Research has shown that a greater adherence to the Mediterranean diet is associated with a reduced risk of major chronic disease. However, the existing literature leads to debate for different ...issues, such as the measurement of the adherence to the Mediterranean diet, the use of a wide variety of dietary indices with various food components and the large heterogeneity across the studies. In order to summarise the evidence and evaluate the validity of the association between the adherence to the Mediterranean diet and multiple health outcomes, an umbrella review of the evidence across meta-analyses of observational studies and randomised clinical trials (RCTs) was performed. Thirteen meta-analyses of observational studies and 16 meta-analyses of RCTs investigating the association between the adherence to the Mediterranean diet and 37 different health outcomes, for a total population of over than 12 800 000 subjects, were identified. A robust evidence, supported by a P-value<0.001, a large simple size, and not a considerable heterogeneity between studies, for a greater adherence to the Mediterranean diet and a reduced the risk of overall mortality, cardiovascular diseases, coronary heart disease, myocardial infarction, overall cancer incidence, neurodegenerative diseases and diabetes was found. For most of the site-specific cancers, as well as for inflammatory and metabolic parameters, the evidence was only suggestive or weak and further studies are needed to draw firmer conclusions. No evidence, on the other hand, was reported for bladder, endometrial and ovarian cancers, as well as for LDL (low density lipoprotein)-cholesterol levels.
. Sofi F, Valecchi D, Bacci D, Abbate R, Gensini GF, Casini A, Macchi C (Centro S. Maria agli Ulivi, Onlus IRCCS; Thrombosis Centre, University of Florence; Azienda Ospedaliero‐Universitaria ...Careggi, Florence, Italy) Physical activity and risk of cognitive decline: a meta‐analysis of prospective studies. J Intern Med 2011; 269: 107–117.
Objective. The relationship between physical activity and cognitive function is intriguing but controversial. We performed a systematic meta‐analysis of all the available prospective studies that investigated the association between physical activity and risk of cognitive decline in nondemented subjects.
Methods. We conducted an electronic literature search through MedLine, Embase, Google Scholar, Web of Science, The Cochrane Library and bibliographies of retrieved articles up to January 2010. Studies were included if they analysed prospectively the association between physical activity and cognitive decline in nondemented subjects.
Results. After the review process, 15 prospective studies (12 cohorts) were included in the final analysis. These studies included 33 816 nondemented subjects followed for 1–12 years. A total of 3210 patients showed cognitive decline during the follow‐up. The cumulative analysis for all the studies under a random‐effects model showed that subjects who performed a high level of physical activity were significantly protected (−38%) against cognitive decline during the follow‐up (hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.54–0.70; P < 0.00001). Furthermore, even analysis of low‐to‐moderate level exercise also showed a significant protection (−35%) against cognitive impairment (HR 0.65, 95% CI 0.57–0.75; P < 0.00001).
Conclusion. This is the first meta‐analysis to evaluate the role of physical activity on cognitive decline amongst nondemented subjects. The present results suggest a significant and consistent protection for all levels of physical activity against the occurrence of cognitive decline.
Objective To systematically review all the prospective cohort studies that have analysed the relation between adherence to a Mediterranean diet, mortality, and incidence of chronic diseases in a ...primary prevention setting. Design Meta-analysis of prospective cohort studies.Data sources English and non-English publications in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials from 1966 to 30 June 2008. Studies reviewed Studies that analysed prospectively the association between adherence to a Mediterranean diet, mortality, and incidence of diseases; 12 studies, with a total of 1 574 299 subjects followed for a time ranging from three to 18 years were included.Results The cumulative analysis among eight cohorts (514 816 subjects and 33 576 deaths) evaluating overall mortality in relation to adherence to a Mediterranean diet showed that a two point increase in the adherence score was significantly associated with a reduced risk of mortality (pooled relative risk 0.91, 95% confidence interval 0.89 to 0.94). Likewise, the analyses showed a beneficial role for greater adherence to a Mediterranean diet on cardiovascular mortality (pooled relative risk 0.91, 0.87 to 0.95), incidence of or mortality from cancer (0.94, 0.92 to 0.96), and incidence of Parkinson’s disease and Alzheimer’s disease (0.87, 0.80 to 0.96).Conclusions Greater adherence to a Mediterranean diet is associated with a significant improvement in health status, as seen by a significant reduction in overall mortality (9%), mortality from cardiovascular diseases (9%), incidence of or mortality from cancer (6%), and incidence of Parkinson’s disease and Alzheimer’s disease (13%). These results seem to be clinically relevant for public health, in particular for encouraging a Mediterranean-like dietary pattern for primary prevention of major chronic diseases.
Summary
Philadelphia‐negative myeloproliferative neoplasms are considered to be acquired thrombophilic states. Thromboses, both arterial and venous (not rarely in unusual sites), are often the ...initial events leading to the diagnosis. After diagnosis, the yearly incidence of thrombotic events is highly variable, and ranges from approximately 1% to 10%. The identification of patients at risk who may benefit from antithrombotic therapy remains a challenge, and it is currently based on age and history of thrombotic events. However, the predictive value of these clinical characteristics is rather limited. Few prospective studies and even fewer interventional randomized studies are available, and there are no studies designed to formally validate the use of risk stratification. The implementation of laboratory parameters such as leukocytosis and/or the JAK2 V617F mutation into a scoring system may be of interest. The mechanisms at work leading to thrombosis remain largely speculative, but are likely to be complex and multifactorial, with a prominent role of cell–cell interactions, mostly owing to qualitative changes. The long‐term treatment options to prevent thrombosis are, schematically, aspirin alone as primary prevention for the low‐risk patients, and cytoreduction combined with aspirin for the other patients. In very low‐risk young essential thrombocythemia patients, abstention can even be considered. The optimal duration of anticoagulation after a thrombotic event is not established. All antithrombotic therapies should be balanced with the hemorrhagic risk, which can also be increased in these patients.
Essentials
Hypodysfibrinogenemia is rarely reported among the congenital fibrinogen disorders.
This first systematic literature review led to identification of 51 hypodysfibrinogenemic cases.
...Diagnosis based only on functional/antigenic fibrinogen ratio may be insufficient.
Family studies show an incomplete segregation of mutation with the clinical phenotypes.
Summary
Background
Hypodysfibrinogenemia is a rare disease characterized by decreased levels of a dysfunctional fibrinogen. It shares features with both hypo‐ and dysfibrinogenemia, although with specific molecular patterns and clinical phenotypes.
Objectives
To better define the genetics, the diagnosis and the clinical features of hypodysfibrinogenemia.
Patients/Methods
A systematic literature search led to 167 records. After removal of duplicates, screening and full‐text reviewing, 56 molecular and/or clinical studies were analyzed, including a novel FGB missense mutation in a woman with a mild bleeding phenotype.
Results
A total of 32 single causative mutations were reported, mainly in the COOH‐terminal region of the γ or Aα chains at heterozygous or homozygous state. Seven additional hypodysfibrinogenemias were due to compound heterozygosity. The hypofibrinogenemic phenotypes were a result of an impaired assembly or secretion or an increased clearance of the fibrinogen variant, whereas the dysfibrinogenemic phenotype was mainly a result of a defective fibrin polymerization and an abnormal calcium or tPA binding. Among 51 identified index cases, a functional/antigenic fibrinogen ratio < 0.7 had a sensitivity of 86% for the diagnosis of hypodysfibrinogenemia. Eleven patients (22%) were asymptomatic at time of diagnosis, 23 (45%) had a mild bleeding phenotype with mainly obstetrical or gynecologic‐related hemorrhage and 22 (43%) had experienced at least one thrombotic event, including 23 venous and eight arterial thromboses.
Conclusions
This first systematic review on hypodysfibrinogenemia shows the heterogeneity of causative mutations and that misdiagnosis could occur in relation to the functional and antigenic fibrinogen levels. Family studies reveal an incomplete segregation of the mutation with the clinical phenotype.
Introduction
Intracerebral hemorrhage (ICH) is associated with high morbidity and mortality in patients with congenital afibrinogenaemia. Details on location of cerebral haemorrhage, management and ...neurological outcomes are lacking.
Methods
We performed a retrospective study on Egyptian children with congenital afibrinogenaemia who experienced ICH, in order to estimate frequency, symptoms and neurological outcomes.
Results
Among 58 children with congenital afibrinogenaemia treated on demand, 18 (31%) had an history of ICH (28 episodes). The first ICH occurred at a median age of 1 year (Q1‐Q3 1–7 years). Impaired consciousness level, vomiting and seizures were the most common presenting symptoms. Spontaneous bleeding was associated with a more severe clinical presentation and worse neurological outcomes, including hydrocephaly and impaired cognitive development. Only half of ICH events (n = 14) were treated in less than 24 h from the onset of symptoms. Fibrinogen replacement by Fresh Frozen Plasma (FFP), cryoprecipitate or fibrinogen concentrates was administered in seven (25%), 19 (68%) and three (10%) ICH events, respectively. Overall, seven (25%) ICH occurring in four patients required a surgical intervention. After the ICH, six patients started secondary prophylaxis. The cumulative incidence of ICH at 10 years was 35% (95% CI 23–51) and at 20 years was 40% (95 CI% 26.7–58.8).
