Treatment challenges in and outside a network setting: Head and neck cancers

Head and neck cancer (HNC) is a rare disease that can affect different sites and is characterized by variable incidence and 5-year survival rates across Europe. Multiple factors need to be considered when choosing the most appropriate treatment for HNC patients, such as age, comorbidities, social issues, and especially whether to prefer surgery or radiation-based protocols. Given the complexity of this scenario, the creation of a highly specialized multidisciplinary team is recommended to guarantee the best oncological outcome and prevent or adequately treat any adverse effect. Data from literature suggest that the multidisciplinary team-based approach is beneficial for HNC patients and lead to improved survival rates. This result is likely due to improved diagnostic and staging accuracy, a more efficacious therapeutic approach and enhanced communication across disciplines. Despite the benefit of MTD, it must be noted that this approach requires considerable time, effort and financial resources and is usually more frequent in highly organized and high-volume centers. Literature data on clinical research suggest that patients treated in high-accrual centers report better treatment outcomes compared to patients treated in low-volume centers, where a lower radiotherapy-compliance and worst overall survival have been reported. There is general agreement that treatment of rare cancers such as HNC should be concentrated in high volume, specialized and multidisciplinary centers. In order to achieve this goal, the creation of international collaboration network is fundamental. The European Reference Networks for example aim to create an international virtual advisory board, whose objectives are the exchange of expertise, training, clinical collaboration and the reduction of disparities and enhancement of rationalize migration across Europe. The purpose of our work is to review all aspects and challenges in and outside this network setting planned for the management of HNC patients.

Understanding context dependency in the response of forest understorey plant communities to nitrogen deposition

Understorey communities can dominate forest plant diversity and strongly affect forest ecosystem structure and function. Understoreys often respond sensitively but inconsistently to drivers of ecological change, including nitrogen (N) deposition. Nitrogen deposition effects, reflected in the concept of critical loads, vary greatly not only among species and guilds, but also among forest types. Here, we characterize such context dependency as driven by differences in the amounts and forms of deposited N, cumulative deposition, the filtering of N by overstoreys, and available plant species pools. Nitrogen effects on understorey trajectories can also vary due to differences in surrounding landscape conditions; ambient browsing pressure; soils and geology; other environmental factors controlling plant growth; and, historical and current disturbance/management regimes. The number of these factors and their potentially complex interactions complicate our efforts to make simple predictions about how N deposition affects forest understoreys. We review the literature to examine evidence for context dependency in N deposition effects on forest understoreys. We also use data from 1814 European temperate forest plots to test the ability of multi-level models to characterize context-dependent understorey responses across sites that differ in levels of N deposition, community composition, local conditions and management history. This analysis demonstrated that historical management, and plot location on light and pH-fertility gradients, significantly affect how understorey communities respond to N deposition. We conclude that species' and communities' responses to N deposition, and thus the determination of critical loads, vary greatly depending on environmental contexts. This complicates our efforts to predict how N deposition will affect forest understoreys and thus how best to conserve and restore understorey biodiversity. To reduce uncertainty and incorporate context dependency in critical load setting, we should assemble data on underlying environmental conditions, conduct globally distributed field experiments, and analyse a wider range of habitat types.

Mitochondrial transplantation prolongs cold ischemia time in murine heart transplantation

Cold ischemia time (CIT) causes ischemia‒reperfusion injury to the mitochondria and detrimentally effects myocardial function and tissue viability. Mitochondrial transplantation replaces damaged mitochondria and enhances myocardial function and tissue viability. Herein we investigated the efficacy of mitochondrial transplantation in enhancing graft function and viability after prolonged CIT.

Prognostic impact of MYD88 mutation, proliferative index and cell origin in diffuse large B cell lymphoma

Diffuse large B-cell lymphoma, among non-Hodgkin lymphomas, is one of the most frequent subtypes. Clinical laboratory data and post-treatment outcomes are scarce in the Brazilian population.

The use of simulation in the design of Milk-Run intralogistics systems

Action of ginger essential oil (Zingiber officinale) encapsulated in proteins ultrafine fibers on the antimicrobial control in situ

The ultrafine fibers were produced using a polymeric blend of soy protein isolate (SPI), polyethylene oxide (PEO), and zein at a ratio of 1:1:1 (v/v/v) by electrospinning. The ginger essential oil (GEO) was encapsulated in the ultrafine fibers and the morphology, Fourier-Transform Infrared Spectroscopy (FTIR) analysis, thermal properties and relative crystallinity were evaluated. The antimicrobial activity of ginger essential oil was evaluated against five bacteria (Listeria monocytogenes, Staphylococcus aureus, Escherichia coli 0157:H7, Salmonella typhimurium, and Pseudomonas aeruginosa). Based on the preliminary tests, the concentration of GEO selected to add in the polymer solution was 12% (v/v; GEO/polymer solution). The fiber produced with 12% (v/v) GEO was used for antimicrobial analysis and in situ application (in fresh Minas cheese) against L. monocytogenes by micro-atmosphere. The ultrafine fibers produced, regardless the concentration of the essential oil, presented homogeneous morphology with cylindrical shape without the presence of beads. The application of the active fibers containing 12% GEO showed high potential to be applied in food packaging to reduce microbial contamination.

Religion and spirituality as predictors of patient-reported outcomes in adults with congenital heart disease around the globe

Religion and spirituality can be resources for internal strength and resilience, and may assist with managing life's challenges. Prior studies have been undertaken primarily in countries with high proportions of religious/spiritual people. We investigated (i) whether being religious/spiritual is an independent predictor of patient-reported outcomes (PROs) in a large international sample of adults with congenital heart disease, (ii) whether the individual level of importance of religion/spirituality is an independent predictor for PROs, and (iii) if these relationships are moderated by the degree to which the respective countries are religious or secular.

Geographical variation and predictors of physical activity level in adults with congenital heart disease

Physical activity is important to maintain and promote health. This is of particular interest in patients with congenital heart disease (CHD) where acquired heart disease should be prevented. The World Health Organization (WHO) recommends a minimum of 2.5 h/week of physical activity exceeding 3 metabolic equivalents (METS) to achieve positive health effects. It is unknown whether physical activity levels (PAL) in adult CHD patients differ by country of origin.

Chromatin Remodeling BAF155 Subunit Regulates the Genesis of Basal Progenitors in Developing Cortex

The abundance of basal progenitors (BPs), basal radial glia progenitors (bRGs) and basal intermediate progenitors (bIPs), in primate brain has been correlated to the high degree of cortical folding. Here we examined the role of BAF155, a subunit of the chromatin remodeling BAF complex, in generation of cortical progenitor heterogeneity. The conditional deletion of BAF155 led to diminished bIP pool and increased number of bRGs, due to delamination of apical RGs. We found that BAF155 is required for normal activity of neurogenic transcription factor PAX6, thus controlling the expression of genes that are involved in bIP specification, cell-cell interaction, and establishment of adherens junction. In a PAX6-dependent manner, BAF155 regulates the expression of the CDC42 effector protein CEP4, thereby controlling progenitor delamination. Furthermore, BAF155-dependent chromatin remodeling seems to exert a specific role in the genesis of BPs through the regulation of human RG-specific genes (such as Foxn4) that possibly acquired evolutionary significance.

Gemcitabine loaded microbubbles for targeted chemo-sonodynamic therapy of pancreatic cancer

Pancreatic cancer remains one of the most lethal forms of cancer with a 10-year survival of <1%. With little improvement in survival rates observed in the past 40 years, there is a significant need for new treatments or more effective strategies to deliver existing treatments. The antimetabolite gemcitabine (Gem) is the most widely used form of chemotherapy for pancreatic cancer treatment, but is known to produce significant side effects when administered systemically. We have previously demonstrated the benefit of combined chemo-sonodynamic therapy (SDT), delivered using oxygen carrying microbubbles (O 2 MB), as a targeted treatment for pancreatic cancer in a murine model of the disease. In this manuscript, we report the preparation of a biotin functionalised Gem ligand for attachment to O 2 MBs (O 2 MB-Gem). We demonstrate the effectiveness of chemo-sonodynamic therapy following ultrasound-targeted-microbubble-destruction (UTMD) of the O 2 MB-Gem and a Rose Bengal loaded O 2 MB (O 2 MB-RB) as a targeted treatment for pancreatic cancer. Specifically, UTMD using the O 2 MB-Gem and O 2 MB-RB conjugates reduced the viability of MIA PaCa-2, PANC-1, BxPC3 and T110299 pancreatic cancer cells by >60% (p < 0.001) and provided significant tumour growth delay (>80%, p < 0.001) compared to untreated animals when human xenograft MIA PaCa-2 tumours were treated in SCID mice. The toxicity of the O 2 MB-Gem conjugate was also determined in healthy non-tumour bearing MF1 mice and revealed no evidence of renal or hepatic damage. Therefore, the results presented in this manuscript suggest that chemo-sonodynamic therapy using the O 2 MB-Gem and O 2 MB-RB conjugates, is potentially an effective targeted and safe treatment modality for pancreatic cancer.