Post-graduate medical education in public health: The case of Italy and a call for action

Public health technical expertise is of crucial importance to inform decision makers\u2019 action in the field of health and its broader determinants. Improving education and training of public health professionals for both practice and research is the starting point to strengthen the role of public health so that current health challenges can be efficiently tackled. At the Association of Schools of Public Health in the European Region (ASPHER) Deans\u2019 & Directors\u2019 2017 Annual Retreat, we presented the structure and management of public health training system in Italy, and we reported recent data on Italian public health specialists\u2019 educational experience, employment opportunities and job satisfaction. Public health training in Italy is implemented in the context of the post-graduate medical education residency programme in Hygiene and Preventive Medicine, delivered by 34 University-based Schools of Public Health. We report relatively high employment rates across the county and wide spectrum of career opportunities for young public health specialists. However, job security is low and training expectations only partially met. We call upon other Schools of Public Health to scale up the survey within the broad ASPHER community in a shared and coordinated action of systematically collecting useful data that can inform the development of public health education and training models, their implementation and fruitful interaction with population health, health systems and services

Metallic brackets bonded with resin-reinforced glass lonomer cements under different enamel conditions

Objective: To assess the shear bond strength of metallic orthodontic brackets bonded with either Fuji Ortho or Ortho Glass LC resin-reinforced glass ionomer cements to enamel surfaces under different conditions, namely, enamel without etching, enamel conditioned with 37% phosphoric acid and enamel conditioned with Transbond Plus Self Etching Primer (TPSEP). Materials and Methods: One hundred and five bovine inferior incisors were divided into seven groups (n = 15). In group 1 (control) Transbond XT was used according to the manufacturer's recommendations. In groups 2, 3, and 4 all using Fuji Ortho LC, the brackets were bonded, respectively, to enamel nonetched, enamel etched with 37% phosphoric acid, and enamel etched with TPSEP. In groups 5, 6, and 7, the bonding was performed using Ortho Glass LC under the same enamel conditions observed in the other experimental groups. After 24 hours, shear bond strength tests were performed for all samples at a crosshead speed of 0.5 mm/min. Results: The results (MPa) showed no statistically significant difference between groups 1, 3, and 4 (P >.05). However, such groups were statistically superior to the others (P .05). Group 5 showed the lowest shear strength value, which was also statistically inferior to the other groups (P <.05). Conclusions: Regardless of the enamel treatment, Fuji Ortho LC yielded shear strength values superior to those from Ortho Glass LC.76470070

Sleep-wake sensitive mechanisms of adenosine release in the basal forebrain of rodents : an in vitro study

Adenosine acting in the basal forebrain is a key mediator of sleep homeostasis. Extracellular adenosine concentrations increase during wakefulness, especially during prolonged wakefulness and lead to increased sleep pressure and subsequent rebound sleep. The release of endogenous adenosine during the sleep-wake cycle has mainly been studied in vivo with microdialysis techniques. The biochemical changes that accompany sleep-wake status may be preserved in vitro. We have therefore used adenosine-sensitive biosensors in slices of the basal forebrain (BFB) to study both depolarization-evoked adenosine release and the steady state adenosine tone in rats, mice and hamsters. Adenosine release was evoked by high K+, AMPA, NMDA and mGlu receptor agonists, but not by other transmitters associated with wakefulness such as orexin, histamine or neurotensin. Evoked and basal adenosine release in the BFB in vitro exhibited three key features: the magnitude of each varied systematically with the diurnal time at which the animal was sacrificed; sleep deprivation prior to sacrifice greatly increased both evoked adenosine release and the basal tone; and the enhancement of evoked adenosine release and basal tone resulting from sleep deprivation was reversed by the inducible nitric oxide synthase (iNOS) inhibitor, 1400 W. These data indicate that characteristics of adenosine release recorded in the BFB in vitro reflect those that have been linked in vivo to the homeostatic control of sleep. Our results provide methodologically independent support for a key role for induction of iNOS as a trigger for enhanced adenosine release following sleep deprivation and suggest that this induction may constitute a biochemical memory of this state

RASSF1A–LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2

Genomic instability is a key hallmark of cancer leading to tumour heterogeneity and therapeutic resistance. ​BRCA2 has a fundamental role in error-free DNA repair but also sustains genome integrity by promoting ​RAD51 nucleofilament formation at stalled replication forks. ​CDK2 phosphorylates ​BRCA2 (pS3291-​BRCA2) to limit stabilizing contacts with polymerized ​RAD51; however, how replication stress modulates ​CDK2 activity and whether loss of pS3291-​BRCA2 regulation results in genomic instability of tumours are not known. Here we demonstrate that the Hippo pathway kinase ​LATS1 interacts with ​CDK2 in response to genotoxic stress to constrain pS3291-​BRCA2 and support ​RAD51 nucleofilaments, thereby maintaining genomic fidelity during replication stalling. We also show that ​LATS1 forms part of an ​ATR-mediated response to replication stress that requires the tumour suppressor ​RASSF1A. Importantly, perturbation of the ​ATR–​RASSF1A–​LATS1 signalling axis leads to genomic defects associated with loss of ​BRCA2 function and contributes to genomic instability and ‘BRCA-ness’ in lung cancers

Patterns of male-specific inter-population divergence in Europe, West Asia and North Africa

We typed 1801 males from 55 locations for the Y-specific binary markers YAP! DYZ3, SRY10831 and the (CA)n microsatellites YCAII and DYS413. Phylogenetic relationships of chromosomes with the same binary haplotype were condensed in seven large one-step networks! which accounted for 95% of all chromosomes. Their coalescence ages were estimated based on microsatellite diversity. The three largest and oldest networks undergo sharp frequency changes in three areas. The more recent network; 3.1A clearly discriminates between Western and Eastern European populations. Pairwise Pst showed an overall increment with increasing geographic distance but with a slope greatly reduced when compared to previous reports. BI sectioning the entire data set according to geographic and linguistic criteria, we found higher Fst-on-distance slopes within Europe than in West Asia or across the tno continents

Analogue peptides for the immunotherapy of human acute myeloid leukemia

Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies