For glioblastoma, the tumor microenvironment (TME) is pivotal to support tumor progression and therapeutic resistance. TME consists of several types of stromal, endothelial and immune cells, which are recruited by cancer stem cells (CSCs) to influence CSC phenotype and behavior. TME also promotes the establishment of specific conditions such as hypoxia and acidosis, which play a critical role in glioblastoma chemoresistance, interfering with angiogenesis, apoptosis, DNA repair, oxidative stress, immune escape, expression and activity of multi-drug resistance (MDR)-related genes. Finally, the blood brain barrier (BBB), which insulates the brain microenvironment from the blood, is strongly linked to the drug-resistant phenotype of glioblastoma, being a major physical and physiological hurdle for the delivery of chemotherapy agents into the brain. Here, we review the features of the glioblastoma microenvironment, focusing on their involvement in the phenomenon of chemoresistance; we also summarize recent advances in generating systems to modulate or bypass the BBB for drug delivery into the brain. Genetic aspects associated with glioblastoma chemoresistance and current immune-based strategies, such as checkpoint inhibitor therapy, are described too.

Gender-based medicine is an innovative branch of biomedical research and represents a new perspective for the future of health research. Many studies have been published on gender medicine in adults but very few data regarding children are available. A literature search covering articles published between 1stJuly, 2006 and 1st February, 2017 and concerning children only was conducted using multiple keywords and standardized terminology in Pubmed database. The search was limited to English-language publications. All relevant articles on endocrines, neurological, psychiatric, gastrointestinal, immunological, oncological, rheumatic, pneumological disorders, infectious diseases and analgesia were evaluated and pertinent articles were included in this review. Most of the available studies on gender disparity in childhood are about endocrine and neuro-psychiatric disorders, while there are few data in other areas of medicine. Even if several studies on pediatric gender differences can be found on literature, few of them move forwards to analyze the reasons of the observed diversity. No data on pharmacokinetic and pharmacodynamic differences between boys and girls can be found. Hence, more efforts should be directed to investigate these topics in childhood.

Background: Resurgence of pertussis in the post-vaccination era has been reported in Western countries. A shift of cases from school-age children to adolescents, adults and children under 1 year of age has been described in the last decade, and mortality rates in infants are still sustained. We aimed to review and discuss the possible vaccination strategies which can be adopted in order to improve the pertussis control, by searches of Pubmed, and websites of US and European Centers for Disease Control and Prevention, between 1st January 2002, and 1st March 2013. Discussion: The following vaccination strategies have been retrieved and analysed: the cocooning strategy, the immunization of pregnant women and newborns, vaccination programs for preschool children, adolescents, adults and health-care workers. Cost-effectiveness studies provide some contrasting data, mainly supporting both maternal vaccination and cocooning. Adolescent and/or adult vaccination seems to be cost-effective, however data from observational studies suggest that this vaccination strategy, used alone, leads to a reduced pertussis burden globally, but does not affect the disease incidence in infants. Moreover, substantial logistical and economic difficulties have to be overcome to vaccinate the largest number of individuals. Summary: The simultaneous use of more than one strategy, including cocooning strategy plus vaccination of adolescents and adults, seems to be the most reasonable preventive measure. The development of new highly immunogenic and efficacious pertussis vaccines continues to be a primary objective for the control of pertussis.

Previous meta-analyses regarding the performance of interferon-gamma release assays (IGRAs) for tuberculosis diagnosis in children yielded contrasting results, probably due to different inclusion/exclusion criteria.

Ibuprofen is the most widely used non-steroidal anti-inflammatory drug (NSAID) for the treatment of inflammation, mild-to-moderate pain and fever in children, and is the only NSAID approved for use in children aged ≥3 months. Its efficacy and safety profile have led to its increasing use in paediatric care, even without medical prescription. However, an increase of suspected adverse reactions to ibuprofen has been noted in concomitance with the raised, often medically unsupervised, consumption of the drug. The purpose of this work was a critical review of the paediatric literature over the last 15 years on side effects and adverse events associated with ibuprofen, in order to highlight circumstances associated with higher risks and to promote safe and appropriate use of this drug. The literature from 2000 to date demonstrates that gastrointestinal events are rare, but (when they occur) include both upper and lower digestive tract lesions. Dehydration plays an important role in triggering renal damage, so ibuprofen should not be given to patients with diarrhoea and vomiting, with or without fever. Likewise, ibuprofen should never be administered to patients who are sensitive to it or to other NSAIDs. It is contraindicated in neonates and in children with wheezing and persistent asthma and/or during varicella. Most of the analysed studies reported adverse events when ibuprofen was being used for fever symptoms or flu-like syndrome. Ibuprofen should not be used as an antipyretic, except in rare cases. Ibuprofen remains the drug of first choice in the treatment of inflammatory pain in children.

Peripheral quantitative computed tomography provides an automatical scan analysis of trabecular and cortical bone compartments, calculating not only their bone mineral density (BMD), but also bone geometrical parameters, such as marrow and cortical Cross-Sectional Area (CSA), Cortical Thickness (CoTh), both periosteal and endosteal circumference, as well as biomechanical parameters like Cross-Sectional Moment of Inertia (CSMI), a measure of bending, polar moment of inertia, indicating bone strength in torsion, and Strength Strain Index (SSI). Also CSA of muscle and fat can be extracted. Muscles, which are thought to stimulate bones to adapt their geometry and mineral content, are determinant to preserve or increase bone strength; thus, pQCT provides an evaluation of the functional ‘muscle-bone unit’, defined as BMC/muscle CSA ratio. This functional approach to bone densitometry can establish if bone strength is normally adapted to the muscle force, and if muscle force is adequate for body size, providing more detailed insights to targeted strategies for the prevention and treatment of bone fragility. The present paper offers an extensive review of technical features of pQCT and its possible clinical application in the diagnostic of bone status as well as in the monitoring of the skeleton’s health follow-up.