The Effects of Optogenetic Activation of Astrocytes on Spike-and-Wave Discharges in Genetic Absence Epileptic Rats

Background: Absence seizures (petit mal seizures) are characterized by a brief loss of consciousness without loss of postural tone. The disease is diagnosed by an electroencephalogram (EEG) showing spike–wave discharges (SWD) caused by hypersynchronous thalamocortical (TC) oscillations. There has been an explosion of research highlighting the role of astrocytes in supporting and modulating neuronal activity. Despite established in vitro evidence, astrocytes’ influence on the TC network remains to be elucidated in vivo in the absence epilepsy (AE). Purpose: In this study, we investigated the role of astrocytes in the generation and modulation of SWDs. We hypothesize that disturbances in astrocytes’ function may affect the pathomechanism of AE. Methods: To direct the expression of channelrhodopsin-2 (ChR2) rAAV8-GFAP-ChR2(H134R)-EYFP or to control the effect of surgical intervention, AAV-CaMKIIa-EYFP was injected into the ventrobasal nucleus (VB) of the thalamus of 18 animals. After four weeks following the injection, rats were stimulated using blue light (~473 nm) and, simultaneously, the electrophysiological activity of the frontal cortical neurons was recorded for three consecutive days. The animals were then perfused, and the brain tissue was analyzed by confocal microscopy. Results: A significant increase in the duration of SWD without affecting the number of SWD in genetic absence epileptic rats from Strasbourg (GAERS) compared to control injections was observed. The duration of the SWD was increased from 12.50 ± 4.41 s to 17.44 ± 6.07 following optogenetic stimulation in GAERS. The excitation of the astrocytes in Wistar Albino Glaxo Rijswijk (WAG-Rij) did not change the duration of SWD; however, stimulation resulted in a significant increase in the number of SWD from 18.52 ± 11.46 bursts/30 min to 30.17 ± 18.43 bursts/30 min. Whereas in control injection, the duration and the number of SWDs were similar at pre- and poststimulus. Both the background and poststimulus average firing rates of the SWD in WAG-Rij were significantly higher than the firing recorded in GAERS. Conclusion: These findings suggest that VB astrocytes play a role in modulating the SWD generation in both rat models with distinct mechanisms and can present an essential target for the possible therapeutic approach for AE

Roles of the systemic inflammatory response biomarkers in the diagnosis of cancer patients with solid tumors

Aim: Cancer is still considered as one of the leading causes of mortality worldwide. Various tumor factors have been used for the diagnosis and follow-up of solid tumors; however, their clinical features remains controversial in terms of their diagnostic, prognostic, and predictive values. In this study, we aimed to investigate the use of the systemic inflammatory response biomarkers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), in the diagnosis of solid tumors. Method: We retrospectively analyzed the records of 256 patients with solid tumors, including lung, breast, liver, and pancreatic cancers, who were diagnosed at the outpatient clinics of our institution between January 2017 and July 2018. The neutrophil, lymphocyte, monocyte, and platelet counts were measured using a hematology analyzer and the results were analyzed statistically. Results: The results of the receiver operating characteristic analysis showed that the NLR and LMR could be statistically reliable biomarkers, with area under the curve (AUC) values of 0.574 (p = 0.017) and 0.596 (p = 0.002). However, the PLR statistically failed to discriminate the patients and the control subjects, with AUC values of 0.545 (p = 0.148). Conclusions: Certain systemic inflammatory response biomarkers, such as the NLR and LMR, can play roles in the clinical diagnosis of patients with solid tumors

EEG & Eye Tracking user experiments for spatial memory task on maps

The aim of this research is to evaluate the use of ET and EEG for studying the cognitive processes of expert and novice map users and to explore these processes by comparing two types of spatial memory experiments through cognitive load measurements. The first experiment consisted of single trials and participants were instructed to study a map stimulus without any time constraints in order to draw a sketch map afterwards. According to the ET metrics (i.e., average fixation duration and the number of fixations per second), no statistically significant differences emerged between experts and novices. A similar result was also obtained with EEG Frontal Alpha Asymmetry calculations. On the contrary, in terms of alpha power across all electrodes, novices exhibited significantly lower alpha power, indicating a higher cognitive load. In the second experiment, a larger number of stimuli were used to study the effect of task difficulty. The same ET metrics used in the first experiment indicated that the difference between these user groups was not statistically significant. The cognitive load was also extracted using EEG event-related spectral power changes at alpha and theta frequency bands. Preliminary data exploration mostly suggested an increase in theta power and a decrease in alpha power

Exploring the cognitive load of expert and novice map users using EEG and eye tracking

The main objective of this research is to explore the cognitive processes of expert and novice map users during the retrieval of map-related information, within varying difficulty levels (i.e., easy, moderate, hard), by using eye tracking and electroencephalogram (EEG). In this context, we present a spatial memory experiment consisting of a large number of stimuli to study the effect of task difficulty on map users' behavior through cognitive load measurements. Next to the reaction time and success rate, we used fixation and saccade related eye tracking metrics (i.e., average fixation duration, the number of fixations per second, saccade amplitude and saccade velocity), and EEG power spectrum (i.e., event-related changes in alpha and theta frequency bands) to identify the cognitive load. While fixation metrics indicated no statistically significant difference between experts and novices, saccade metrics proved the otherwise. EEG power spectral density analysis, on the other side, suggested an increase in theta (i.e., event-related synchronization) and a decrease in alpha (except moderate tasks) (i.e., event-related desynchronization) at all difficulty levels of the task for both experts and novices, which is an indicator of cognitive load. Although no significant difference emerged between two groups, we found a significant difference in their overall performances when the participants were classified as good and relatively bad learners. Triangulating EEG results with the recorded eye tracking data and the qualitative analysis of focus maps indeed provided a detailed insight on the differences of the individuals' cognitive processes during this spatial memory task

Digital sketch maps and eye tracking statistics as instruments to obtain insights into spatial cognition

This paper explores map users' cognitive processes in learning, acquiring and remembering information presented via screen maps. In this context, we conducted a mixed-methods user experiment employing digital sketch maps and eye tracking. On the one hand, the performance of the participants was assessed based on the order with which the objects were drawn and the influence of visual variables (e.g. presence & location, size, shape, color). On the other hand, trial durations and eye tracking statistics such as average duration of fixations, and number of fixations per seconds were compared. Moreover, selected AoIs (Area of Interests) were explored to gain a deeper insight on visual behavior of map users. Depending on the normality of the data, we used either two-way ANOVA or Mann-Whitney U test to inspect the significance of the results. Based on the evaluation of the drawing order, we observed that experts and males drew roads first whereas; novices and females focused more on hydrographic object. According to the assessment of drawn elements, no significant differences emerged between neither experts and novices, nor females and males for the retrieval of spatial information presented on 2D maps with a simple design and content. The differences in trial durations between novices and experts were not statistically significant while both studying and drawing. Similarly, no significant difference occurred between female and male participants for either studying or drawing. Eye tracking metrics also supported these findings. For average duration of fixation, there was found no significant difference between experts and novices, as well as between females and males. Similarly, no significant differences were found for the mean number of fixation

Weak field and slow motion limits in energy-momentum powered gravity

We explore the weak field and slow motion limits, Newtonian and Post-Newtonian limits, of the energy-momentum powered gravity (EMPG), viz., the energy-momentum squared gravity (EMSG) of the form $f(T_{\mu\nu}T^{\mu\nu})=\alpha (T_{\mu\nu}T^{\mu\nu})^{\eta}$ with $\alpha$ and $\eta$ being constants. We have shown that EMPG with $\eta\geq0$ and general relativity (GR) are not distinguishable by local tests, say, the Solar System tests; as they lead to the same gravitational potential form, PPN parameters, and geodesics for the test particles. However, within the EMPG framework, $M_{\rm ast}$, the mass of an astrophysical object inferred from astronomical observations such as planetary orbits and deflection of light, corresponds to the effective mass $M_{\rm eff}(\alpha,\eta,M)=M+M_{\rm empg}(\alpha,\eta,M)$, $M$ being the actual physical mass and $M_{\rm empg}$ being the modification due to EMPG. Accordingly, while in GR we simply have the relation $M_{\rm ast}=M$, in EMPG we have $M_{\rm ast}=M+M_{\rm empg}$. Within the framework of EMPG, if there is information about the values of $\{\alpha,\eta\}$ pair or $M$ from other independent phenomena (from cosmological observations, structure of the astrophysical object, etc.), then in principle it is possible to infer not only $M_{\rm ast}$ alone from astronomical observations, but $M$ and $M_{\rm empg}$ separately. For a proper analysis within EMPG framework, it is necessary to describe the slow motion condition (also related to the Newtonian limit approximation) by $|p_{\rm eff}/\rho_{\rm eff}|\ll1$ (where $p_{\rm eff}=p+p_{\rm empg}$ and $\rho_{\rm eff}=\rho+\rho_{\rm empg}$), whereas this condition leads to $|p/\rho|\ll1$ in GR.Comment: 12 pages, no figures and table

Ocjena apsorpcije, djelotvornosti protiv bakterije Escherichia coli i citotoksičnosti krutih lipidnih nanočestica s moksifloksacinom

Moxifloxacin (MOX) is an important antibiotic commonly used in the treatment of recurrent Escherichia coli (E. coli) infections. The aim of this study was to investigate its antibacterial efficiency when used with solid lipid nanoparticles (SNLs) and nanostructured lipid carriers (NLCs) as delivery vehicles. For this purpose we designed two SLNs (SLN1 and SLN2) and two NLCs (NLC1 and NLC2) of different characteristics (particle size, size distribution, zeta potential, and encapsulation efficiency) and loaded them with MOX to determine its release, antibacterial activity against E. coli, and their cytotoxicity to the RAW 264.7 monocyte/macrophage-like cell line in vitro. With bacterial uptake of 57.29 %, SLN1 turned out to be significantly more effective than MOX given as standard solution, whereas SLN2, NLC1, and NLC2 formulations with respective bacterial uptakes of 50.74 %, 39.26 %, and 32.79 %, showed similar activity to standard MOX. Cytotoxicity testing did not reveal significant toxicity of nanoparticles, whether MOX-free or MOX-loaded, against RAW 264.7 cells. Our findings may show the way for a development of effective lipid carriers that reduce side effects and increase antibacterial treatment efficacy in view of the growing antibiotic resistance.Moksifloksacin je važan antibiotik koji se često rabi za liječenje rekurentne infekcije bakterijom Escherichia coli (E. coli). Cilj je ovog istraživanja bio ocijeniti njegovu djelotvornost u formulaciji s krutim lipidnim nanočesticama (engl. solid lipid nanoparticles, krat. SNL) i nanostrukturiranim lipidnim nosačima (engl. nanostructured lipid carriers, krat. NLC) kao njegovim vehikulima. U tu smo svrhu osmislili dva SLN-a (SLN1 I SLN2) te dva NLC-a (NLC1 i NLC2) različitih svojstava (veličine čestice, raspodjele veličina, zeta potencijala i sposobnosti enkapsulacije) te ih obogatili moksifloksacinom kako bismo utvrdili njegovo otpuštanje, djelovanje protiv E. coli i citotoksičnost za makrofagnu staničnu liniju RAW 264.7 in vitro. S bakterijskom apsorpcijom od 57,29 %, SLN1 se pokazao značajno djelotvornijim vehikulom moksifloksacina od njegove standardne formulacije (otopine), a formulacije s SLN2, NLC1 odnosno NLC2 s odgovarajućim apsorpcijama od 50,74 %, 39,26 % odnosno 32,79 % iskazale su djelotvornost sličnu onoj standardnog antibiotika. Test citotoksičnosti nije pokazao značajnu toksičnost nanočestica bez obzira na to jesu li sadržavale moksifloksacin ili nisu. Naši rezultati upućuju na mogući smjer razvoja djelotvornih lipidnih nosača kojima bi se mogle smanjiti nuspojave i povećati antibakterijska djelotvornost liječenja s obzirom na sve veću bakterijsku rezistentnost

Comparison of anatomical and functional outcomes of different surgical techniques in myopic macular hole without retinal detachment

AIM: To define the anatomic and functional outcomes of pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling, inverted ILM flap and free ILM patch graft technique for the treatment of myopic macular hole (MH) without retinal detachment. METHODS: Sixty-four eyes of 64 patients who underwent PPV for myopic MH were included. Group 1 consists of patients underwent ILM peeling (n=26), and Groups 2 and 3 consists of patient underwent free ILM patch graft (n=20) and inverted ILM flap procedure (n=18) respectively. Outcomes following surgery were MH closure and best corrected visual acuity (BCVA) in logMAR at 6mo. RESULTS: Closure of MH was obtained in 20 eyes (76.9%) of the Group 1, in 16 eyes (80%) of the Group 2 and in 16 eyes (88.9%) of the Group 3. The mean preoperative and postoperative BCVA was 1.60±0.53 logMAR and 1.27±0.58 logMAR, respectively (P<0.05). There was no significant difference in the postoperative BCVA and anatomical closure rates in the three groups. Although the anatomical closure rate did not differ significantly in the groups, closure of MH tended to be better in the inverted ILM flap technique group at 6mo. CONCLUSION: Different surgical techniques may provide favorable visual and anatomical results for myopic MH surgery. ILM flap techniques offer higher closure rates compared to ILM peeling technique. However, in terms of visual outcomes, the study reveals no difference in three surgical techniques

Screening Λ\Lambda in a new modified gravity model

We study a new model of Energy-Momentum Squared Gravity (EMSG), called Energy-Momentum Log Gravity (EMLG), constructed by the addition of the term $f(T_{\mu\nu}T^{\mu\nu})=\alpha \ln(\lambda\,T_{\mu\nu}T^{\mu\nu})$, envisaged as a correction, to the Einstein-Hilbert action with cosmological constant $\Lambda$. The choice of this modification is made as a specific way of including new terms in the right-hand side of the Einstein field equations, resulting in constant effective inertial mass density and, importantly, leading to an explicit exact solution of the matter energy density in terms of redshift. We look for viable cosmologies, in particular, an extension of the standard $\Lambda$CDM model. EMLG provides an effective dynamical dark energy passing below zero at large redshifts, accommodating a mechanism for screening $\Lambda$ in this region, in line with suggestions for alleviating some of the tensions that arise between observational data sets within the standard $\Lambda$CDM model. We present a detailed theoretical investigation of the model and then constrain the free parameter $\alpha'$, a normalisation of $\alpha$, using the latest observational data. The data does not rule out the $\Lambda$CDM limit of our model ($\alpha'= 0$), but prefers slightly negative values of the EMLG model parameter ($\alpha'= -0.032\pm 0.043$), which leads to the screening of $\Lambda$. We also discuss how EMLG relaxes the persistent tension that appears in the measurements of $H_0$ within the standard $\Lambda$CDM model.Comment: 17 pages, 11 figures, 1 table; matches the version published in EPJ