Through a comprehensive analysis of Italy's estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we aimed to understand the patterns of health loss and response ...of the health-care system, and offer evidence-based policy indications in light of the demographic transition and government health spending in the country.
Estimates for Italy were extracted from GBD 2017. Data on Italy are presented for 1990 and 2017, on prevalence, causes of death, years of life lost, years lived with disability, disability-adjusted life-years (DALYs), life expectancy at birth and at age 65 years, healthy life expectancy, and Healthcare Access and Quality (HAQ) Index. We compared the estimates for Italy with those of 15 other western European countries.
The quality of the universal health system and healthy behaviours contribute to favourable overall health, even in comparison with other western European countries. In 2017, life expectancy and HAQ Index score in Italy were among the highest globally, with life expectancy at birth reaching 85·3 years for females and 80·8 for males in 2017, ranking Italy eighth globally for females and sixth for males, and an HAQ Index score of 94·9 in 2016 compared with 81·54 in 1990, keeping Italy ranked as ninth globally. Between 1990 and 2017 age-standardised death rates for cardiovascular diseases decreased by 53·7% (95% uncertainty interval −56·1 to −51·4), for neoplasms decreased by 28·2% (−32·3 to −24·6), and for transport injuries decreased by 62·1% (−64·6 to −59·2). However, population ageing is causing an increase in the burden of specific diseases, such as Alzheimer's disease and other dementias (DALYs increased by 77·9% 68·4 to 87·2) and pancreatic (DALYs increased by 39·7% 28·4 to 51·7) and uterine cancers (DALYs increased by 164·7% 129·7 to 202·5). Behavioural risk factors, which are potentially modifiable, still have a strong effect, particularly on cardiovascular diseases and neoplasms. For instance, in 2017, 44 400 (41 200 to 47 800) cancer deaths were attributed to smoking, 12 000 (9600 to 14 800) to alcohol use, and 9500 (5400 to 14 200) to high body-mass index, while 47 000 (31 100 to 65 700) deaths due to cardiovascular diseases could be attributed to high LDL cholesterol, 28 700 (19 700 to 38 500) to diets low in whole grains, and 15 900 (8500 to 24 900) to low physical activity.
Italy provides an interesting example of the results that can be achieved by a mix of relatively healthy lifestyles and a universal health system. Two main issues require attention, population ageing and gradual decrease of public health financing, which both pose several challenges to the future of Italy's health status. Our findings should be useful to Italy's policy makers and health system experts elsewhere.
Bill & Melinda Gates Foundation.
Objective
This article reviews current headache disability measures and clinical need, as well as presenting the rationale for a new measure addressing work‐related disability in migraine patients ...and the steps devoted to this aim.
Background
Episodic and chronic migraine (EM and CM) constitute an enormous economic burden to societies, and the vast majority of this burden is attributable to indirect costs, ie those associated with productivity loss. A measure of work‐related disability is therefore needed to quantify the impact of EM and CM on patients' ability to carry out work tasks.
Methods
We briefly present the advantages and disadvantages of the disability measures that have been most commonly used for this purpose and the rationale for developing a new measure.
Results
The entire process of development of HEADWORK, a questionnaire designed to assess work‐related disability, is presented together with short‐term sensitivity to change.
Conclusions
Current headache disability measures need improvement. HEADWORK is a valid, reliable, and sensitive questionnaire to address the amount and severity of work‐related difficulties and of the factors contributing to such difficulties. HEADWORK is suitable for daily clinical practice, epidemiological research and for clinical trials, and potentially to define work‐related disability weights for the calculation of migraine indirect costs.
Tamoxifen resistance is a major hurdle in the treatment of estrogen receptor (ER)-positive breast cancer. The mechanisms of tamoxifen resistance are not fully understood although several underlying ...molecular events have been suggested. Recently, we identified autoantibodies reacting with membrane-associated ERα (anti-ERα Abs) in sera of breast cancer patients, able to promote tumor growth. Here, we investigated whether anti-ERα Abs purified from sera of ER-positive breast cancer patients could contribute to tamoxifen resistance. Anti-ERα Abs inhibited tamoxifen-mediated effects on cell cycle and proliferation in MCF-7 cells. Moreover, anti-ERα Abs hampered the tamoxifen-mediated reduction of tumor growth in SCID mice xenografted with breast tumor. Notably, simvastatin-mediated disaggregation of lipid rafts, where membrane-associated ERα is embedded, restored tamoxifen sensitivity, preventing anti-ERα Abs effects. In conclusion, detection of serum anti-ERα Abs may help predict tamoxifen resistance and concur to appropriately inform therapeutic decisions concerning hormone therapy in ER-positive breast cancer patients.
