1,128 research outputs found
Biomolecules and Cardiovascular Diseases in Women
No full text: Although cardiovascular diseases (CVD) are the leading cause of non-communicable diseases-dependent death worldwide, their effects are still largely underestimated in women [...]
PETRA: un sistema integrato per la gestione dei dati archeologici
No full textThis paper describes a database management system created for organising the data which emerged during an investigation conducted by a team from the University of Florence in Petra, Jordan. The subject of the research are Crusader settlements in Transjordan and, in particular, the castle system of the Petra valley; the study employed a methodological approach based on so-called “light archaeology”, that is a set of methods typical of European Medieval archaeology like “landscape archaeology” and “standing structure archaeology”. The study, which is still in progress, has revealed the key role of Petra in the territorial organisation of Transjordan during the Crusader period. By focusing on Wu’ayra, the most important fortress of the Petra valley, by means of a series of trial trenches, the project has documented the different settlement stages of the site. It is now apparent that the site was defended by a double wall overhanging the surrounding wadi with a single access and fourteen square towers on the outer ring and the inner walls, and an extreme defence nucleus, the fortified church, inside the cassero, in the centre of the system. Of the nine stages studied so far, three concern the Crusader settlement, one a very short occupation by the Ayyubids, and five correspond to the phase of abandonment of the castle with subsequent occasional use by Bedouin communities. The investigation will eventually evolve into a wide ranging study of the Crusader border, from Antioch to Aqaba. The computer project consists of a database management system, which is based on a Java servlet, a software which uses the HTTP protocol to generate and submit HTML pages “on demand”, and which can be viewed using a common Internet browser. This helps communication and simplifies access to data, which can also be shared on-line. Future developments will include spatial information, based on freely available GIS software. A particular feature of this investigation is the close connection which is maintained between computer technology and archaeological methods, which envisages new forms of co-operation in interdisciplinary research and new skills that draw from both disciplines
Fatal asthma in a young patient with severe bronchial hyperresponsiveness but stable peak flow records.
No full textWe report the sudden death of a 16 yr old boy with asthma. At presentation, the patient had symptoms of active asthma, mild bronchoconstriction, severe airway hyperresponsiveness to methacholine, and increased variability of peak expiratory flow records. After the patient was placed on inhaled beclomethasone (1 mg b.i.d preceded by inhaled fenoterol 0.4 mg b.i.d) he rapidly felt better, lung function improved, but airway responsiveness remained severe. Four months later, on the day he died, he was well until a fatal attack of asthma occurred around midnight without identifiable precipitating factors. Taken to hospital, he was dead on arrival. Necroscopy and microscopy showed the characteristic features of asthma death. This case report suggests that; a) asthma death may occur suddenly and unexpectedly; b) asthma death may not be prevented by long-term treatment with high-dose inhaled beclomethasone; c) severe bronchial hyperresponsiveness, even in the presence of stable peak flow records, may identify asthmatic patients at risk of sudden death
Human cell-based anti-inflammatory effects of rosiglitazone
No full textPurpose: The C-X-C motif chemokine ligand 10 (CXCL10) participates in diabetes and diabetic cardiomyopathy development from the early stages. Rosiglitazone (RGZ) exhibits anti-inflammatory properties and can target cardiomyocytes secreting CXCL10, under interferon (IFN)γ and tumor necrosis factor (TNF)α challenge. Cardiomyocyte remodeling, CD4 + T cells and dendritic cells (DCs) significantly contribute to the inflammatory milieu underlying and promoting disease development. We aimed to study the effect of RGZ onto inflammation-induced secretion of CXCL10, IFNγ, TNFα, interleukin (IL)-6 and IL-8 by human CD4 + T and DCs, and onto IFNγ/TNFα-dependent signaling in human cardiomyocytes associated with chemokine release. Methods: Cells maintained within an inflammatory-like microenvironment were exposed to RGZ at near therapy dose (5 μM). ELISA quantified cytokine secretion; qPCR measured mRNA expression; Western blot analyzed protein expression and activation; immunofluorescent analysis detected intracellular IFNγ/TNFα-dependent trafficking. Results: In human CD4 + T cells and DCs, RGZ inhibited CXCL10 release likely with a transcriptional mechanism, and reduced TNFα only in CD4 + T cells. In human cardiomyocytes, RGZ impaired IFNγ/TNFα signal transduction, blocking the phosphorylation/nuclear translocation of signal transducer and activator of transcription 1 (Stat1) and nuclear factor-kB (NF-kB), in association with a significant decrease in CXCL10 expression, IL-6 and IL-8 release. Conclusion: As the combination of Th1 biomarkers like CXCL10, IL-8, IL-6 with classical cardiovascular risk factors seems to improve the accuracy in predicting T2D and coronary events, future studies might be desirable to further investigate the anti-Th1 effect of RGZ
Comparison between the effect of VDR agonists and current immunomodulating drugs on cxc110 secretion by human skeletal muscle cells
No full textStructural magnetic resonance imaging for the early diagnosis of dementia due to Alzheimer's disease in people with mild cognitive impairment
