Detection of reactive oxygen and nitrogen species by electron paramagnetic resonance (EPR) technique

During the last decade there has been growing interest in physical-chemical oxidation processes and the behavior of free radicals in living systems. Radicals are known as intermediate species in a variety of biochemical reactions. Numerous techniques, assays and biomarkers have been used to measure reactive oxygen and nitrogen species (ROS and RNS), and to examine oxidative stress. However, many of these assays are not entirely satisfactory or are used inappropriately. The purpose of this chapter is to review current EPR (Electron Paramagnetic Resonance) spectroscopy methods for measuring ROS, RNS, and their secondary products, and to discuss the strengths and limitations of specific methodological approaches

Viable Health Games: Elements for Success

The main purpose of this study is to identify the elements of children's health games that have a positive impact on children’s health. The investigation is done by evaluating previous health game studies concentrating on children and five health affairs (such as asthma, cancer, diabetes, nutrition and obesity). In order to do so, firstly the topic of children’s health games is explained through its roots, as it is an interdisciplinary topic pertinent with many other fields. For this reason, the topics regarding the children’s health games as games, video games, children’s gameplay, and serious games along with health, relevant health affairs, and health promotion were covered. Secondly, the meta-study was conducted with the 56 articles on children’s health games. These 56 articles were analyzed with the coding technique defined by Charmaz’s Grounded Theory Method (Charmaz, 2006) for finding out which elements of children’s health games have a positive impact on children’s health promotion. The main result suggests that, although there are 24 different elements found and listed which all positive in their nature, their positive impact is a matter of how they are used or implemented through the consumption cycle of children’s health games and how all these elements interact with each other. In addition to this, a pragmatic proposal is formulated for possibly better or more successful health games. The study concludes with the declaration of the limitations encountered through the research and the recommendations for future research.siirretty Doriast

