Search results for: exposure pathways

Authors: Hafiz Arbab Sakandar

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Time-restricted intermittent fasting (TRIF) impacts host’s physiology and health. Plenty of health benefits have been reported for TRIF in animal models. However, limited studies have been conducted on humans especially in underdeveloped economies. Here, we designed a study to investigate the impact of TRIF/Ramadan fasting (16:8) on the modulation of gut-microbiome structure, metabolic pathways, and predicted metabolites and explored the correlation among them at different time points (during and after the month of Ramadan) in Pakistani Expats living in China. We observed different trends of Shannon-Wiener index in different subjects; however, all subjects showed substantial change in bacterial diversity with the progression of TRIF. Moreover, the changes in gut microbial structure by the end of TRIF were higher vis-a-vis in the beginning, significant difference was observed among individuals. Additionally, metabolic pathways analysis revealed that amino acid, carbohydrate and energy metabolism, glycan biosynthesis metabolism of cofactors and vitamins were significantly affected by TRIF. Pyridoxamine, glutamate, citrulline, arachidonic acid, and short chain fatty acid showed substantial difference at different time points based on the predicted metabolism. In conclusion, these results contribute to further our understanding about the key relationship among, dietary intervention (TRIF), gut microbiome structure and function. The preliminary results from study demonstrate significant potential for elucidating the mechanisms underlying gut microbiome stability and enhancing the effectiveness of microbiome-tailored interventions among the Pakistani populace. Nonetheless, extensive, and rigorous large-scale research on the Pakistani population is necessary to expound on the association between diet, gut microbiome, and overall health.

Keywords: gut microbiome, health, fasting, functionality

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Authors: Mamdouh Milad Adly Morkos

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Despite having the greatest rates of mortality and morbidity in the world, low- and middle-income (LMIC) nations trail high-income nations in terms of the number of clinical trials, the number of qualified researchers, and the amount of research information specific to their people. Health inequities and the use of precision medicine may be hampered by a lack of local genomic data, clinical pharmacology and pharmacometrics competence, and training opportunities. These issues can be solved by carrying out health care infrastructure development, which includes data gathering and well-designed clinical pharmacology training in LMICs. It will be advantageous if there is international cooperation focused at enhancing education and infrastructure and promoting locally motivated clinical trials and research. This paper outlines various instances where clinical pharmacology knowledge could be put to use, including pharmacogenomic opportunities that could lead to better clinical guideline recommendations. Examples of how clinical pharmacology training can be successfully implemented in LMICs are also provided, including clinical pharmacology and pharmacometrics training programmes in Africa and a Tanzanian researcher's personal experience while on a training sabbatical in the United States. These training initiatives will profit from advocacy for clinical pharmacologists' employment prospects and career development pathways, which are gradually becoming acknowledged and established in LMICs. The advancement of training and research infrastructure to increase clinical pharmacologists' knowledge in LMICs would be extremely beneficial because they have a significant role to play in global health

Keywords: electromagnetic solar system, nano-material, nano pharmacology, pharmacovigilance, quantum theoryclinical simulation, education, pharmacology, simulation, virtual learning low- and middle-income, clinical pharmacology, pharmacometrics, career development pathways

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Authors: Hajar Hajmohammadi, Paul Pfeffer, Anna De Simoni, Jim Cole, Chris Griffiths, Sally Hull, Benjamin Heydecker

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Background: There is strong interest in the relationship between short-term air pollution exposure and human health. Most studies in this field focus on serious health effects such as death or hospital admission, but air pollution exposure affects many people with less severe impacts, such as exacerbations of respiratory conditions. A lack of quantitative analysis and inconsistent findings suggest improved methodology is needed to understand these effectsmore fully. Method: We developed a time series regression model to quantify the relationship between daily NOₓ concentration and Asthma exacerbations requiring oral steroids from primary care settings. Explanatory variables include daily NOₓ concentration measurements extracted from 8 available background and roadside monitoring stations in east London and daily ambient temperature extracted for London City Airport, located in east London. Lags of NOx concentrations up to 21 days (3 weeks) were used in the model. The dependent variable was the daily number of oral steroid courses prescribed for GP registered patients with asthma in east London. A mixed distribution model was then fitted to the significant lags of the regression model. Result: Results of the time series modelling showed a significant relationship between NOₓconcentrations on each day and the number of oral steroid courses prescribed in the following three weeks. In addition, the model using only roadside stations performs better than the model with a mixture of roadside and background stations.

Keywords: air pollution, time series modeling, public health, road transport

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Authors: Liang Ning, Chung Hau Yin

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Angiogenesis is the process of new blood vessel development. It has been recognized as a therapeutic target for blocking cancer growth four decades ago. Vascular sprouting is initiated by pro-angiogenic factors. Vascular endothelial cell growth factor (VEGF) plays a central role in angiogenic initiation, many patients with cancer or ocular neovascularization have been benefited from anti-VEGF therapy. Emerging approaches impacting in the later stages of vessel remodeling and maturation are expected to improve clinical efficacy. TIE receptor as well as the corresponding angiopoietin ligands, were identified as another endothelial cell specific receptor tyrosine kinase signaling system. Much efforts were made to reduce the activity of angiopoietin-TIE receptor axis. Two eudesmane-type sesquiterpenes from laggera alata, namely, 15-dihydrocostic acid and ilicic acid were found with strong anti-angiogenic properties in zebrafish model. Meanwhile, the mRNA expression levels of VEGFR2 and TIE2 pathway related genes were down-regulated in the sesquiterpenes treated zebrafish embryos. Besides, in human umbilical vein endothelial cells (HUVECs), the sesquiterpenes have the ability to inhibit VEGF-induced HUVECs proliferation and migration at non-toxic concentration. Moreover, angiopoietin-2 induced TIE2 phosphorylation was inhibited by the sesquiterpenes, the inhibitory effect was detected in angiopoietin-1 induced HUVECs proliferation as well. Thus, we hypothesized the anti-angiogenic activity of the compounds may via the inhibition of VEGF and TIE2 related pathways. How the compounds come into play as the pathways inhibitors need to be evaluated in the future.