Conclusion
In our cohort of children with congenital afibrinogenaemia, ICH was very frequent and associated with adverse neurological outcomes and death. Further studies are required to determine whether primary prophylaxis starting early in childhood is indicated after diagnosis.
The corpus callosum (CC) has been shown to be susceptible to atrophy in Alzheimer disease (AD) as a correlate of wallerian degeneration or retrogenesis. However, when and where these 2 mechanisms ...intervene is still unclear.
In 3 memory clinics, we recruited 38 patients with amnestic mild cognitive impairment (MCI), 38 patients with mild AD, and 40 healthy controls (HC). Combining voxel-based morphometry and diffusion tensor imaging, we investigated CC white matter (WM) density and fractional anisotropy (FA), radial diffusivity (DR), and axial diffusivity (DA).
Compared with HC, patients with amnestic MCI showed reduced WM density in the anterior CC subregion; however, FA, DR, and DA did not differ between the 2 groups. Significant changes were found in patients with mild AD compared with HC in the anterior and posterior CC regions. These differences were evident in both voxel-based morphometry and diffusion tensor imaging analyses. Specifically, we found reduced callosal WM density in the genu, posterior body, and splenium; decreased FA and increased DR in the anterior CC subregion; and increased DA, with no difference in the FA, in the posterior CC subregion.
Callosal changes are already present in patients with amnestic mild cognitive impairment (MCI) and mild Alzheimer disease (AD). The precocious involvement of the anterior callosal subregion in amnestic MCI extends to posterior regions in mild AD. Two different mechanisms might contribute to the white matter changes in mild AD: wallerian degeneration in posterior subregions of the corpus callosum (suggested by increased axial diffusivity without fractional anisotropy modifications) and a retrogenesis process in the anterior callosal subregions (suggested by increased radial diffusivity without axial diffusivity modifications).
Summary
Congenital dysfibrinogenemia is a qualitative congenital fibrinogen disorder characterized by normal antigen levels of a dysfunctional fibrinogen. The diagnosis is usually based on ...discrepancies between fibrinogen activity and antigen levels, but could require more specialized techniques for the assessment of fibrinogen function, owing to some limitations in routine assays. Molecular abnormalities, which are frequently heterozygous missense mutations localized in exon 2 of FGA and exon 8 of FGG, lead to defects in one or more phases of fibrinogen to fibrin conversion, fibrin network formation, and other important functions of fibrinogen. The clinical phenotype is highly heterogeneous, from no manifestations to bleeding and/or thrombotic events. Asymptomatic propositi and relatives with the predisposing genotype are at risk of developing adverse outcomes during the natural course of the disease. Correlations between genotype and phenotype have not yet been clearly established, with the exception of some abnormal fibrinogens that severely increase the risk of thrombosis. Functional analysis of polymerization and fibrinolysis, structural studies of the fibrin network and the viscoelastic properties of fibrin clot could help to predict the phenotype of congenital dysfibrinogenemia, but have not yet been evaluated in detail. The management is essentially based on personal and family history; however, even individuals who are still asymptomatic and without a family history should be carefully assessed and monitored. Particular situations, such as pregnancy, delivery, and surgery, require a multidisciplinary approach.
A series of novel (C^N) cyclometallated Au(III) complexes of general formula Au(py(b)-H)L(1)L(2)(n+) (py(b)-H = C^N cyclometallated 2-benzylpyridine, L(1) and L(2) being chlorido, phosphane or ...glucosethiolato ligands, n = 0 or 1) have been synthesized and fully characterized using different techniques, including NMR, IR and far-IR, mass spectrometry, as well as elemental analysis. The crystal structure of one compound has been solved using X-ray diffraction methods. All compounds were tested in vitro in five human cancer cell lines including the lung, breast, colon and ovarian cancer cells. For comparison purposes, all compounds were also tested in a model of healthy human cells from the embryonic kidney. Notably, all new compounds were more toxic than their cyclometallated precursor bearing two chlorido ligands, and the derivative bearing one phosphane ligand presented the most promising toxicity profile in our in vitro screening, displaying a p53 dependent activity in colorectal cancer HCT116 cells. Finally, for the first time C^N cyclometallated gold(III) complexes were shown to be potent inhibitors of the zinc finger protein PARP-1, involved in the mechanism of cisplatin resistance.
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