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Currently available human stress monitoring devices are either very inaccurate or rely on a strictly controlled laboratory environment. In this paper, we present the novel concept of a practical portable device for long-term monitoring of human stress in natural environment and an algorithm for calculation of the stress phenomenon. The concept envisages two synchronized blocks measuring a wider range of physiological parameters. One device will be placed on the forearm or fingers of the non-dominant hand, the other on the chest.

Samples taken from the human brain (Globus Pallidus) have been investigated by physical techniques such as light microscopy, scanning electron microscopy, transmission electron microscopy, Mössbauer spectroscopy and SQUID magnetometry. SEM-EDX/TEM investigation reveals multielemental composition of hematite and magnetite nanocrystals with sizes ranging from 40 nm to 100 nm and hematite microcrystals from 3 μm to 7 μm. Room temperature Mössbauer spectra show quadrupole doublets assigning to hematite and ferrihydrite. SQUID measurements of temperature dependence of the mass magnetic susceptibility between T = 2 – 300 K at DC field B 0 = 0.1 T, the field dependence of the mass magnetization taken at the fixed temperature T 0 = 2.0 and 4.6 K and the zero-field cooled and field cooled magnetization experiments (ZFCM/FCM) confirm a presence of ferrimagnetic phases such as maghemite and/or magnetite with hysteresis loops surviving until the room temperature. Differences between these measurements from the point of view of iron oxides detected can indicate important processes in human brain and interactions between ferritin as a physiological source of iron and surrounding environment.

Iron is very important element for functioning of the brain. Its concentration changes with aging the brain or during disease. The aim of our work was the histological examination of content of ferritin and free iron (unbound) in brain cortex in association with Aβ plaques from their earliest stages of accumulation in amyloid plaque forming APP/PS1 transgenic mice. Light microscopy revealed the onset of plaques formation at 8-monthage. Detectable traces of free iron and no ferritin were found around plaques at this age, while the rate of their accumulation in and around Aβ plaques was elevated at 13 months of age. Ferritin accumulated mainly on the edge of Aβ plaques, while the smaller amount of free iron was observed in the plaque-free tissue, as well as in and around Aβ plaques. We conclude that free iron and ferritin accumulation follows the amyloid plaques formation. Quantification of cortical iron and ferritin content can be an important marker in the diagnosis of Alzheimer’s disease.

BackgroundAlzheimer’s disease (AD) is the most common neurodegenerative disease and type 2 diabetes (T2D) plays an important role in conferring the risk for AD. Although AD and T2D share common features, the common molecular mechanisms underlying these two diseases remain elusive.MethodsMice with different AD- and/or tauopathy-linked genetic backgrounds (APPswe/PS1dE9, Tau P301L and APPswe/PS1dE9/Tau P301L) were fed for 6 months with standard diet or typical Western diet (TWD). After behavioral and metabolic assessments of the mice, the effects of TWD on global gene expression as well as dystrophic neurite and microglia pathology were elucidated. Consequently, mechanistic aspects related to autophagy, cell survival, phagocytic uptake as well as Trem2/Dap12 signaling pathway, were assessed in microglia upon modulation of PI3K-Akt signaling. To evaluate whether the mouse model-derived results translate to human patients, the effects of diabetic phenotype on microglial pathology were assessed in cortical biopsies of idiopathic normal pressure hydrocephalus (iNPH) patients encompassing β-amyloid pathology.ResultsTWD led to obesity and diabetic phenotype in all mice regardless of the genetic background. TWD also exacerbated memory and learning impairment in APPswe/PS1dE9 and Tau P301L mice. Gene co-expression network analysis revealed impaired microglial responses to AD-related pathologies in APPswe/PS1dE9 and APPswe/PS1dE9/Tau P301L mice upon TWD, pointing specifically towards aberrant microglial functionality due to altered downstream signaling of Trem2 and PI3K-Akt. Accordingly, fewer microglia, which did not show morphological changes, and increased number of dystrophic neurites around β-amyloid plaques were discovered in the hippocampus of TWD mice. Mechanistic studies in mouse microglia revealed that interference of PI3K-Akt signaling significantly decreased phagocytic uptake and proinflammatory response. Moreover, increased activity of Syk-kinase upon ligand-induced activation of Trem2/Dap12 signaling was detected. Finally, characterization of microglial pathology in cortical biopsies of iNPH patients revealed a significant decrease in the number of microglia per β-amyloid plaque in obese individuals with concomitant T2D as compared to both normal weight and obese individuals without T2D.ConclusionsCollectively, these results suggest that diabetic phenotype in mice and humans mechanistically associates with abnormally reduced microglial responses to β-amyloid pathology and further suggest that AD and T2D share overlapping pathomechanisms, likely involving altered immune function in the brain.

Type 2 diabetes (T2D) increases the risk of Alzheimer’s disease (AD). Even though these two diseases share common molecular pathways, the mechanisms remain elusive. To shed light into these mechanisms, mice with different AD- and/or tauopathy-linked genetic backgrounds were utilized; APPswe/PS1dE9 (A+Tw), Tau P301L (AwT+), and APPswe/PS1dE9/Tau P301L (A+T+). Feeding these mice with typical Western diet (TWD) led to obesity and diabetic phenotype as compared to respective mice with a standard diet. TWD also exacerbated memory and learning impairment in A+Tw and AwT+, but not in A+T+ mice. Furthermore, RNA sequencing of mouse hippocampal samples revealed altered responses to AD-related pathologies in A+Tw and A+T+ mice upon TWD, pointing specifically towards aberrant microglial functionality and PI3K-Akt signaling. Accordingly, fewer microglia alongside an increased number of dystrophic neurites around β-amyloid plaques, and impaired PI3K-Akt signaling, were discovered in the hippocampus of TWD mice. Mechanistic elucidation revealed that disruption of the PI3K-Akt signaling pathway by pharmacological or genetic approaches significantly decreased the phagocytic uptake and proinflammatory response as well as increased the activity of Syk-kinase upon ligand-induced activation of Trem2/Dap12 signaling in mouse microglia. Finally, characterization of microglial pathology in cortical biopsies of idiopathic normal pressure hydrocephalus (iNPH) patients harboring β-amyloid plaques revealed a significant decrease in the number of microglia per β-amyloid plaque in obese iNPH patients with T2D as compared to both normal weight and obese iNPH patients without T2D. Collectively, these results suggest that the peripheral diabetic phenotype in mice and humans associates with reduced microglial response to β-amyloid pathology.

V této práci se popisují naše počáteční experimenty ve vývoji „on-line“ senzoru na monitoring koncentrace citrátu sodného (Na3C6H2O7) v mimo mozkovém proudění krve v průběhu hemodialýzy. Přesný a rychlý monitoring by umožnil regulaci koncentrace citrátu a návrat do krevního řečiště těla v jeho původních hodnotách, tím pacienta významně méně zatíženého než v přítomnosti. Nedávno jsme se soustředili na stanovení koncentrace měřením elektrické impedance a odrazivosti ve zkoumané krvi. Našim cílem je zkoumat trendy vlivu těchto signálů na koncentraci a vyvinout vhodnou metodiku, která může být použita později v senzorech. Částečně začínáme pracovat také na citlivosti metodiky, přičemž bychom rádi výpočtem dosáhli ekvivalentní elektrický model řešení. To je založeno na elektrochemickém dvouvrstvém modelu a korespondenci s Cole-Cole grafy In this paper, we describe our initial steps in the development of online sensor to monitor the tri-sodium citrate concentration in extra-cerebral blood flow during haemodialysis. Accurate and fast monitoring would allow the regulation of the concentration of citrate returning to the human bloodstream to its original values, thereby, making the patient significantly less burdened than at present. In the early stages, we focused on the determination of concentration by measuring of electrical impedance and reflection in the collected blood. Our aim is to study the trends of influencing these signals by concentration and to develop a suitable methodology that can be used later in the sensor. In part, we begin working on the selectivity of the methodology that we would like to achieve by calculating the equivalent electrical model of the solution. It is based on the electrochemical double layer model and the corresponding Cole-Cole graphs.