Keywords: Laggera alata, eudesmane-type sesquiterpene, anti-angiogenesis, VEGF, angiopoietin, TIE2

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Authors: Shabnam Sarwar, Franck Lacoeuille, Nadia Withofs, Roland Hustinx

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After the development of a potential surrogate of MAA, and its successful application for the diagnosis of pulmonary embolism in artificially embolized rats’ lungs, this microparticulate system were radiolabelled with gallium-68 to synthesize 68Ga-SBMP with high radiochemical purity >99%. As a prerequisite step of clinical trials, 68Ga- labelled starch based microparticles (SBMP) were analysed for their in-vivo behavior in small animals. The purpose of the presented work includes the ex-vivo biodistribution studies of 68Ga-SBMP in order to assess the activity uptake in target organs with respect to time, excretion pathways of the radiopharmaceutical, %ID/g in major organs, T/NT ratios, in-vivo stability of the radiotracer and subsequently the microparticles in the target organs. Radiolabelling of starch based microparticles was performed by incubating it with 68Ga generator eluate (430±26 MBq) at room temperature and pressure without using any harsh reaction condition. For Ex-vivo biodistribution studies healthy White Wistar rats weighing between 345-460 g were injected intravenously 68Ga-SBMP 20±8 MBq, containing about 2,00,000-6,00,000 SBMP particles in a volume of 700µL. The rats were euthanized at predefined time intervals (5min, 30min, 60min and 120min) and their organ parts were cut, washed, and put in the pre-weighed tubes and measured for radioactivity counts through automatic Gamma counter. The 68Ga-SBMP produced >99% RCP just after 10-20 min incubation through a simple and robust procedure. Biodistribution of 68Ga-SBMP showed that initially just after 5 min post injection major uptake was observed in the lungs following by blood, heart, liver, kidneys, bladder, urine, spleen, stomach, small intestine, colon, skin and skeleton, thymus and at last the smallest activity was found in brain. Radioactivity counts stayed stable in lungs with gradual decrease with the passage of time, and after 2h post injection, almost half of the activity were seen in lungs. This is a sufficient time to perform PET/CT lungs scanning in humans while activity in the liver, spleen, gut and urinary system decreased with time. The results showed that urinary system is the excretion pathways instead of hepatobiliary excretion. There was a high value of T/NT ratios which suggest fine tune images for PET/CT lung perfusion studies henceforth further pre-clinical studies and then clinical trials should be planned in order to utilize this potential lung perfusion agent.

Keywords: starch based microparticles, gallium-68, biodistribution, target organs, excretion pathways

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Authors: Linghua Kong, Xinxia Chen, Mika Gissler, Catharina Lavebratt

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Background: Prenatal exposure to preeclampsia has been associated with an increased risk of offspring attention-deficit/hyperactivity disorders (ADHD), autism spectrum disorder (ASD), and intellectual disability. However, little is known about the association between prenatal exposure to severe preeclampsia and neurodevelopmental and psychiatric disorders in offspring. Objective: This study aimed to assess the risk of maternal preeclampsia combined with perinatal problems, specifically low birth weight and prematurity, on offspring neuropsychiatric disorders. Methods: All singleton live births in Finland between 1996 and 2014 (n=1 012 723) were followed up in nation-wide registries until 2018. Main exposures included pre-eclampsia, small for gestational age, and delivery before 34 gestational weeks. Offspring neurodevelopmental and psychiatric disorders (ICD-10 codes) were examined as outcomes variables. Offspring birth year, sex, maternal age at delivery, parity, marital status at birth, mother's country of birth, maternal smoking, maternal gestational diabetes, maternal use of psychotropic medication during pregnancy, and maternal systemic inflammatory diseases were used as covariates. Risks for neurodevelopmental and psychiatric disorders were estimated using Cox proportional hazards modeling. Results: Of the 1 012 723 offspring, 25 901 (2.6%) were exposed to preeclampsia, and 93 281 (9.2%) were diagnosed with a neuropsychiatric disorder. Compared to births unexposed to preeclampsia, small for gestational age or delivery before 34 gestational weeks, those exposed to preeclampsia only had a 21% increase in the likelihood of any neuropsychiatric disorders after adjusting for potential confounding (adjusted HR=1.21, 95% CI: 1.15-1.26), while exposure to preeclampsia combined with small for gestational age or delivery before 34 gestational weeks had a more than twofold increased risk of having a child with neuropsychiatric disorders (adjusted HR=2.16, 95% CI: 2.02-2.32). The adjusted HR for neuropsychiatric disorders in offspring with small for gestational age or delivery before 34 gestational weeks only was 1.79 (95% CI: 1.73-1.83). In addition, the risk estimate in offspring exposed to both preeclampsia and perinatal problems was greater than those only exposed to preeclampsia for having personality disorders (adjusted HR=1.66; 95% CI: 1.07-2.57), intellectual disabilities (adjusted HR=3.47; 95% CI: 2.86-4.22), specific developmental disorders (adjusted HR=2.91; 95% CI: 2.69-3.15), ASD (adjusted HR=1.75; 95% CI: 1.42-2.17), ADHD and conduct disorders (adjusted HR=2.00; 95%CI: 1.76-2.27), and other behavioral and emotional disorders (adjusted HR=2.09; 95% CI: 1.84-2.37). Conclusion: In utero exposure to severe preeclampsia increased the risk of several neurodevelopmental and psychiatric disorders in offspring. Our findings are relevant to women with hypertensive disorders with regard to pregnancy consultation and management and may yield effective clues for the prevention of neurodevelopmental and psychiatric disorders in childhood.

Keywords: low birth weight, neurodevelopmental disorders, preeclampsia, prematurity, psychiatric disorders

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Authors: Veronica Barragan, Ligia Luna, Maria Patricia Zambrano, Carlos Bulnes, Eduardo Diaz, Talima Pearson

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Leptospirosis impacts animal production and is responsible for important economic losses in the pig industry. Infection is associated with reproductive failures that lead to abortions, stillbirth, and perinatal mortality. The leptospira serogroups that have been traditionally linked to disease in pigs are Pomona, Australis, and Tarassovi. Unfortunately, knowledge about pig leptospirosis is biased towards infection in large-scale commercial farms from developed countries, where exposure is usually limited to host-specific serotypes. The aim of our study is to describe leptospirosis in pigs from rural communities located in the coast of Ecuador-South America, where leptospirosis is endemic. A particularity of these pigs is that, because they are usually raised in the backyard of their owner’s houses, exposure to other leptospira excreted by other animals is likely to occur. Therefore, we collected 420 kidney samples from pigs sacrificed at a local slaughterhouse, and Leptospira positivity was tested in all samples by amplifying the Lipl32 gen. Our results show pathogenic Leptospira positivity in 19.3% (81/420) of pigs. Microaglutination test was performed in 60 PCR positive samples with titers >1:100 in 17 pigs, titers of 1:50 in 28 pigs, and no MAT titers in 15 pigs even though Leptospira DNA was found in their kidneys. Interestingly, reacting serovars were very diverse, with 18.3% of pig sera reacting with two or more serovars. Additionally, serovar Canicola was found in 16.7% of pigs followed by Tarassovi (10%), Australis (6.7%), Pyogenes (5%), Icterohaemorrhageae (1.7%), and Grippotyphosa (1.7%). It is also important to highlight that most of the analyzed animals came from small-scale farms where pigs may be exposed to the pathogen by exposure to other domestic and peridomestic animals such as rats, dogs, horses, donkeys, and even wildlife. This would explain the finding of non-pig adapted Leptospira serovars such as Canicola, which is commonly reported in dogs.

