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1.
Int J Mol Sci ; 24(20)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37895048

RESUMO

Lactate represents the main product of pyruvate reduction catalyzed by the lactic dehydrogenase family of enzymes. Cancer cells utilize great quantities of glucose, shifting toward a glycolytic metabolism. With the contribution of tumor stromal cells and under hypoxic conditions, this leads toward the acidification of the extracellular matrix. The ability to shift between different metabolic pathways is a characteristic of breast cancer cells and is associated with an aggressive phenotype. Furthermore, the preliminary scientific evidence concerning the levels of circulating lactate in breast cancer points toward a correlation between hyperlactacidemia and poor prognosis, even though no clear linkage has been demonstrated. Overall, lactate may represent a promising metabolic target that needs to be investigated in breast cancer.


Assuntos
Neoplasias da Mama , Ácido Láctico , Humanos , Feminino , Ácido Láctico/metabolismo , Neoplasias da Mama/metabolismo , Glucose/metabolismo , Glicólise
2.
J Med Internet Res ; 23(1): e24983, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33411670

RESUMO

BACKGROUND: The death toll of COVID-19 topped 170,000 in Europe by the end of May 2020. COVID-19 has caused an immense psychological burden on the population, especially among doctors and nurses who are faced with high infection risks and increased workload. OBJECTIVE: The aim of this study was to compare the mental health of medical professionals with nonmedical professionals in different European countries during the COVID-19 pandemic. We hypothesized that medical professionals, particularly those exposed to COVID-19 at work, would have higher levels of depression, anxiety, and stress. We also aimed to determine their main stressors and most frequently used coping strategies during the crisis. METHODS: A cross-sectional online survey was conducted during peak COVID-19 months in 8 European countries. The questionnaire included demographic data and inquired whether the participants were exposed to COVID-19 at work or not. Mental health was assessed via the Depression Anxiety Stress Scales32 (23.53)-21 (DASS-21). A 12-item checklist on preferred coping strategies and another 23-item questionnaire on major stressors were completed by medical professionals. RESULTS: The sample (N=609) consisted of 189 doctors, 165 nurses, and 255 nonmedical professionals. Participants from France and the United Kingdom reported experiencing severe/extremely severe depression, anxiety, and stress more often compared to those from the other countries. Nonmedical professionals had significantly higher scores for depression and anxiety. Among medical professionals, no significant link was reported between direct contact with patients with COVID-19 at work and anxiety, depression, or stress. "Uncertainty about when the epidemic will be under control" caused the most amount of stress for health care professionals while "taking protective measures" was the most frequently used coping strategy among all participants. CONCLUSIONS: COVID-19 poses a major challenge to the mental health of working professionals as a considerable proportion of our participants showed high values for depression, anxiety, and stress. Even though medical professionals exhibited less mental stress than nonmedical professionals, sufficient help should be offered to all occupational groups with an emphasis on effective coping strategies.


Assuntos
COVID-19/psicologia , Pessoal de Saúde/psicologia , Saúde Mental/normas , Estresse Psicológico/epidemiologia , COVID-19/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Feminino , Humanos , Internet , Masculino , Pandemias , SARS-CoV-2/isolamento & purificação , Inquéritos e Questionários
3.
Sci Rep ; 14(1): 21333, 2024 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-39266659

RESUMO

Even during the third wave of the COVID-19 pandemic health professionals were facing mental health challenges. The aim of this study was to examine the mental health of doctors, nurses and other professional groups in Europe and to identify differences between the professional groups. We conducted a cross-sectional online survey in 8 European countries. We asked for demographic data, whether the participants were exposed to COVID-19 at work, for main information sources about the pandemic, the Depression Anxiety Stress Scales (DASS-21), and major stressors. A MANCOVA was carried out to find predictors of mental health among health care professionals. The sample (N = 1398) consisted of 237 physicians, 459 nurses, and 351 other healthcare professionals and 351 non-medical professionals with no direct involvement in patient care. The mean mental health of all groups was affected to a mild degree. Major predictors for depression and anxiety were the profession group with higher scores especially in the group of the nurses and working directly with COVID-patients. In the third wave of the COVID-19 pandemic, the psychological burden on health professionals has remained high, with being nurse and working directly with COVID19 patients being particular risk factors for mental distress. We found as a main result that nurses scored significantly higher on depression and anxiety than practitioners.


