Search results for: anti-tubercular therapy induced hepatotoxicity
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Search results for: anti-tubercular therapy induced hepatotoxicity

120 Effect of Non-Thermal Plasma, Chitosan and Polymyxin B on Quorum Sensing Activity and Biofilm of Pseudomonas aeruginosa

Authors: Alena Cejkova, Martina Paldrychova, Jana Michailidu, Olga Matatkova, Jan Masak

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Increasing the resistance of pathogenic microorganisms to many antibiotics is a serious threat to the treatment of infectious diseases and cleaning medical instruments. It should be added that the resistance of microbial populations growing in biofilms is often up to 1000 times higher compared to planktonic cells. Biofilm formation in a number of microorganisms is largely influenced by the quorum sensing regulatory mechanism. Finding external factors such as natural substances or physical processes that can interfere effectively with quorum sensing signal molecules should reduce the ability of the cell population to form biofilm and increase the effectiveness of antibiotics. The present work is devoted to the effect of chitosan as a representative of natural substances with anti-biofilm activity and non- thermal plasma (NTP) alone or in combination with polymyxin B on biofilm formation of Pseudomonas aeruginosa. Particular attention was paid to the influence of these agents on the level of quorum sensing signal molecules (acyl-homoserine lactones) during planktonic and biofilm cultivations. Opportunistic pathogenic strains of Pseudomonas aeruginosa (DBM 3081, DBM 3777, ATCC 10145, ATCC 15442) were used as model microorganisms. Cultivations of planktonic and biofilm populations in 96-well microtiter plates on horizontal shaker were used for determination of antibiotic and anti-biofilm activity of chitosan and polymyxin B. Biofilm-growing cells on titanium alloy, which is used for preparation of joint replacement, were exposed to non-thermal plasma generated by cometary corona with a metallic grid for 15 and 30 minutes. Cultivation followed in fresh LB medium with or without chitosan or polymyxin B for next 24 h. Biofilms were quantified by crystal violet assay. Metabolic activity of the cells in biofilm was measured using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) colorimetric test based on the reduction of MTT into formazan by the dehydrogenase system of living cells. Activity of N-acyl homoserine lactones (AHLs) compounds involved in the regulation of biofilm formation was determined using Agrobacterium tumefaciens strain harboring a traG::lacZ/traR reporter gene responsive to AHLs. The experiments showed that both chitosan and non-thermal plasma reduce the AHLs level and thus the biofilm formation and stability. The effectiveness of both agents was somewhat strain dependent. During the eradication of P. aeruginosa DBM 3081 biofilm on titanium alloy induced by chitosan (45 mg / l) there was an 80% decrease in AHLs. Applying chitosan or NTP on the P. aeruginosa DBM 3777 biofilm did not cause a significant decrease in AHLs, however, in combination with both (chitosan 55 mg / l and NTP 30 min), resulted in a 70% decrease in AHLs. Combined application of NTP and polymyxin B allowed reduce antibiotic concentration to achieve the same level of AHLs inhibition in P. aeruginosa ATCC 15442. The results shown that non-thermal plasma and chitosan have considerable potential for the eradication of highly resistant P. aeruginosa biofilms, for example on medical instruments or joint implants.

Keywords: anti-biofilm activity, chitosan, non-thermal plasma, opportunistic pathogens

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119 Comparing Radiographic Detection of Simulated Syndesmosis Instability Using Standard 2D Fluoroscopy Versus 3D Cone-Beam Computed Tomography

Authors: Diane Ghanem, Arjun Gupta, Rohan Vijayan, Ali Uneri, Babar Shafiq

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Introduction: Ankle sprains and fractures often result in syndesmosis injuries. Unstable syndesmotic injuries result from relative motion between the distal ends of the tibia and fibula, anatomic juncture which should otherwise be rigid, and warrant operative management. Clinical and radiological evaluations of intraoperative syndesmosis stability remain a challenging task as traditional 2D fluoroscopy is limited to a uniplanar translational displacement. The purpose of this pilot cadaveric study is to compare the 2D fluoroscopy and 3D cone beam computed tomography (CBCT) stress-induced syndesmosis displacements. Methods: Three fresh-frozen lower legs underwent 2D fluoroscopy and 3D CIOS CBCT to measure syndesmosis position before dissection. Syndesmotic injury was simulated by resecting the (1) anterior inferior tibiofibular ligament (AITFL), the (2) posterior inferior tibiofibular ligament (PITFL) and the inferior transverse ligament (ITL) simultaneously, followed by the (3) interosseous membrane (IOM). Manual external rotation and Cotton stress test were performed after each of the three resections and 2D and 3D images were acquired. Relevant 2D and 3D parameters included the tibiofibular overlap (TFO), tibiofibular clear space (TCS), relative rotation of the fibula, and anterior-posterior (AP) and medial-lateral (ML) translations of the fibula relative to the tibia. Parameters were measured by two independent observers. Inter-rater reliability was assessed by intraclass correlation coefficient (ICC) to determine measurement precision. Results: Significant mismatches were found in the trends between the 2D and 3D measurements when assessing for TFO, TCS and AP translation across the different resection states. Using 3D CBCT, TFO was inversely proportional to the number of resected ligaments while TCS was directly proportional to the latter across all cadavers and ‘resection + stress’ states. Using 2D fluoroscopy, this trend was not respected under the Cotton stress test. 3D AP translation did not show a reliable trend whereas 2D AP translation of the fibula was positive under the Cotton stress test and negative under the external rotation. 3D relative rotation of the fibula, assessed using the Tang et al. ratio method and Beisemann et al. angular method, suggested slight overall internal rotation with complete resection of the ligaments, with a change < 2mm - threshold which corresponds to the commonly used buffer to account for physiologic laxity as per clinical judgment of the surgeon. Excellent agreement (>0.90) was found between the two independent observers for each of the parameters in both 2D and 3D (overall ICC 0.9968, 95% CI 0.995 - 0.999). Conclusions: The 3D CIOS CBCT appears to reliably depict the trend in TFO and TCS. This might be due to the additional detection of relevant rotational malpositions of the fibula in comparison to the standard 2D fluoroscopy which is limited to a single plane translation. A better understanding of 3D imaging may help surgeons identify the precise measurements planes needed to achieve better syndesmosis repair.

Keywords: 2D fluoroscopy, 3D computed tomography, image processing, syndesmosis injury

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118 Brittle Fracture Tests on Steel Bridge Bearings: Application of the Potential Drop Method

Authors: Natalie Hoyer

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Usually, steel structures are designed for the upper region of the steel toughness-temperature curve. To address the reduced toughness properties in the temperature transition range, additional safety assessments based on fracture mechanics are necessary. These assessments enable the appropriate selection of steel materials to prevent brittle fracture. In this context, recommendations were established in 2011 to regulate the appropriate selection of steel grades for bridge bearing components. However, these recommendations are no longer fully aligned with more recent insights: Designing bridge bearings and their components in accordance with DIN EN 1337 and the relevant sections of DIN EN 1993 has led to an increasing trend of using large plate thicknesses, especially for long-span bridges. However, these plate thicknesses surpass the application limits specified in the national appendix of DIN EN 1993-2. Furthermore, compliance with the regulations outlined in DIN EN 1993-1-10 regarding material toughness and through-thickness properties requires some further modifications. Therefore, these standards cannot be directly applied to the material selection for bearings without additional information. In addition, recent findings indicate that certain bridge bearing components are subjected to high fatigue loads, necessitating consideration in structural design, material selection, and calculations. To address this issue, the German Center for Rail Traffic Research initiated a research project aimed at developing a proposal to enhance the existing standards. This proposal seeks to establish guidelines for the selection of steel materials for bridge bearings to prevent brittle fracture, particularly for thick plates and components exposed to specific fatigue loads. The results derived from theoretical analyses, including finite element simulations and analytical calculations, are verified through component testing on a large-scale. During these large-scale tests, where a brittle failure is deliberately induced in a bearing component, an artificially generated defect is introduced into the specimen at the predetermined hotspot. Subsequently, a dynamic load is imposed until the crack initiation process transpires, replicating realistic conditions akin to a sharp notch resembling a fatigue crack. To stop the action of the dynamic load in time, it is important to precisely determine the point at which the crack size transitions from stable crack growth to unstable crack growth. To achieve this, the potential drop measurement method is employed. The proposed paper informs about the choice of measurement method (alternating current potential drop (ACPD) or direct current potential drop (DCPD)), presents results from correlations with created FE models, and may proposes a new approach to introduce beach marks into the fracture surface within the framework of potential drop measurement.