Keywords: Leptospira, Lipl32, peridomestic, pig, serovar

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Authors: Ronald Villamar-Torres, Michael Staudt, Christopher Viot

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Cotton Gossypium hirsutum L. is one of the most important industrial crops, producing the world leading natural textile fiber, but is very prone to arthropod attacks that reduce crop yield and quality. Cotton cultivation, therefore, makes an outstanding use of chemical pesticides. In reaction to herbivorous arthropods, cotton plants nevertheless show natural defense reactions, in particular through volatile organic compounds (VOCs) emissions. These natural defense mechanisms are nowadays underutilized but have a very high potential for cotton cultivation, and elucidating their genetic bases will help to improve their use. Simulating herbivory attacks by mechanical wounding of cotton plants in greenhouse, we studied by qPCR the changes in gene expression for genes of the terpenoids biosynthesis pathway. Differentially expressed genes corresponded to higher levels of the terpenoids biosynthesis pathway and not to enzymes synthesizing particular terpenoids. The genes were mapped on the G. hirsutum L. reference genome; their global relationships inside the general metabolic pathways and the biosynthesis of secondary metabolites were visualized with iPath2. The chromatographic profiles of VOCs emissions indicated first monoterpenes and sesquiterpenes emissions, dominantly four molecules known to be involved in plant reactions to arthropod attacks. As a result, the study permitted to identify potential key genes for the emission of volatile terpenoids by cotton plants in reaction to an arthropod attack, opening possibilities for molecular-assisted cotton breeding in benefit of smallholder cotton growers.

Keywords: biosynthesis pathways, cotton, mechanisms of plant defense, terpenoids, volatile organic compounds

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Authors: Justin A. Udie, Subhes C. Bhatthacharyya, Leticia Ozawa-Meida

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The impact of climate change is severe in the Niger Delta and critical oil and gas infrastructures are vulnerable. This is partly due to lack of specific impact assessment framework to assess impact indices on both existing and new infrastructures. The purpose of this paper is to develop a framework for the assessment of climate change impact on critical oil and gas infrastructure in the region. Comparative and documentary methods as well as analysis of frameworks were used to develop a flexible, integrated and conceptual four dimensional framework underpinning; 1. Scoping – the theoretical identification of inherent climate burdens, review of exposure, adaptive capacities and delineation of critical infrastructure; 2. Vulnerability assessment – presents a systematic procedure for the assessment of infrastructure vulnerability. It provides real time re-scoping, practical need for data collection, analysis and review. Physical examination of systems is encouraged to complement the scoped data and ascertain the level of exposure to relevant climate risks in the area; 3. New infrastructure – consider infrastructures that are still at developmental level. It seeks to suggest the inclusion of flexible adaptive capacities in original design of infrastructures in line with climate threats and projections; 4. The Mainstreaming Climate Impact Assessment into government’s environmental decision making approach. Though this framework is designed specifically for the estimation of exposure, adaptive capacities and criticality of vulnerable oil and gas infrastructures in the Niger Delta to climate burdens; it is recommended for researchers and experts as a first-hand generic and practicable tool which can be used for the assessment of other infrastructures perceived as critical and vulnerable. The paper does not provide further tools that synch into the methodological approach but presents pointers upon which a pragmatic methodology can be developed.

Keywords: adaptation, assessment, conceptual, climate, change, framework, vulnerability

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Authors: Xiaolian Jiang, Dongling Liu, Kun Liu

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Aims: To examine the prevalence of POST-TRAUMATIC STRESS DISORDER (PTSD) symptoms among Tibetan adolescents in heavily-hit disaster area three years after Yushu earthquake, and to explore the interactions of the psycho-social-genetic risk factors. Methods: This was a three-stage study. Firstly, demographic variables，PTSD Checklist-Civilian Version （PCL-C），the Internality、Powerful other、Chance Scale，（IPC），Coping Style Scale（CSS），and the Social Support Appraisal（SSA）were used to explore the psychosocial factors of PTSD symptoms among adolescent survivors. PCL-C was used to examine the PTSD symptoms among 4072 Tibetan adolescents，and the Structured Clinical Interview for DSM-IV Disorders（SCID）was used by psychiatrists to make the diagnosis precisely. Secondly，a case-control trial was used to explore the relationship between PTSD and gene polymorphisms. 287adolescents diagnosed with PTSD were recruited in study group, and 280 adolescents without PTSD in control group. Polymerase chain reaction-restriction fragment length polymorphism technology（PCR-RFLP）was used to test gene polymorphisms. Thirdly，SPSS 22.0 was used to explore the interactions of the psycho-social-genetic risk factors of PTSD on the basis of the above results. Results and conclusions: 1．The prevalence of PTSD was 9.70%. 2．The predictive psychosocial factors of PTSD included earthquake exposure, support from others, imagine, abreact, tolerant, powerful others and family support. 3．Synergistic interactions between A1 gene of DRD2 TaqIA and the external locus of control, negative coping style, severe earthquake exposure were found. Antagonism interactions between A1 gene of DRD2 TaqIA and poor social support was found. Synergistic interactions between A1/A1 genotype and the external locus of control, negative coping style were found. Synergistic interactions between 12 gene of 5-HTTVNTR and the external locus of control, negative coping style, severe earthquake exposure were found. Synergistic interactions between 12/12 genotype and the external locus of control, negative coping style, severe earthquake exposure were also found.

Keywords: adolescents, earthquake, PTSD, risk factors

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Authors: Reza Sadeghi

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In this study, microwave heating was employed for controlling Oryzaephilus mercator. adults infesting stored Iranian dried fig. For this purpose, the dried fig samples were artificially infested with O. mercator and then heated in a microwave oven (2450 MHz) at the power outputs of 450, 720, and 900 W for 10, 20, 30, and 40 s, respectively. Subsequently, changes in the colors of the product samples under the effects of the varied microwave applications were investigated in terms of lightness (ΔL*), redness (Δa*), and yellowness (Δb*) using an image processing technique. The results revealed that both parameters of microwave power and exposure time had significant impacts on the pest mortality rates (p<0.01). In fact, a direct positive relationship was obtained between the mortality rate and microwave irradiation power. Complete mortality was achieved for the pest at the power of 900 W and exposure time of 40 s. The dried fig samples experienced fewer changes in their color parameters. Considering the successful pest control and acceptable changes in the product quality, microwave irradiation can be introduced as an appropriate alternative to chemical fumigants.

Keywords: colorimetric assay, microwave heating, Oryzaephilus mercator, mortality

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Authors: Xiquan Weng, Chaoge Wang, Guoqin Xu, Wentao Lin

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Objective: Cold exposure and exercise serve as two powerful physiological stimuli to launch the conversion of fat-accumulating white adipose tissue (WAT) into energy-dissipating brown adipose tissue (BAT). So far, it remains to be elucidated whether exercise plus cold exposure can produce an addictive effect on promoting WAT browning. Methods: 64 SD rats were subjected to high-fat and high-sugar diets for 9-week and successfully established an obesity model. They were randomly divided into 8 groups: normal control group (NC), normal exercise group (NE), continuous cold control group (CC), continuous cold exercise group (CE), intermittent cold control group (IC) and intermittent cold exercise group (IE). For continuous cold exposure, the rats stayed in a cold environment all day; For intermittent cold exposure, the rats were exposed to cold for only 4h per day. The protocol for treadmill exercises were as follows: 25m/min (speed), 0°C (slope), 30mins each time, an interval for 10 mins between two exercises, twice/two days, lasting for 5 weeks. Sampling were conducted on the 5th weekend. The body length and weight of the rats were measured, and the Lee's index was calculated. The visceral fat rate (VFR), subcutaneous fat rate (SFR), brown fat rate (BrFR) and body fat rate (BoFR) were measured by Micro-CT LCT200, and the expression of UCP1 protein in inguinal fat was examined by Western-blot. SPSS 22.0 was used for statistical analysis of the experimental results, and the ANOVA analysis was performed between groups (P < 0.05 was significant). Results: (1) Compared with the NC group, the weight of obese rats was significantly declined in the NE, CE and IE groups (P < 0.05), the Lee's index of obese rats significantly declined in the CE group (P < 0.05). Compared with the NE group, the weight of obese rats was significantly declined in the CE and IE groups (P < 0.05). (2)Compared with the NC group, the VFR and BoFR of the rats significantly declined in the NE, CE and IE groups (P < 0.05), the SFR of the rats significantly declined in the CE and IE groups (P < 0.05), and the BFR of the rats was significantly higher in the CC and IC groups (P < 0.05), respectively. Compared with the NE group, the VFR and BoFR of the rats significantly declined in the CE group (P < 0.05), the SFR of the rats was significantly higher in the CC and IS groups (P < 0.05), and the BrFR of the rats was significantly higher in the IC group (P < 0.05). (3)Compared with the NC group, the up-regulation of UCP1 protein expression in the inguinal fat of the rats was significant in the NE, CC, CE, IC and IE groups (P < 0.05). Compared with the NE group, the up-regulation of UCP1 protein expression in the inguinal fat of the rats was significant in the CC, CE and IE groups (P < 0.05). Conclusions: Exercise in the continuous and intermittent cold, especially in the former, can effectively decline the weight and body fat rate of obese rats. This is related to the effect of cold and exercise on the browning of white fat in rats.

Keywords: cold, browning of white fat, exercise, obesity

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Authors: Alireza Monzavi Chaleshtari, Mahnaz Aliakbari Dehkordi, Nazila Esmaeili, Ahmad Alipour, Amin Asadi Hieh

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Headache disorders are one of the most common disorders of the nervous system and are associated with suffering, disability, and financial costs for patients. Mindfulness as a lifestyle, in line with human nature, has the ability to affect the emotional system, i.e. thoughts, body sensations, raw emotions and action impulses of people. The aim of this study was to test the fit of structural model of mindfulness and severity of headache mediated by resilience and perfectionism in patients with migraine. Methods: The statistical population of this study included all patients with migraine referred to neurologists in Tehran in the spring and summer of 1401. The inclusion criteria were diagnosis of migraine by a neurologist, not having mental disorders or other physical diseases, and having at least a diploma. According to the number of research variables, 180 people were selected by convenience sampling method, which online answered the Ahvaz perfectionism questionnaire (AMQ), Connor and Davidson resilience questionnaire (CD-RISC), Ahvaz migraine headache questionnaire (APS) and 5-factor mindfulness questionnaire ((MAAS). Data were analyzed using structural equation modeling and Amos software. Results: The results showed that the direct pathways of mindfulness were not significant for severe headache (P <0.05), but other direct pathways - mindfulness to resilience, mindfulness to perfectionism, resilience to severe headache and perfectionism to severe headache), Was significant (P <0.01). After modifying and removing the non-significant paths, the final model fitted. Mediating variables Resilience and perfectionism mediated all paths of predictor variables to the criterion. Conclusion: According to the findings of the present study, mindfulness in migraine patients reduces the severity of headache by promoting resilience and reducing perfectionism.

Keywords: migraine, headache severity, mindfulness, resilience, perfectionism

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Authors: Sonam Sandal, Susan Verghese P.

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The phrase "environmental tobacco smoke" (ETS) refers to exposure to tobacco smoke that isn't from your own smoking but instead is caused by being in close proximity to someone else's cigar, cigarette, or pipe smoke. Environmental cigarette smoke is one of the main contributors to indoor air pollution (IAP), which is exceedingly harmful to human health and results in millions of deaths each year, according to the World Health Organization. Sidestream smoke (SS), which is discharged from a cigarette's burning end in between puffs, is the primary cause of ETS. The bulk of the ETS residue is composed of gases that are produced while smoking through the cigarette paper, mainstream smoke (MS) ingested, and side stream smoke emitted while inhaling a puff from the burning end. Each of these mixtures—SS, ETS, and MS—is an aerosol composed of an IAP-causing vapor phase and a particle phase. Therefore, indoor air-cleaning equipment designed to remove particles will not significantly alter nicotine exposure but will alter the concentrations of other dangerous substances, including particulate matter (PM), PM 2.5, and PM 10. In conclusion, indoor airborne contaminants pose serious risks to human health. ETS degrades the air quality, and when someone breathes this bad air, it weakens their lungs and makes them more susceptible to COVID-19.

Keywords: pm 10, covid-19, indoor air pollution, cigarette smoke., pm 2.5

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Authors: Klea Ramaj

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Objectives: There have recently been increasing calls to better understand the intergenerational transmission of adverse childhood experiences (ACEs). In particular, little is known about the links between maternal (ACEs), maternal stress, maternal depression, and child abuse against toddlers in countries in South-East Europe. This paper, therefore, aims to present new descriptive data on the epidemiology of maternal mental well-being and maternal ACEs in the capital of Albania, Tirana. It also aims to advance our understanding of the overlap between maternal stress, maternal depression, maternal exposure to ACEs, and child abuse toward two-to-three-year-old. Methods: This is a cross-sectional study conducted with a representative sample of 328 mothers of two-to-three-year-olds, recruited through public nurseries located in 8 diverse socio-economic and geographical areas in Tirana, Albania. Maternal stress was measured through the perceived stress scale (α = 0.78); maternal depression was measured via the patient health questionnaire (α = 0.77); maternal exposure to ACEs was captured via the ACEs international questionnaire (α = 0.77); and child maltreatment was captured via ISPCAN ICAST-P (α = 0.66). The main outcome examined here will be child maltreatment. The paper will first present estimates of maternal stress, depression, and child maltreatment by demographic groups. It will then use multiple regression to examine associations between child maltreatment and risk factors in the domains of maternal stress, maternal depression, and maternal ACEs. Results: Mothers' mean age was 32.3 (SD = 4.24), 87.5% were married, 51% had one child, and 83.5% had completed higher education. Analyses show high levels of stress and exposure to childhood adversity among mothers in Tirana. 97.5% of mothers perceived stress during the last month, and 89% had experienced at least one childhood adversity as measured by the ACE questionnaire, with 20.2% having experienced 4+ ACEs. Analyses show significant positive associations between maternal ACEs and maternal stress r(325) = 0.25, p = 0.00. Mothers with a high number of ACEs were more likely to abuse their children r(327) = .43, p = 0.00. 32% of mothers have used physical discipline with their 2–3-year-old, 84% have used psychological discipline, and 35% have neglected their toddler at least once or twice. The mothers’ depression levels were also positively and significantly associated with child maltreatment r(327) = .34, p = 0.00. Conclusions: This study provides cross-sectional data on the link between maternal exposure to early adversity, maternal mental well-being, and child maltreatment within the context of Tirana, Albania. The results highlight the importance of establishing policies that encourage maternal support, positive parenting, and family well-being in order to help break the cycle of transgenerational violence.