Towards the detection of tonotopic reorganisation in the human auditory cortex

Peripheral hearing loss not only causes a reduction in hearing sensitivity (increase in hearing threshold) but also leads to problems in suprathreshold hearing – such as difficulty understanding speech in noise – and is often associated with tinnitus. Animal research has suggested that such impairments may be related to changes in central auditory processing arising as a consequence of a reduction in peripheral auditory output (Norena and Farley 2013). The auditory cortex is tonotopically organised, with neighbouring parts of the cortex responding to neighbouring frequencies. In animals, peripheral hearing loss has been shown to cause large-scale tonotopic reorganisation in auditory cortex, whereby neurons responsive to frequencies affected by the hearing loss (typically higher frequencies), shift their tuning towards less affected (lower) frequencies. Tonotopic reorganisation in auditory cortex has been investigated in several studies using functional magnetic resonance imaging (fMRI) to non-invasively assess cortical frequency tuning properties in humans. However, it is unclear whether these measurements are sufficiently sensitive to detect hearing loss induced reorganisation. This thesis presents three complementary studies concerned with developing fMRI methods for effective measurement of tonotopic properties of the human auditory cortex. Voxel-wise measures of cortical frequency preference and selectivity, and summary measures of organisation are evaluated in normal-hearing subjects. The impact of hearing loss on these measurements is assessed. To estimate cortical frequency tuning properties, blood oxygen level-dependent (BOLD) fMRI responses to sounds with a wide range of frequencies were recorded from normal-hearing participants in three studies to derive the preferred frequency and selectivity of discrete cortical areas. The three studies presented serve to: 1) optimise the fMRI tonotopic mapping procedure, 2) measure tonotopic cortical magnification, and 3) develop methods for measuring tonotopic reorganisation in subjects with hearing loss. The first study investigated sources of error from experimental factors and suggests how procedures can be optimised for tonotopic mapping fMRI experiments to maximise the validity of tonotopic estimates. The impact of acoustic scanner noise on estimates of tonotopic properties was assessed by comparing tonotopic property estimates derived from data collected using either a sparse acquisition protocol, in which acoustic stimuli are presented in silence but fewer data points are acquired, or a continuous acquisition protocol, where stimulus are presented during data acquisition with typical acoustic scanner noise and more data points are acquired. Frequency preference and selectivity were also estimated using different statistical methods of fitting models to BOLD activity, measured in response to narrowband noise (NBN) stimuli from 8 normal-hearing subjects at 7T; population receptive field modelling (pRF) or calculating the centroid and spread of frequency response profiles estimated using general linear modelling (GLM). Acoustic scanner noise was found to systematically bias preferred frequency estimates, presumably because it masked some frequencies of the acoustic stimuli. The distribution and range of preferred frequencies derived from the GLM analysis were more biased than those derived from the pRF analysis but the spatial location of high- and low- frequency regions, relative to the frequency range afforded by the analysis, appeared to be robust to these biases. The results suggest that using a sparse acquisition protocol and pRF analysis achieves preferred frequency estimates that best reflect the true neuronal frequency tuning properties. It has been shown in other sensory systems, that the cortical surface allocated to a given region in sensory space is proportional to its behavioural importance. For example, visual studies have demonstrated that proportionally more cortical area dedicated to the centre of the visual field than to the periphery (Wandell, Dumoulin, and Brewer 2007). This cortical magnification function has been well characterised in visual cortex using fMRI (Dumoulin and Wandell 2008). Tonotopic magnification in the human auditory cortex (the cortical distance spanned by a given frequency) is still unknown but we expect it to follow behavioural relevance as in the visual system. The second study of this thesis aimed to measure and describe tonotopic cortical magnification in normal-hearing subjects. The auditory cortical magnification function was calculated in 8 normal-hearing subjects from voxel-wise estimates of preferred frequency derived using a pRF analysis from fMRI data acquired using a sparse acquisition protocol at 7T. Cortical magnification was estimated for two mirror-symmetric tonotopic gradients located on Heschl's gyrus in each hemisphere by characterising the relationship between cortical distance and preferred frequency with the best fitting of four functions: linear, logarithmic, cochlear frequency tuning and behavioural frequency discrimination. Preferred frequency transformed by a behavioural frequency discrimination scale provided the best fit, suggesting that the cortical tonotopic magnification function directly reflects frequency discrimination. Estimates of the cortical magnification function provide a global measure and characterisation of cortical organisation of the auditory cortex which may be able to detect and summarise tonotopic reorganization in hearing loss subjects. Understanding the retinotopic organisation and cortical magnification of the human visual cortex was critical to investigate retinotopic reorganisation following localised periphery deprivation (Wandell and Smirnakis 2009; Baseler et al. 2011). Likewise, for auditory research, understanding tonotopic magnification will benefit studies of tonotopic reorganisation and its possibility as a generation mechanism for chronic tinnitus. The third study of this thesis develops a better control for future studies of tonotopic reorganisation in subjects with hearing loss, and its potential as a mechanism for supra-threshold hearing deficits and chronic tinnitus, which is not addressed directly in the current literature. In participants with hearing loss, BOLD responses to frequencies affected by the hearing loss are expected to be reduced, potentially skewing the shape of the measured frequency response functions and biasing cortical preferred frequency estimates. Two methodological procedures were proposed to address these issues. The first is to simulate hearing loss in normal-hearing controls in order to replicate the biases expected for hearing-impaired subjects. The second, tested here in normal-hearing controls with simulated hearing loss, is a novel data analysis method that accounts for variations in sensation level due to hearing loss to alleviate the biases of hearing loss on estimates of preferred frequency. Tonotopic properties of auditory cortex were estimated in seven normal-hearing subjects using a sparse acquisition sequence at 3T and a pRF analysis, either in the presence or absence of a continuous threshold-elevating noise simulating a steeply sloping high-frequency hearing loss. Steeply sloping high-frequency hearing loss has been suggested to lead to tonotopic reorganisation (Sereda, Hall, et al. 2011), providing a realistic case for assessment of the proposed methods. In addition, a modified population receptive field modelling method was implemented that attempted to minimize the effect of hearing loss on tonotopic property estimates by taking into account the hearing thresholds in its fitting procedure. The results show that using the unmodified pRF method for simulated hearing loss data results in expected biases in preferred frequency and tuning width estimates, and that the modified method reduces these biases and results in tonotopic maps closer to ones estimated from normal-hearing data. These results represent a key step towards studying the effects of hearing loss on the tonotopic organisation in human auditory cortex using BOLD fMRI, and understanding their potential perceptual consequences. The work presented in this thesis provides actionable methodologies that could potentially improve the study of hearing-loss-induced tonotopic reorganisation in human auditory cortex