Keywords: beach marking, bridge bearing design, brittle fracture, design for fatigue, potential drop

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117 Academic Major, Gender, and Perceived Helpfulness Predict Help-Seeking Stigma

Authors: Tran Tran

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Mental health issues are prevalent among Vietnamese undergraduate students, and they are greatly exacerbated during the COVID-19 pandemic for this population. While there is empirical evidence supporting the effectiveness and efficiency of therapy on mental health issues among college students, the rates of Vietnamese college students seeking professional mental health services were alarmingly low. Multiple factors can prevent those in need from finding support. The Internalized Stigma Model posits that public stigma directly affects intentions to seek psychological help via self-stigma and attitudes toward seeking help. However, little research has focused on what factors can predict public stigma toward seeking professional psychological support, especially among this population. A potential predictor is academic majors since academic majors can influence undergraduate students' perceptions, attitudes, and intentions. A study suggested that students who have completed two or more psychology courses have a more positive attitude toward seeking care for mental health issues and reduced stigma, which might be attributed to increased mental health literacy. In addition, research has shown that women are more likely to utilize mental health services and have lower stigma than men. Finally, studies have also suggested that experience of mental health services can increase endorsement of perceived need and lower stigma. Thus, it is expected that perceived helpfulness from past service uses can reduce stigma. This study aims to address this gap in the literature and investigate which factors can predict public stigma, specifically academic major, gender, and perceived helpfulness, potentially suggesting an avenue of prevention and ultimately improving the well-being of Vietnamese college students. The sample includes 408 undergraduate students (Mage = 20.44; 80.88% female) Hanoi city, Vietnam. Participants completed a pen-and-paper questionnaire. Students completed the Stigma Scale for Receiving Psychological Help, which yielded a mean public stigma score. Participants also completed a measurement assessing their perceived helpfulness of their university’s counseling center, which included eight subscales: future self-development, learning issues, career counseling, medical and health issues, mental health issues, conflicts between teachers and students, conflicts between parents and students, and interpersonal relationships. Items were summed to create a composite perceived helpfulness score. Finally, participants provided demographic information. This included gender, which was dichotomized between female and other. Additionally, it included academic major, which was also similarly dichotomized between psychology and other (e.g., natural science, social science, and pedagogy & social work). Linear relationships between public stigma and gender, academic major, and perceived helpfulness were analyzed individually with a regression model. Findings suggested that academic major, gender, and perceived counseling center's helpfulness predicted stigma against seeking professional psychological help. Specifically, being a psychology major predicted lower levels of public stigma (β = -.25, p < .001). Additionally, gender female predicted lower levels of public stigma (β = -.11, p < .05). Lastly, higher levels of perceived helpfulness of the counseling center also predicted lower levels of public stigma (β = -.16, p < .01). The study’s results offer potential intervention avenues to help reduce stigma and increase well-being for Vietnamese college students.

Keywords: stigma, vietnamese college students, counseling services, help-seeking

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116 Formulation and Optimization of Self Nanoemulsifying Drug Delivery System of Rutin for Enhancement of Oral Bioavailability Using QbD Approach

Authors: Shrestha Sharma, Jasjeet K. Sahni, Javed Ali, Sanjula Baboota

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Introduction: Rutin is a naturally occurring strong antioxidant molecule belonging to bioflavonoid category. Due to its free radical scavenging properties, it has been found to be beneficial in the treatment of various diseases including inflammation, cancer, diabetes, allergy, cardiovascular disorders and various types of microbial infections. Despite its beneficial effects, it suffers from the problem of low aqueous solubility which is responsible for low oral bioavailability. The aim of our study was to optimize and characterize self-nanoemulsifying drug delivery system (SNEDDS) of rutin using Box-Behnken design (BBD) combined with a desirability function. Further various antioxidant, pharmacokinetic and pharmacodynamic studies were performed for the optimized rutin SNEDDS formulation. Methodologies: Selection of oil, surfactant and co-surfactant was done on the basis of solubility/miscibility studies. Sefsol+ Vitamin E, Solutol HS 15 and Transcutol P were selected as oil phase, surfactant and co-surfactant respectively. Optimization of SNEDDS formulations was done by a three-factor, three-level (33)BBD. The independent factors were Sefsol+ Vitamin E, Solutol HS15, and Transcutol P. The dependent variables were globule size, self emulsification time (SEF), % transmittance and cumulative percentage drug released. Various response surface graphs and contour plots were constructed to understand the effect of different factor, their levels and combinations on the responses. The optimized Rutin SNEDDS formulation was characterized for various parameters such as globule size, zeta potential, viscosity, refractive index , % Transmittance and in vitro drug release. Ex vivo permeation studies and pharmacokinetic studies were performed for optimized formulation. Antioxidant activity was determined by DPPH and reducing power assays. Anti-inflammatory activity was determined by using carrageenan induced rat paw oedema method. Permeation of rutin across small intestine was assessed using confocal laser scanning microscopy (CLSM). Major findings:The optimized SNEDDS formulation consisting of Sefsol+ Vitamin E - Solutol HS15 -Transcutol HP at proportions of 25:35:17.5 (w/w) was prepared and a comparison of the predicted values and experimental values were found to be in close agreement. The globule size and PDI of optimized SNEDDS formulation was found to be 16.08 ± 0.02 nm and 0.124±0.01 respectively. Significant (p˂0.05) increase in percentage drug release was achieved in the case of optimized SNEDDS formulation (98.8 %) as compared to rutin suspension. Furthermore, pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability compared with that of the suspension. Antioxidant assay results indicated better efficacy of the developed formulation than the pure drug and it was found to be comparable with ascorbic acid. The results of anti-inflammatory studies showed 72.93 % inhibition for the SNEDDS formulation which was significantly higher than the drug suspension 46.56%. The results of CLSM indicated that the absorption of SNEDDS formulation was considerably higher than that from rutin suspension. Conclusion: Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing oral bioavailability and efficacy of Rutin.

Keywords: rutin, oral bioavilability, pharamacokinetics, pharmacodynamics

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115 Numerical Modeling of Timber Structures under Varying Humidity Conditions

Authors: Sabina Huč, Staffan Svensson, Tomaž Hozjan

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Timber structures may be exposed to various environmental conditions during their service life. Often, the structures have to resist extreme changes in the relative humidity of surrounding air, with simultaneously carrying the loads. Wood material response for this load case is seen as increasing deformation of the timber structure. Relative humidity variations cause moisture changes in timber and consequently shrinkage and swelling of the material. Moisture changes and loads acting together result in mechano-sorptive creep, while sustained load gives viscoelastic creep. In some cases, magnitude of the mechano-sorptive strain can be about five times the elastic strain already at low stress levels. Therefore, analyzing mechano-sorptive creep and its influence on timber structures’ long-term behavior is of high importance. Relatively many one-dimensional rheological models for rheological behavior of wood can be found in literature, while a number of models coupling creep response in each material direction is limited. In this study, mathematical formulation of a coupled two-dimensional mechano-sorptive model and its application to the experimental results are presented. The mechano-sorptive model constitutes of a moisture transport model and a mechanical model. Variation of the moisture content in wood is modelled by multi-Fickian moisture transport model. The model accounts for processes of the bound-water and water-vapor diffusion in wood, that are coupled through sorption hysteresis. Sorption defines a nonlinear relation between moisture content and relative humidity. Multi-Fickian moisture transport model is able to accurately predict unique, non-uniform moisture content field within the timber member over time. Calculated moisture content in timber members is used as an input to the mechanical analysis. In the mechanical analysis, the total strain is assumed to be a sum of the elastic strain, viscoelastic strain, mechano-sorptive strain, and strain due to shrinkage and swelling. Mechano-sorptive response is modelled by so-called spring-dashpot type of a model, that proved to be suitable for describing creep of wood. Mechano-sorptive strain is dependent on change of moisture content. The model includes mechano-sorptive material parameters that have to be calibrated to the experimental results. The calibration is made to the experiments carried out on wooden blocks subjected to uniaxial compressive loaded in tangential direction and varying humidity conditions. The moisture and the mechanical model are implemented in a finite element software. The calibration procedure gives the required, distinctive set of mechano-sorptive material parameters. The analysis shows that mechano-sorptive strain in transverse direction is present, though its magnitude and variation are substantially lower than the mechano-sorptive strain in the direction of loading. The presented mechano-sorptive model enables observing real temporal and spatial distribution of the moisture-induced strains and stresses in timber members. Since the model’s suitability for predicting mechano-sorptive strains is shown and the required material parameters are obtained, a comprehensive advanced analysis of the stress-strain state in timber structures, including connections subjected to constant load and varying humidity is possible.

Keywords: mechanical analysis, mechano-sorptive creep, moisture transport model, timber

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114 Ectopic Osteoinduction of Porous Composite Scaffolds Reinforced with Graphene Oxide and Hydroxyapatite Gradient Density

Authors: G. M. Vlasceanu, H. Iovu, E. Vasile, M. Ionita

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Herein, the synthesis and characterization of chitosan-gelatin highly porous scaffold reinforced with graphene oxide, and hydroxyapatite (HAp), crosslinked with genipin was targeted. In tissue engineering, chitosan and gelatin are two of the most robust biopolymers with wide applicability due to intrinsic biocompatibility, biodegradability, low antigenicity properties, affordability, and ease of processing. HAp, per its exceptional activity in tuning cell-matrix interactions, is acknowledged for its capability of sustaining cellular proliferation by promoting bone-like native micro-media for cell adjustment. Genipin is regarded as a top class cross-linker, while graphene oxide (GO) is viewed as one of the most performant and versatile fillers. The composites with natural bone HAp/biopolymer ratio were obtained by cascading sonochemical treatments, followed by uncomplicated casting methods and by freeze-drying. Their structure was characterized by Fourier Transform Infrared Spectroscopy and X-ray Diffraction, while overall morphology was investigated by Scanning Electron Microscopy (SEM) and micro-Computer Tomography (µ-CT). Ensuing that, in vitro enzyme degradation was performed to detect the most promising compositions for the development of in vivo assays. Suitable GO dispersion was ascertained within the biopolymer mix as nanolayers specific signals lack in both FTIR and XRD spectra, and the specific spectral features of the polymers persisted with GO load enhancement. Overall, correlations between the GO induced material structuration, crystallinity variations, and chemical interaction of the compounds can be correlated with the physical features and bioactivity of each composite formulation. Moreover, the HAp distribution within follows an auspicious density gradient tuned for hybrid osseous/cartilage matter architectures, which were mirrored in the mice model tests. Hence, the synthesis route of a natural polymer blend/hydroxyapatite-graphene oxide composite material is anticipated to emerge as influential formulation in bone tissue engineering. Acknowledgement: This work was supported by the project 'Work-based learning systems using entrepreneurship grants for doctoral and post-doctoral students' (Sisteme de invatare bazate pe munca prin burse antreprenor pentru doctoranzi si postdoctoranzi) - SIMBA, SMIS code 124705 and by a grant of the National Authority for Scientific Research and Innovation, Operational Program Competitiveness Axis 1 - Section E, Program co-financed from European Regional Development Fund 'Investments for your future' under the project number 154/25.11.2016, P_37_221/2015. The nano-CT experiments were possible due to European Regional Development Fund through Competitiveness Operational Program 2014-2020, Priority axis 1, ID P_36_611, MySMIS code 107066, INOVABIOMED.

Keywords: biopolymer blend, ectopic osteoinduction, graphene oxide composite, hydroxyapatite

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113 Dissocial Personality in Adolescents

Authors: Tsirekidze M., Aprasidze T.

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Introduction: The problem of dissocial behavior is at the heart of the social sciences and psychiatry; however, it should be noted that its psychiatric aspect is little studied, and some issues of the problem are still controversial. This is complicated by the diversity of terminological concepts in defining “dissocial behavior”, “behavioral disorder”, “abnormal behavior”, “deviant behavior”, “delinquent behavior”, etc. In literature, there is no comprehensive definition of the essence of dissociative behavior. Numerous attempts to systematize dissociative disorders should also be considered unsatisfactory, which is primarily related to the lack of solid criteria for defining this group of disorders. According to the clinical classification, dissocial behavior is divided into psychotic and non-psychotic forms. Such differentiation is conditional in nature since it is not always possible to draw precise, clear distinctions between these forms, and in addition, there is a transition of a behavior disorder or so-called intermediate forms. One group of authors distinguishes two main forms of deviant behavior in terms of both theoretical and practical significance - non-pathological and pathological. In recent years, especially, the non-pathological form of behavior disorder has become topical. It refers to a large group of forms of deviant behavior, the emergence of which is associated with psychologically full-fledged reactions of children and adolescents to stressful situations and extreme conditions. According to the authors, its concept is understandable-it is difficult to draw a line between psychologically understandable reactions and psychogenically induced reactive states. In addition, the concept of "normal" child and adolescent is, to some extent, a vague concept, as in medicine, any definition of the norm. From a practical (more precisely, pragmatic) point of view, the term "abnormal behavioral disorder" undoubtedly makes sense, especially for the purpose of forensic psychiatric examination. Non-pathological deviation mainly includes transient situational reactions, microsocial-pedagogical backwardness, and character accentuation.Deviant behavior was predominantly manifested in a non-pathological form, which, in our opinion, is due to the difficult socio-economic situation of the country, moral-ethical deprivation, and expressed frustration. By itself, society is an indicator of deviation. Add to this situation complicated factors such as micro-social-pedagogical leave, unfavorable family environment, and parenting defects. Consideration is also given to the connection of acceptable deviation with the personal structural features of the adolescent. Aim: The topic of our discussion is the dissocial behavior of the non-psychotic register. Methods: We surveyed 120 adolescents with deviant behaviors. 61% of them were diagnosed with various neuropsychiatric disorders. Results: Abnormal forms of deviant behavior were observed in 13%, and non-pathological forms in -69%. A combination of non-pathological and pathological forms was present in 10% of cases. In the case of non-pathological deviation, microsocial-pedagogical acceptance was revealed in 62%, character accentuation in 22%; during the pathological forms, pathological reactions were observed in 21%, and abnormal formation of the person -21%. Conclusion: It should be emphasized that in case of any of the above defects, if the so-called family psychosis, and medical and pedagogical habilitation measures for the adolescent, it is quite possible to prevent the abnormal development of the child's personality, correct his character, regulate behavior and develop positive labor-social relations.

Keywords: dissocial personality, deviant behavior, dissocial, delinquent behavior

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112 Testicular Differential MicroRNA Expression Derived Occupational Risk Factor Assessment in Idiopathic Non-obstructive Azoospermia Cases

Authors: Nisha Sharma, Mili Kaur, Ashutosh Halder, Seema Kaushal, Manoj Kumar, Manish Jain

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Purpose: To investigate microRNAs (miRNA) as an epigenomic etiological factor in idiopathic non-obstructive azoospermia (NOA). In order to achieve the same, an association was seen between occupational exposure to radiation, thermal, and chemical factors and idiopathic cases of non-obstructive azoospermia, and later, testicular differential miRNA expression profiling was done in exposure group NOA cases. Method: It is a prospective study in which 200 apparent idiopathic male factor infertility cases, who have been advised to undergo testicular fine needle aspiration (FNA) evaluation, are recruited. A detailed occupational history was taken to understand the possible type of exposure due to the nature and duration of work. A total of 26 patients were excluded upon XY-FISH and Yq microdeletion tests due to the presence of genetic causes of infertility, 6 hypospermatogeneis (HS), six Sertoli cell-only syndrome (SCOS), and six normospermatogeneis patients testicular FNA samples were used for RNA isolation followed by small RNA sequencing and nCounter miRNA expression analysis. Differential miRNA expression profile of HS and SCOS patients was done. A web-based tool, miRNet, was used to predict the interacting compounds or chemicals using the shortlisted miRNAs with high fold change. The major limitation encountered in this study was the insufficient quantity of testicular FNA sample used for total RNA isolation, which resulted in a low yield and RNA integrity number (RIN) value. Therefore, the number of RNA samples admissible for differential miRNA expression analysis was very small in comparison to the total number of patients recruited. Results: Differential expression analysis revealed 69 down-regulated and 40 up-regulated miRNAs in HS and 66 down-regulated and 33 up-regulated miRNAs in SCOS in comparison to normospermatogenesis controls. The miRNA interaction analysis using the miRNet tool showed that the differential expression profiles of HS and SCOS patients were associated with arsenic trioxide, bisphenol-A, calcium sulphate, lithium, and cadmium. These compounds are reproductive toxins and might be responsible for miRNA-mediated epigenetic deregulation leading to NOA. The association between occupational risk factor exposure and the non-exposure group of NOA patients was not statistically significant, with ꭓ2 (3, N= 178) = 6.70, p= 0.082. The association between individual exposure groups (radiation, thermal, and chemical) and various sub-types of NOA is also not significant, with ꭓ2 (9, N= 178) = 15.06, p= 0.089. Functional analysis of HS and SCOS patients' miRNA profiles revealed some important miR-family members in terms of male fertility. The miR-181 family plays a role in the differentiation of spermatogonia and spermatocytes, as well as the transcriptional regulation of haploid germ cells. The miR-34 family is expressed in spermatocytes and round spermatids and is involved in the regulation of SSCs differentiation. Conclusion: The reproductive toxins might adopt the miRNA-mediated mechanism of disease development in idiopathic cases of NOA. Chemical compound induced; miRNA-mediated epigenetic deregulation can give a future perspective on the etiopathogenesis of the disease.

