lecture A1-I Evolving Needs in Pathology Education

The Joint Programming Initiative was originally created as a Member States-led initiative in Europe. It aims to address “grand challenges” to the EU and global society by coordinating national research pro-grammes to increase the impact and effectiveness of research efforts. Neurodegenerative diseases (ND) and dementia in particular, represent one of the world’s most pressing medical and societal challenges and the solutions are likely beyond the scope and resources of any single country. JPND aims to find causes, develop cures and identify better ways of caring for people with neurodegenerative diseases. Although JPND originally a European initiative, it global, 30 countries JPND medicine life each longer life expectancy without is our brain health: neurodegenerative dementia one third of the aging populations 85 years of age, mental health disorders including addictions 12% entire and neurodevelopmental disorders 15% European global mea-surements We analyzed changes in dendritic morphology and spine density on associative layer IIIc cortical projecting neurons and large layer V subcortical projecting pyramidal neurons to establish age-related changes within microcircuitries of the human prefrontal cortex (Brodmann area 9). Postmortem human brain tissue of adults was processed using the rapid Golgi method in two age groups: 38 – 64 years (n = 8) and 72 – 91 years, (n = 7). Neuropathological findings were unre-markable in all analyzed brain specimens. From each layer, the basal dendritic arbor and side dendritic branches from 10 – 15 well-impregnated pyramidal neurons per subject were three-dimensionally recon-structed using Neurolucida software. Soma size, total dendritic length, total segment number, individual segment length and spine density were quantitatively analyzed. Regarding layer V neurons, no significant differences were observed between adults and the elderly, either for dendritic morphology or for the spine density. The interindividual differences in the elderly group were however higher than in adults. Regarding associative layer IIIc pyramidal neurons, the mean values of spine density, on both side branches and basal dendrites, were 20–25% lower in the elderly than in adults (p = 0.07). In two aged cases the spine density was around mean level of adult and in the remaining aged subjects values were lower than in all adult subjects. These data show that the dendritic morphology and synaptic connectivity of the major classes of principal neurons in higher order associative areas are largely preserved in aging, while the connectivity of associative cortico-cortical layers is more prone to regression. is accumulating that in cardiometabolic diseases changes in glycosylation are not only biomarkers, but functional effectors that actively participate in disease is a kinase involved in DNA damage response (DDR), regulation of response to oxidative stress, autophagy and mitophagy. Mutations in the ATM gene in humans result in ataxia-telangiectasia disease (A-T) characterized by a variety of symptoms with neurodegeneration and premature ageing among them. In this study, we have focused on the process of senescence in A-T cells. Given that brain is one of the most affected organs in A-T, we turned our attention to neural progenitor cells (NPCs) derived from A-T reprogrammed fibroblasts. We observed that A-T NPCs obtained through neural differentiation of iPSCs in 5% oxygen possessed some features of senescence including increased activity of SA-β-gal and secretion of IL6 and IL8 in comparison to control NPCs. This phenotype of A-T NPC was accompanied by elevated oxidative stress resulting in 4-HNE protein modification. A-T NPCs exhibited symptoms of impaired autophagy and mitophagy with lack of response to chloroquine treatment. Additional sources of oxidative stress like increased oxygen concentration and re-spectively aggravated the phenotype of senescence and the process of mitophagy. The by transcriptional analysis of several NPCs reacted to the treatment. We conclude that oxidative stress may be responsible for the phenotype of senescence and impairment of autophagy in A-T NPCs. Our results point to senescent A-T cells as a potential therapeutic target in this disease. Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is increasingly recognised as an important precursor disease state of alpha-synucle-inopathies. This parasomnia is characterized by a history of recurrent nocturnal dream enactment behaviour, loss of skeletal muscle atonia, and increased pha-sic muscle activity during REM sleep. Neuroimaging studies of striatal dopamine transporter uptake tracer signalling suggest increasing dopaminergic deficit across the continuum of the alpha-synucleinopathies, with early sleep dysfunction suggestive of early cau-date dysfunction. We will discuss the implication of utilising this window of the opportunity in the disease process to intervene, and to potentially abort, further development of neurodegenerative process. The changes in sleep-wake process over the lifespan are well established. Epidemiological data show that 50–65% of older adults report impaired sleep quality (SQ). This impairment can rather be attributed to health status and various psychosocial factors than to the aging process per se. The results of our previous study showed the expectedly impaired SQ in nursing home residents, best predicted by self-perceived health and functional ability. The aims of the current study were to examine SQ of older adults living in different arrangements and to examine factors contributing to their SQ. Participants were 334 older adults (73% fe-males) from Zagreb. Half were the NH residents and half OH residents. Their dominant age was 78 years, varying between 69 and 100 years. All were ambula-tory, without diagnosis of dementia. Trained inter-viewers collected data individually, through structured interviews in nursing homes and in gerontology center. Questionnaire comprised of general questions, questions to assess self-perceived health and standardized scales to measure social participation, functional ability, life satisfaction, and SQ. SQ was assessed by the Pittsburgh Sleep Quality Index (PSQI). Our results showed PSQI score greater than 5, indicating poor SQ in 60% of older adults. In NH residents the percentage was higher than in OH residents (71% vs. 50%, p < .001). Selected set of predictors explained small but significant proportion of variance in PSQI score and 7 domains. Predictors explained the highest proportion of variance in the use of sleep medication (22.6%) and subjective SQ (21%). Expectedly, women had poorer total PSQI, longer sleep PSQI, sleep functional predicted shorter sleep latency daytime functioning. There is a need to identify reliable predictors of mild cognitive impairment (MCI) and dementia due to Alzheimer’s disease (AD) in normal elderly people to en able timely intervention. The Mini‐Mental State Examination (MMSE) is the best‐known and the most often used short screening tool for providing an overall measure of cognitive impairment in clinical, research, and community settings. However, MMSE is not actually a mental status examination designed to detect dementia as it was originally developed to dif-ferentiate organic from functional psychiatric patients. The MMSE has low sensitivity in detecting dementia as as poor specificity, and low negative (NPV), and positive predictive values (PPV), in ear-ly-stage A recent systematic review not role hidden-goal task (HGT) in the human subject target navigational imaged positive cells counted for each Results correlated to lesion the composition of unknown substances on a molecular basis. Methods. The study included 80 age matched subjects from the Reference Center for Glaucoma, UHC “Sestre milosrdnice”, divided into two groups 1) 40 glaucoma patients and 2) a control group comprising 40 patients with cataracts. For the purpose of molecular analysis, all aqueous humor samples were collected at the start of the glaucoma or cataract surgery. FTIR spectra of the samples dried on transparent silicon windows were obtained in a transmission mode, followed by principal component analysis (PCA) modeling of the recorded spectra. Results. FTIR spectra with vibrational modes specific to glaucoma and cataract were examined. In the chemomet-ric analysis of the spectroscopic data, all 40 (100%) of the cataract eyes were correctly diagnosed as the cataract group and all 40 (100%) glaucoma eyes were diagnosed as the glaucoma group, demonstrating a distinct correlation between studied eye diseases and their FTIR spectra. conclusions. FTIR spectroscopy combined with the chemometrics has proven to be a promising method for molecular analysis of the aqueous humor as the differentiation between eyes with cataract and glaucoma has been achieved. Separation of the two groups of FTIR spectra in the created PCA statistical model also indicates that this method may have a promising role in the discovery of glaucoma biomarkers. possible and have piloted a project to collect DNA and phenotype data of ADR cases using international standardized phenotypic criteria. Patients with ADRs (N=860) and controls were genotyped for pharmacogenes. Univariate and multi-variate prediction of ADRs were carried by means of binary logistic regression in order to identify novel associations or validate findings in cohorts of patients with well-defined phenotypes. Results. We developed a comprehensive knowledge repository of actionable pharmacogenes. HALMED developed a method for informing physicians or pharmacists and their patients about a possible pharmacogenetic involvement in the ADR pathogenesis. An anonymized copy of the test results has been used for the interpretation of possible signals. Several publications from this project have been published, depending on the medication in question (warfarin, statins, clopidogrel, methotrexate, AEDs, psych