Keywords: child maltreatment, maternal mental well-being, intergenerational abuse, Tirana, Albania

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Authors: Leandra Prempeh, Emily Malugen

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Prenatal drug exposure can have a molecular impact on the hypothalamic and reward genes that regulate feeding behavior. This can impact feeding regulation, resulting in feeding difficulties and growth failure. This was potentially seen in “McKayla,” a 19- month old girl with a history of in-utero drug exposure, patent ductus arteriosus, and gastroesophageal reflux disease who presented for intensive day treatment feeding therapy. She was diagnosed with Avoidant Restrictive Food Intake Disorder, described as total food refusal and meeting 100% of her caloric needs from a gastrostomy tube. The primary goals during intensive feeding therapy were to increase her oral intake and decrease her reliance on supplementation with formula. Several behavioral antecedent manipulations were implemented to establish consistent responding and make progress towards treatment goals. This included multiple modified bolus placements (using underloaded and Nuk brush), reinforcement contingencies, and variety fading before stability was finally achieved. Following, increasing retention of bites then increasing volume and variety were goals targeted. From treatment onset to the last 3 days of treatment, McKayla's rate of rapid acceptance of bite presentations increased significantly from 33.33% to 93.13%, rapid swallowing went from 0.00% to 92.32%, and her percentage of inappropriate mealtime behavior and expels decreased from 58.33% and 100% to 2.31% and 7.68%, respectively. Overall, the treatment team successfully introduced and increased the bite size of 7 pureed foods, generalize the treatment to caregivers with high integrity, and began facilitating tube weaning. She was receiving about 33.42% of her needs by mouth at the time of discharge. Other nutritional concerns addressed during treatment included drinking a nutritionally complete drink out of an open cup and age appropriate growth. McKayla continued to have emesis almost daily, as was her baseline before starting treatment; however, the frequency during mealtime decreased. Overall, McKayla responded well to treatment. She had a very slow response to treatment and required a lot of antecedent manipulations to establish consistent responding. As the literature suggests, [drug]-exposed neonates, like McKayla, may be at increased risk for nutritional and growth challenges that may persist throughout development. This supports the need for longterm follow-up of infant growth.

Keywords: behavioral intervention, feeding problems, in-utero drug exposure, intensive multidisciplinary intervention

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Authors: Hussain Mustatab Wahedi, Sun You Kim

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Skin acts as a barrier against the harmful environmental factors. Integrity and timely recovery of the skin from injuries and harmful effects of radiations is thus very important. This study aimed to investigate the importance of Sirt1 in the recovery of skin from UVB-induced damage and cutaneous wounds by using natural and synthetic novel Sirt1 activators. Juglone, known as a natural Pin1 inhibitor, and NED416 a novel synthetic Sirt1 activator were checked for their ability to regulate the expression and activity of Sirt1 and hence photo-damage and wound healing in cultured skin cells (NHDF and HaCaT cells) and mouse model by using Sirt1 siRNA knockdown, cell migration assay, GST-Pulldown assay, western blot analysis, tube formation assay, and immunohistochemistry. Interestingly, Sirt1 knockdown inhibited skin cell migration in vitro. Juglone up regulated the expression of Sirt1 in both the cell lines under normal and UVB irradiated conditions, enhanced Sirt1 activity and increased the cell viability by reducing reactive oxygen species synthesis and apoptosis. Juglone promoted wound healing by increasing cell migration and angiogenesis through Cdc42/Rac1/PAK, MAPKs and Smad pathways in skin cells. NED416 upregulated Sirt1 expression in HaCaT and NHDF cells as well as increased Sirt1 activity. NED416 promoted the process of wound healing in early as well as later stages by increasing macrophage recruitment, skin cell migration, and angiogenesis through Cdc42/Rac1 and MAPKs pathways. So, both these compounds activated Sirt1 and promoted the process of wound healing thus pointing towards the possible role of Sirt1 in skin regeneration and wound healing.

Keywords: skin regeneration, wound healing, Sirt1, UVB light

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Authors: Anjan Hazra, Nirjhar Dasgupta, Chandan Sengupta, Sauren Das

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Tea (Camellia sinensis) has received substantial attention from the scientific world time to time, not only for its commercial importance, but also for its demand to the health-conscious people across the world for its extensive use as potential sources of antioxidant supplement. These health-benefit traits primarily rely on some regulatory networks of different metabolic pathways. Development of microsatellite markers from the conserved genomic regions is being worthwhile for studying the genetic diversity of closely related species or self-pollinated species. Although several SSR markers have been reported, in tea the trait-specific Simple Sequence Repeats (SSRs) are yet to be identified, which can be used for marker assisted breeding technique. MicroRNAs are endogenous, noncoding, short RNAs directly involved in regulating gene expressions at the post-transcriptional level. It has been found that diversity in miRNA gene interferes the formation of its characteristic hair pin structure and the subsequent function. In the present study, the precursors of small regulatory RNAs (microRNAs) has been fished out from tea Expressed Sequence Tag (EST) database. Furthermore, the simple sequence repeat motifs within the putative miRNA precursor genes are also identified in order to experimentally validate their existence and function. It is already known that genic-SSR markers are very adept and breeder-friendly source for genetic diversity analysis. So, the potential outcome of this in-silico study would provide some novel clues in understanding the miRNA-triggered polymorphic genic expression controlling specific metabolic pathways, accountable for tea quality.

Keywords: micro RNA, simple sequence repeats, tea quality, trait specific marker

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Authors: Sahana Selladurai, Christine DeWolf

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Lung surfactant comprises a lipid-protein film that coats the alveolar surface and serves to prevent alveolar collapse upon repeated breathing cycles. Exposure of lung surfactant to high concentrations of airborne pollutants, for example tropospheric ozone in smog, can chemically modify the lipid and protein components. These chemical changes can impact the film functionality by decreasing the film’s collapse pressure (minimum surface tension attainable), altering it is mechanical and flow properties and modifying lipid reservoir formation essential for re-spreading of the film during the inhalation process. In this study, we use Langmuir monolayers spread at the air-water interface as model membranes where the compression and expansion of the film mimics the breathing cycle. The impact of ozone exposure on model lung surfactant films is measured using a Langmuir film balance, Brewster angle microscopy and a pendant drop tensiometer as a function of film and sub-phase composition. The oxidized films are analyzed using mass spectrometry where lipid and protein oxidation products are observed. Oxidation is shown to reduce surface activity, alter line tension (and film morphology) and in some cases visibly reduce the viscoelastic properties of the film when compared to controls. These reductions in functionality of the films are highly dependent on film and sub-phase composition, where for example, the effect of oxidation is more pronounced when using a physiologically relevant buffer as opposed to water as the sub-phase. These findings can lead to a better understanding on the impact of continuous exposure to high levels of ozone on the mechanical process of breathing, as well as understanding the roles of certain lung surfactant components in this process.