Keywords: microRNA, non-obstructive azoospermia (NOA), occupational exposure, hypospermatogenesis (HS), Sertoli cell only syndrome (SCOS)

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111 Correlation of Clinical and Sonographic Findings with Cytohistology for Diagnosis of Ovarian Tumours

Authors: Meenakshi Barsaul Chauhan, Aastha Chauhan, Shilpa Hurmade, Rajeev Sen, Jyotsna Sen, Monika Dalal

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Introduction: Ovarian masses are common forms of neoplasm in women and represent 2/3rd of gynaecological malignancies. A pre-operative suggestion of malignancy can guide the gynecologist to refer women with suspected pelvic mass to a gynecological oncologist for appropriate therapy and optimized treatment, which can improve survival. In the younger age group preoperative differentiation into benign or malignant pathology can decide for conservative or radical surgery. Imaging modalities have a definite role in establishing the diagnosis. By using International Ovarian Tumor Analysis (IOTA) classification with sonography, costly radiological methods like Magnetic Resonance Imaging (MRI) / computed tomography (CT) scan can be reduced, especially in developing countries like India. Thus, this study is being undertaken to evaluate the role of clinical methods and sonography for diagnosis of the nature of the ovarian tumor. Material And Methods: This prospective observational study was conducted on 40 patients presenting with ovarian masses, in the Department of Obstetrics and Gynaecology, at a tertiary care center in northern India. Functional cysts were excluded. Ultrasonography and color Doppler were performed on all the cases.IOTA rules were applied, which take into account locularity, size, presence of solid components, acoustic shadow, dopper flow etc . Magnetic Resonance Imaging (MRI) / computed tomography (CT) scans abdomen and pelvis were done in cases where sonography was inconclusive. In inoperable cases, Fine needle aspiration cytology (FNAC) was done. The histopathology report after surgery and cytology report after FNAC was correlated statistically with the pre-operative diagnosis made clinically and sonographically using IOTA rules. Statistical Analysis: Descriptive measures were analyzed by using mean and standard deviation and the Student t-test was applied and the proportion was analyzed by applying the chi-square test. Inferential measures were analyzed by sensitivity, specificity, negative predictive value, and positive predictive value. Results: Provisional diagnosis of the benign tumor was made in 16(42.5%) and of the malignant tumor was made in 24(57.5%) patients on the basis of clinical findings. With IOTA simple rules on sonography, 15(37.5%) were found to be benign, while 23 (57.5%) were found to be malignant and findings were inconclusive in 2 patients (5%). FNAC/Histopathology reported that benign ovarian tumors were 14 (35%) and 26(65%) were malignant, which was taken as the gold standard. The clinical finding alone was found to have a sensitivity of 66.6% and a specificity of 90.9%. USG alone had a sensitivity of 86% and a specificity of 80%. When clinical findings and IOTA simple rules of sonography were combined (excluding inconclusive masses), the sensitivity and specificity were 83.3% and 92.3%, respectively. While including inconclusive masses, sensitivity came out to be 91.6% and specificity was 89.2. Conclusion: IOTA's simple sonography rules are highly sensitive and specific in the prediction of ovarian malignancy and also easy to use and easily reproducible. Thus, combining clinical examination with USG will help in the better management of patients in terms of time, cost and better prognosis. This will also avoid the need for costlier modalities like CT, and MRI.

Keywords: benign, international ovarian tumor analysis classification, malignant, ovarian tumours, sonography

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110 Migration as a Trigger Causing Change to the Levant Literary Modernism

Authors: Aathira Peedikaparambil Somasundaran

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The beginning of the 20th century marked the perios when a new generation of Lebanese radicals sowed the seeds for the second phase of Levant literary modernism, situated in the Levant. Beirut, during this era popularly fit every radical writer’s criterion owing to its weakened censorship and political control, despite the absence of a protective womb for the development of literary modernism, caused by the natively prevalent political unsettlement. The third stage of literary modernization, in which scholars used Western-inspired critical techniques to better understand their own cultures, coincides with the time period examined in this paper, which involved the international-inspired critical analysis of native cultural stimulants, which raised questions among Arab freethinking intellectuals. Locals who ventured outside recognised the difference between the West's progress and their own nations' stagnation. The awareness of such ‘gap of success’ aroused an ambition from journalists, authors, and proletarian revolutionaries who had studied in Europe, and finally developed enlightened ideas. Some Middle Eastern authors and artists only adopted current social and political frameworks after discovering western modernity. After learning about the upheavals that were happening in the West, these thinkers aspired to bring about equally broad drastic developments in their own country's social, political, and cultural milieu. These occurrences illustrate the increased power of migration to alter the cultural and literary scene in the Levant. The paper intends to discuss the different effects of migration that contributed to Levant literary modernism. The exploration of these factors as causes begins with addressing the politically influenced activism, that has always been a relevant part of Beirut, and then diving into the psychological effects of migration in the individuals of the society, which might have induced an accommodability to alien thoughts and ideas over time, as a coping mechanism. Nature or environmental stimuli, a common trigger for any creative output, often having the highest influence during travel will be identified and analysed to inspect the extent of its impact on the exchange of ideas that resulted in Levant modernism. The efficiency of both the stimulating component of travel and the diaspora of the indigenous, a by-product of travel in catalysing modernism in the Levant has to be proven in order to understand how migration indirectly affected the transmission and adoption of ideas in Levant literature. The paper will revisit the events revolving around these key players and platforms like Shir, to understand how the Lebanese literature, tied down in poetry drastically mutated under the leadership of Adonis, Yusuf et Khal, and other pioneers of Levant literary modernism. The conclision will identify the triggers that helped authors overcome personal and geographical barriers to unite the West and the Levant, and investigate the extent to which the bi-directional migration prompted a transformation in the local poetry. Consequently, the paper aims to shed light into the unique factor that provoked the shift in the literary scene of Twentieth century in the Middle East.

Keywords: literature, modernism, Middle East, levant, Beirut

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109 Hygrothermal Interactions and Energy Consumption in Cold Climate Hospitals: Integrating Numerical Analysis and Case Studies to Investigate and Analyze the Impact of Air Leakage and Vapor Retarding

Authors: Amir E. Amirzadeh, Richard K. Strand

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Moisture-induced problems are a significant concern for building owners, architects, construction managers, and building engineers, as they can have substantial impacts on building enclosures' durability and performance. Computational analyses, such as hygrothermal and thermal analysis, can provide valuable information and demonstrate the expected relative performance of building enclosure systems but are not grounded in absolute certainty. This paper evaluates the hygrothermal performance of common enclosure systems in hospitals in cold climates. The study aims to investigate the impact of exterior wall systems on hospitals, focusing on factors such as durability, construction deficiencies, and energy performance. The study primarily examines the impact of air leakage and vapor retarding layers relative to energy consumption. While these factors have been studied in residential and commercial buildings, there is a lack of information on their impact on hospitals in a holistic context. The study integrates various research studies and professional experience in hospital building design to achieve its objective. The methodology involves surveying and observing exterior wall assemblies, reviewing common exterior wall assemblies and details used in hospital construction, performing simulations and numerical analyses of various variables, validating the model and mechanism using available data from industry and academia, visualizing the outcomes of the analysis, and developing a mechanism to demonstrate the relative performance of exterior wall systems for hospitals under specific conditions. The data sources include case studies from real-world projects and peer-reviewed articles, industry standards, and practices. This research intends to integrate and analyze the in-situ and as-designed performance and durability of building enclosure assemblies with numerical analysis. The study's primary objective is to provide a clear and precise roadmap to better visualize and comprehend the correlation between the durability and performance of common exterior wall systems used in the construction of hospitals and the energy consumption of these buildings under certain static and dynamic conditions. As the construction of new hospitals and renovation of existing ones have grown over the last few years, it is crucial to understand the effect of poor detailing or construction deficiencies on building enclosure systems' performance and durability in healthcare buildings. This study aims to assist stakeholders involved in hospital design, construction, and maintenance in selecting durable and high-performing wall systems. It highlights the importance of early design evaluation, regular quality control during the construction of hospitals, and understanding the potential impacts of improper and inconsistent maintenance and operation practices on occupants, owner, building enclosure systems, and Heating, Ventilation, and Air Conditioning (HVAC) systems, even if they are designed to meet the project requirements.

Keywords: hygrothermal analysis, building enclosure, hospitals, energy efficiency, optimization and visualization, uncertainty and decision making

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108 Effect of Radioprotectors on DNA Repair Enzyme and Survival of Gamma-Irradiated Cell Division Cycle Mutants of Saccharomyces pombe

Authors: Purva Nemavarkar, Badri Narain Pandey, Jitendra Kumar

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Introduction: The objective was to understand the effect of various radioprotectors on DNA damage repair enzyme and survival in gamma-irradiated wild and cdc mutants of S. pombe (fission yeast) cultured under permissive and restrictive conditions. DNA repair process, as influenced by radioprotectors, was measured by activity of DNA polymerase in the cells. The use of single cell gel electrophoresis assay (SCGE) or Comet Assay to follow gamma-irradiation induced DNA damage and effect of radioprotectors was employed. In addition, studying the effect of caffeine at different concentrations on S-phase of cell cycle was also delineated. Materials and Methods: S. pombe cells grown at permissive temperature (250C) and/or restrictive temperature (360C) were followed by gamma-radiation. Percentage survival and activity of DNA Polymerase (yPol II) were determined after post-irradiation incubation (5 h) with radioprotectors such as Caffeine, Curcumin, Disulphiram, and Ellagic acid (the dose depending on individual D 37 values). The gamma-irradiated yeast cells (with and without the radioprotectors) were spheroplasted by enzyme glusulase and subjected to electrophoresis. Radio-resistant cells were obtained by arresting cells in S-phase using transient treatment of hydroxyurea (HU) and studying the effect of caffeine at different concentrations on S-phase of cell cycle. Results: The mutants of S. pombe showed insignificant difference in survival when grown under permissive conditions. However, growth of these cells under restrictive temperature leads to arrest in specific phases of cell cycle in different cdc mutants (cdc10: G1 arrest, cdc22: early S arrest, cdc17: late S arrest, cdc25: G2 arrest). All the cdc mutants showed decrease in survival after gamma radiation when grown at permissive and restrictive temperatures. Inclusion of the radioprotectors at respective concentrations during post irradiation incubation showed increase in survival of cells. Activity of DNA polymerase enzyme (yPol II) was increased significantly in cdc mutant cells exposed to gamma-radiation. Following SCGE, a linear relationship was observed between doses of irradiation and the tail moments of comets. The radioprotection of the fission yeast by radioprotectors can be seen by the reduced tail moments of the yeast comets. Caffeine also exhibited its radio-protective ability in radio-resistant S-phase cells obtained after HU treatment. Conclusions: The radioprotectors offered notable radioprotection in cdc mutants when added during irradiation. The present study showed activation of DNA damage repair enzyme (yPol II) and an increase in survival after treatment of radioprotectors in gamma irradiated wild type and cdc mutants of S. pombe cells. Results presented here showed feasibility of applying SCGE in fission yeast to follow DNA damage and radioprotection at high doses, which are not feasible with other eukaryotes. Inclusion of caffeine at 1mM concentration to S phase cells offered protection and did not decrease the cell viability. It can be proved that at minimal concentration, caffeine offered marked radioprotection.

Keywords: radiation protection, cell cycle, fission yeast, comet assay, s-phase, DNA repair, radioprotectors, caffeine, curcumin, SCGE

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107 Clinical Presentation and Immune Response to Intramammary Infection of Holstein-Friesian Heifers with Isolates from Two Staphylococcus aureus Lineages

Authors: Dagmara A. Niedziela, Mark P. Murphy, Orla M. Keane, Finola C. Leonard

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Staphylococcus aureus is the most frequent cause of clinical and subclinical bovine mastitis in Ireland. Mastitis caused by S. aureus is often chronic and tends to recur after antibiotic treatment. This may be due to several virulence factors, including attributes that enable the bacterium to internalize into bovine mammary epithelial cells, where it may evade antibiotic treatment, or evade the host immune response. Four bovine-adapted lineages (CC71, CC97, CC151 and ST136) were identified among a collection of Irish S. aureus mastitis isolates. Genotypic variation of mastitis-causing strains may contribute to different presentations of the disease, including differences in milk somatic cell count (SCC), the main method of mastitis detection. The objective of this study was to investigate the influence of bacterial strain and lineage on host immune response, by employing cell culture methods in vitro as well as an in vivo infection model. Twelve bovine adapted S. aureus strains were examined for internalization into bovine mammary epithelial cells (bMEC) and their ability to induce an immune response from bMEC (using qPCR and ELISA). In vitro studies found differences in a variety of virulence traits between the lineages. Strains from lineages CC97 and CC71 internalized more efficiently into bovine mammary epithelial cells (bMEC) than CC151 and ST136. CC97 strains also induced immune genes in bMEC more strongly than strains from the other 3 lineages. One strain each of CC151 and CC97 that differed in their ability to cause an immune response in bMEC were selected on the basis of the above in vitro experiments. Fourteen first-lactation Holstein-Friesian cows were purchased from 2 farms on the basis of low SCC (less than 50 000 cells/ml) and infection free status. Seven cows were infected with 1.73 x 102 c.f.u. of the CC97 strain (Group 1) and another seven with 5.83 x 102 c.f.u. of the CC151 strain (Group 2). The contralateral quarter of each cow was inoculated with PBS (vehicle). Clinical signs of infection (temperature, milk and udder appearance, milk yield) were monitored for 30 days. Blood and milk samples were taken to determine bacterial counts in milk, SCC, white blood cell populations and cytokines. Differences in disease presentation in vivo between groups were observed, with two animals from Group 2 developing clinical mastitis and requiring antibiotic treatment, while one animal from Group 1 did not develop an infection for the duration of the study. Fever (temperature > 39.5⁰C) was observed in 3 animals from Group 2 and in none from Group 1. Significant differences in SCC and bacterial load between groups were observed in the initial stages of infection (week 1). Data is also being collected on cytokines and chemokines secreted during the course of infection. The results of this study suggest that a strain from lineage CC151 may cause more severe clinical mastitis, while a strain from lineage CC97 may cause mild, subclinical mastitis. Diversity between strains of S. aureus may therefore influence the clinical presentation of mastitis, which in turn may influence disease detection and treatment needs.

Keywords: Bovine mastitis, host immune response, host-pathogen interactions, Staphylococcus aureus

Procedia PDF Downloads 157
106 Characteristics of Plasma Synthetic Jet Actuator in Repetitive Working Mode

Authors: Haohua Zong, Marios Kotsonis

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Plasma synthetic jet actuator (PSJA) is a new concept of zero net mass flow actuator which utilizes pulsed arc/spark discharge to rapidly pressurize gas in a small cavity under constant-volume conditions. The unique combination of high exit jet velocity (>400 m/s) and high actuation frequency (>5 kHz) provides a promising solution for high-speed high-Reynolds-number flow control. This paper focuses on the performance of PSJA in repetitive working mode which is more relevant to future flow control applications. A two-electrodes PSJA (cavity volume: 424 mm3, orifice diameter: 2 mm) together with a capacitive discharge circuit (discharge energy: 50 mJ-110 mJ) is designed to enable repetitive operation. Time-Resolved Particle Imaging Velocimetry (TR-PIV) system working at 10 kHz is exploited to investigate the influence of discharge frequency on performance of PSJA. In total, seven cases are tested, covering a wide range of discharge frequencies (20 Hz-560 Hz). The pertinent flow features (shock wave, vortex ring and jet) remain the same for single shot mode and repetitive working mode. Shock wave is issued prior to jet eruption. Two distinct vortex rings are formed in one cycle. The first one is produced by the starting jet whereas the second one is related with the shock wave reflection in cavity. A sudden pressure rise is induced at the throat inlet by the reflection of primary shock wave, promoting the shedding of second vortex ring. In one cycle, jet exit velocity first increases sharply, then decreases almost linearly. Afterwards, an alternate occurrence of multiple jet stages and refresh stages is observed. By monitoring the dynamic evolution of exit velocity in one cycle, some integral performance parameters of PSJA can be deduced. As frequency increases, the jet intensity in steady phase decreases monotonically. In the investigated frequency range, jet duration time drops from 250 µs to 210 µs and peak jet velocity decreases from 53 m/s to approximately 39 m/s. The jet impulse and the expelled gas mass (0.69 µN∙s and 0.027 mg at 20 Hz) decline by 48% and 40%, respectively. However, the electro-mechanical efficiency of PSJA defined by the ratio of jet mechanical energy to capacitor energy doesn’t show significant difference (o(0.01%)). Fourier transformation of the temporal exit velocity signal indicates two dominant frequencies. One corresponds to the discharge frequency, while the other accounts for the alternation frequency of jet stage and refresh stage in one cycle. The alternation period (300 µs approximately) is independent of discharge frequency, and possibly determined intrinsically by the actuator geometry. A simple analytical model is established to interpret the alternation of jet stage and refresh stage. Results show that the dynamic response of exit velocity to a small-scale disturbance (jump in cavity pressure) can be treated as a second-order under-damping system. Oscillation frequency of the exit velocity, namely alternation frequency, is positively proportional to exit area, but inversely proportional to cavity volume and throat length. Theoretical value of alternation period (305 µs) agrees well with the experimental value.

Keywords: plasma, synthetic jet, actuator, frequency effect

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105 How Obesity Sparks the Immune System and Lessons from the COVID-19 Pandemic

Authors: Husham Bayazed

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Purpose of Presentation: Obesity and overweight are among the biggest health challenges of the 21st century, according to the WHO. Obviously, obese individuals suffer different courses of disease – from infections and allergies to cancer- and even respond differently to some treatment options. Of note, obesity often seems to predispose and triggers several secondary diseases such as diabetes, arteriosclerosis, or heart attacks. Since decades it seems that immunological signals gear inflammatory processes among obese individuals with the aforementioned conditions. This review aims to shed light how obesity sparks or rewire the immune system and predisposes to such unpleasant health outcomes. Moreover, lessons from the Covid-19 pandemic ascertain that people living with pre-existing conditions such as obesity can develop severe acute respiratory syndrome (SARS), which needs to be elucidated how obesity and its adjuvant inflammatory process distortion contribute to enhancing severe COVID-19 consequences. Recent Findings: In recent clinical studies, obesity was linked to alter and sparks the immune system in different ways. Adipose tissue (AT) is considered as a secondary immune organ, which is a reservoir of tissue-resident of different immune cells with mediator release, making it a secondary immune organ. Adipocytes per se secrete several pro-inflammatory cytokines (IL-6, IL-4, MCP-1, and TNF-α ) involved in activation of macrophages resulting in chronic low-grade inflammation. The correlation between obesity and T cells dysregulation is pivotal in rewiring the immune system. Of note, autophagy occurrence in adipose tissues further rewire the immune system due to flush and outburst of leptin and adiponectin, which are cytokines and influencing pro-inflammatory immune functions. These immune alterations among obese individuals are collectively incriminated in triggering several metabolic disorders and playing role in increasing cancers incidence and susceptibility to different infections. During COVID-19 pandemic, it was verified that patients with pre-existing obesity being at greater risk of suffering severe and fatal clinical outcomes. Beside obese people suffer from increased airway resistance and reduced lung volume, ACE2 expression in adipose tissue seems to be high and even higher than that in lungs, which spike infection incidence. In essence, obesity with pre-existence of pro-inflammatory cytokines such as LI-6 is a risk factor for cytokine storm and coagulopathy among COVID-19 patients. Summary: It is well documented that obesity is associated with chronic systemic low-grade inflammation, which sparks and alter different pillars of the immune system and triggers different metabolic disorders, and increases susceptibility of infections and cancer incidence. The pre-existing chronic inflammation in obese patients with the augmented inflammatory response against the viral infection seems to increase the susceptibility of these patients to developing severe COVID-19. Although the new weight loss drugs and bariatric surgery are considered as breakthrough news for obesity treatment, but preventing is easier than treating it once it has taken hold. However, obesity and immune system link new insights dispute the role of immunotherapy and regulating immune cells treating diet-induced obesity.

Keywords: immunity, metabolic disorders, cancer, COVID-19

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104 Organisational Mindfulness Case Study: A 6-Week Corporate Mindfulness Programme Significantly Enhances Organisational Well-Being

Authors: Dana Zelicha

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A 6-week mindfulness programme was launched to improve the well being and performance of 20 managers (including the supervisor) of an international corporation in London. A unique assessment methodology was customised to the organisation’s needs, measuring four parameters: prioritising skills, listening skills, mindfulness levels and happiness levels. All parameters showed significant improvements (p < 0.01) post intervention, with a remarkable increase in listening skills and mindfulness levels. Although corporate mindfulness programmes have proven to be effective, the challenge remains the low engagement levels at home and the implementation of these tools beyond the scope of the intervention. This study has offered an innovative approach to enforce home engagement levels, which yielded promising results. The programme launched with a 2-day introduction intervention, which was followed by a 6-week training course (1 day a week; 2 hours each). Participants learned all basic principles of mindfulness such as mindfulness meditations, Mindfulness Based Stress Reduction (MBSR) techniques and Mindfulness Based Cognitive Therapy (MBCT) practices to incorporate into their professional and personal lives. The programme contained experiential mindfulness meditations and innovative mindfulness tools (OWBA-MT) created by OWBA - The Well Being Agency. Exercises included Mindful Meetings, Unitasking and Mindful Feedback. All sessions concluded with guided discussions and group reflections. One fundamental element of this programme was engagement level outside of the workshop. In the office, participants connected with a mindfulness buddy - a team member in the group with whom they could find support throughout the programme. At home, participants completed online daily mindfulness forms that varied according to weekly themes. These customised forms gave participants the opportunity to reflect on whether they made time for daily mindfulness practice, and to facilitate a sense of continuity and responsibility. At the end of the programme, the most engaged team member was crowned the ‘mindful maven’ and received a special gift. The four parameters were measured using online self-reported questionnaires, including the Listening Skills Inventory (LSI), Mindfulness Attention Awareness Scale (MAAS), Time Management Behaviour Scale (TMBS) and a modified version of the Oxford Happiness Questionnaire (OHQ). Pre-intervention questionnaires were collected at the start of the programme, and post-intervention data was collected 4-weeks following completion. Quantitative analysis using paired T-tests of means showed significant improvements, with a 23% increase in listening skills, a 22% improvement in mindfulness levels, a 12% increase in prioritising skills, and an 11% improvement in happiness levels. Participant testimonials exhibited high levels of satisfaction and the overall results indicate that the mindfulness programme substantially impacted the team. These results suggest that 6-week mindfulness programmes can improve employees’ capacities to listen and work well with others, to effectively manage time and to experience enhanced satisfaction both at work and in life. Limitations noteworthy to consider include the afterglow effect and lack of generalisability, as this study was conducted on a small and fairly homogenous sample.

Keywords: corporate mindfulness, listening skills, organisational well being, prioritising skills, mindful leadership

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103 Hypothalamic Para-Ventricular and Supra-Optic Nucleus Histo-Morphological Alterations in the Streptozotocin-Diabetic Gerbils (Gerbillus Gerbillus)

Authors: Soumia Hammadi, Imane Nouacer, Lamine Hamida, Younes A. Hammadi, Rachid Chaibi

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Aims and objective: In the present work, we investigate the impact of both acute and chronic diabetes mellitus induced by streptozotocin (STZ) on the hypothalamus of the small gerbil (Gerbillus gerbillus). In this purpose, we aimed to study the histologic structure of the gerbil’s hypothalamic supraoptic (NSO) and paraventricular nucleus (NPV) at two distinct time points: two days and 30 days after diabetes onset. Methods: We conducted our investigation using 19 adult male gerbils weighing 25 to 28 g, divided into three groups as follow: Group I: Control gerbils (n=6) received an intraperitoneal injection of citrate buffer. Group II: STZ-diabetic gerbils (n=8) received a single intraperitoneal injection of STZ at a dose of 165 mg/kg of body weight. Diabetes onset (D0) is considered with the first hyperglycemia level exceeding 2,5 g/L. This group was further divided into two subgroups: Group II-1: Experimental Gerbils, at acute state of diabetes (n=8) sacrificed after 02 days of diabetes onset, Group II-2: Experimental Gerbils at chronic state of diabetes (n=7) sacrificed after 30 days of diabetes onset. Two and 30 days after diabetes onset, gerbils had blood drawn from the retro-orbital sinus into EDTA tubes. After centrifugation at -4°C, plasma was frozen at -80°C for later measurement of Cortisol, ACTH, and insulin. Afterward, animals were decapitated; their brain was removed, weighed, fixed in aqueous bouin, and processed and stained with Toluidine Bleu stain for histo-stereological analysis. A comparison was done with control gerbils treated with citrate buffer. Results: Compared to control gerbils, at 02 Days post diabetes onset, the neuronal somata of the paraventricular (NPV) and supraoptic nuclei (NSO) expressed numerous vacuoles of various sizes, we distinct also a neuronal juxtaposition and several unidentifiable vacuolated profiles were also seen in the neuropile. At the same time, we revealed the presence of à shrunken and condensed nuclei, which seem to touch the parvocellular neurons ( NPV); this leads us to suggest the presence of an apoptotic process in the early stage of diabetes. At 30 days of diabetes mellitus, the NPV manifests a few neurons with a distant appearance, in addition the magnocellular neurons in both NPV and NSO were hypertrophied with a rich euchromatin nucleus, a well-defined nucleolus, and a granular cytoplasm. Despite the neuronal degeneration at this stage, unexpectedly, ACTH registers a continuous significant high level compared to the early stage of diabetes mellitus and to control gerbils. Conclusion: The results suggest that the induction of diabetes mellitus using STZ in the small gerbils lead to alterations in the structure and morphology of the hypothalamus and hyper-secretion of ACTH and cortisol, possibly indicating hyperactivity of the hypothalamo-pituitary adrenal axis (HPA) during both the early and later stages of the disease. The subsequent quantitative evaluation of CRH, immunehistochemical evaluation of apoptosis, and oxidative stress assessment could corroborate our results.

Keywords: diabetes type 1., streptozotocin., small gerbil., hypothalamus., paraventricular nucleus., supraoptic nucleus.

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102 Medical Examiner Collection of Comprehensive, Objective Medical Evidence for Conducted Electrical Weapons and Their Temporal Relationship to Sudden Arrest

Authors: Michael Brave, Mark Kroll, Steven Karch, Charles Wetli, Michael Graham, Sebastian Kunz, Dorin Panescu

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Background: Conducted electrical weapons (CEW) are now used in 107 countries and are a common law enforcement less-lethal force practice in the United Kingdom (UK), United States of America (USA), Canada, Australia, New Zealand, and others. Use of these devices is rarely temporally associated with the occurrence of sudden arrest-related deaths (ARD). Because such deaths are uncommon, few Medical Examiners (MEs) ever encounter one, and even fewer offices have established comprehensive investigative protocols. Without sufficient scientific data, the role, if any, played by a CEW in a given case is largely supplanted by conjecture often defaulting to a CEW-induced fatal cardiac arrhythmia. In addition to the difficulty in investigating individual deaths, the lack of information also detrimentally affects being able to define and evaluate the ARD cohort generally. More comprehensive, better information leads to better interpretation in individual cases and also to better research. The purpose of this presentation is to provide MEs with a comprehensive evidence-based checklist to assist in the assessment of CEW-ARD cases. Methods: PUBMED and Sociology/Criminology data bases were queried to find all medical, scientific, electrical, modeling, engineering, and sociology/criminology peer-reviewed literature for mentions of CEW or synonymous terms. Each paper was then individually reviewed to identify those that discussed possible bioelectrical mechanisms relating CEW to ARD. A Naranjo-type pharmacovigilance algorithm was also employed, when relevant, to identify and quantify possible direct CEW electrical myocardial stimulation. Additionally, CEW operational manuals and training materials were reviewed to allow incorporation of CEW-specific technical parameters. Results: Total relevant PUBMED citations of CEWs were less than 250, and reports of death extremely rare. Much relevant information was available from Sociology/Criminology data bases. Once the relevant published papers were identified, and reviewed, we compiled an annotated checklist of data that we consider critical to a thorough CEW-involved ARD investigation. Conclusion: We have developed an evidenced-based checklist that can be used by MEs and their staffs to assist them in identifying, collecting, documenting, maintaining, and objectively analyzing the role, if any, played by a CEW in any specific case of sudden death temporally associated with the use of a CEW. Even in cases where the collected information is deemed by the ME as insufficient for formulating an opinion or diagnosis to a reasonable degree of medical certainty, information collected as per the checklist will often be adequate for other stakeholders to use as a basis for informed decisions. Having reviewed the appropriate materials in a significant number of cases careful examination of the heart and brain is likely adequate. Channelopathy testing should be considered in some cases, however it may be considered cost prohibitive (aprox $3000). Law enforcement agencies may want to consider establishing a reserve fund to help manage such rare cases. The expense may stay the enormous costs associated with incident-precipitated litigation.

Keywords: ARD, CEW, police, TASER

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101 Feasibility of an Extreme Wind Risk Assessment Software for Industrial Applications

Authors: Francesco Pandolfi, Georgios Baltzopoulos, Iunio Iervolino

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The impact of extreme winds on industrial assets and the built environment is gaining increasing attention from stakeholders, including the corporate insurance industry. This has led to a progressively more in-depth study of building vulnerability and fragility to wind. Wind vulnerability models are used in probabilistic risk assessment to relate a loss metric to an intensity measure of the natural event, usually a gust or a mean wind speed. In fact, vulnerability models can be integrated with the wind hazard, which consists of associating a probability to each intensity level in a time interval (e.g., by means of return periods) to provide an assessment of future losses due to extreme wind. This has also given impulse to the world- and regional-scale wind hazard studies.Another approach often adopted for the probabilistic description of building vulnerability to the wind is the use of fragility functions, which provide the conditional probability that selected building components will exceed certain damage states, given wind intensity. In fact, in wind engineering literature, it is more common to find structural system- or component-level fragility functions rather than wind vulnerability models for an entire building. Loss assessment based on component fragilities requires some logical combination rules that define the building’s damage state given the damage state of each component and the availability of a consequence model that provides the losses associated with each damage state. When risk calculations are based on numerical simulation of a structure’s behavior during extreme wind scenarios, the interaction of component fragilities is intertwined with the computational procedure. However, simulation-based approaches are usually computationally demanding and case-specific. In this context, the present work introduces the ExtReMe wind risk assESsment prototype Software, ERMESS, which is being developed at the University of Naples Federico II. ERMESS is a wind risk assessment tool for insurance applications to industrial facilities, collecting a wide assortment of available wind vulnerability models and fragility functions to facilitate their incorporation into risk calculations based on in-built or user-defined wind hazard data. This software implements an alternative method for building-specific risk assessment based on existing component-level fragility functions and on a number of simplifying assumptions for their interactions. The applicability of this alternative procedure is explored by means of an illustrative proof-of-concept example, which considers four main building components, namely: the roof covering, roof structure, envelope wall and envelope openings. The application shows that, despite the simplifying assumptions, the procedure can yield risk evaluations that are comparable to those obtained via more rigorous building-level simulation-based methods, at least in the considered example. The advantage of this approach is shown to lie in the fact that a database of building component fragility curves can be put to use for the development of new wind vulnerability models to cover building typologies not yet adequately covered by existing works and whose rigorous development is usually beyond the budget of portfolio-related industrial applications.

Keywords: component wind fragility, probabilistic risk assessment, vulnerability model, wind-induced losses

Procedia PDF Downloads 181
100 Diabetic Screening in Rural Lesotho, Southern Africa

Authors: Marie-Helena Docherty, Sion Edryd Williams

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The prevalence of diabetes mellitus is increasing worldwide. In Sub-Saharan Africa, type 2 diabetes represents over 90% of all types of diabetes with the number of diabetic patients expected to rise. This represents a huge economic burden in an area already contending with high rates of other significant diseases, including the highest worldwide prevalence of HIV. Diabetic complications considerably impact on morbidity and mortality. The epidemiological data for the region quotes high rates of retinopathy (7-63%), neuropathy (27-66%) and microalbuminuria (10-83%). It is therefore imperative that diabetic screening programmes are established. It is recognised that in many parts of the developing world the implementation and management of such programmes is limited by a lack of available resources. The International Diabetes Federation produced guidelines in 2012 taking these limitations into account suggesting that all diabetic patients should have access to basic screening. These guidelines are consistent with the national diabetic guidelines produced by the Lesotho Medical Council. However, diabetic care in Lesotho is delivered at the local level, with variable levels of quality. A cross sectional study was performed in the outpatient department of Maluti Hospital in Mapoteng, Lesotho, a busy rural hospital in the Berea district. Demographic data on gender, age and modality of treatment were collected over a six-week time period. Information regarding 3 basic screening parameters was obtained. These parameters included eye screening (defined as a documented ophthalmology review within the last 12 months), foot screening (defined as a documented foot health assessment by any health care professional within the last 12 months) and secondary prevention (defined as a documented blood pressure and lipid profile reading within the last 12 months). These parameters were selected on the basis of the absolute minimum level of resources in Maluti Hospital. Renal screening was excluded, as the hospital does not have access to reliable renal profile checks or urinalysis. There is however a fully functioning on-site ophthalmology department run by a senior ophthalmologist with the ability to provide retinal photography, retinal surgery and photocoagulation therapy. Data was collected on 183 type 2 diabetics. 112 patients were male and 71 were female. The average age was 43 years. 4 patients were diet controlled, 140 patients were on oral hypoglycaemic agents (metformin and/or glibenclamide), and 39 patients were on a combination of insulin and oral hypoglycaemics. In the preceding 12 months, 5 patients had undergone eye screening (3%), 24 patients had undergone foot screening (13%), and 31 patients had lipid profile testing (17%). All patients had a documented blood pressure reading (100%). Our results show that screening is poorly performed in the basic indicators suggested by the IDF and the Lesotho Medical Council. On the basis of these results, a screening programme was developed using the mnemonic SaFE; secondary prevention, foot and eye care. This is simple, memorable and transferable between healthcare professionals. In the future, the expectation would be to expand upon this current programme to include renal screening, and to further develop screening pertaining to secondary prevention.

Keywords: Africa, complications, rural, screening

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99 (Anti)Depressant Effects of Non-Steroidal Antiinflammatory Drugs in Mice

Authors: Horia Păunescu

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Purpose: The study aimed to assess the depressant or antidepressant effects of several Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in mice: the selective cyclooxygenase-2 (COX-2) inhibitor meloxicam, and the non-selective COX-1 and COX-2 inhibitors lornoxicam, sodium metamizole, and ketorolac. The current literature data regarding such effects of these agents are scarce. Materials and methods: The study was carried out on NMRI mice weighing 20-35 g, kept in a standard laboratory environment. The study was approved by the Ethics Committee of the University of Medicine and Pharmacy „Carol Davila”, Bucharest. The study agents were injected intraperitoneally, 10 mL/kg body weight (bw) 1 hour before the assessment of the locomotor activity by cage testing (n=10 mice/ group) and 2 hours before the forced swimming tests (n=15). The study agents were dissolved in normal saline (meloxicam, sodium metamizole), ethanol 11.8% v/v in normal saline (ketorolac), or water (lornoxicam), respectively. Negative and positive control agents were also given (amitryptilline in the forced swimming test). The cage floor used in the locomotor activity assessment was divided into 20 equal 10 cm squares. The forced swimming test involved partial immersion of the mice in cylinders (15/9cm height/diameter) filled with water (10 cm depth at 28C), where they were left for 6 minutes. The cage endpoint used in the locomotor activity assessment was the number of treaded squares. Four endpoints were used in the forced swimming test (immobility latency for the entire 6 minutes, and immobility, swimming, and climbing scores for the final 4 minutes of the swimming session), recorded by an observer that was "blinded" to the experimental design. The statistical analysis used the Levene test for variance homogeneity, ANOVA and post-hoc analysis as appropriate, Tukey or Tamhane tests.Results: No statistically significant increase or decrease in the number of treaded squares was seen in the locomotor activity assessment of any mice group. In the forced swimming test, amitryptilline showed an antidepressant effect in each experiment, at the 10 mg/kg bw dosage. Sodium metamizole was depressant at 100 mg/kg bw (increased the immobility score, p=0.049, Tamhane test), but not in lower dosages as well (25 and 50 mg/kg bw). Ketorolac showed an antidepressant effect at the intermediate dosage of 5 mg/kg bw, but not so in the dosages of 2.5 and 10 mg/kg bw, respectively (increased the swimming score, p=0.012, Tamhane test). Meloxicam and lornoxicam did not alter the forced swimming endpoints at any dosage level. Discussion: 1) Certain NSAIDs caused changes in the forced swimming patterns without interfering with locomotion. 2) Sodium metamizole showed a depressant effect, whereas ketorolac proved antidepressant. Conclusion: NSAID-induced mood changes are not class effects of these agents and apparently are independent of the type of inhibited cyclooxygenase (COX-1 or COX-2). Disclosure: This paper was co-financed from the European Social Fund, through the Sectorial Operational Programme Human Resources Development 2007-2013, project number POSDRU /159 /1.5 /S /138907 "Excellence in scientific interdisciplinary research, doctoral and postdoctoral, in the economic, social and medical fields -EXCELIS", coordinator The Bucharest University of Economic Studies.

Keywords: antidepressant, depressant, forced swim, NSAIDs

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98 Nanocomposite Effect Based on Silver Nanoparticles and Anemposis Californica Extract as Skin Restorer

Authors: Maria Zulema Morquecho Vega, Fabiola CarolinaMiranda Castro, Rafael Verdugo Miranda, Ignacio Yocupicio Villegas, Ana lidia Barron Raygoza, Martin enrique MArquez Cordova, Jose Alberto Duarte Moller

Abstract:

Background: Anemopsis californica, also called (tame grass) belongs to the Saururaceae family small, green plant. The blade is long and wide. Gives a white flower. The plant population is only found in humid, swampy habitats, it grows where there is water, along the banks of streams and water holes. In the winter, it dries up. The leaves, rhizomes, or roots of this plant have been used to treat a range of diseases. Some of its healing properties are used to treat wounds, cold and flu symptoms, spasmodic cough, infection, pain and inflammation, burns, swollen feet, as well as lung ailments, asthma, circulatory problems (varicose veins), rheumatoid arthritis, purifies blood, helps in urinary and digestive tract diseases, sores and healing, for headache, sore throat, diarrhea, kidney pain. The tea made from the leaves and roots is used to treat uterine cancer, womb cancer, relieves menstrual pain and stops excessive bleeding after childbirth. It is also used as a gynecological treatment for infections, hemorrhoids, candidiasis and vaginitis. Objective: To study the cytotoxicity of gels prepared with silver nanoparticles in AC extract combined with chitosan, collagen and hyaluronic acid as an alternative therapy for skin conditions. Methods: The Ag NPs were synthesized according to the following method. A 0.3 mg/mL solution is prepared in 10 ml of deionized water, adjust to pH 12 with NaOH, stirring is maintained constant magnetic and a temperature of 80 °C. Subsequently, 100 ul of a 0.1 M AgNO3 solution and kept stirring constantly for 15 min. Once the reaction is complete, measurements are performed by UV-Vis. A gel was prepared in a 5% solution of acetic acid with the respective nanoparticles and AC extract of silver in the extract of AC. Chitosan is added until the process begins to occur gel. At that time, collagen will be added in a ratio of 3 to 5 drops, and later, hyaluronic acid in 2% of the total compound formed. Finally, after resting for 24 hours, the cytotoxic effect of the gels was studied. in the presence of highly positive bacteria Staphylococcus aureus and highly negative for Escherichia coli. Cultures will be incubated for 24 hours in the presence of the compound and compared with the reference. Results: Silver nanoparticles obtained had a spherical shape and sizes among 20 and 30 nm. UV-Vis spectra confirm the presence of silver nanoparticles showing a surface plasmon around 420 nm. Finally, the test in presence of bacteria yield a good antibacterial property of this nanocompound and tests in people were successful. Conclusion: Gel prepared by biogenic synthesis shown beneficious effects in severe acne, acne vulgaris and wound healing with diabetic patients.

Keywords: anemopsis californica, nanomedicina, biotechnology, biomedicine

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97 Measuring Green Growth Indicators: Implication for Policy

Authors: Hanee Ryu

Abstract:

The former president Lee Myung-bak's administration of Korea presented “green growth” as a catchphrase from 2008. He declared “low-carbon, green growth” the nation's vision for the next decade according to United Nation Framework on Climate Change. The government designed omnidirectional policy for low-carbon and green growth with concentrating all effort of departments. The structural change was expected because this slogan is the identity of the government, which is strongly driven with the whole department. After his administration ends, the purpose of this paper is to quantify the policy effect and to compare with the value of the other OECD countries. The major target values under direct policy objectives were suggested, but it could not capture the entire landscape on which the policy makes changes. This paper figures out the policy impacts through comparing the value of ex-ante between the one of ex-post. Furthermore, each index level of Korea’s low-carbon and green growth comparing with the value of the other OECD countries. To measure the policy effect, indicators international organizations have developed are considered. Environmental Sustainable Index (ESI) and Environmental Performance Index (EPI) have been developed by Yale University’s Center for Environmental Law and Policy and Columbia University’s Center for International Earth Science Information Network in collaboration with the World Economic Forum and Joint Research Center of European Commission. It has been widely used to assess the level of natural resource endowments, pollution level, environmental management efforts and society’s capacity to improve its environmental performance over time. Recently OCED publish the Green Growth Indicator for monitoring progress towards green growth based on internationally comparable data. They build up the conceptual framework and select indicators according to well specified criteria: economic activities, natural asset base, environmental dimension of quality of life and economic opportunities and policy response. It considers the socio-economic context and reflects the characteristic of growth. Some selected indicators are used for measuring the level of changes the green growth policies have induced in this paper. As results, the CO2 productivity and energy productivity show trends of declination. It means that policy intended industry structure shift for achieving carbon emission target affects weakly in the short-term. Increasing green technologies patents might result from the investment of previous period. The increasing of official development aids which can be immediately embarked by political decision with no time lag present only in 2008-2009. It means international collaboration and investment to developing countries via ODA has not succeeded since the initial stage of his administration. The green growth framework makes the public expect structural change, but it shows sporadic effect. It needs organization to manage it in terms of the long-range perspectives. Energy, climate change and green growth are not the issue to be handled in the one period of the administration. The policy mechanism to transfer cost problem to value creation should be developed consistently.

Keywords: comparing ex-ante between ex-post indicator, green growth indicator, implication for green growth policy, measuring policy effect

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96 Pre-conditioning and Hot Water Sanitization of Reverse Osmosis Membrane for Medical Water Production

Authors: Supriyo Das, Elbir Jove, Ajay Singh, Sophie Corbet, Noel Carr, Martin Deetz

Abstract:

Water is a critical commodity in the healthcare and medical field. The utility of medical-grade water spans from washing surgical equipment, drug preparation to the key element of life-saving therapy such as hydrotherapy and hemodialysis for patients. A properly treated medical water reduces the bioburden load and mitigates the risk of infection, ensuring patient safety. However, any compromised condition during the production of medical-grade water can create a favorable environment for microbial growth putting patient safety at high risk. Therefore, proper upstream treatment of the medical water is essential before its application in healthcare, pharma and medical space. Reverse Osmosis (RO) is one of the most preferred treatments within healthcare industries and is recommended by all International Pharmacopeias to achieve the quality level demanded by global regulatory bodies. The RO process can remove up to 99.5% of constituents from feed water sources, eliminating bacteria, proteins and particles sizes of 100 Dalton and above. The combination of RO with other downstream water treatment technologies such as Electrodeionization and Ultrafiltration meet the quality requirements of various pharmacopeia monographs to produce highly purified water or water for injection for medical use. In the reverse osmosis process, the water from a liquid with a high concentration of dissolved solids is forced to flow through an especially engineered semi-permeable membrane to the low concentration side, resulting in high-quality grade water. However, these specially engineered RO membranes need to be sanitized either chemically or at high temperatures at regular intervals to keep the bio-burden at the minimum required level. In this paper, we talk about Dupont´s FilmTec Heat Sanitizable Reverse Osmosis membrane (HSRO) for the production of medical-grade water. An HSRO element must be pre-conditioned prior to initial use by exposure to hot water (80°C-85°C) for its stable performance and to meet the manufacturer’s specifications. