An Approach to Assess the Impact of Tutorials in Video Games

Video games are an established medium that provides interactive entertainment beyond pure enjoyment in many contexts. Game designers create dedicated tutorials to teach players the game mechanisms and rules, such as the conventions for interaction, control schemes, core game mechanics, etc. While effective tutorial design is considered a crucial aspect to support this learning process, the existing literature approaches focus on designing ad hoc tutorials for specific game genres rather than investigating the impact of different tutorial styles on game learnability and player engagement. In this paper, we tackle this challenge by presenting a general-purpose approach aimed at supporting game designers in the identification of the most suitable tutorial style for a specific genre of video games. The approach is evaluated in the context of a simple first-person shooter (FPS) mainstream video game built by the authors through a controlled comparative user experiment involving 46 players

Hypokalemia during the early phase of refeeding in patients with cancer

OBJECTIVE: Refeeding syndrome occurs in patients with severe malnutrition when refeeding begins after a long period of starvation. This syndrome increases the risk of clinical complications and mortality. Hypophosphatemia is considered the primary characteristic of the syndrome. The aim of our study was to investigate the presence of other electrolyte alterations in patients with cancer during the early stage of refeeding. METHODS: In this observational study, we enrolled 34 patients with cancer of the upper aerodigestive tract receiving upfront radiotherapy who were also enrolled in a nutrition program. A caloric intake assessment, anthropometric measurements and biochemical laboratory tests were performed. RESULTS: Significant weight loss (∼20%) was found in these patients. In the patients receiving artificial nutrition, we found lower levels of potassium and total protein compared with those who were fed orally (p = 0.03 for potassium and 0.02 for protein, respectively). Patients on enteral tube feeding had a higher caloric intake compared with those who were fed orally (25±5 kcal/kg/day vs. 10±2 kcal/kg/day). CONCLUSION: Hypokalemia, like hypophosphatemia, could be a complication associated with refeeding in patients with cancer. Hypokalemia was present in the early stages of high-calorie refeeding

Cancer acidity: An ultimate frontier of tumor immune escape and a novel target of immunomodulation

The link between cancer metabolism and immunosuppression, inflammation and immune escape has generated major interest in investigating the effects of low pH on tumor immunity. Indeed, microenvironmental acidity may differentially impact on diverse components of tumor immune surveillance, eventually contributing to immune escape and cancer progression. Although the molecular pathways underlying acidity-related immune dysfunctions are just emerging, initial evidence indicates that antitumor effectors such as T and NK cells tend to lose their function and undergo a state of mostly reversible anergy followed by apoptosis, when exposed to low pH environment. At opposite, immunosuppressive components such as myeloid cells and regulatory T cells are engaged by tumor acidity to sustain tumor growth while blocking antitumor immune responses. Local acidity could also profoundly influence bioactivity and distribution of antibodies, thus potentially interfering with the clinical efficacy of therapeutic antibodies including immune checkpoint inhibitors. Hence tumor acidity is a central regulator of cancer immunity that orchestrates both local and systemic immunosuppression and that may offer a broad panel of therapeutic targets. This review outlines the fundamental pathways of acidity-driven immune dysfunctions and sheds light on the potential strategies that could be envisaged to potentiate immune-mediated tumor control in cancer patients

Sarcopenia and Appendicular Muscle Mass as Predictors of Impaired Fasting Glucose/Type 2 Diabetes in Elderly Women

Elderly women exhibit a high risk of type 2 diabetes (T2D), but no definitive data exist about the possible role of postmenopausal increases in visceral adiposity, the loss of lean body mass, or decreases in the sum of the lean mass of arms and legs (appendicular skeletal muscle mass (ASMM)). This retrospective, longitudinal study investigated whether body composition (bioelectrical impedance analysis) predicted the development of impaired fasting glucose (IFG) or T2D in a cohort of 159 elderly women (age: 71 5 years, follow-up: 94 months) from southern Italy (Clinical Nutrition and Geriatric Units of the “Mater Domini” University Hospital in Catanzaro, Calabria region, and the “P. Giaccone ”University Hospital in Palermo, Sicily region). Sarcopenia was defined in a subgroup of 128 women according to the EWGSOP criteria as the presence of low muscle strength (handgrip strength <16 kg) plus low muscle mass (reported as appendicular skeletal muscle mass <15 kg). Participants with a low ASMM had a higher IFG/T2D incidence than those with a normal ASMM (17% vs. 6%, p-adjusted = 0.044); this finding was independent of BMI, fat mass, waist circumference, and habitual fat intake (OR = 3.81, p = 0.034). A higher incidence of IFG/T2D was observed in the subgroup with sarcopenia than those without sarcopenia (33% vs. 7%, p-adjusted = 0.005) independent of BMI and fat mass (OR = 6.75, p = 0.007). In conclusion, this study demonstrates that elderly women with low ASMM had a higher probability of developing IFG/T2D. Further studies are needed to confirm these results in men and in other age groups

The impact of endometriosis on dietary choices and activities of everyday life: a cross-sectional study

IntroductionEndometriosis is characterized by ectopic endometrial tissue and severe pain; frequently, women afflicted by this condition resort to non-medical interventions, such as dietary modifications. The aim of this study is to assess the impact of endometriosis on dietary patterns and quality of life.MethodsAn online survey was conducted among Italian women with endometriosis to gather self-reported demographic, clinical, dietary habit, and daily life data post-diagnosis.ResultsA total of 4,078 participants were included. Following an endometriosis diagnosis, 66% reported changes in eating habits, and 92% experienced a decline in daily life. Respondents chose dietary interventions: gluten-free (15%), anti-inflammatory (8%), Mediterranean (7.1%), or ketogenic (4%) diets, to improve health and reduce symptoms. The study revealed a shift in eating habits, with increased consumption of vegetables, fruits (10%), cereals, legumes (6.6%), and fish (4.5%), while reducing dairy products (18.4%), soy-containing foods (6.7%), and high saturated fats (8%). Eating habit changes correlated with endometriosis stages and worsened daily life. Educational level, endometriosis stages, years of symptoms, and eating habit changes linked to changes in daily life.ConclusionOur findings emphasize the importance of monitoring eating behaviors to prevent unhealthy habits and malnutrition in women with endometriosis. Further studies are needed to evaluate how different diets impact symptoms and enhance daily life for these individuals

Counteracting gemcitabine+nab-paclitaxel induced dysbiosis in KRAS wild type and KRASG12D mutated pancreatic cancer in vivo model

Pancreatic cancer (PC) has a very low survival rate mainly due to late diagnosis and refractoriness to therapies. The latter also cause adverse effects negatively affecting the patients' quality of life, often requiring dose reduction or discontinuation of scheduled treatments, compromising the chances of cure. We explored the effects of a specific probiotic blend on PC mice xenografted with KRAS wild-type or KRASG12D mutated cell lines alone or together with gemcitabine+nab-paclitaxel treatment to then assess tumor volume and clinical pathological variables. Beside a semi-quantitative histopathological evaluation of murine tumor and large intestine samples, histochemical and immunohistochemical analyses were carried out to evaluate collagen deposition, proliferation index Ki67, immunological microenvironment tumor-associated, DNA damage markers and also mucin production. Blood cellular and biochemical parameters and serum metabolomics were further analyzed. 16S sequencing was performed to analyze the composition of fecal microbiota. Gemcitabine+nab-paclitaxel treatment impaired gut microbial profile in KRAS wild-type and KRASG12D mice. Counteracting gemcitabine+nab-paclitaxel- induced dysbiosis through the administration of probiotics ameliorated chemotherapy side effects and decreased cancer-associated stromatogenesis. Milder intestinal damage and improved blood count were also observed upon probiotics treatment as well as a positive effect on fecal microbiota, yielding an increase in species richness and in short chain fatty acids producing- bacteria. Mice' serum metabolomic profiles revealed significant drops in many amino acids upon probiotics administration in KRAS wild-type mice while in animals transplanted with PANC-1 KRASG12D mutated all treated groups showed a sharp decline in serum levels of bile acids with respect to control mice. These results suggest that counteracting gemcitabine+nab-paclitaxel-induced dysbiosis ameliorates chemotherapy side effects by restoring a favorable microbiota composition. Relieving adverse effects of the chemotherapy through microbiota manipulation could be a desirable strategy in order to improve pancreatic cancer patients' quality of life and to increase the chance of cure

Mitochondrial Alterations Induced by the p13II Protein of Human T-cell Leukemia Virus Type 1 CRITICAL ROLE OF ARGININE RESIDUES

Abstract Human T-cell leukemia virus type 1 encodes a number of "accessory" proteins of unclear function; one of these proteins, p13II, is targeted to mitochondria and disrupts mitochondrial morphology. The present study was undertaken to unravel the function of p13II through (i) determination of its submitochondrial localization and sequences required to alter mitochondrial morphology and (ii) an assessment of the biophysical and biological properties of synthetic peptides spanning residues 9–41 (p139–41), which include the amphipathic mitochondrial-targeting sequence of the protein. p139–41 folded into an α helix in micellar environments. Fractionation and immunogold labeling indicated that full-length p13II accumulates in the inner mitochondrial membrane. p139–41 induced energy-dependent swelling of isolated mitochondria by increasing inner membrane permeability to small cations (Na+, K+) and released Ca2+ from Ca2+-preloaded mitochondria. These effects as well as the ability of full-length p13II to alter mitochondrial morphology in cells required the presence of four arginines, forming the charged face of the targeting signal. The mitochondrial effects of p139–41 were insensitive to cyclosporin A, suggesting that full-length p13II might alter mitochondrial permeability through a permeability transition pore-independent mechanism, thus distinguishing it from the mitochondrial proteins Vpr and X of human immunodeficiency virus type 1 and hepatitis B virus, respectively

Efficacy of conventional versus innovative therapies for treating skin wounds in veterinary medicine

open16siINTRODUCTION: The skin is the largest organ of mammals. The loss of skin integrity may induce important dysfunctions or even death. For superficial wounds, the endogenous healing mechanisms in combination with traditional wound care are sufficient to achieve functional repair. In contrast, in larger wounds, like third and fourth degree burns, chronic wound or deep ulcers it is difficult to obtain the restitutio ad integrum and fibrosis and/or scar tissue develops1,2. The aim of this study was to verify the efficacy of conventional and innovative topic treatments on skin regeneration, induced experimentally in sheep. To achieve this goal different types of investigations (clinical, molecular, histological, immunohistochemical) were performed. METHODS: Six skin lesions (4x4cm) were surgically created on the back of six healthy adult sheep; every single wound was destined, in a randomized way, to one of the following treatments: Acemannan gel, Manuka Honey, hyaluronic acid, Plasma3 (ionized gas), allogeneic mesenchymal stem cells isolated from peripheral blood (PB-MSCs). The sixth wound was the placebo. Biopsies were collected with a surgical punch (0,6x0,6 cm) at time T0, T15 and T40 days. Lesions were clinically evaluated considering the presence and color of wound fluid, the state of hydration, the wound surface/surroundings and other parameters. Histological examinations considered crust formation, re-epithelization and epidermal thickness, dermis edema, extension of granulation tissue, acute and chronic inflammation. Immunohistochemistry for evaluation of inflammation, vascularization and cell proliferation was performed using CD3, CD20, MHCII, von Willebrand factor (vWF) and KI67 antibodies. Furthermore, Real time-PCR investigated genes as V ascular endothelial growth factors (VEGF), Transforming growth factor beta 1(TGFβ1), Vimentin (VIM), Collagen 1α1 (Col1α1) and hair Keratin (hKER). RESULTS: Clinically, the lesions treated with plasma healed more rapidly respect to other treatments and a reduced bacterial load was observed. At T7 wounds treated with stem cells and plasma were less macerated than lesions treated with other therapies. At T15 the wounds treated with hyaluronic acid showed a normal state of hydration while lesions treated with Manuka Honey exhibited a normal hydration from the third week only (Acemannan gel at fourth week). From the second week onwards all wounds did not show presence of fluid and exhibited a dry and clean secondary layer. All lesions, excluded wounds treated with acemannan gel, presented a red (hyaluronic acid and plasma) and dark red (Manuka Honey, PB-MSCs) granulation tissue starting from the first week. Molecular analysis showed a correspondence between clinical and molecular/histologic results. For instance, VEGF mRNA expression confirms angiogenetic events observed at histological level while TGF-β, CD3 and CD20 mRNA/protein expression indicated the presence/absence of inflammation in the used treatments. DISCUSSION & CONCLUSIONS: Innovative therapies led to surprising results regarding regeneration of mammalian skin. Indeed, on the basis of clinical analysis, wounds treated with plasma and MSC healed more rapidly. Further examinations are ongoing in order to elucidate possible mechanisms explaining these differences. REFERENCES: 1S.Y. Broeckx, S. Maes, T. Martinello, et al (2014) Equine epidermis: a source of epithelial-like stem/progenitor cells with in vitro and in vivo regenerative capacities Stem Cells Dev, pp 1134-48. 2J.H. Spaas, C. Gomiero, S.Y. Broeckx, et al (2016) Wound healing markers after autologous and allogeneic epithelial-like stem cell treatment Cytotherapy 2016 (in press). 3E. Martines, M. Zuin, R. Cavazzana, et al. (2009) A novel plasma source for sterilization of living tissues, New J. Phys. 11, 115014.openPatruno, MARCO VINCENZO; Gomiero, Chiara; Martinello, Tiziana; Perazzi, Anna; Gemignani, F; DE BENEDICTIS, GIULIA MARIA; Ferro, Silvia; Zuin, M; Martines, E; Cordaro, Luigi; Brun, Paola; Maccatrozzo, Lisa; Broeckx, Sy; Spaas, Jh; Chiers, K; Iacopetti, IlariaPatruno, MARCO VINCENZO; Gomiero, Chiara; Martinello, Tiziana; Perazzi, Anna; Gemignani, F; DE BENEDICTIS, GIULIA MARIA; Ferro, Silvia; Zuin, M; Martines, E; Cordaro, Luigi; Brun, Paola; Maccatrozzo, Lisa; Broeckx, Sy; Spaas, Jh; Chiers, K; Iacopetti, Ilari