From Pathogens to People: Enhancing Reporting and Surveillance for more Effective Control of Disease Outbreaks

Infectious disease outbreaks are a threat to global health and security. Current systems for early and effective reporting and monitoring of pathogens and other health threats, and high-quality surveillance of human diseases, face a number of challenges including incomplete and fragmented early warning and governance systems that are under-incentivised and under-resourced. We propose a number of opportunities for the G20 leaders to address these challenges, including: (1) establishing an ‘Emerging Health Threat Data Platform’ as a public good for independent, co-ordinated and scientist-led reporting and surveillance of pathogens; (2) supporting the development of a framework to incentivise scientists to participate in the platform and; (3) enhancing population health surveillance and vital registration systems through technical and financial investments in both the short and longer term

Chromosome 7 monosomy and deletions in myeloproliferative diseases

We studied deletion and monosomy of chromosome 7 in 150 patients with myeloproliferative diseases. We found 8/150 patients with monosomy 7 by cytogenetics and 4/150 with deletions of the long arm of chromosome 7 by restriction fragment length polymorphism (RFLP) analysis performed with Southern and polymerase chain reaction. To overcome limitation of RFLP analysis, we restricted loss of heterozygosity study with microsatellites to 45 patients, observing deletion 7q31.1 in 7/45 patients. In all patients with molecular alterations the deletion was observed only in myeloid cells, while the monosomy was detected in both myeloid precursor and lymphocytes. This finding suggests a CD34-totipotent stem cell origin for the monosomy and a colony forming unit - granulocyte, erythrocyte, monocyte, megakaryocytes (CFU-GEMM) stem cell origin for the deletions

A priori-defined Mediterranean-like dietary pattern predicts cardiovascular events better in north Europe than in Mediterranean countries

The Mediterranean Diet (MD) is a model of healthy eating contributing to a favorable health status, but its clinical usefulness is still debated. The aim of this study was to relate the adherence to MD with the incidence of cardio/cerebro-vascular events (VEs) in north and south European participants of the IMPROVE study

Inhibitors of apoptosis proteins (IAPs) expression and their prognostic significance in hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Similarly to other tumor types, an imbalance between unrestrained cell proliferation and impaired apoptosis appears to be a major unfavorable feature of hepatocellular carcinoma (HCC). The members of IAP family are key regulators of apoptosis, cytokinesis and signal transduction. IAP survival action is antagonized by specific binding of Smac/DIABLO and XAF1. This study aimed to investigate the gene and protein expression pattern of IAP family members and their antagonists in a series of human HCCs and to assess their clinical significance.</p> <p>Methods</p> <p>Relative quantification of IAPs and their antagonist genes was assessed by quantitative Real Time RT-PCR (qPCR) in 80 patients who underwent surgical resection for HCC. The expression ratios of XIAP/XAF1 and of XIAP/Smac were also evaluated. Survivin, XIAP and XAF1 protein expression were investigated by immunohistochemistry. Correlations between mRNA levels, protein expression and clinicopathological features were assessed. Follow-up data were available for 69 HCC patients. The overall survival analysis was estimated according to the Kaplan-Meier method.</p> <p>Results</p> <p>Survivin and Livin/ML-IAP mRNAs were significantly over-expressed in cancer tissues compared to non-neoplastic counterparts. Although Survivin immunoreactivity did not correlate with qPCR data, a significant relation was found between higher Survivin mRNA level and tumor stage, tumor grade and vascular invasion.</p> <p>The mRNA ratio XIAP/XAF1 was significantly higher in HCCs than in cirrhotic tissues. Moreover, high XIAP/XAF1 ratio was an indicator of poor prognosis when overall survival was estimated and elevated XIAP immunoreactivity was significantly associated with shorter survival.</p> <p>Conclusion</p> <p>Our study demonstrates that alterations in the expression of IAP family members, including Survivin and Livin/ML-IAP, are frequent in HCCs. Of interest, we could determine that an imbalance in XIAP/XAF1 mRNA expression levels correlated to overall patient survival, and that high XIAP immunoreactivity was a poor prognostic factor.</p

Intake of food rich in saturated fat in relation to subclinical atherosclerosis and potential modulating effects from single genetic variants

The relationship between intake of saturated fats and subclinical atherosclerosis, as well as the possible influence of genetic variants, is poorly understood and investigated. We aimed to investigate this relationship, with a hypothesis that it would be positive, and to explore whether genetics may modulate it, using data from a European cohort including 3,407 participants aged 54–79 at high risk of cardiovascular disease. Subclinical atherosclerosis was assessed by carotid intima-media thickness (C-IMT), measured at baseline and after 30 months. Logistic regression (OR; 95% CI) was employed to assess the association between high intake of food rich in saturated fat (vs. low) and: (1) the mean and the maximum values of C-IMT in the whole carotid artery (C-IMTmean, C-IMTmax), in the bifurcation (Bif-), the common (CC-) and internal (ICA-) carotid arteries at baseline (binary, cut-point ≥ 75th), and (2) C-IMT progression (binary, cut-point &gt; zero). For the genetic-diet interaction analyses, we considered 100,350 genetic variants. We defined interaction as departure from additivity of effects. After age- and sex-adjustment, high intake of saturated fat was associated with increased C-IMTmean (OR:1.27;1.06–1.47), CC-IMTmean (OR:1.22;1.04–1.44) and ICA-IMTmean (OR:1.26;1.07–1.48). However, in multivariate analysis results were no longer significant. No clear associations were observed between high intake of saturated fat and risk of atherosclerotic progression. There was no evidence of interactions between high intake of saturated fat and any of the genetic variants considered, after multiple testing corrections. High intake of saturated fats was not independently associated with subclinical atherosclerosis. Moreover, we did not identify any significant genetic-dietary fat interactions in relation to risk of subclinical atherosclerosis

Laterality, manual strength and precision performance

Right handers are frequent in some particular sports, and this is probably related to a technical and tactical advantage for them (1), but sometimes athletes in typical left-handers\u2019 roles are not strongly left-handed. The aim of this study was to investigate differences in performance by athletes who use their right or left hand consistently in both daily activities and their sport (R=right-handers; L=left-handers) and by athletes who are right-handed in daily activities but left-handed in their sport (I=inconsistent). Methods Laterality assessment through the Edinburgh test(2) and resulting from the hand used in the sport; identification and comparison of manual Maximal Strength (MS), Kinesthetic Strength Differentation (KSD) and Movement Frequency (MF) in R, L, I (R hand vs L hand); identification and comparison of the best and worst hand for each in R, L, I. MS and KSD were measured by dynamometer in different hand-grip trials of maximal strength and 75% MS. MF was measured by counting the maximal comma numbers performed when writing for 30 seconds(3). Subjects Medium-high level athletes (N56; R=22, L=22, I=12), highly trained (hours per week: avg 9.8 \u2013 SD 3.04) in open-skill sports: handball (21), basketball (7), volleyball (9), fencing (5), judo (1), hockey (9), table-tennis (2) and squash (2). Results Comparison of right and left hands (Mann-Whitney test): in the MS test, only the R group shows significant differences (p&lt;0,01); in the KSD test only the I group shows significant differences (p&lt;0.05); in the MF test all 3 groups show significant differences (p&lt;0.01). Comparing the 3 groups as regards the best hand (Wilcoxon test), only the KSD test shows significant differences between R (left hand) and I (left hand) (p&lt;0.01). In the L (right hand) and I (right hand) groups, the differences are in the weakest hand (p&lt;0.05). Conclusions In the MS test the best results are achieved with the hand preferred for sports; in the KSD test the opposite is the case for R and L. By contrast, in the MF test the best results are attained by R and L with the sports hand, but by I with the preferred for daily activities. References 1. Grouios et al (2000). Do left-handed competitors have an innate superiority in sports? Percept Mot Skills, V. 90; 1273-1282 2. Oldfield R.C. (1971). The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia V. 9, Is 1; 97-113 3. Carbonaro G. et al (1988). La valutazione dello sport nei giovani. Societ\ue0 stampa sportiva, Rom

Interhemispheric Transfer Time in Sportsmen

The authors’ aim was to compare interhemispheric transfer time between 2 groups: highly skilled sportsmen and control subjects. Left- and right-handed individuals were included in the study. The Poffenberger paradigm was used to measure the crossed–uncrossed difference, representing the time to transfer information from one hemisphere to the other. No difference in laterality was found, but the results revealed a greater crossed–uncrossed difference in the skilled sportsmen than in the controls. The authors suggest that this may be due to more highly developed within-hemisphere integration of inputs and outputs, at the expense of cross-hemisphere integration

Ultrastructural localization of advanced glycation end products and beta2-microglobulin in dialysis amyloidosis

BACKGROUND: beta2-microglobulin (beta2m) is considered to be the amyloidogenic precursor in dialysis-related amyloidosis (DRA, Abeta2M amyloidosis). beta2m modified with advanced glycation end products (AGE) may be an important factor in the pathogenesis of DRA. The presence of AGE in beta2m-positive amyloid deposits and surrounding macrophages has been demonstrated by immunohistochemical techniques in light microscopy. METHODS: In order to better define the localization of beta2m and AGE in amyloid deposits and in cells, carpal tunnel connective tissues obtained from surgical specimens in six patients with DRA were studied by mmunohistochemistry and electron microscopy, using the avidine-biotine complex and immunogold staining procedures, respectively. A polyclonal rabbit anti-human beta2m and two monoclonal mouse anti-AGE antibodies [AG-1 anti-imidazolone and AG-10 anti-N(epsilon)-carboxymethyl-lysine] enabled us to label their respective antigens at the optical and ultrastructural level. RESULTS: with both techniques, extracellular amyloid deposits strongly reacted with anti-beta2m and anti-AGE antibodies, although the immunoreactivity of beta2m was more intense. Macrophage-like synovial cells (CD-68 positive) surrounding amyloid deposits were also immunoreactive for beta2m and AGE, which were detected in lysosomes and in intracellular fibrillar material. Anti-AGE reactivity was also evident in collagenous structures in the absence of beta2m or amyloid deposits, supporting the proposal that AGE modification of collagen might have pathogenic relevance in the development of DRA. CONCLUSIONS: The co-localization of AGE and beta2m, both intra- and extra-cellularly, in amyloid fibrils was confirmed by immunoelectron microscopy; however, the positivity of collagen to anti-AGE antibodies and a different pattern of intracellular localization suggest that molecules other than beta2m may also be modified by AGE and may be involved in the pathogenesis of DRA