BACKGROUND: Spatial navigation deficits are early symptoms of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is the most important genetic risk factor for AD. This study investigated effects of APOE genotype on spatial navigation in biomarker-defined individuals with amnestic mild cognitive impairment (aMCI) and associations of AD biomarkers and atrophy of AD-related brain regions with spatial navigation. METHODS: 107 participants, cognitively normal older adults (CN, n = 48) and aMCI individuals stratified into AD aMCI (n = 28) and non-AD aMCI (n = 31) groups, underwent cognitive assessment, brain MRI, and spatial navigation assessment using the Virtual Supermarket Test with egocentric and allocentric tasks and a self-report questionnaire. Cerebrospinal fluid (CSF) biomarkers (amyloid-β1-42, phosphorylated tau181 and total tau) and amyloid PET imaging were assessed in aMCI participants. RESULTS: AD aMCI participants had the highest prevalence of APOE ε4 carriers and worst allocentric navigation. CSF levels of AD biomarkers and atrophy in AD-related brain regions were associated with worse allocentric navigation. Between-group differences in spatial navigation and associations with AD biomarkers and regional brain atrophy were not influenced by APOE genotype. Self-reported navigation ability was similar across groups and unrelated to spatial navigation performance. CONCLUSIONS: These findings suggest that allocentric navigation deficits in aMCI individuals are predominantly driven by AD pathology, independent of APOE genotype. This highlights the role of AD pathology as measured by biomarkers, rather than genetic status, as a major factor in navigational impairment in aMCI, and emphasizes the assessment of spatial navigation as a valuable tool for early detection of AD.

• MeSH
• Alzheimer Disease * genetics   cerebrospinal fluid   diagnostic imaging   complications   physiopathology   pathology   MeSH
• Amyloid beta-Peptides cerebrospinal fluid   MeSH
• Apolipoprotein E4 * genetics   MeSH
• Apolipoproteins E * genetics   MeSH
• Atrophy MeSH
• Biomarkers cerebrospinal fluid   MeSH
• Genotype MeSH
• Cognitive Dysfunction * genetics   cerebrospinal fluid   diagnostic imaging   physiopathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Brain pathology   diagnostic imaging   MeSH
• Neuropsychological Tests MeSH
• Peptide Fragments cerebrospinal fluid   MeSH
• Positron-Emission Tomography MeSH
• Spatial Navigation * physiology   MeSH
• tau Proteins cerebrospinal fluid   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Hepatitis B (VHB) and C (VHC) are significant global public health issues, particularly for certain risk groups. In the Czech Republic, individuals who inject drugs (IDUs), incarcerated people, and those with high-risk sexual behaviours are especially susceptible. This research investigates the epidemiology, risk factors, and effects of both diseases on these groups. It analyzes the incidence of VHB and VHC in Czechia over the last twenty years in the post-vaccine era, compares their occurrence, and identifies factors influencing their rates. A total of 28,160 VHB and VHC cases reported in the Czech Republic from 2000 to 2021 were analyzed, categorized into acute and chronic forms. Specifically, there were 8,762 cases of VHB and 19,398 cases of VHC. The research employed quantitative methods and descriptive data analysis. A spatial visualization of disease occurrence per 100,000 inhabitants in Czech districts was conducted for the years 2000, 2010, and 2020 to compare disease development and the risk group of IDUs across districts. For VHB, transmission primarily occurs through intravenous drug use or risky sexual behaviour, with IDUs, men who have sex with men, and promiscuous individuals being the most at-risk groups. For VHC, sexual transmission is less common, with IDUs being the most at-risk group. Many VHC cases have been recorded in prisons, often due to shared razors or amateur tattooing and piercing. This discovery underscores the necessity for focused interventions and thorough strategies to address both diseases in high-risk communities.

• MeSH
• Adult MeSH
• Hepatitis B * epidemiology   MeSH
• Hepatitis C * epidemiology   MeSH
• Incidence MeSH
• Substance Abuse, Intravenous epidemiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Risk-Taking MeSH
• Risk Factors MeSH
• Prisoners statistics & numerical data   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

Even though cognitive testing in animals is widespread, many issues remain open - for example the influence of behavioural parameters on cognitive performance, stability of cognitive performance upon repeated testing, or comparability of cognitive variables across different tasks (i.e. cross-contextual consistency). In this study we tested thirty six male Long Evans laboratory rats and assessed their cognitive performance in two standard tasks of spatial navigation - Active allothetic place avoidance and Morris water maze test. Using multivariate analyses, we detected different aspects of cognition within these complex tasks (the ability to learn fast, cognitive flexibility, general ability to solve a task successfully). We found that consistency of cognitive performance in these two tasks (estimates of cognitive repeatability) differed substantially, reflecting differences in the experimental procedures. Moreover, we inspected cognitive performance of the animals in more detail by creating a correlation matrix of factors derived from these procedures. Nevertheless, we found no correlation and therefore no indication of a general cognitive ability in spatial navigation using these two tasks. In addition, we found no link between personality and cognition when correlating cognitive performance of the animals with parameters from personality tests, which were derived from a previous study conducted on the same animals. These findings highlight a task-dependent nature of cognitive performance in these two tasks of spatial navigation and suggest that general cognitive ability in spatial navigation may not be reliably inferred from these two tasks, while also indicating no evident link between cognition and personality in this context.

• MeSH
• Maze Learning physiology   MeSH
• Behavior, Animal physiology   MeSH
• Cognition * physiology   MeSH
• Rats MeSH
• Personality physiology   MeSH
• Rats, Long-Evans MeSH
• Spatial Navigation * physiology   MeSH
• Avoidance Learning physiology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Alzheimer's disease (AD), a leading cause of dementia worldwide, is a multifactorial neurodegenerative disorder characterized by amyloid-beta plaques, tauopathy, neuronal loss, neuro-inflammation, brain atrophy, and cognitive deficits. AD manifests as familial early-onset (FAD) with specific gene mutations or sporadic late-onset (LOAD) caused by various genetic and environmental factors. Numerous transgenic rodent models have been developed to understand AD pathology development and progression. The TgF344-AD rat model is a double transgenic model that carries two human gene mutations: APP with the Swedish mutation and PSEN-1 with delta exon 9 mutations. This model exhibits a complete repertoire of AD pathology in an age-dependent manner. This review summarizes multidisciplinary research insights gained from studying TgF344-AD rats in the context of AD pathology. We explore neuropathological findings; electrophysiological assessments revealing disrupted synaptic transmission, reduced spatial coding, network-level dysfunctions, and altered sleep architecture; behavioral studies highlighting impaired spatial memory; alterations in excitatory-inhibitory systems; and molecular and physiological changes in TgF344-AD rats emphasizing their age-related effects. Additionally, the impact of various interventions studied in the model is compiled, underscoring their role in bridging gaps in understanding AD pathogenesis. The TgF344-AD rat model offers significant potential in identifying biomarkers for early detection and therapeutic interventions, providing a robust platform for advancing translational AD research. Key words Alzheimer's disease, Transgenic AD models, TgF344-AD rats, Spatial coding.

• MeSH
• Alzheimer Disease * genetics   pathology   metabolism   MeSH
• Amyloid beta-Protein Precursor genetics   metabolism   MeSH
• Rats MeSH
• Humans MeSH
• Disease Models, Animal * MeSH
• Brain pathology   metabolism   MeSH
• Rats, Inbred F344 MeSH
• Rats, Transgenic * MeSH
• Presenilin-1 genetics   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The disease currently known as frontotemporal dementia (FTD) has undergone a complex evolution from its first description by Arnold Pick and later by Alois Alzheimer, through the first clinicopathological criteria introduced by David Neary and David Mann, to its current nomenclatural perception as a complex clinicopathological entity. Currently, Frontotemporal lobar degeneration is viewed as a heterogeneous syndrome caused by progressive degeneration of the frontal and temporal lobes of the brain. Clinically, it can manifest as three syndromes of frontotemporal dementia (behavioral variant of FTD, progressive non-fluent aphasia and semantic dementia) but also as so-called "overlap" syndromes involving corticobasal degeneration and progressive supranuclear palsy. Its prevalence is about 10 % among all dementias and 40 % among dementias with onset between 45 and 65 years of age. The clinical manifestation of the different subtypes varies, the common denominator being behavioral disturbances and impairment of fatic, gnostic and executive functions. Mnestic and visuo-spatial functions, although preserved for a relatively long time, are superimposed by personality disintegration, fatic, gnostic and executive dysfunction. Compared with Alzheimer's disease, it generally has an earlier age of onset, a more rapid course and more devastating impairment of individual cognitive domains. FTD has a heritability of more than 30 % according to current knowledge. The main genes involved are MAPT, C9orf72 and GRN. More rarely affected genes are VCP, TDP-43, FUS and CHMP2B. In our article, we focus on the genetics of FTD and the clinic-genetic-pathological correlations. We also aim to provide a plastic picture of how individual mutations affect the molecular mechanisms of neurodegeneration.

• MeSH
• Epigenesis, Genetic genetics   MeSH
• Frontotemporal Dementia * diagnosis   genetics   classification   MeSH
• Genetic Testing methods   MeSH
• Humans MeSH
• Primary Progressive Nonfluent Aphasia diagnosis   genetics   MeSH
• Progranulins genetics   MeSH
• tau Proteins genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Animals and humans receive the most critical information from parts of the environment that are immediately inaccessible and highly dynamic. The brain must effectively process potential interactions between elements in such an environment to make appropriate decisions in critical situations. We trained male Long-Evans rats to discriminate static and dynamic spatial stimuli and to generalize novel dynamic spatial stimuli displayed on an inaccessible computer screen. We provide behavioral evidence indicating that rats encode dynamic visuospatial situations by constructing internal static representations that capture meaningful future interactions between objects. These observations support previous findings in humans that such internal static representations can encapsulate relevant spatiotemporal information of dynamic environments. This mechanism would allow animals and humans to process complex time-changing situations neatly.

• MeSH
• Behavior, Animal physiology   MeSH
• Rats MeSH
• Rats, Long-Evans * MeSH
• Space Perception * physiology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Children in agricultural areas are exposed to organophosphate (OP) and pyrethroid (PYR) insecticides. This explorative study investigated child exposure to OPs and PYRs, comparing temporal and spatial exposure variability within and among urine, wristbands, and dust samples. METHODS: During spraying season 2018, 38 South African children in two agricultural areas (Grabouw/Hex River Valley) and settings (farm/village) participated in a seven-day study. Child urine and household dust samples were collected on days 1 and 7. Children and their guardians were wearing silicone wristbands for seven days. Intraclass correlation coefficients (ICCs) evaluated temporal agreements between repeated urine and dust samples, Spearman rank correlations (Rs) evaluated the correlations among matrices, and linear mixed-effect models investigated spatial exposure predictors. A risk assessment was performed using reverse dosimetry. RESULTS: Eighteen OPs/PYRs were targeted in urine, wristbands, and dust. Levels of chlorpyrifos in dust (ICC = 0.92) and diethylphosphate biomarker in urine (ICC = 0.42) showed strong and moderate temporal agreement between day 1 and day 7, respectively. Weak agreements were observed for all others. There was mostly a weak correlation among the three matrices (Rs = -0.12 to 0.35), except for chlorpyrifos in dust and its biomarker 3,5,6-trichloro-2-pyridinol in urine (Rs = 0.44). No differences in exposure levels between living locations were observed. However, 21% of the urine biomarker levels exceeded the health-risk threshold for OP exposure. CONCLUSIONS: Observed high short-term variability in exposure levels during spraying season highlights the need for repeated sampling. The weak correlation between the exposure matrices points to different environmental and behavioral exposure pathways. Exceeding risk thresholds for OP should be further investigated.

• Publication type
• Journal Article MeSH

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a common adult leukemia characterized by the accumulation of neoplastic mature B cells in blood, bone marrow, lymph nodes, and spleen. The disease biology remains unresolved in many aspects, including the processes underlying the disease progression and relapses. However, studying CLL in vitro poses a considerable challenge due to its complexity and dependency on the microenvironment. Several approaches are utilized to overcome this issue, such as co-culture of CLL cells with other cell types, supplementing culture media with growth factors, or setting up a three-dimensional (3D) culture. Previous studies have shown that 3D cultures, compared to conventional ones, can lead to enhanced cell survival and altered gene expression. 3D cultures can also give valuable information while testing treatment response in vitro since they mimic the cell spatial organization more accurately than conventional culture. METHODS: In our study, we investigated the behavior of CLL cells in two types of material: (i) solid porous collagen scaffolds and (ii) gel composed of carboxymethyl cellulose and polyethylene glycol (CMC-PEG). We studied CLL cells' distribution, morphology, and viability in these materials by a transmitted-light and confocal microscopy. We also measured the metabolic activity of cultured cells. Additionally, the expression levels of MYC, VCAM1, MCL1, CXCR4, and CCL4 genes in CLL cells were studied by qPCR to observe whether our novel culture approaches lead to increased adhesion, lower apoptotic rates, or activation of cell signaling in relation to the enhanced contact with co-cultured cells. RESULTS: Both materials were biocompatible, translucent, and permeable, as assessed by metabolic assays, cell staining, and microscopy. While collagen scaffolds featured easy manipulation, washability, transferability, and biodegradability, CMC-PEG was advantageous for its easy preparation process and low variability in the number of accommodated cells. Both materials promoted cell-to-cell and cell-to-matrix interactions due to the scaffold structure and generation of cell aggregates. The metabolic activity of CLL cells cultured in CMC-PEG gel was similar to or higher than in conventional culture. Compared to the conventional culture, there was (i) a lower expression of VCAM1 in both materials, (ii) a higher expression of CCL4 in collagen scaffolds, and (iii) a lower expression of CXCR4 and MCL1 (transcript variant 2) in collagen scaffolds, while it was higher in a CMC-PEG gel. Hence, culture in the material can suppress the expression of a pro-apoptotic gene (MCL1 in collagen scaffolds) or replicate certain gene expression patterns attributed to CLL cells in lymphoid organs (low CXCR4, high CCL4 in collagen scaffolds) or blood (high CXCR4 in CMC-PEG).

• MeSH
• Cell Culture Techniques methods   MeSH
• Leukemia, Lymphocytic, Chronic, B-Cell * pathology   metabolism   MeSH
• Gels chemistry   MeSH
• Collagen * chemistry   pharmacology   MeSH
• Humans MeSH
• Polyethylene Glycols * chemistry   MeSH
• Receptors, CXCR4 metabolism   MeSH
• Carboxymethylcellulose Sodium * chemistry   pharmacology   MeSH
• Cell Culture Techniques, Three Dimensional methods   MeSH
• Tissue Scaffolds * chemistry   MeSH
• Cell Survival drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Given the key roles of the cerebellum in motor, cognitive, and affective operations and given the decline of brain functions with aging, cerebellar circuitry is attracting the attention of the scientific community. The cerebellum plays a key role in timing aspects of both motor and cognitive operations, including for complex tasks such as spatial navigation. Anatomically, the cerebellum is connected with the basal ganglia via disynaptic loops, and it receives inputs from nearly every region in the cerebral cortex. The current leading hypothesis is that the cerebellum builds internal models and facilitates automatic behaviors through multiple interactions with the cerebral cortex, basal ganglia and spinal cord. The cerebellum undergoes structural and functional changes with aging, being involved in mobility frailty and related cognitive impairment as observed in the physio-cognitive decline syndrome (PCDS) affecting older, functionally-preserved adults who show slowness and/or weakness. Reductions in cerebellar volume accompany aging and are at least correlated with cognitive decline. There is a strongly negative correlation between cerebellar volume and age in cross-sectional studies, often mirrored by a reduced performance in motor tasks. Still, predictive motor timing scores remain stable over various age groups despite marked cerebellar atrophy. The cerebello-frontal network could play a significant role in processing speed and impaired cerebellar function due to aging might be compensated by increasing frontal activity to optimize processing speed in the elderly. For cognitive operations, decreased functional connectivity of the default mode network (DMN) is correlated with lower performances. Neuroimaging studies highlight that the cerebellum might be involved in the cognitive decline occurring in Alzheimer's disease (AD), independently of contributions of the cerebral cortex. Grey matter volume loss in AD is distinct from that seen in normal aging, occurring initially in cerebellar posterior lobe regions, and is associated with neuronal, synaptic and beta-amyloid neuropathology. Regarding depression, structural imaging studies have identified a relationship between depressive symptoms and cerebellar gray matter volume. In particular, major depressive disorder (MDD) and higher depressive symptom burden are associated with smaller gray matter volumes in the total cerebellum as well as the posterior cerebellum, vermis, and posterior Crus I. From the genetic/epigenetic standpoint, prominent DNA methylation changes in the cerebellum with aging are both in the form of hypo- and hyper-methylation, and the presumably increased/decreased expression of certain genes might impact on motor coordination. Training influences motor skills and lifelong practice might contribute to structural maintenance of the cerebellum in old age, reducing loss of grey matter volume and therefore contributing to the maintenance of cerebellar reserve. Non-invasive cerebellar stimulation techniques are increasingly being applied to enhance cerebellar functions related to motor, cognitive, and affective operations. They might enhance cerebellar reserve in the elderly. In conclusion, macroscopic and microscopic changes occur in the cerebellum during the lifespan, with changes in structural and functional connectivity with both the cerebral cortex and basal ganglia. With the aging of the population and the impact of aging on quality of life, the panel of experts considers that there is a huge need to clarify how the effects of aging on the cerebellar circuitry modify specific motor, cognitive, and affective operations both in normal subjects and in brain disorders such as AD or MDD, with the goal of preventing symptoms or improving the motor, cognitive, and affective symptoms.

• MeSH
• Depressive Disorder, Major * MeSH
• Adult MeSH
• Consensus MeSH
• Quality of Life MeSH
• Humans MeSH
• Magnetic Resonance Imaging methods   MeSH
• Cerebellum pathology   MeSH
• Cross-Sectional Studies MeSH
• Aged MeSH
• Aging MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

To understand the environmental determinants of physical activity (PA), precise spatial localization is crucial. This cross-sectional study focuses on the spatiotemporal distribution of PA among Czech adolescents (n = 171) using Global Positioning System loggers and accelerometers. The results showed that adolescents spent most of their time in sedentary behavior, with 57.2% and 58.5% of monitored time at home and school, respectively. The park and playground had the lowest proportion of sedentary behavior but also the lowest amount of moderate to vigorous PA (MVPA). However, when considering the time spent in each domain, the highest proportion of MVPA was seen in publicly accessible playgrounds (13.3% of the time). Chi-square analysis showed that the relative distribution of different PA intensities did not differ across spatial domains. Based on these results, the authors propose 2 key strategies for increasing MVPA in adolescents: Increase the time spent in activity-supportive environments, such as parks and playgrounds, and design techniques to increase MVPA at home and school settings.

• MeSH
• Accelerometry * MeSH
• Residence Characteristics MeSH
• Adolescent Behavior psychology   MeSH
• Exercise * MeSH
• Transportation methods   MeSH
• Geographic Information Systems * MeSH
• Play and Playthings MeSH
• Humans MeSH
• Adolescent MeSH
• Cross-Sectional Studies MeSH
• Sedentary Behavior * MeSH
• Schools MeSH
• Parks, Recreational MeSH
• Environment Design MeSH
• Check Tag
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH