Predicting success in the worldwide start-up network

By drawing on large-scale online data we construct and analyze the time-varying worldwide network of professional relationships among start-ups. The nodes of this network represent companies, while the links model the flow of employees and the associated transfer of know-how across companies. We use network centrality measures to assess, at an early stage, the likelihood of the long-term positive performance of a start-up, showing that the start-up network has predictive power and provides valuable recommendations doubling the current state of the art performance of venture funds. Our network-based approach not only offers an effective alternative to the labour-intensive screening processes of venture capital firms, but can also enable entrepreneurs and policy-makers to conduct a more objective assessment of the long-term potentials of innovation ecosystems and to target interventions accordingly

Detection of Helicobacter pylori by PCR on gastric biopsy specimens taken for CP test: comparison with histopathological analysis.

The aims of the present study were: (i) to assess whether H. pylori could be succesfully detected by PCR from the same biopsy sample used for CPtest; and ii) to evaluate CPtest comparatively to both PCR and histology for detection of H. pylori infection in dyspeptic patients. Three antral gastric biopsies were collected from each of 80 consecutive dyspeptic patients undergoing oesophagogastroduodenoscopy. Two biopsies were for histology (gold standard), one for CPtest, scored at 20min, 1h and 24h for the presence of urease activity. Gastric biopsy was then removed from CPtest and used for ureC-targeted PCR. Fifty-five (68.7%) patients were positive for H. pylori infection by histology. CPtest yielded an overall diagnostic accuracy of 93.8% (95% CI: 91–96.4%), regardless of observation period. No erroneous categorization of H. pylori status occurred using PCR, yielding sensitivity, specificity, positive and negative predictive values, and overall diagnostic accuracy of 100%. Our results suggest that H. pylori can be detected by PCR in gastric biopsies previously taken for CPtest, so reducing the workload of the endoscopist by saving additional biopsies for culture analysis and susceptibility tests

Preclinical and clinical evidence for a distinct regulation of mu opioid and type 1 cannabinoid receptor genes expression in obesity

Among endogenous signaling networks involved in both rewarding and homeostatic mechanisms of obesity, a relevant role is played by the endocannabinoid (ECS) and the opioid (EOS) systems. We here studied the transcriptional regulation of ECS and EOS genes in the hypothalamus of Diet-induced obesity rats, a preclinical model of obesity, as well as in humans with obesity and healthy controls. A significant and selective increase in type 1 cannabinoid receptor gene (Cnr1) expression was observed at the beginning of obesity development (5 weeks on high fat diet) as well as after 21 weeks of high diet exposure. After 5 weeks on high fat diet, selective up-regulation of mu opioid receptor gene (Oprm1) expression was also observed. Consistently, epigenetic studies showed a selective and significant decrease in DNA methylation at specific CpG sites at both gene promoters in overweight rats, but only after 5 weeks on high fat diet. Moreover, significantly lower levels of DNA methylation were observed at selected CpG sites of both receptor gene promoters, analyzed in peripheral blood mononuclear cells from younger (<30 years old) humans with obesity, as well as in those with shorter time length from disease onset. Taken together, we here provide evidence of selective, synergistic and time-dependent transcriptional regulation of CNR1 and OPRM1 genes in overweight rats, as well as in human subjects. These alterations in genes regulation could contribute to the development of the obese phenotype, and we thus suggest CNR1 and OPRM1 epigenetic modulation as possible biomarkers of obesity development. Due to the reversible nature of the epigenetic hallmark, our data might also open new avenue to early environmental strategies of intervention

Modulation of pain sensitivity by chronic consumption of highly palatable food followed by abstinence: emerging role of fatty acid amide hydrolase

There is a strong relationship between palatable diet and pain sensitivity, and the cannabinoid and opioid systems might play an important role in this correlation. The palatable diet used in many animal models of obesity is the cafeteria (CAF) diet, based on human food with high sugar, salt, and fat content. In this study, we investigated whether long-term exposure to a CAF diet could modify pain sensitivity and explored the role of the cannabinergic system in this modification. Male Sprague–Dawley rats were divided into two groups: one fed with standard chow only (CO) and the other with extended access (EA) to a CAF diet. Hot plate and tail flick tests were used to evaluate pain sensitivity. At the end of a 40-day CAF exposure, EA rats showed a significant increase in the pain threshold compared to CO rats, finding probably due to up-regulation of CB1 and mu-opioid receptors. Instead, during abstinence from palatable foods, EA animals showed a significant increase in pain sensibility, which was ameliorated by repeated treatment with a fatty acid amide hydrolase inhibitor, PF-3845 (10 mg/kg, intraperitoneally), every other day for 28 days. Ex vivo analysis of the brains of these rats clearly showed that this effect was mediated by mu-opioid receptors, which were up-regulated following repeated treatment of PF-3845. Our data add to the knowledge about changes in pain perception in obese subjects, revealing a key role of CB1 and mu-opioid receptors and their possible pharmacological crosstalk and reinforcing the need to consider this modulation in planning effective pain management for obese patients

Oleoylethanolamide decreases frustration stress-induced binge-like eating in female rats: a novel potential treatment for binge-eating disorder

Binge-eating disorder (BED) is the most frequent eating disorder, for which current pharmacotherapies show poor response rates and safety concerns, thus highlighting the need for novel treatment options. The lipid-derived messenger oleoylethanolamide (OEA) acts as a satiety signal inhibiting food intake through the involvement of central noradrenergic and oxytocinergic neurons. We investigated the anti-binge effects of OEA in a rat model of binge-like eating, in which, after cycles of intermittent food restrictions/refeeding and palatable food consumptions, female rats show a binge-like intake of palatable food, following a 15-min exposure to their sight and smell (“frustration stress”). Systemically administered OEA dose-dependently (2.5, 5, and 10 mg kg–1) prevented binge-like eating. This behavioral effect was associated with a decreased activation (measured by mapping the expression of c-fos, an early gene widely used as a marker of cellular activation) of brain areas responding to stress (such as the nucleus accumbens and amygdala) and to a stimulation of areas involved in the control of food intake, such as the VTA and the PVN. These effects were paralleled, also, to the modulation of monoamine transmission in key brain areas involved in both homeostatic and hedonic control of eating. In particular, a decreased dopaminergic response to stress was observed by measuring dopamine extracellular concentrations in microdialysates from the nucleus accumbens shell, whereas an increased serotonergic and noradrenergic tone was detected in tissue homogenates of selected brain areas. Finally, a decrease in corticotropin-releasing factor (CRF) mRNA levels was induced by OEA in the central amygdala, while an increase in oxytocin mRNA levels was induced in the PVN. The restoration of a normal oxytocin receptor density in the striatum paralleled the oxytocinergic stimulation produced by OEA. In conclusion, we provide evidence suggesting that OEA might represent a novel potential pharmacological target for the treatment of binge-like eating behavior