19 , Comorbidade , Infecções por Coronavirus/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Multimorbidade , Análise Multivariada , Pandemias , Pneumonia Viral/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Fatores Sexuais
18.
Neurobiol Dis ; 35(2): 278-85, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19481149

RESUMO

The early effects of the diabetic milieu on retinal tissue and their relation to the Renin-Angiotensin system (RAS) activation are poorly known. Here we investigated RAS signaling in retinas explanted from adult rats exposed for 48 h to high glucose (HG), with or without the Angiotensin Converting Enzyme inhibitor enalaprilat, which blocks RAS. HG was observed to i) initiate a phosphotyrosine-dependent signaling cascade; ii) up-regulate Angiotensin(1) Receptor (AT(1)R); iii) activate src tyrosine kinase and increase phosphorylation of Pyk2, PLCgamma1 and ERK1/2; and iv) activate Akt and the transcription factor CREB. In the presence of enalaprilat, tyrosine phosphorylation signal and AT(1)R upregulation decreased and activation of PLCgamma1 and CREB reverted, showing their relation to RAS signaling. In line with Akt activation, no apoptosis or synapse degeneration was found. Müller glia was activated, but in a RAS-independent manner. Our results suggest that, in early phases of HG exposure, a pro-survival cell program may be induced in the retina.


Assuntos
Glucose/metabolismo , Sistema Renina-Angiotensina/fisiologia , Retina/fisiologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Enalaprilato/farmacologia , Quinase 2 de Adesão Focal/metabolismo , Técnicas In Vitro , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosfolipase C gama/metabolismo , Fosfotirosina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Retina/efeitos dos fármacos , Neurônios Retinianos/efeitos dos fármacos , Neurônios Retinianos/fisiologia , Fatores de Tempo , Quinases da Família src/metabolismo
20.
Ital J Pediatr ; 45(1): 130, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31639023

RESUMO

Recombinant human growth hormone (rhGH) is an approved and effective treatment for short children born small for gestational age (SGA). Prevalence of children eligible for treatment as SGA is reported to be 1:1800. The latest data from the National Registry of Growth Hormone therapy (RNAOC) showed that the number of children treated with SGA indication is still small (prevalence 0.37/100,000) and these children are significantly less reported than those treated for growth hormone deficiency (GHD), although GHD prevalence is 1:4000-1:10,000. This means that many short children born SGA are still not properly identified, and therefore not treated with rhGH, or misdiagnosed as GHD. This article provides some practical tools for the identification of children eligible for rhGH treatment.


Assuntos
Estatura , Hormônio do Crescimento Humano/deficiência , Hormônio do Crescimento Humano/uso terapêutico , Recém-Nascido Pequeno para a Idade Gestacional , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Itália , Masculino , Guias de Prática Clínica como Assunto
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