Keywords: lung surfactant, oxidation, ozone, viscoelasticity

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Authors: Nur Ilya Farhana Md Noh, Zakiah Ahmad

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Heat treatment on timbers is a process of applying heat to modify and equip the timbers with new improvised characteristics. It is environmental friendly compared to the common practice of treating timber by chemical preservatives. Malaysian hardwood timbers; Pauh Kijang and Kapur in green condition were heat treated at 150°C, 170°C, 190°C and 210°C in a specially design electronic furnace in one hour duration. The objectives were to determine the effect of heat treatment on bending strength properties of heat treated Pauh Kijang and Kapur in term of Modulus of Elasticity (MOE) and Modulus of Rupture (MOR) and to examine the significance changes at each temperature levels applied. Untreated samples for each species were used as a control sample. The results indicated that the bending strength properties for both species of timbers were affected by the heat exposure. Both MOE and MOR values for heat treated Pauh Kijang were increased when subjected to the specified temperature levels except at 210°C. The values were dropped compared to the control sample and sample treated at 190°C. Heat treated Kapur shows the same pattern of increment on its MOE and MOR values after exposure to heat at three temperature levels used and the values dropped at 210°C. However, differ to Pauh Kijang, even though there were decrement occurred at 210°C but the value is still higher compared to the control sample. The increments of MOE and MOR values are an indicator that heat treatment had successfully improvised the bending strength properties of these two species of hardwood timber. As the good strength of Malaysian timbers used as structural material is limited in numbers and expensive, heat treating timber with low strength properties is an alternative way to overcome this issue. Heat treatment is an alternative method need to be explored and made available in Malaysia as this country is still practicing chemical preservative treatment on the timbers.

Keywords: bending strength, hardwood timber, heat treatment, modulus of elasticity (MOE), modulus of rupture (MOR)

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Authors: Shelly Sharma, Pooja Chadha

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Humans are exposed to pesticides and insecticides either directly or indirectly. Exposure to these pesticides may lead to acute toxicity to mammals and non-target organisms. Chlorpyrifos (CPF) is a broad spectrum organophosphate pesticide widely used in various countries of the world. The aim of the present study was to assess the toxicity associated with chlorpyrifos exposure and possible mitigating effect of cow urine against genotoxic and toxic effects in rat brain induced by chlorpyrifos. For this purpose LD50 was determined and rats were orally administered with 1/8th of LD50 (19mg/kg b.wt). Brain samples were taken after 24hrs, 48hrs and 72hrs of treatment. A significant increase in the % tail DNA was observed along with the increase in MDA levels of brain tissues in chlorpyrifos treated groups as compared to control. Cow urine treated groups show decrease in DNA damage and MDA levels as compared to CPF treated group. The study indicates that cow urine has ameliorative potential against neurotoxicity and genotoxicity induced by CPF. Cow urine is considered rich in vitamin A, E and volatile fatty acids which provide antioxidant potential to it. Thus, it can be used as a genoprotective agent.

Keywords: comet assay, brain, cow urine, genotoxicity, toxicity

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Authors: Erin M. Durke, Monica L. McEntee, Meilu He, Suresh Dhaniyala

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Aerosols are one of the most important and significant surfaces in the atmosphere. They can influence weather, absorption, and reflection of light, and reactivity of atmospheric constituents. A notable feature of aerosol particles is the presence of a surface charge, a characteristic imparted via the aerosolization process. The existence of charge can complicate the interrogation of aerosol particles, so many researchers remove or neutralize aerosol particles before characterization. However, the charge is present in real-world samples, and likely has an effect on the physical and chemical properties of an aerosolized material. In our studies, we aerosolized different materials in an attempt to characterize the charge imparted via the aerosolization process and determine what impact it has on the aerosolized materials’ properties. The metal oxides, TiO₂ and SiO₂, were aerosolized expulsively and then characterized, using several different techniques, in an effort to determine the surface charge imparted upon the particles via the aerosolization process. Particle charge distribution measurements were conducted via the employment of a custom scanning mobility particle sizer. The results of the charge distribution measurements indicated that expulsive generation of 0.2 µm SiO₂ particles produced aerosols with upwards of 30+ charges on the surface of the particle. Determination of the degree of surface charging led to the use of non-traditional techniques to explore the impact of additional surface charge on the overall reactivity of the metal oxides, specifically TiO₂. TiO₂ was aerosolized, again expulsively, onto a gold-coated tungsten mesh, which was then evaluated with transmission infrared spectroscopy in an ultra-high vacuum environment. The TiO₂ aerosols were exposed to O₂, H₂, and CO, respectively. Exposure to O₂ resulted in a decrease in the overall baseline of the aerosol spectrum, suggesting O₂ removed some of the surface charge imparted during aerosolization. Upon exposure to H₂, there was no observable rise in the baseline of the IR spectrum, as is typically seen for TiO₂, due to the population of electrons into the shallow trapped states and subsequent promotion of the electrons into the conduction band. This result suggests that the additional charge imparted via aerosolization fills the trapped states, therefore no rise is seen upon exposure to H₂. Dosing the TiO₂ aerosols with CO showed no adsorption of CO on the surface, even at lower temperatures (~100 K), indicating the additional charge on the aerosol surface prevents the CO molecules from adsorbing to the TiO₂ surface. The results observed during exposure suggest that the additional charge imparted via aerosolization impacts the interaction with each probe gas.

Keywords: aerosols, charge, reactivity, infrared

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Authors: Deginet Aklilu, Tianqi Wang, Endwoke Amsalu, Wei Feng, Zhiwei Li, Xia Li, Lixin Tao, Yanxia Luo, Moning Guo, Xiangtong Liu, Xiuhua Guo

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Extreme temperature-related cardiovascular diseases (CVDs) have become a growing public health concern. However, the impact of temperature on the cause of specific CVDs has not been well studied in the study area. The objective of this study was to assess the impact of temperature on cause-specific cardiovascular hospital admissions in Beijing, China. We obtained data from 172 large general hospitals from the Beijing Public Health Information Center Cardiovascular Case Database and China. Meteorological Administration covering 16 districts in Beijing from 2013 to 2017. We used a time-stratified case crossover design with a distributed lag nonlinear model (DLNM) to derive the impact of temperature on CVD in hospitals back to 27 days on CVD admissions. The temperature data were stratified as cold (extreme and moderate ) and hot (moderate and extreme ). Within five years (January 2013-December 2017), a total of 460,938 (male 54.9% and female 45.1%) CVD admission cases were reported. The exposure-response relationship for hospitalization was described by a "J" shape for the total and cause-specific. An increase in the six-day moving average temperature from moderate hot (30.2 °C) to extreme hot (36.9 °C) resulted in a significant increase in CVD admissions of 16.1%(95% CI = 12.8%-28.9%). However, the effect of cold temperature exposure on CVD admissions over a lag time of 0-27 days was found to be non significant, with a relative risk of 0.45 (95% CI = 0.378-0.55) for extreme cold (-8.5 °C)and 0.53 (95% CI = 0.47-0.60) for moderate cold (-5.6 °C). The results of this study indicate that exposure to extremely high temperatures is highly associated with an increase in cause-specific CVD admissions. These finding may guide to create and raise awareness of the general population, government and private sectors regarding on the effects of current weather conditions on CVD.

Keywords: admission, Beijing, cardiovascular diseases, distributed lag non linear model, temperature

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Authors: Jul Endawati

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The composite element of 20 mm in thickness were manufactured using high volume fly ash, silica fume as alternative hydraulic binders and Portland cement Type II. Pine wood shavel as by product of local small wood working industries were used as the composite filler. The elements were given in situ wet and dry treatment for 9 months. Visually there is no fiber degradation as a result of the interaction of the environment. The assessment were done to the elements bending strength and dimensional properties. Increase in MoR after 180 days of exposure shown that mechanically this degradation is not seen yet. The increment of MoR (213%) compare to that of 28 days might be affected by the formation of calcium hydroxide (CH) or ettringite in the transition zone. The use of pozzolan showed also a delay or minimize degradation of composites while improving the pore structure, and minimize the mineralization of the fiber bond with the cement matrix. The water absorption is 4,22% at 180 days, 7,94% at 120 days and 12,38% at 28 days, in line with the 68% decrease in Thickness Swelling (TS). This unoccured degradation could also be affected by the presence of silica fume in the binder matrix. After 270 days of exposure under tropical condition, the flexural strength started to decrease.

Keywords: durability, fly ash, natural fibre, silica fume

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Authors: Morgane Chatard, Clémentine Puech, Nathalie Perek, Frédéric Roche

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Several neurological disorders are linked to repeated hypoxia. The impact of such repeated hypoxic stress, on endothelial cells function of the blood-brain barrier (BBB) is little studied in the literature. Indeed, the study of hypoxic stress in cellular pathways is complex using hypoxia exposure because HIF 1α (factor induced by hypoxia) has a short half life. Our study presents an innovative induction method of repeated hypoxic stress, more reproducible, which allows us to study its impacts on an in vitro contact co-culture BBB model. Repeated hypoxic stress was induced by hydralazine (a mimetic agent of hypoxia pathway) during two hours and repeated during 24 hours. Then, BBB integrity was assessed by permeability measurements (transendothelial electrical resistance and membrane permeability), tight junction protein expressions (cell-ELISA and confocal microscopy) and by studying expression and activity of efflux transporters. First, this study showed that repeated hypoxic stress leads to a BBB’s dysfunction illustrated by a significant increase in permeability. This loss of membrane integrity was linked to a significant decrease of tight junctions’ protein expressions, facilitating a possible transfer of potential cytotoxic compounds in the brain. Secondly, we demonstrated that brain microvascular endothelial cells had set-up defence mechanism. These endothelial cells significantly increased the activity of their efflux transporters which was associated with a significant increase in their expression. In conclusion, repeated hypoxic stress lead to a loss of BBB integrity with a decrease of tight junction proteins. In contrast, endothelial cells increased the expression of their efflux transporters to fight against cytotoxic compounds brain crossing. Unfortunately, enhanced efflux activity could also lead to reducing pharmacological drugs delivering to the brain in such hypoxic conditions.

Keywords: BBB model, efflux transporters, repeated hypoxic stress, tigh junction proteins

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Authors: Kaoutar Chbihi, Aziza Menouni, Emilie Hardy, Matteo Creta, Nathalie Grova, An Van Nieuwenhuyse, Lode Godderis, Samir El Jaafari, Radu-Corneliu Duca

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Industrial products and materials are often treated with additional compounds like brominated flame retardants (BFRs) and heavy metals in order to prevent their ignition, increase their functionality and improve their performance like electrical conductivity. Consequently, this could potentially expose children to harmful chemicals through indoor dust and through hand-to-mouth or toy-chewing behaviors. The aim of this study was to assess the exposure of Moroccan children aged 5-11 years to BFRs and heavy metal elements and investigate their impacts on the epigenetic profile, namely through global DNA methylation modifications. First, parents were asked to answer a questionnaire on children’s lifestyle, then blood and urine samples were collected from (n= 93) children, following the ethical guidelines, for biomonitoring and DNA methylation analysis, using a set of solid phase extraction (SPE), LC-MS/MS, GC-MS/MS and ICP/MS techniques. BFRs were detected in 54.84% of samples with a median concentration of 0.01 nmol/mL (range: 0.004-0.051 nmol/mL), while metal elements were detected in more than 90% of samples. No association was found between BFRs and global DNA methylation, unlike metal element levels that showed significant variations with global DNA methylation biomarkers, namely 5-mdC, 5-OH-mdC and N⁶-mA levels. To conclude, Moroccan children could be significantly exposed to flame retardant compounds and heavy metal elements through several routes, such as dust or equipment usage and are therefore susceptible to the adverse health effects that could be linked with such chemicals. Further research is required to assess the exposure to environmental pollutants among the Moroccan population in order to protect Moroccan health and prevent the incidence of diseases.

Keywords: biomonitoring, children, DNA methylation, epigenetics, flame retardants, heavy metals, Morocco

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Authors: Prarthana Gowda, Tushar Sakorikar, Siva K. Reddy, Darim B. Ferry, Abha Misra

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Graphene, a two-dimensional carbon allotrope has demonstrated excellent electrical, mechanical and optical properties. A tunable band gap of grapheme demonstrated broad band absorption of light with a response time of picoseconds, however it suffers a fast recombination of the photo generated carriers. Many reports have explored to overcome this problem; in this presentation, we discuss defect induced enhanced photoresponse in a few layer graphene (FLG) due to exposure of infrared (IR) radiation. The two and four-fold enhancement in the photocurrent is achieved by addition of multiwalled carbon nano tubes (MWCNT) to an FLG surface and also creating the wrinkles in the FLG (WG) respectively. In our study, it is also inferred that the photo current generation is highly dependent on the morphological defects on the graphene. It is observed that the FLG (without defects) generates the photo current instantaneously, and after a prolonged exposure to the IR radiation decays the generation rate. Importantly, the presence of MWCNT on FLG enhances the stability and WG presented both stable as well as enhanced photo response.