Assuntos
Ansiedade , COVID-19 , Depressão , Pessoal de Saúde , Saúde Mental , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , Estudos Transversais , Masculino , Feminino , Europa (Continente)/epidemiologia , Adulto , Pessoal de Saúde/psicologia , Pessoa de Meia-Idade , Depressão/epidemiologia , Ansiedade/epidemiologia , Inquéritos e Questionários , SARS-CoV-2/isolamento & purificação , Estresse Psicológico/epidemiologia , Pandemias , Angústia Psicológica , Enfermeiras e Enfermeiros/psicologia
4.
J Neural Transm (Vienna) ; 120(3): 469-76, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22955957

RESUMO

Botulinum toxin type A (BTX-A) represents the gold standard therapy for focal spasticity after stroke, with low prevalence of complications, reversibility, and efficacy in reducing spastic hypertonia. Current guidelines suggest the employment of a dosage up to 600 units (U) of BTX-A to treat spasticity after stroke, to avoid important adverse effects and the development of antibodies against the neurotoxin. In recent years, NT 201, a new BTX-A free of complexing proteins, has been used for treating several movement disorders, showing safety and efficacy in upper limb spasticity. In a prospective, non-randomized, open-label study, we studied the efficacy and safety of higher doses of BTX-A NT 201 (up to 840 U) in 25 consecutive patients with upper and lower limb spasticity after stroke, evaluated at 30 and 90 days after injections. Before and after the treatment, the grade of spasticity, the disability, and spasticity-related pain were extensively measured. After 30 days of follow-up, a great reduction of spasticity and pain with improvement of disability was observed. The effects were still present at 90 days of follow-up. No major adverse events were observed. Higher doses of BTX-A NT 201 appeared to be safe and efficacious in patients with upper and lower limb spasticity after stroke. However, further investigations are needed to determine its reproducibility in larger case series or randomized clinical trials and to observe the absence of antibodies against the neurotoxin also after repeated injections.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Espasticidade Muscular/tratamento farmacológico , Fármacos Neuromusculares/administração & dosagem , Acidente Vascular Cerebral/complicações , Idoso , Feminino , Humanos , Extremidade Inferior , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/etiologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Extremidade Superior
5.
Cell Mol Life Sci ; 69(5): 741-62, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21997383

RESUMO

The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin resistance, dyslipidemia and hypertension. At the molecular level, metabolic syndrome is accompanied not only by dysregulation in the expression of adipokines (cytokines and chemokines), but also by alterations in levels of leptin, a peptide hormone released by white adipose tissue. These changes modulate immune response and inflammation that lead to alterations in the hypothalamic 'bodyweight/appetite/satiety set point,' resulting in the initiation and development of metabolic syndrome. Metabolic syndrome is a risk factor for neurological disorders such as stroke, depression and Alzheimer's disease. The molecular mechanism underlying the mirror relationship between metabolic syndrome and neurological disorders is not fully understood. However, it is becoming increasingly evident that all cellular and biochemical alterations observed in metabolic syndrome like impairment of endothelial cell function, abnormality in essential fatty acid metabolism and alterations in lipid mediators along with abnormal insulin/leptin signaling may represent a pathological bridge between metabolic syndrome and neurological disorders such as stroke, Alzheimer's disease and depression. The purpose of this review is not only to describe the involvement of brain in the pathogenesis of metabolic syndrome, but also to link the pathogenesis of metabolic syndrome with neurochemical changes in stroke, Alzheimer's disease and depression to a wider audience of neuroscientists with the hope that this discussion will initiate more studies on the relationship between metabolic syndrome and neurological disorders.


Assuntos
Síndrome Metabólica/complicações , Síndrome Metabólica/patologia , Doenças do Sistema Nervoso/etiologia , Adipocinas/metabolismo , Moduladores de Receptores de Canabinoides/metabolismo , Ceramidas/metabolismo , Humanos , Insulina/metabolismo , Resistência à Insulina , Leptina/metabolismo , Metabolismo dos Lipídeos , Fatores de Risco
6.
Alzheimers Dement ; 9(2): 113-22, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23245560

RESUMO

BACKGROUND: Frailty is a clinical syndrome generally associated with a greater risk for adverse outcomes such as falls, disability, institutionalization, and death. Cognition and dementia have already been considered as components of frailty, but the role of frailty as a possible determinant of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) has been poorly investigated. We estimated the predictive role of frailty syndrome on incident dementia and its subtypes in a nondemented, Italian, older population. METHODS: We evaluated 2581 individuals recruited from the Italian Longitudinal Study on Aging sample population consisting of 5632 subjects aged 65 to 84 years and with a 3.9-year median follow-up. A phenotype of frailty according to a modified measurement of Cardiovascular Health Study criteria was operationalized. Dementia, AD, and VaD were classified using current published criteria. RESULTS: Over a 3.5-year follow-up, 65 of 2581 (2.5%) older subjects, 16 among 252 frail individuals (6.3%), of which 9 were affected by VaD (3.6%), developed overall dementia. In a proportional hazards model, frailty syndrome was associated with a significantly increased risk of overall dementia (adjusted hazard ratio: 1.85; 95% confidence interval: 1.01-3.40) and, in particular, VaD (adjusted hazard ratio: 2.68; 95% confidence interval: 1.16-7.17). The risk of AD or other types of dementia did not significantly change in frail individuals in comparison with subjects without frailty syndrome. CONCLUSION: In our large population-based sample, frailty syndrome was a short-term predictor of overall dementia and VaD.


Assuntos
Demência Vascular/epidemiologia , Idoso Fragilizado , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Demência Vascular/complicações , Feminino , Humanos , Incidência , Itália , Masculino , Síndrome
8.
Eur Geriatr Med ; 14(5): 953-960, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37603190

RESUMO

CONTEXT: The assessment of decision-making ability of older adults with cognitive impairment is a complex challenge that geriatricians often face in relation to risk-taking situations (driving, aging in place, financial decisions, etc.). However, there are no clear and consensual practice guidelines. An overview of current practices and needs seemed necessary. METHODS: We co-created and conducted an online survey to describe practice and knowledge, among European geriatricians. The survey was structured in 3 parts: a description of the professional's practice regarding cognitive impairment, a specific questionnaire about everyday risky decision-making evaluation and an investigation of the clinician's knowledge about relevant ethical and legal recommendations. Each part consisted of both multiple choice and open questions, analyzed through descriptive statistics and qualitative analysis methods. RESULTS: Based on the responses of 123 geriatricians across Europe, our survey showed that clinical interview is the cornerstone of geriatric assessment of decision-making ability of patients with mild to moderate dementia. When faced with risk-taking dilemma situations, geriatricians tend to favor a context of safety above autonomy, but they can support risky decision-making if it is consistent with the patient's previous lifestyle, depending on the degree of risk to self and others, on the decision-making ability assessed, and if there is some form of shared decision-making. CONCLUSION: Assessing decision-making ability is challenging for geriatricians, who in our study relied more on their clinical interview and global cognitive tests than more in-depth evaluations. Supporting independent decision-making, when associated with risk-taking, requires better detection and anticipation shared with the patient environment.

9.
Biomedicines ; 11(5)2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-37239089

RESUMO

BACKGROUND: Older adults with mood disorders constitute a heterogeneous group in a complex spectrum interlinked with physical comorbidities. Worldwide, Bipolar disorders in older people (OABD) remain underestimated and underdiagnosed. OABD is challenging in the clinical setting and is associated with adverse outcomes (increased risk of anti-social behaviour triggered by inappropriate drugs and increased incidence of health deficits, including cancer). This article aims to describe the state of the art of OABD in the Italian framework and provide a new field of research. METHODS: We performed an overview of the literature, selecting our target population (over 65 years) and synthesising the main challenging issues. By exploiting the Italian database from the Minister of Health in 2021, we analysed epidemiological data in the age range 65-74 years and 75-84 years old. RESULTS: Females showed the highest prevalence and incidence in both groups, with a regional difference across the country but more evident in the Autonomous Provinces of Bolzano and Trento for the 65-74 years range. Several projects recently focused on this topic, and the urgency to define better the epidemiological framework is mandatory. CONCLUSIONS: This study represented the first attempt to report the comprehensive Italian framework on OABD aimed at fostering research activities and knowledge.

10.
JMIR Public Health Surveill ; 9: e45664, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37672320

RESUMO

BACKGROUND: The COVID-19 pandemic severely affected everyday life and working conditions for most Europeans, particularly health care professionals (HCPs). Over the past 3 years, various policies have been implemented in various European countries. Studies have reported on the worsening of mental health, work-related stress, and helpful coping strategies. However, having a closer look is still necessary to gain more information on the psychosocial stressors and unmet needs of HCPs as well as nonmedical staff. OBJECTIVE: This study aimed to obtain quantitative information on job-related stressors of physicians and nurses and the coping strategies of HCPs and nonmedical staff at 2 periods of the COVID-19 pandemic. By further analyzing qualitative comments, we wanted to gain more information on the psychosocial stressors and unmet needs of HCPs as well as nonmedical staff on different levels of experience. METHODS: A cross-sectional survey was conducted at 2 time points during the COVID-19 pandemic in several European countries. The first study period (T1) lasted between April 1 and June 20, 2020, and the second study period (T2) lasted between November 25, 2021, and February 28, 2022. On a quantitative level, we used a questionnaire on stressors for physicians and nurses and a questionnaire on coping strategies for HCPs and nonmedical staff. Quantitative data were descriptively analyzed for mean values and differences in stressors and coping strategies. Qualitative data of free-text boxes of HCPs and nonmedical staff were analyzed via thematic analysis to explore the experiences of the individuals. RESULTS: T1 comprised 609 participants, and T2 comprised 1398 participants. Overall, 296 participants made 438 qualitative comments. The uncertainty about when the pandemic would be controlled (T1: mean 2.28, SD 0.85; T2: mean 2.08, SD 0.90) and the fear of infecting the family (T1: mean 2.26, SD 0.98; T2: mean 2.02, SD 1.02) were the most severe stressors identified by physicians and nurses in both periods. Overall, the use of protective measures (T1: mean 2.66, SD 0.60; T2: mean 2.66, SD 0.60) and acquiring information about COVID-19 (T1: mean 2.29, SD 0.82; T2: mean 1.99, SD 0.89) were identified as the most common coping strategies for the entire study population. Using thematic analysis, we identified 8 themes of personal experiences on the micro, meso, and macro levels. Measures, working conditions, feelings and emotions, and social climate were frequently mentioned topics of the participants. In T1, feelings of isolation and uncertainty were prominent. In T2, feelings of exhaustion were expressed and vaccination was frequently discussed. Moreover, unmet psychosocial needs were identified. CONCLUSIONS: There is a need for improvement in pandemic preparedness. Targeted vocational education measures and setting up of web-based mental health support could be useful to bridge gaps in psychosocial support needs in future crises.


