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Alzheimer’s disease (AD), the most common progressive neurodegenerative disorder, is characterized by severe cognitive decline and personality changes as a result of synaptic and neuronal loss. The defining clinicopathological hallmarks of the disease are deposits of amyloid precursor protein (APP)-derived amyloid-β peptides (Aβ) in the brain parenchyma, and intracellular aggregates of truncated and hyperphosphorylated tau protein in neurofibrillary tangles (NFT). At the cellular and molecular levels, many intertwined pathological mechanisms that relate Aβ and tau pathology with a transcription factor p53 have been revealed. p53 is activated in response to various stressors that threaten genomic stability. Depending on damage severity, it promotes neuronal death or survival, predomimantly via transcription-dependent mechanisms that affect expression of apoptosis-related target genes. Levels of p53 are enhanced in the AD brain and maintain sustained tau hyperphosphorylation, whereas intracellular Aβ directly contributes to p53 pool and promotes downstream p53 effects. The review summarizes the role of p53 in neuronal function, discusses the interactions of p53, tau, and Aβ in the normal brain and during the progression of AD pathology, and considers the impact of the most prominent hereditary risk factors of AD on p53/tau/Aβ interactions. A better understanding of this intricate interplay would provide deeper insight into AD pathology and might offer some novel therapeutic targets for the improvement of treatment options. In this regard, drugs and natural compounds targeting p53 pathway are of growing interest in neuroprotection as they may represent promising therapeutic approaches in the prevention of oxidative stress-dependent pathological processes underlying AD. Keywords: p53, Aβ, tau, oxidative stress, neuronal apoptosis, Alzheimer's disease

Association of oxidative stress with carcinogenesis is well known, but not understood well, as is pathophysiology of oxidative stress generated during different types of anti-cancer treatments. Moreover, recent findings indicate that cancer associated lipid peroxidation might eventually help defending adjacent nonmalignant cells from cancer invasion. Therefore, untargeted metabolomics studies designed for advanced translational and clinical studies are needed to understand the existing paradoxes in oncology, including those related to controversial usage of antioxidants aiming to prevent or treat cancer. In this short review we have tried to put emphasis on the importance of pathophysiology of oxidative stress and lipid peroxidation in cancer development in relation to metabolic adaptation of particular types of cancer allowing us to conclude that adaptation to oxidative stress is one of the main driving forces of cancer pathophysiology. With the help of metabolomics many novel findings are being achieved thus encouraging further scientific breakthroughs. Combined with targeted qualitative and quantitative methods, especially immunochemistry, further research might reveal bio-signatures of individual patients and respective malignant diseases, leading to individualized treatment approach, according to the concepts of modern integrative medicine. Keywords: Carcinogenesis, Cancer, Oxidative stress, Lipid peroxidation, 4-hydroxynonenal, Glutathione, Metabolomics, Immunochemistry, Biomarkers, Omics science

For the preparation of Gamma Knife (GK) treatments of brain tumours, a head CT examination is necessary when using a new CT-based convolution dose calculation algorithm included in Leksell Gamma Plan software (version 10.1.1). The purpose of this study was to measure the organ doses in paediatric anthropomorphic phantoms during a head CT scan and compare them with the measured GK treatment doses. CT doses were measured with radiophotoluminescence (RPL) dosimeters and compared with results of MC simulations. Measured doses for organs within the CT scan volume were comparable for both phantoms. The highest organ CT dose was evaluated for eyes: 27.6 ± 0.2 mGy and 27.3 ± 0.6 mGy for 5 and 10 year old phantom respectively. Doses for organs not included in the scan volume decreased with distance from the scan volume and were on average 3.5 times higher for the 5 year old phantom compared with the 10 year old phantom. Comparison of measured and MC dose values showed good agreement. For the 10 year old phantom, CT doses were 22%, 6%, 5% and 3% of the GK dose for thyroid, lungs, eyes and breasts respectively. Enhancement of the total organ doses for the whole GK treatment due to CT scanning is not negligible but nevertheless, the use of the new convolution algorithm seems reasonable.

The study elucidated the association between the COMT Val108/158Met polymorphism and smoking in patients with schizophrenia, patients with alcohol dependence and healthy control subjects. The stepwise logistic regression (odds ratio (OR)=1.56, 95% confidence interval (CI)=1.10–2.23, P=0.014) and the χ2 test (P=0.008) revealed that the COMT Val/Val genotype was significantly associated with smoking in healthy male subjects. Although the hypothesis of the study was that COMT Val108/158Met genotypes will be significantly associated with smoking in schizophrenia and alcohol dependence, our study showed for the first time the lack of significant association between smoking and COMT Val108/158Met polymorphism in schizophrenia, and confirmed no association between smoking and COMT Val108/158Met in alcoholism.

Obesity in children and adolescents is a worldwide health problem, characterized by various somatic, psychosocial and psychiatric complications, and is often associated with adult obesity and related complications. Brain-derived neurotrophic factor (BDNF) is a neurotrophin with important roles in feeding behavior, food intake regulation, energy metabolism and weight control. A common polymorphism of the BDNF genotype (Val66Met) has been associated with various forms of eating disorders, alterations in body mass index (BMI) values and obesity in adult populations. The aim of this study was to determine the association between the gene variants of the BDNF Val66Met polymorphism and obesity in 300 healthy Caucasian children and adolescents of the same ethnic background of Croatian origin, subdivided according to the BMI percentile, but without any form of eating disorders. The frequency of the Met/Met, Met/Val and Val/Val genotypes, Met and Val alleles, and Met carriers (the combined Met/Met and Met/Val genotypes versus the homozygous Val/Val genotype) differed significantly between underweight, normal weight, overweight and obese children, and the presence of one or two Met alleles contributed to this significant effect. These results showed for the first time the significant association between the presence of one or two Met alleles and obesity in ethnically homogenous groups of healthy Caucasian children and adolescents. These data confirmed the major role of BDNF in energy metabolism, food regulation and BMI.