AVALANCHE DISASTER REVIEW IN TURKEY

One of the natural disasters encountered mostly on barren slopes and in the spring season, in the mountainous parts and high plateaus of Turkey, in Central and Eastern Anatolia, is avalanche. Especially in heavy snow areas of the Eastern Anatolia, people living in villages and hamlets far from the city centers, lose their lives and homes, roads are closed. Energy pilons and energy transmission lines are destroyed due to heavy snow accumulation and avalanches. During snow storms, excessive snow accumulation on flat and earthen roofs, and icing on eaves adversly affect the living conditions of people. Every year, about 25 people lives are lost in avalanche accidents in urban areas, very few at winter tourism locations, and the loss of property is not clearly known. In this study, the present situation of the areal distribution of avalanche events, their distribution in time, and in this context, the recent avalanche mapping, modelling and simulation studies that have been done so far are exemplified. Based on the data available, avalanche-hazardous zones in Turkey are identified, the analysis of avalanche data for the period 1950–2019 is given. The structural and non-structural measures necessary to control the avalanche problem are defined. Opinions are shared on the necessity of coordination among the state institutions working on avalanche disaster prevention.One of the natural disasters encountered mostly on barren slopes and in the spring season, in the mountainous parts and high plateaus of Turkey, in Central and Eastern Anatolia, is avalanche. Especially in heavy snow areas of the Eastern Anatolia, people living in villages and hamlets far from the city centers, lose their lives and homes, roads are closed. Energy pilons and energy transmission lines are destroyed due to heavy snow accumulation and avalanches. During snow storms, excessive snow accumulation on flat and earthen roofs, and icing on eaves adversly affect the living conditions of people. Every year, about 25 people lives are lost in avalanche accidents in urban areas, very few at winter tourism locations, and the loss of property is not clearly known. In this study, the present situation of the areal distribution of avalanche events, their distribution in time, and in this context, the recent avalanche mapping, modelling and simulation studies that have been done so far are exemplified. Based on the data available, avalanche-hazardous zones in Turkey are identified, the analysis of avalanche data for the period 1950–2019 is given. The structural and non-structural measures necessary to control the avalanche problem are defined. Opinions are shared on the necessity of coordination among the state institutions working on avalanche disaster prevention

Generalised periodic epileptiform discharges: clinical features, neuroradiological evaluation and prognosis in 37 adult patients

AbstractGeneralised periodic epileptiform discharges (GPEDs) are very rare patterns and are classified as periodic short-interval diffuse discharges (PSIDDs), periodic long-interval diffuse discharges (PLIDDs) and suppression-burst patterns according to the interval between the discharges.In this study we analysed the demographics, history of the seizures during the current illness, mental status, diagnosis, metabolic abnormalities, neuroimaging studies and prognosis of 37 adult patients who had GPEDs in their EEGs. Ages ranged from 17 to 82 years (mean 45 years). There were 19 males and 18 females. The most common aetiology of GPEDs was metabolic and/or infectious disease which was established in 22 patients (59.5%). Other aetiologies included subacute sclerosing panencephalitis (SSPE) in 11 patients (29.7%) and Creutzfeld–Jakob disease (CJD) in 4 patients (10.8%). We showed that structural lesions were found in most of the patients with GPEDs, but concurrent metabolic abnormalities and/or infectious diseases were also detected. Consciousness was impaired and clinical conditions were poor in various degrees in all of the patients when GPEDs were seen. Relatively little is known regarding the mechanism of GPEDs.When GPEDs are seen in EEG, the patient should carefully be checked for metabolic abnormalities and/or infectious diseases and intracranial lesions. GPEDs may be helpful in the determination of prognosis, showing the poor prognosis especially in cases when suppression-burst pattern is seen

Virus-specific CD4+ T cells: ready for direct attack

CD4+ T cells are classically thought to orchestrate adaptive immune responses. But recent studies demonstrate that they can also kill infected cells directly. A new paper shows that highly efficient processing of Epstein Barr virus (EBV) glycoproteins for presentation on MHC class II makes virus-transformed B cells susceptible to lysis by CD4+ T cells. Thus, antiviral vaccines should aim to stimulate both helper and cytolytic CD4+ T cells

«Күлтегін», «Білге қаған» және «Тоныкөк» жырларындағы ортақ мотивтер: көне түркілік дүниетаным бейнесі

Тасқа қашалған «Күлтегін», «Білге қаған», «Тоныкөк» туындыларында (VIIIIX ғғ.) көк түріктердің дүние туралы түсінігі, наным-сенімі мен әдет-ғұрыптары, басынан кешкен қилы кезеңдері мен мықты мемлекет құрудағы жеке тұлғалардың орны сипатталады. Тарихи-шежірелік жырлардағы көне түркілік дүниетанымды анықтауда «Тәңірі» концептісінің орны ерекше. Жарылқаушы Көк Тәңірі олардың бойына ұлы Түрік мемлекетін құруда айрықша қуат, күш-жігер, жауынгерлік рух берген. Мемлекетаралық дипломатия, мемлекет іргесін нығайтудағы жеңісті жорықтар, дара тұлғалардың мемлекет іргесін нығайтудағы ерекше қызметтері мен олардың өмірден өтуі, бүкілхалықтық деңгейде аза тұтуы, наным-сенімдері мен әдет-ғұрыптары, тіршілік ортасы, табиғатқа қатысы суреттелген.Мақалада сюжеттік байланыстар негізінде «Тәңірі», «Мемлекет», «Қаған», «Батыр», «Ел бірлігі», «Аруақ», тағы басқа микроконцептілер талданады.Уақыттың күрделі сипаты, ел бірлігін сақтаудағы ақылдың қуаты, жау мемлекетке қарсы күрес идеологиясы, тағы басқа белгілер сараланып, ежелгі түркілік «Әлем» концептісінің өзіндік ерекшеліктері қарастырылған. «Білге қаған» жыры мен «Күлтегін» жырында ұқсастық пен ортақ авторлық қолтаңба, пайымдау байқалады.Баяндалатын жорықтар сарынында жақындықтың болуы – жыр қаһармандарының қатар өмір кешуімен, жорықтарға бірлесе аттануымен байланысты. «Білге қаған» жырынан байқалатын басты сипаттың бірі – ата-баба, ағайын-туыс – ұрпақ арасындағы байланыстың аса құрметтелуі. Ежелгі түрік дәстүр-салтында аруақты сыйлау, құрметтеу орныққаны жырда нақтылана түседі. «Тоныкөк» жырында Түрік қағанатының мемлекет болып қалыптасуындағы тарихи кезеңдері баяндалады. Жырда Тоныкөк ұзақ жасаған, ақылман, тек кеңесші ғана емес, қағанға түрік елінің ел болып қалыптасуына өлшеусіз үлес қосқан, қаһарман болып суреттеледі

Nitric Oxide Levels in Patients with Psoriasis Treated with Methotrexate

Psoriasis is a chronic, recurrent, inflammatory, and hyperproliferative disease. Recently there have been studies regarding increases in the levels of NO in inflammatory dermatoses including psoriasis. In this study, 22 patients with psoriasis were scored with PASI (psoriasis area and severity index) and the levels of serum nitrite-nitrate were evaluated before and after therapy with methotrexate (Mtx). The results were compared with age- and sex-matched healthy volunteers. The relation of the results with the clinical severity and the cumulative Mtx dose were also evaluated. The serum levels of nitrite-nitrate of the psoriatic patients with active lesions were found to be significantly higher than the levels of the healthy volunteers and the patients after therapy. The elevated nitrite-nitrate serum levels in the inflammatory period may suggest the possible role of this mediator in the etiopathogenesis of psoriasis and the potential future use of No inhibitors in the treatment of psoriasis

Assessment and characterisation of turkish hypovirulent isolates of cryphonectria parasitica (Murr.) Barr.

Hypovirulent isolates of Cryphonectria parasitica on chestnut trees were collected from abnormal cankers in eastern and western Turkey. Laboratory tests showed differences between these isolates in morphological and physiological characters and in their virulence in culture. The majority of selected isolates of C. parasitica contained dsRNA, but some of the hypovirulent ones were dsRNA-free. The decrease in damage severity in Turkey is possibly a consequence of the occurrence of hypovirulent isolates and the biological control resulting from their natural spread

Bioisosteric modification on melatonin: synthesis of new naphthalene derivatives, in vitro antioxidant activity and cytotoxicity studies

Melatonin (MLT) is a strong free radical scavenger that protects the body from the deleterious effects of excess oxidants. Synthesis of MLT analogue compounds with antioxidant potency has recently attracted the interest of researchers. In general, the strategy consists of modifying the groups in the different sites of the indole ring or replacing the indole ring with an analogue. As part of our ongoing research, the antioxidant capacity and cytotoxicity of newly synthesized MLT analogue naphthalene derivatives were evaluated. The radical scavenging activity was tested by a 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Most of the synthesized compounds showed significant antioxidant activity in comparison to MLT. The structure-activity relationship was identified. The in vitro cytotoxic effects of the synthesized compounds were also investigated in CHO-K1 cells using the MTT assay