Background and aims
Glycogen storage disease type Ib (GSD1b) is a rare metabolic and immune disorder caused by a deficiency in the glucose-6-phosphate transporter (G6PT) and characterized by impaired ...glucose homeostasis, myeloid dysfunction, and long-term risk of hepatocellular adenomas. Despite maximal therapy, based on a strict diet and on granulocyte colony-stimulating factor treatment, long-term severe complications still develop. Understanding the pathophysiology of GSD1b is a prerequisite to develop new therapeutic strategies and depends on the availability of animal models. The G6PT-KO mouse mimics the human disease but is very fragile and rarely survives weaning. We generated a conditional G6PT-deficient mouse as an alternative model for studying the long-term pathophysiology of the disease. We utilized this conditional mouse to develop an inducible G6PT-KO model to allow temporally regulated G6PT deletion by the administration of tamoxifen (TM).
Methods
We generated a conditional G6PT-deficient mouse utilizing the CRElox strategy. Histology, histochemistry, and phenotype analyses were performed at different times after TM-induced G6PT inactivation. Neutrophils and monocytes were isolated and analyzed for functional activity with standard techniques.
Results
The G6PT-inducible KO mice display the expected disturbances of G6P metabolism and myeloid dysfunctions of the human disorder, even though with a milder intensity.
Conclusions
TM-induced inactivation of G6PT in these mice leads to a phenotype which mimics that of human GSD1b patients. The conditional mice we have generated represent an excellent tool to study the tissue-specific role of the
G6PT
gene and the mechanism of long-term complications in GSD1b.
Background
Idiopathic intracranial hypertension (IIH) is associated with obesity, and obesity is associated with binge eating disorder (BED). The aim of this paper is to address the presence and ...impact of BED in patients undergoing an IIH diagnostic protocol.
Methods
This was a cross-sectional study. Consecutive patients suspected of IIH underwent neurological, neuro-ophthalmologic and psychological examinations, neuroimaging studies and intracranial pressure (ICP) measurements through lumbar puncture in the recumbent position. IIH diagnosis was based on International Classification of Headache Disorders, 2nd Edition criteria; BED diagnosis was based on Diagnostic and Statistical Manual of Mental Disorders, 5th Edition criteria. The presence of oligoclonal bands (OCBs) in the cerebrospinal fluid was also assessed.
Results
Forty-five patients were enrolled: 33 were diagnosed with IIH and five of them (15%) were obese with BED. Compared to non-obese patients, those who were obese, and particularly those who were obese with BED, were more likely to have an IIH diagnosis (χ2 = 14.3; p = 0.001), ICP > 200 mmH2O (χ2 = 12.7; p = 0.002) and history of abuse or neglect (χ2 = 11.2; p = 0.004). No association with OCBs was found.
Conclusions
We reported for the first time the presence of BED among patients with IIH and showed that BED is associated to IIH, ICP and history of abuse or neglect.
Abstract Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare congenital leukodystrophy caused by mutations in the MLC1 gene that encodes a membrane protein of unknown function. ...In the brain MLC1 protein is mainly expressed in astrocyte end-feet, localizes in lipid rafts and associates with the dystrophin glycoprotein complex (DGC). Using pull-down and co-fractionation assays in cultured human and rat astrocytes, we show here that MLC1 intracellular domains pull-down the DGC proteins syntrophin, dystrobrevin, Kir4.1 and caveolin-1, the structural protein of caveolae, thereby supporting a role for DGC and caveolar structures in MLC1 function. By immunostaining and subcellular fractionation of cultured rat or human astrocytes treated with agents modulating caveolin-mediated trafficking, we demonstrate that MLC1 is also expressed in intracellular vesicles and endoplasmic reticulum and undergoes caveolae/raft-mediated endocytosis. Inhibition of endocytosis, cholesterol lowering and protein kinases A- and C-mediated MLC1 phosphorylation favour the expression of membrane-associated MLC1. Because pathological mutations prevent MLC1 membrane expression, the identification of substances regulating MLC1 intracellular trafficking is potentially relevant for the therapy of MLC.
Assessing the feasibility, technical implications, and clinical benefits of peripheral nerve stimulation (PNS) performed by an implantable pulse generator (IPG) located close to the stimulation site.
...Selected patients were affected by neuropathic pain associated with a documented peripheral nerve lesion, refractory to conventional surgical or pharmacological treatment. A PNS system specifically designed for peripheral placement (Neurimpulse, Padova, Italy) was implanted and followed for six months, recording the degree of patient's satisfaction (PGI-I questionnaire), the pain numerical rating scale (NRS) and the quality of life (SF36 questionnaire), as well as any change in drug regimen and work capability. The statistical significance of differences was determined by the paired Student's t-test.
A total of 58 patients were referred to permanent IPG implantation. Stimulation failure due to lead damage or dislocation was noticed in two cases (3.4%) in six months. At the follow-up end, the relative NRS reduction averaged -58 ± 30% (p < 10
) and was greater than 50% in 69% of the cases. Quality-of-life physical and mental indices were increased by 18% (p < 0.005) and 29% (p < 0.0005), respectively. The administration of antalgic drugs was stopped in 55% and reduced in 16% of the patients. Low-energy stimulation was possible in most cases, resulting in an IPG estimated life of 80 ± 35 months.
Successful PNS was achieved with a stimulation system designed for peripheral location. This new technology reduced the incidence of lead-related adverse events and the energy cost of the treatment.
The objective of this study was to describe the functional profiles of patients with Parkinson's disease (PD), and the relationships between impairment in body functions, limitations in activities, ...and environmental factors, using the World Health Organization's International Classification of Functioning, Disability, and Health (ICF). Patients were consecutively enrolled, and the ICF checklist was administered. Two count-based indices were developed: 'extension', containing ICF categories rated with qualifiers 1-4 and 'severity', containing ICF categories rated with qualifiers 3-4. Categories rated with qualifiers 1-4 in at least 50% of patients are described separately. Spearman's correlation analysis was carried out to identify the relationships between impairments in body functions (BF) and body structures, activities and participation, and environmental factors (EF); linear regressions were performed to identify the best predictors of performance indices in activities and participation. A total of 96 patients were enrolled; 34 categories rated with qualifiers 1-4 in at least 50% of patients are reported, and most of them describe impairment in movement-related functions and limitations in mobility and self-care. Performance indices are significantly lower than capacity and significant relationships with both BF impairments and EF are observed. High difficulties in activities and participation performance are connected with both presence of severe BF symptoms and relevant barriers in EF. Both BF and EF play a relevant role in improving functioning of the patients with PD. The connection between EF barriers and severe problems in activities and participation performance suggests the need of fostering participation of patients with PD by promoting facilitators among EFs. Methodologies and tools are needed to couple information on symptoms, on the difficulties in executing activities, and on environmental features.
Among reprogrammed metabolic pathways described in cancer stem cells, aberrant lipid metabolism has recently drawn increasing attention. Our study aimed to explore the contribution of fatty acids ...(FA) in the regulation of stem-like features in intrahepatic cholangiocarcinoma (iCCA).
We previously identified a functional stem-like subset in human iCCA by using a 3D sphere (SPH) model in comparison to parental cells grown as monolayer (MON). In this study, quantification of intracellular free FA and lipidomic analysis (triacylglycerol TAG composition, de novo synthesis products) were performed by LC-MS and LC-MS/QTOF, respectively, in both SPH and MON.
Stem-like SPH showed a superior content of free FA (citric, palmitic, stearic and oleic acids) and unsaturated TAG. Molecularly, SPH showed upregulation of key metabolic enzymes of de novo FA biosynthesis (AceCS1, ACLY, ACAC, FASN, ACSL1) as well as of the mTOR signaling pathway. In iCCA patients (n=68), tissue expression levels of FASN, a key gene involved in FA synthesis, correlated with five-year overall survival. Interference with FASN activity in SPH cells through both specific gene silencing (siRNA) or pharmacological inhibition (orlistat) decreased sphere-forming ability and expression of stem-like markers. In a murine xenograft model obtained by injection of iCCA-SPH cells, FASN inhibition by orlistat or injection of FASN-silenced cells significantly reduced tumor growth and expression of stem-like genes.
An altered FA metabolism contributes to maintenance of a stem-like phenotype in iCCA. FASN inhibition may be a new potential approach to interfere with the progression of this deadly disease.
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•The stem cells in intrahepatic cholangiocarcinoma (iCCA) exhibit disrupted fatty acid metabolism and increased production of specific fatty acids.•Exposure of iCCA cells to fatty acids results in a notable increase in tumor stem cell program.•FASN is upregulated in iCCA SPH and its expression correlates with poor prognosis in CCA patients.•Depletion of FASN or its inhibition reduces the aggressive characteristics of the iCCA cancer stem cell subset
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