The fundamental group and torsion group of Beauville surfaces

We give a survey on the fundamental group of surfaces isogenous to a higher product. If the surfaces are regular, e.g. if they are Beauville surfaces, the first homology group is a finite group. We present a MAGMA script which calculates the first homology groups of regular surfaces isogenous to a product.Comment: 14 pages; MAGMA script included; v2: minor corrections, final version to appear in the Proceedings of the Conference "Beauville Surfaces and Groups", Newcastle University (UK), 7-9th June 201

Brainstem Auditory Evoked Potentials' Diagnostic Accuracy for Hearing Loss: Systematic Review and Meta-Analysis

Background: Microvascular decompression (MVD) utilizes brainstem auditory evoked potential (BAEP) intraoperative monitoring to reduce the risk of iatrogenic hearing loss. Studies report varying efficacy and hearing loss rates during MVD with intraoperative monitoring. Objectives: This study aims to perform a comprehensive review and study of diagnostic accuracy of BAEPs during MVD to predict hearing loss in studies published from January 1984 to December 2013. Methods: The PubMed/MEDLINE and World Science databases were searched. Studies performed MVD for trigeminal neuralgia, hemifacial spasm, glossopharyngeal neuralgia or geniculate neuralgia and monitored intraoperative BAEPs to prevent hearing loss. Retrospectively, BAEP parameters were compared with postoperative hearing. The diagnostic accuracy of significant change in BAEPs, which includes loss of response, was tested using summary receiver operative curve and diagnostic odds ratio (DOR). Results: A total of 13 studies were included in the analysis with a total of 2,540 cases. Loss of response pooled sensitivity, specificity, and DOR with 95% confidence interval being 74% (60–84%), 98% (88–100%), and 69.3 (18.2–263%), respectively. The similar significant change results were 88% (77–94%), 63% (40–81%), and 9.1 (3.9–21.6%). Conclusion: Patients with hearing loss after MVD are more likely to have shown loss of BAEP responses intraoperatively. Loss of responses has high specificity in evaluating hearing loss. Patients undergoing MVD should have BAEP monitoring to prevent hearing loss

Physical activity regulates tnfα and il-6 expression to counteract inflammation in cystic fibrosis patients

Background: Cystic fibrosis (CF) is one of the most common inherited diseases. It is characterised by a severe decline in pulmonary function associated with metabolic perturbations and an increased production of inflammatory cytokines. The key role of physical activity (PA) in improving the health status of CF patients and reducing lung function decline has recently been demonstrated. This study evaluated interleukin-6 (IL-6) and tumour necrosis factor α (TNFα) expression in two subgroups of CF patients classified based on PA. Methods: We selected 85 CF patients; half of them regularly undertook supervised PA in the three years leading up to the study and half of them were not physically active. Patients were analysed for serum IL-6 and TNFα levels using enzyme-linked immunosorbent assays. Results: We found that the expression levels of IL-6 and TNFα differed in terms of their regulation by PA. In particular, TNFα levels negatively correlated with FEV1% decrease/year and FEV1% decrease (p = 0.023 and p = 0.02, respectively), and positively correlated with serum fasting glucose (p = 0.019) in PA CF patients. In contrast, in the NPA subgroup, TNFα levels were positively correlated with IL-6 (p = 0.001) and negatively correlated with adiponectin (p = 0.000). In addition, multiple logistic regression analysis confirmed that PA is an independent modulator of the inflammatory state. Conclusions: PA modulates inflammatory processes in CF patients by regulating the secretion of pro-inflammatory cytokines and thus ameliorating lung function. Our data show that PA is a useful complementary strategy in the management of CF and that TNFα may be a marker of these effects of PA

Acute disseminated encephalomyelitis onset : evaluation based on vaccine adverse events reporting systems

OBJECTIVE: To evaluate epidemiological features of post vaccine acute disseminated encephalomyelitis (ADEM) by considering data from different pharmacovigilance surveillance systems. METHODS: The Vaccine Adverse Event Reporting System (VAERS) database and the EudraVigilance post-authorisation module (EVPM) were searched to identify post vaccine ADEM cases. Epidemiological features including sex and related vaccines were analysed. RESULTS: We retrieved 205 and 236 ADEM cases from the EVPM and VAERS databases, respectively, of which 404 were considered for epidemiological analysis following verification and causality assessment. Half of the patients had less than 18 years and with a slight male predominance. The time interval from vaccination to ADEM onset was 2-30 days in 61% of the cases. Vaccine against seasonal flu and human papilloma virus vaccine were those most frequently associated with ADEM, accounting for almost 30% of the total cases. Mean number of reports per year between 2005 and 2012 in VAERS database was 40\ub121.7, decreasing after 2010 mainly because of a reduction of reports associated with human papilloma virus and Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B vaccines. CONCLUSIONS: This study has a high epidemiological power as it is based on information on adverse events having occurred in over one billion people. It suffers from lack of rigorous case verification due to the weakness intrinsic to the surveillance databases used. At variance with previous reports on a prevalence of ADEM in childhood we demonstrate that it may occur at any age when post vaccination. This study also shows that the diminishing trend in post vaccine ADEM reporting related to Diphtheria, Pertussis, Tetanus, Polio and Haemophilus Influentiae type B and human papilloma virus vaccine groups is most likely due to a decline in vaccine coverage indicative of a reduced attention to this adverse drug reactio

Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity and insulin resistance

Resumen del póster presentado a la Conferencia: FASEB SRC: Liver Biology: Fundamental Mechanisms and Translational Applications, celebrada en Keystone-Colorado (US) del 6 al 11 de julio de 2014.[Background and Aims: Accumulation evidence links obesity-induced inflammation as an important contributor to the induction of insulin resistance. Moreover, insulin resistance plays a key role in the pathophysiology of obesity-related diseases such as type 2 diabetes and non alcoholic fatty liver disease. Cyclooxygenase-1 and -2 catalyze the first step in prostanoid biosynthesis. Since adult hepatocytes fail to induce COX-2 expression regardless of the pro-inflammatory factors used, we have evaluated whether this lack of expression under mild pro-inflammatory conditions might constitute a permissive condition for the onset of insulin resistance. [Methods]: We evaluated the role of COX-2 expression in hepatocytes in a model of insulin resistance and altered energy homeostasis induced by high fat diet by metabolic parameters in transgenic mice constitutively expressing human COX-2 in hepatocytes. [Results]: COX-2 expression in hepatocytes protects from high fat diet-induced hepatic steatosis, obesity and hence insulin resistance, as demonstrated by a decreased hepatic steatosis, adiposity and adipocyte area, an enhanced insulin sensitivity and glucose tolerance, decreased plasmatic and hepatic triglycerides and free fatty acids levels, increased adiponectin/leptin ratio and decreased levels of pro-inflammatory cytokines. COX-2 transgenic mice exhibited increased whole body energy expenditure and fatty acid oxidation. Moreover, when hepatic insulin signaling was analyzed, an increase in insulin receptor-mediated Akt phosphorylation was found in hCOX-2 transgenic mice. Similar results were obtained in human and murine hepatic cells expressing a COX-2 transgene. [Conclusion]: Constitutively expression of COX-2 in hepatocytes protects against adiposity, inflammation and hepatic insulin resistance in mice under high fat diet.Peer Reviewe

No signal of interactions between influenza vaccines and drugs used for chronic diseases : a case-by-case analysis of the vaccine adverse event reporting system and vigibase

Background: An increasing number of reports indicates that vaccines against influenza may interact with specific drugs via drug metabolism. To date, actual impact of vaccine-drug interactions observed in the real world clinical practice has not been investigated.Methods: From VAERS and VigiBase, we collected Adverse Event Following Immunization (AEFI) reports for individuals receiving vaccines against influenza recorded as suspect and selected cases where predictable toxicity was recorded with oral anticoagulants, antiepileptics and statins (i.e. hemorrhages, overdosage and rhabdomyolysis, respectively). We applied AEFI and Drug Interaction Probability Scale (DIPS) Algorithms to assess causality of drug-vaccine interactions.Results: 116 AEFI reports submitted to VAERS and 83 from Vigibase were included in our analysis; antiepileptics and statins were related to the highest number of indeterminate/consistent (93.7%; 65.3%) and possible/probable (50%; 57.7%) cases according to the AEFI and DIPS, respectively. The majority of cases occurred within the first week after vaccine administration (5-7days).Conclusion: The relative paucity of detected interactions does not impact on the benefit of the vaccination against influenza, which remains strongly recommended; this does not exclude that closer monitoring for selected patients exposed to concomitant chronic pharmacological therapies and affected by predisposing factors may be useful

Numerical properties of isotrivial fibrations

In this paper we investigate the numerical properties of relatively minimal isotrivial fibrations \varphi \colon X \lr C, where $X$ is a smooth, projective surface and $C$ is a curve. In particular we prove that, if $g(C) \geq 1$ and $X$ is neither ruled nor isomorphic to a quasi-bundle, then K_X^2 \leq 8 \chi(\mO_X)-2; this inequality is sharp and if equality holds then $X$ is a minimal surface of general type whose canonical model has precisely two ordinary double points as singularities. Under the further assumption that $K_X$ is ample, we obtain K_X^2 \leq 8 \chi(\mO_X)-5 and the inequality is also sharp. This improves previous results of Serrano and Tan.Comment: 30 pages. Final version, to appear in Geometriae Dedicat

Hydroxytriazole derivatives as potent and selective aldo-keto reductase 1C3 (AKR1C3) inhibitors discovered by bioisosteric scaffold hopping approach

YesThe aldo-keto reductase 1C3 isoform (AKR1C3) plays a vital role in the biosynthesis of androgens, making this enzyme an attractive target for castration-resistant prostate cancer therapy. Although AKR1C3 is a promising drug target, no AKR1C3-targeted agent has to date been approved for clinical use. Flufenamic acid, a non-steroidal anti-inflammatory drug, is known to potently inhibit AKR1C3 in a non-selective manner as COX off-target effects are also observed. To diminish off-target effects, we have applied a scaffold hopping strategy replacing the benzoic acid moiety of flufenamic acid with an acidic hydroxyazolecarbonylic scaffold. In particular, differently N-substituted hydroxylated triazoles were designed to simultaneously interact with both subpockets 1 and 2 in the active site of AKR1C3, larger for AKR1C3 than other AKR1Cs isoforms. Through computational design and iterative rounds of synthesis and biological evaluation, novel compounds are reported, sharing high selectivity (up to 230-fold) for AKR1C3 over 1C2 isoform and minimal COX1 and COX2 off-target inhibition. A docking study of compound 8, the most interesting compound of the series, suggested that its methoxybenzyl substitution has the ability to fit inside subpocket 2, being involved in π-π staking interaction with Trp227 (partial overlapping) and in a T-shape π-π staking with Trp86. This compound was also shown to diminish testosterone production in the AKR1C3-expressing 22RV1 prostate cancer cell line while synergistic effect was observed when 8 was administered in combination with abiraterone or enzalutamide.University of Turin (Ricerca Locale grant 2014 and 2015) and Prostate Cancer UK grant S12-02