Keywords: graphene, multiwalled carbon nano tubes, wrinkled graphene, photo detector, photo current

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Authors: Betül Sönmez, Aytolan Yıldırım

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Objective: This systematic review aims to methodically analyze studies regarding mobbing behavior prevalence, individuals performing this behavior and the effects of mobbing on Turkish nurses. Background: Worldwide reports on mobbing cases have increased in the past years, a similar trend also observable in Turkey. It has been demonstrated that among healthcare workers, mobbing is significantly widespread in nurses. The number of studies carried out in this regard has also increased. Method: The main criteria for choosing articles in this systematic review were nurses located in Turkey, regardless of any specific date. In November 2014, a search using the keywords 'mobbing, bullying, psychological terror/violence, emotional violence, nurses, healthcare workers, Turkey' in PubMed, Science Direct, Ebscohost, National Thesis Centre database and Google search engine led to 71 studies in this field. 33 studies were not met the inclusion criteria specified for this study. Results: The findings were obtained using the results of 38 studies carried out in the past 13 years in Turkey, a large sample consisting of 8,877 nurses. Analysis of the incidences of mobbing behavior revealed a broad spectrum, ranging from none-slight experiences to 100% experiences. The most frequently observed mobbing behaviors include attacking personality, blocking communication and attacking professional and social reputation. Victims mostly experienced mobbing from their managers, the most common consequence of these actions being psychological effects. Conclusions: The results of studies with various scales indicate exposure of nurses to similar mobbing behavior. The high frequency of exposure of nurses to mobbing behavior in such a large sample highlights the importance of considering this issue in terms of individual and institutional consequences that adversely affect the performance of nurses.

Keywords: mobbing, bullying, workplace violence, nurses, Turkey

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Authors: Eduardo Kanagushiku Pereira, Frank Gregory Cavalcante da Silva, Barbara Soares Gonçalves, Ana Lúcia Bergamasco Galastri, Ronei Luciano Mamoni

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The inflammatory response initiates after the recognition of pathogens by receptors expressed by innate immune cells. Among these receptors, the NLRP3 was associated with the recognition of pathogenic fungi in experimental models. NLRP3 operates forming a multiproteic complex called inflammasome, which actives caspase-1, responsible for the production of the inflammatory cytokines IL-1beta and IL-18. In this study, we aimed to investigate the involvement of NLRP3 in the inflammatory response elicited in macrophages against Paracoccidioides brasiliensis (Pb), the etiologic agent of PCM. Macrophages were differentiated from THP-1 cells by treatment with phorbol-myristate-acetate. Following differentiation, macrophages were stimulated by Pb yeast cells for 24 hours, after previous treatment with specific NLRP3 (3,4-methylenedioxy-beta-nitrostyrene) and/or caspase-1 (VX-765) inhibitors, or specific inhibitors of pathways involved in NLRP3 activation such as: Reactive Oxigen Species (ROS) production (N-Acetyl-L-cysteine), K+ efflux (Glibenclamide) or phagossome acidification (Bafilomycin). Quantification of IL-1beta and IL-18 in supernatants was performed by ELISA. Our results showed that the production of IL-1beta and IL-18 by THP-1-derived-macrophages stimulated with Pb yeast cells was dependent on NLRP3 and caspase-1 activation, once the presence of their specific inhibitors diminished the production of these cytokines. Furthermore, we found that the major pathways involved in NLRP3 activation, after Pb recognition, were dependent on ROS production and K+ efflux. In conclusion, our results showed that NLRP3 participates in the recognition of Pb yeast cells by macrophages, leading to the activation of the NLRP3-inflammasome and production of IL-1beta and IL-18. Together, these cytokines can induce an inflammatory response against P. brasiliensis, essential for the establishment of the initial inflammatory response and for the development of the subsequent acquired immune response.

Keywords: inflammation, IL-1beta, IL-18, NLRP3, Paracoccidioidomycosis

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Authors: Azza A. Ali, Doaa M. Abd El-Latif, Amany M. Gad, Yasser M. A. Elnahas, Karema Abu-Elfotuh

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Background: Exposure to Aluminium (Al) has been increased recently. It is found in food products, food additives, drinking water, cosmetics and medicines. Chronic consumption of Al causes oxidative stress and has been implicated in several chronic disorders. Liver is considered as the major site for detoxification while kidney is involved in the elimination of toxic substances and is a target organ of metal toxicity. Social isolation (SI) or protein malnutrition (PM) also causes oxidative stress and has negative impact on Al-induced nephrotoxicity as well as hepatotoxicity. Coenzyme Q10 (CoQ10) is a powerful intracellular antioxidant with mitochondrial membrane stabilizing ability while wheat grass is a natural product with antioxidant, anti-inflammatory and different protective activities, cocoa is also potent antioxidants and can protect against many diseases. They provide different degrees of protection from the impact of oxidative stress. Objective: To study the impact of social isolation together with Protein malnutrition on nephro- and hepato-toxicity induced by chronic Al exposure in rats as well as to investigate the postulated protection using a combination of Co Q10, wheat grass and cocoa. Methods: Eight groups of rats were used; four served as protected groups and four as un-protected. Each of them received daily for five weeks AlCl3 (70 mg/kg, IP) for Al-toxicity model groups except one group served as control. Al-toxicity model groups were divided to Al-toxicity alone, SI- associated PM (10% casein diet) and Al- associated SI&PM groups. Protection was induced by oral co-administration of CoQ10 (200mg/kg), wheat grass (100mg/kg) and cocoa powder (24mg/kg) combination together with Al. Biochemical changes in total bilirubin, lipids, cholesterol, triglycerides, glucose, proteins, creatinine and urea as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate deshydrogenase (LDH) were measured in serum of all groups. Specimens of kidney and liver were used for assessment of oxidative parameters (MDA, SOD, TAC, NO), inflammatory mediators (TNF-α, IL-6β, nuclear factor kappa B (NF-κB), Caspase-3) and DNA fragmentation in addition to evaluation of histopathological changes. Results: SI together with PM severely enhanced nephro- and hepato-toxicity induced by chronic Al exposure. Co Q10, wheat grass and cocoa combination showed clear protection against hazards of Al exposure either alone or when associated with SI&PM. Their protection were indicated by the significant decrease in Al-induced elevations in total bilirubin, lipids, cholesterol, triglycerides, glucose, creatinine and urea levels as well as ALT, AST, ALP, LDH. Liver and kidney of the treated groups also showed significant decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation, together with significant increase in total proteins, SOD and TAC. Biochemical results were confirmed by the histopathological examinations. Conclusion: SI together with PM represents a risk factor in enhancing nephro- and hepato-toxicity induced by Al in rats. CoQ10, wheat grass and cocoa combination provide clear protection against nephro- and hepatotoxicity as well as the consequent degenerations induced by chronic Al-exposure even when associated with the risk of SI together with PM.

Keywords: aluminum, nephrotoxicity, hepatotoxicity, isolation and protein malnutrition, coenzyme Q10, wheatgrass, cocoa, nutrients combinations

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