Assuntos
COVID-19 , Pandemias , Humanos , Estudos Transversais , Pessoal de Saúde , Europa (Continente)
11.
Front Public Health ; 11: 1077103, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36866103

RESUMO

Objective: To evaluate the impact of the COVID-19 pandemic on first and follow-up visits for cancer outpatients. Methods: This is a multicenter retrospective observational study involving three Comprehensive Cancer Care Centers (CCCCs): IFO, including IRE and ISG in Rome, AUSL-IRCCS of Reggio Emilia, and IRCCS Giovanni Paolo II in Bari) and one oncology department in a Community Hospital (Saint'Andrea Hospital, Rome). From 1 January 2020 and 31 December 2021, we evaluated the volume of outpatient consultations (first visits and follow-up), comparing them with the pre-pandemic year (2019). Results were analyzed by quarter according to the Rt (real-time indicator used to assess the evolution of the pandemic). IFO and IRCCS Giovanni Paolo II were "COVID-free" while AUSL-IRCCS RE was a "COVID-mixed" Institute. Depending on the Rt, Sain't Andrea Hospital experienced a "swinging" organizational pathway (COVID-free/ COVID-mixed). Results: Regarding the "first appointments", in 2020 the healthcare facilities operating in the North and Center of Italy showed a downward trend. In 2021, only AUSL-IRCCS RE showed an upward trend. Regarding the "follow-up", only AUSL IRCCS RE showed a slight up-trend in 2020. In 2021, IFO showed an increasing trend, while S. Andrea Hospital showed a negative plateau. Surprisingly, IRCCS Giovanni Paolo II in Bari showed an uptrend for both first appointment and follow-ups during pandemic and late pandemic except for the fourth quarter of 2021. Conclusions: During the first pandemic wave, no significant difference was observed amongst COVID-free and COVID-mixed Institutes and between CCCCs and a Community Hospital. In 2021 ("late pandemic year"), it has been more convenient to organize COVID-mixed pathway in the CCCCs rather than to keep the Institutions COVID-free. A swinging modality in the Community Hospital did not offer positive results in term of visit volumes. Our study about the impact of COVID-19 pandemic on visit volume in cancer outpatients may help health systems to optimize the post-pandemic use of resources and improve healthcare policies.


Assuntos
COVID-19 , Neoplasias , Humanos , COVID-19/epidemiologia , Pacientes Ambulatoriais , Pandemias , Política de Saúde , Hospitais Comunitários , Neoplasias/epidemiologia
12.
Int J Geriatr Psychiatry ; 27(12): 1218-38, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22396249

RESUMO

OBJECTIVE: In several longitudinal studies, light-to-moderate drinking of alcoholic beverages has been proposed as being protective against the development of age-related changes in cognitive function, predementia syndromes, and cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia). However, contrasting findings also exist. METHOD: The English literature published in this area before September 2011 was evaluated, and information relating to the various factors that may impact upon the relationship between alcohol consumption and dementia or predementia syndromes is presented in the succeeding texts. RESULTS: Light-to-moderate alcohol consumption may be associated with a reduced risk of incident overall dementia and AD; however, protective benefits afforded to vascular dementia, cognitive decline, and predementia syndromes are less clear. The equivocal findings may relate to many of the studies being limited to cross-sectional designs, restrictions by age or gender, or incomplete ascertainment. Different outcomes, beverages, drinking patterns, and study follow-up periods or possible interactions with other lifestyle-related (e.g., smoking) or genetic factors (e.g., apolipoprotein E gene variation) may all contribute to the variability of findings. CONCLUSION: Protective effects of moderate alcohol consumption against cognitive decline are suggested to be more likely in the absence of the AD-associated apolipoprotein E ε4 allele and where wine is the beverage. At present, there is no indication that light-to-moderate alcohol drinking would be harmful to cognition and dementia, and attempts to define what might be deemed beneficial levels of alcohol intake in terms of cognitive performance would be highly problematic and contentious.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Transtornos Cognitivos/etiologia , Demência/etiologia , Envelhecimento , Consumo de Bebidas Alcoólicas/psicologia , Apolipoproteínas E/genética , Cognição/efeitos dos fármacos , Demência/psicologia , Humanos , Fármacos Neuroprotetores/farmacologia , Fatores de Risco
13.
Healthcare (Basel) ; 10(8)2022 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-36011191

RESUMO

Background/rationale: Despite mounting evidence about delirium, this complex geriatric syndrome is still not well managed in clinical contexts. The aging population creates a very demanding area for innovation and technology in healthcare. For instance, an outline of an aging-friendly healthcare environment and clear guidance for technology-supported improvements for people at delirium risk are lacking. Objective: We aimed to foster debate about the importance of technical support in optimizing healthcare professional practice and improving the outcomes for inpatients' at delirium risk. We focused on critical clinical points in the field of delirium worthy of being addressed by a multidisciplinary approach. Methods: Starting from a consensus workshop sponsored by the Management Perfectioning Course based at the Marco Biagi Foundation (Modena, Italy) about clinical issues related to delirium management still not addressed in our healthcare organizations, we developed a requirements' analysis among the representatives of different disciplines and tried to formulate how technology could support the summaries of the clinical issues. We analyzed the national and international panorama by a PubMed consultation of articles with the following keywords in advanced research: "delirium", "delirium management", "technology in healthcare", and "elderly population". Results: Despite international recommendations, delirium remains underdiagnosed, underdetected, underreported, and mismanaged in the acute hospital, increasing healthcare costs, healthcare professionals' job distress, and poor clinical outcomes. Discussion: Although all healthcare professionals recognize delirium as a severe and potentially preventable source of morbidity and mortality for hospitalized older people, it receives insufficient attention in resource allocation and multidisciplinary research. We synthesized how tech-based tools could offer potential solutions to the critical clinical points in delirium management.

14.
Front Oncol ; 12: 828660, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35756683

RESUMO

The outbreak of the coronavirus 2 disease 2019 (COVID-19) puts an enormous burden on healthcare systems worldwide. This may worsen outcomes in patients with severe chronic diseases such as cancer, autoimmune diseases, and immune deficiencies. In this critical situation, only a few available data exist, which do not allow us to provide practical guides for the treatment of oncological or immunocompromised patients. Therefore, a further step forward is needed, addressing the specific needs and demands of frail patients in the pandemic era. Here we aim to present a protocol of a study approved by an ethical committee named "CO.M.E.TA". CO.M.E.TA protocol is a network project involving six Italian institutions and its goals are: i) to measure and compare the impact of the pandemic on the access of cancer and immunocompromised patients to therapies in three Italian regions; ii) to assess how reorganizational measures put in place in these different institutions have impacted specific metrics of performance; iii) to establish a COVID-19 Biobank of biological samples from SARS-CoV-2 infected patients to be used to study immunological alterations in patients with immune frailty.

15.
Front Cell Dev Biol ; 9: 654913, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33912566

RESUMO

Metabolic syndrome (MetS) affects the population worldwide and results from several factors such as genetic background, environment and lifestyle. In recent years, an interplay among autophagy, metabolism, and metabolic disorders has become apparent. Defects in the autophagy machinery are associated with the dysfunction of many tissues/organs regulating metabolism. Metabolic hormones and nutrients regulate, in turn, the autophagy mechanism. Autophagy is a housekeeping stress-induced degradation process that ensures cellular homeostasis. High mobility group box 1 (HMGB1) is a highly conserved nuclear protein with a nuclear and extracellular role that functions as an extracellular signaling molecule under specific conditions. Several studies have shown that HMGB1 is a critical regulator of autophagy. This mini-review focuses on the involvement of HMGB1 protein in the interplay between autophagy and MetS, emphasizing its potential role as a promising biomarker candidate for the early stage of MetS or disease's therapeutic target.

16.
Brain Sci ; 11(1)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466666

RESUMO

Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no cure and no effective diagnostic criteria. The greatest challenge in effectively treating AD is identifying biomarkers specific for each patient when neurodegenerative processes have not yet begun, an outcome that would allow the design of a personalised therapeutic approach for each patient and the monitoring of the therapeutic response during the treatment. We found that the excessive phosphorylation of the amyloid precursor protein (APP) Tyr682 residue on the APP 682YENPTY687 motif precedes amyloid ß accumulation and leads to neuronal degeneration in AD neurons. We proved that Fyn tyrosine kinase elicits APP phosphorylation on Tyr682 residue, and we reported increased levels of APP Tyr682 and Fyn overactivation in AD neurons. Here, we want to contemplate the possibility of using fibroblasts as tools to assess APP Tyr682 phosphorylation in AD patients, thus making the changes in APP Tyr682 phosphorylation levels a potential diagnostic strategy to detect early pathological alterations present in the peripheral cells of AD patients' AD brains.

17.
J Neurol Neurosurg Psychiatry ; 81(4): 433-40, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19965842

RESUMO

OBJECTIVE: The authors investigated the relationship of metabolic syndrome (MetS) and its individual components with incident dementia in a prospective population-based study with a 3.5-year follow-up. METHODS: A total of 2097 participants from a sample of 5632 subjects (65-84 years old) from the Italian Longitudinal Study on Ageing were evaluated. MetS was defined according to the Third Adults Treatment Panel of the National Cholesterol Education Program criteria. Dementia, Alzheimer disease (AD) and vascular dementia (VaD) were classified using current published criteria. RESULTS: MetS subjects (N=918) compared with those without MetS (N=1179) had an increased risk for VaD (1.63% vs 0.85%, adjusted hazard ratio (HR) 3.71, 95% CI 1.40 to 9.83). After excluding 338 subjects with baseline undernutrition, MetS subjects compared with those without MetS had an elevated risk of VaD (adjusted HR, 3.82; 95% CI 1.32 to 11.06). Moreover, those with MetS and high inflammation had a still further higher risk of VaD (multivariate adjusted HR, 9.55; 95% CI 1.17 to 78.17) compared with those without MetS and high inflammation. On the other hand, those with MetS and low inflammation compared with those without MetS and low inflammation did not exhibit a significant increased risk of VaD (adjusted HR, 3.31, 95% CI 0.91 to 12.14). Finally, a synergistic MetS effect versus its individual component effects was verified on the risk of VaD. CONCLUSION: In our population, MetS subjects had an elevated risk of VaD that increased after excluding patients with baseline undernutrition and selecting MetS subjects with high inflammation.


Assuntos
Envelhecimento/fisiologia , Demência Vascular/epidemiologia , Síndrome Metabólica/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Infarto Cerebral/diagnóstico , Infarto Cerebral/epidemiologia , Comorbidade , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Demência Vascular/diagnóstico , Feminino , Seguimentos , Humanos , Inflamação/diagnóstico , Inflamação/epidemiologia , Itália/epidemiologia , Masculino , Síndrome Metabólica/diagnóstico , Estado Nutricional , Vigilância da População , Estudos Prospectivos , Fatores de Risco
18.
Am J Geriatr Psychiatry ; 18(2): 98-116, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20104067

RESUMO

Clinical and epidemiologic research has focused on the identification of risk factors that may be modified in predementia syndromes, at a preclinical and early clinical stage of dementing disorders, with specific attention to the role of depression. Our goal was to provide an overview of these studies and more specifically to describe the prevalence and incidence of depression in individuals with mild cognitive impairment (MCI), the possible impact of depressive symptoms on incident MCI, or its progression to dementia and the possible mechanisms behind the observed associations. Prevalence and incidence of depressive symptoms or syndromes in MCI vary as a result of different diagnostic criteria and different sampling and assessment procedures. The prevalence of depression in individuals with MCI was higher in hospital-based studies (median: 44.3%, range: 9%-83%) than in population-based studies (median: 15.7%, range: 3%-63%), reflecting different referral patterns and selection criteria. Incidence of depressive symptoms varied from 11.7 to 26.6/100 person-years in hospital-based and population-based studies. For depressed normal subjects and depressed patients with MCI, the findings on increased risk of incident MCI or its progression to dementia were conflicting. These contrasting findings suggested that the length of the follow-up period, the study design, the sample population, and methodological differences may be central for detecting an association between baseline depression and subsequent development of MCI or its progression to dementia. Assuming that MCI may be the earliest identifiable clinical stage of dementia, depressive symptoms may be an early manifestation rather than a risk factor for dementia and Alzheimer disease, arguing that the underlying neuropathological condition that causes MCI or dementia also causes depressive symptoms. In this scenario, at least in certain subsets of elderly patients, late-life depression, MCI, and dementia could represent a possible clinical continuum.


