Role of HMGB1 in Cutaneous Melanoma: State of the Art

High-mobility Group Box 1 (HMGB1) is a nuclear protein that plays a key role in acute and chronic inflammation. It has already been studied in several diseases, among them melanoma. Indeed, HMGB1 is closely associated with cell survival and proliferation and may be directly involved in tumor cell metastasis development thanks to its ability to promote cell migration. This research aims to assess the role of this molecule in the pathogenesis of human melanoma and its potential therapeutic role. The research has been conducted on the PubMed database, and the resulting articles are sorted by year of publication, showing an increasing interest in the last five years. The results showed that HMGB1 plays a crucial role in the pathogenesis of skin cancer, prognosis, and therapeutical response to therapy. Traditional therapies target this molecule indirectly, but future perspectives could include the development of new target therapy against HMGB1, thus adding a new approach to the therapy, which has often shown primary and secondary resistance. This could add a new therapy arm which has to be prolonged and specific for each patient

One-Liners

One-Liners from P.T. Borgia, J. Irelan and E.U. Selker, and B.C. Turner and A. Fairfiel

18F-FDG PET-Derived Volume-Based Parameters to Predict Disease-Free Survival in Patients with Grade III Breast Cancer of Different Molecular Subtypes Candidates to Neoadjuvant Chemotherapy

We investigated whether baseline [F-18] Fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET)-derived semiquantitative parameters could predict disease-free survival (DFS) in patients with grade III breast cancer (BC) of different molecular subtypes candidate to neoadjuvant chemotherapy (NAC). For each F-18-FDG-PET/CT scan, the following parameters were calculated in the primary tumor (SUVmax, SUVmean, MTV, TLG) and whole-body (WB_SUVmax, WB_MTV, and WB_TLG). Receiver operating characteristic (ROC) analysis was used to determine the capability to predict DFS and find the optimal threshold for each parameter. Ninety-five grade III breast cancer patients with different molecular types were retrieved from the databases of the University Hospital of Padua and the University Hospital of Ferrara (luminal A: 5; luminal B: 34; luminal B-HER2: 22; HER2-enriched: 7; triple-negative: 27). In luminal B patients, WB_MTV (AUC: 0.75; best cut-off: WB_MTV > 195.33; SS: 55.56%, SP: 100%; p = 0.002) and WB_TLG (AUC: 0.73; best cut-off: WB_TLG > 1066.21; SS: 55.56%, SP: 100%; p = 0.05) were the best predictors of DFS. In luminal B-HER2 patients, WB_SUVmax was the only predictor of DFS (AUC: 0.857; best cut-off: WB_SUVmax > 13.12; SS: 100%; SP: 71.43%; p < 0.001). No parameter significantly affected the prediction of DFS in patients with grade III triple-negative BC. Volume-based parameters, extracted from baseline F-18-FDG PET, seem promising in predicting recurrence in patients with grade III luminal B and luminal B- HER2 breast cancer undergoing NAC

Continuing medical education and evidence-based clinical pathways. Training emergency health workers in Latium, Italy

Background: In recent decades, studies that evaluate training programmes have shown that continuing education for physicians is not very effective in improving performance and behavioural changes. One of our goals was to create a Continuing Medical Education Programme (CMEP) that would result in changing the behaviour of health professionals. In early 2005, a new CMEP was offered to emergency medical services and emergency room professionals to introduce an Emergency Critical Pathway (ECP) for the management of acute stroke patients. This paper illustrates the main characteristics of the educational model and the strategies and activities adopted to realize it. Methods: The training programme was planned and organized applying the concepts and tools of experiential learning, It was organised in three successive phases: 1.) interviews with health professionals to identify their learning ne-eds; 2) training the ECP coordinators/facilitators in a residential setting; and 3) on-site training in small groups of health professionals (6-8), led by a coordinator/facilitator. Results: The CME involved 324 emergency health professionals, Participants positively evaluated both the educational programme and the clinical indications of the protocols. Over six months of the ECP training, health professionals treated 657 stroke patients: 153 (23.3%) were transferred to the stroke unit where 15 (9.8%) were thrombolysed. In the same period of the previous year, the professionals treated 638 patients: 99 (15.5%) were transferred to the stroke unit and no patients were thrombolysed. Conclusion: The application of the new educational methodology has contributed to improved management of stroke patients in Latium.</p

Beta-agonist stimulation ameliorates the phenotype of spinal and bulbar muscular atrophy mice and patient-derived myotubes

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease characterized by the loss of lower motor neurons. SBMA is caused by expansions of a polyglutamine tract in the gene coding for androgen receptor (AR). Expression of polyglutamine-expanded AR causes damage to motor neurons and skeletal muscle cells. Here we investigated the effect of β-agonist stimulation in SBMA myotube cells derived from mice and patients, and in knock-in mice. We show that treatment of myotubes expressing polyglutamine-expanded AR with the β-agonist clenbuterol increases their size. Clenbuterol activated the phosphatidylinositol-3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway and decreased the accumulation of polyglutamine-expanded AR. Treatment of SBMA knock-in mice with clenbuterol, which was started at disease onset, ameliorated motor function and extended survival. Clenbuterol improved muscle pathology, attenuated the glycolytic-to-oxidative metabolic alterations occurring in SBMA muscles and induced hypertrophy of both glycolytic and oxidative fibers. These results indicate that β-agonist stimulation is a novel therapeutic strategy for SBMA

Continuing medical education and evidence-based clinical pathways. Training emergency health workers in Latium, Italy

Background: In recent decades, studies that evaluate training programmes have shown that continuing education for physicians is not very effective in improving performance and behavioural changes. One of our goals was to create a Continuing Medical Education Programme (CMEP) that would result in changing the behaviour of health professionals. In early 2005, a new CMEP was offered to emergency medical services and emergency room professionals to introduce an Emergency Critical Pathway (ECP) for the management of acute stroke patients. This paper illustrates the main characteristics of the educational model and the strategies and activities adopted to realize it. Methods: The training programme was planned and organized applying the concepts and tools of experiential learning, It was organised in three successive phases: 1.) interviews with health professionals to identify their learning ne-eds; 2) training the ECP coordinators/facilitators in a residential setting; and 3) on-site training in small groups of health professionals (6-8), led by a coordinator/facilitator. Results: The CME involved 324 emergency health professionals, Participants positively evaluated both the educational programme and the clinical indications of the protocols. Over six months of the ECP training, health professionals treated 657 stroke patients: 153 (23.3%) were transferred to the stroke unit where 15 (9.8%) were thrombolysed. In the same period of the previous year, the professionals treated 638 patients: 99 (15.5%) were transferred to the stroke unit and no patients were thrombolysed. Conclusion: The application of the new educational methodology has contributed to improved management of stroke patients in Latium.</p

Creativity and Autonomy in Swarm Intelligence Systems

This work introduces two swarm intelligence algorithms -- one mimicking the behaviour of one species of ants (\emph{Leptothorax acervorum}) foraging (a `Stochastic Diffusion Search', SDS) and the other algorithm mimicking the behaviour of birds flocking (a `Particle Swarm Optimiser', PSO) -- and outlines a novel integration strategy exploiting the local search properties of the PSO with global SDS behaviour. The resulting hybrid algorithm is used to sketch novel drawings of an input image, exploliting an artistic tension between the local behaviour of the `birds flocking' - as they seek to follow the input sketch - and the global behaviour of the `ants foraging' - as they seek to encourage the flock to explore novel regions of the canvas. The paper concludes by exploring the putative `creativity' of this hybrid swarm system in the philosophical light of the `rhizome' and Deleuze's well known `Orchid and Wasp' metaphor