No full textBACKGROUND: Mild cognitive impairment (MCI) due to Alzheimer's disease is the symptomatic predementia phase of Alzheimer's disease dementia, characterised by cognitive and functional impairment not severe enough to fulfil the criteria for dementia. In clinical samples, people with amnestic MCI are at high risk of developing Alzheimer's disease dementia, with annual rates of progression from MCI to Alzheimer's disease estimated at approximately 10% to 15% compared with the base incidence rates of Alzheimer's disease dementia of 1% to 2% per year. OBJECTIVES: To assess the diagnostic accuracy of structural magnetic resonance imaging (MRI) for the early diagnosis of dementia due to Alzheimer's disease in people with MCI versus the clinical follow-up diagnosis of Alzheimer's disease dementia as a reference standard (delayed verification). To investigate sources of heterogeneity in accuracy, such as the use of qualitative visual assessment or quantitative volumetric measurements, including manual or automatic (MRI) techniques, or the length of follow-up, and age of participants. MRI was evaluated as an add-on test in addition to clinical diagnosis of MCI to improve early diagnosis of dementia due to Alzheimer's disease in people with MCI. SEARCH METHODS: On 29 January 2019 we searched Cochrane Dementia and Cognitive Improvement's Specialised Register and the databases, MEDLINE, Embase, BIOSIS Previews, Science Citation Index, PsycINFO, and LILACS. We also searched the reference lists of all eligible studies identified by the electronic searches. SELECTION CRITERIA: We considered cohort studies of any size that included prospectively recruited people of any age with a diagnosis of MCI. We included studies that compared the diagnostic test accuracy of baseline structural MRI versus the clinical follow-up diagnosis of Alzheimer's disease dementia (delayed verification). We did not exclude studies on the basis of length of follow-up. We included studies that used either qualitative visual assessment or quantitative volumetric measurements of MRI to detect atrophy in the whole brain or in specific brain regions, such as the hippocampus, medial temporal lobe, lateral ventricles, entorhinal cortex, medial temporal gyrus, lateral temporal lobe, amygdala, and cortical grey matter. DATA COLLECTION AND ANALYSIS: Four teams of two review authors each independently reviewed titles and abstracts of articles identified by the search strategy. Two teams of two review authors each independently assessed the selected full-text articles for eligibility, extracted data and solved disagreements by consensus. Two review authors independently assessed the quality of studies using the QUADAS-2 tool. We used the hierarchical summary receiver operating characteristic (HSROC) model to fit summary ROC curves and to obtain overall measures of relative accuracy in subgroup analyses. We also used these models to obtain pooled estimates of sensitivity and specificity when sufficient data sets were available. MAIN RESULTS: We included 33 studies, published from 1999 to 2019, with 3935 participants of whom 1341 (34%) progressed to Alzheimer's disease dementia and 2594 (66%) did not. Of the participants who did not progress to Alzheimer's disease dementia, 2561 (99%) remained stable MCI and 33 (1%) progressed to other types of dementia. The median proportion of women was 53% and the mean age of participants ranged from 63 to 87 years (median 73 years). The mean length of clinical follow-up ranged from 1 to 7.6 years (median 2 years). Most studies were of poor methodological quality due to risk of bias for participant selection or the index test, or both. Most of the included studies reported data on the volume of the total hippocampus (pooled mean sensitivity 0.73 (95% confidence interval (CI) 0.64 to 0.80); pooled mean specificity 0.71 (95% CI 0.65 to 0.77); 22 studies, 2209 participants). This evidence was of low certainty due to risk of bias and inconsistency. Seven studies reported data on the atrophy of the medial temporal lobe (mean sensitivity 0.64 (95% CI 0.53 to 0.73); mean specificity 0.65 (95% CI 0.51 to 0.76); 1077 participants) and five studies on the volume of the lateral ventricles (mean sensitivity 0.57 (95% CI 0.49 to 0.65); mean specificity 0.64 (95% CI 0.59 to 0.70); 1077 participants). This evidence was of moderate certainty due to risk of bias. Four studies with 529 participants analysed the volume of the total entorhinal cortex and four studies with 424 participants analysed the volume of the whole brain. We did not estimate pooled sensitivity and specificity for the volume of these two regions because available data were sparse and heterogeneous. We could not statistically evaluate the volumes of the lateral temporal lobe, amygdala, medial temporal gyrus, or cortical grey matter assessed in small individual studies. We found no evidence of a difference between studies in the accuracy of the total hippocampal volume with regards to duration of follow-up or age of participants, but the manual MRI technique was superior to automatic techniques in mixed (mostly indirect) comparisons. We did not assess the relative accuracy of the volumes of different brain regions measured by MRI because only indirect comparisons were available, studies were heterogeneous, and the overall accuracy of all regions was moderate. AUTHORS' CONCLUSIONS: The volume of hippocampus or medial temporal lobe, the most studied brain regions, showed low sensitivity and specificity and did not qualify structural MRI as a stand-alone add-on test for an early diagnosis of dementia due to Alzheimer's disease in people with MCI. This is consistent with international guidelines, which recommend imaging to exclude non-degenerative or surgical causes of cognitive impairment and not to diagnose dementia due to Alzheimer's disease. In view of the low quality of most of the included studies, the findings of this review should be interpreted with caution. Future research should not focus on a single biomarker, but rather on combinations of biomarkers to improve an early diagnosis of Alzheimer's disease dementia
Analysis of the Drug Related Emergency Department Admissions in Tuscany: The FARO Project
No full textIntroduction: The FARO project is an Italian multiregional project of
active surveillance of drug safety in emergency department (ED). [1]
Aim: We analyzed all the individual case safety reports (ICSRs)
collected in the FARO database in the first three years of the project
for the Tuscany region. We also analyzed the contribution of the
project to the Tuscany reports.