Assuntos
Transtornos Cognitivos/complicações , Demência/complicações , Depressão/complicações , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/classificação , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Demência/diagnóstico , Demência/epidemiologia , Depressão/diagnóstico , Depressão/epidemiologia , Avaliação Geriátrica , Humanos , Incidência , Pessoa de Meia-Idade , Modelos Psicológicos , Prevalência , Fatores de Risco , Síndrome
19.
Brain Inj ; 24(9): 1108-12, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20569045

RESUMO

BACKGROUND: In rehabilitation settings, motor imagery, motor observation and mirror therapy serve as techniques for the recovery of paretic upper limb in patients with movement disorders after stroke, whereas botulinum toxin type A (BTX-A) offers the best treatment for focal spasticity. CASE REPORTS: After haemorrhagic stroke, three patients (two men and one woman, mean age: 61.2 +/- 7.03) presented with hemiparesis of the left or right hand and arm with flexion of fingers, wrist and elbow, with no disturbance to sensitivity but with loss of use handoff the limb to write, eat or dress. After BTX-A injections, the patients underwent a daily rehabilitation programme based on motor imagery and motor observation for 1 month. Before and after the combined treatment, the motor function, spasticity and functional deficits of the patient were extensively measured. After a 3-month follow-up, upper limb spasticity measured with the Modified Ashworth Scale had worsened, yet the associated score remained lower than that at baseline. However, in these three patients a large improvement of motor function of the hemiparetic upper limb was observed. CONCLUSION: Combined treatment may be a viable rehabilitation option in post-stroke patients with disability to upper-extremity motor function, however further investigations are needed to determine its reproducibility in larger case series or clinical trials.


Assuntos
Toxinas Botulínicas Tipo A/uso terapêutico , Espasticidade Muscular/tratamento farmacológico , Fármacos Neuromusculares/uso terapêutico , Paresia/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Extremidade Superior/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espasticidade Muscular/fisiopatologia , Paresia/fisiopatologia , Paresia/reabilitação , Acidente Vascular Cerebral/fisiopatologia , Reabilitação do Acidente Vascular Cerebral , Resultado do Tratamento
20.
J Alzheimers Dis ; 16(3): 467-70, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19276539

RESUMO

Very recent findings confirmed that S-adenosylmethionine (SAM) can exert a direct effect on glutathione S-transferase (GST) activity. Alzheimer's disease (AD) is accompanied by reduced GST activity, diminished SAM, and increased S-adenosyl homocysteine (SAH), the downstream metabolic product resulting from SAM-mediated transmethylation reactions, when deprived of folate. Therefore, these findings underscored the critical role of SAM in maintenance of neuronal health, suggesting a possible role of SAM as a neuroprotective dietary supplement in AD. Given recent findings from clinical trials in which omega-3 polyunsturated fatty acids (PUFA) supplementation was effective only in very mild AD subgroups or mild cognitive impairment (MCI), we suggest intervention trials using measures of dietary supplementation (dietary omega-3 PUFA and SAM plus B vitamin supplementation) to determine if such supplements will reduce the risk for cognitive decline in very mild AD and MCI. Therefore, key supplements are not necessarily working in isolation, and the most profound impact, or in some cases the only impact, is noted very early in the course of AD, suggesting that nutriceutical supplements may bolster pharmacological approaches well past the window where supplements can work on their own.


Assuntos
Doença de Alzheimer/metabolismo , Ácidos Graxos Insaturados/metabolismo , S-Adenosil-Homocisteína/metabolismo , S-Adenosilmetionina/metabolismo , Doença de Alzheimer/terapia , Animais , Demência/metabolismo , Humanos
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