Methods: A total of 9 hospitals contributed to the FARO project in
Tuscany. Dedicated monitors screened everyday ED visits using key
words related to possible adverse drug reactions (ADR) (e.g., druginduced,
reaction to drug). Then, all the selected ED visits were
manually revised and only those caused by an ADR were reported as
ICSRs first in the FARO database, and finally in the national pharmacovigilance
network.
Results: In the three-year period 2020-2022, in Tuscany we reported
the following number of ICSRs: 5043, 9267 and 7133. In the same
period, the ICSRs of the FARO which contributed to the total of
yearly Tuscan reports were 1100 (22%), 474 (5%) and 1574 (22%) for
2020, 2021 and 2022, respectively. Most of the patients of the FARO
project ICSRs were in the 18-65 years group. The seriousness of
ICSRs were equally distributed between ‘‘not serious’’ (52%) and
‘‘serious’’ (48%). Among the ‘‘serious’’ ICSRs, 555 were classified as
‘‘other condition medically significant’’, 401 ‘‘hospitalization’’, 18
‘‘life-threating’’, 6 ‘‘death’’ and 1 ‘‘permanent disability’’. The most
reported outcome was ‘‘recovering’’ (58%). Acetylsalicylic acid was
the most reported suspected active substance (50.3% ‘‘serious’’ and
49.7% ‘‘not serious’’), followed by warfarin (63.4% ‘‘serious’’ and
36.6% ‘‘not serious’’), and amoxicillin-clavulanate (43.9% ‘‘serious’’
and 56.2% ‘‘not serious’’). The three most reported System Organ
Classes were ‘‘gastrointestinal disorders’’ (20%), ‘‘skin and subcutaneous
tissue disorders’’ (14%), and ‘‘nervous system disorders’’
(10%). The three most reported Preferred Term were ‘‘anemia’’ (160),
‘‘epistaxis’’ (147), and ‘‘urticaria’’ (116).
Conclusion: The ED is a privilege observatory for pharmacovigilance,
offering the possibility to intercept ADRs in an outpatient
setting that may result in hospitalization. The FARO project contributed
for more than 20% of the regional ICSRs, with a noticeable
reduction during 2021 due to the massive reporting storm of COVID-
19 vaccine ICSRs
The phosphodiesterase 5 inhibitor tadalafil regulates lipidic homeostasis in human skeletal muscle cell metabolism
No full textPURPOSE:
Tadalafil seems to ameliorate insulin resistance and glucose homeostasis in humans. We have previously reported that tadalafil targets human skeletal muscle cells with an insulin (I)-like effect. We aim to evaluate in human fetal skeletal muscle cells after tadalafil or I: (i) expression profile of I-regulated genes dedicated to cellular energy control, glycolitic activity or microtubule formation/vesicle transport, as GLUT4, PPARγ, HK2, IRS-1, KIF1C, and KIFAP3; (ii) GLUT4, Flotillin-1, and Caveolin-1 localization, all proteins involved in energy-dependent cell trafficking; (iii) activation of I-targeted paths, as IRS-1, PKB/AKT, mTOR, P70/S6K. Free fatty acids intracellular level was measured. Sildenafil or a cGMP synthetic analog were used for comparison; PDE5 and PDE11 gene expression was evaluated in human fetal skeletal muscle cells.
METHODS:
RTq-PCR, PCR, western blot, free fatty acid assay commercial kit, and lipid stain non-fluorescent assay were used.
RESULTS:
Tadalafil upregulated I-targeted investigated genes with the same temporal pattern as I (GLUT4, PPARγ, and IRS-1 at 3 h; HK2, KIF1C, KIFAP3 at 12 h), re-localized GLUT4 in cell sites positively immune-decorated for Caveolin-1 and Flotillin-1, suggesting the involvement of lipid rafts, induced specific residue phosphorylation of IRS-1/AKT/mTOR complex in association with free fatty acid de novo synthesis. Sildenafil or GMP analog did not affect GLUT4 trafficking or free fatty acid levels.
CONCLUSION:
In human fetal skeletal muscle cells tadalafil likely favors energy storage by modulating lipid homeostasis via IRS-1-mediated mechanisms, involving activation of I-targeted genes and intracellular cascade related to metabolic control. Those data provide some biomolecular evidences explaining, in part, tadalafil-induced favorable control of human metabolism shown by clinical studies
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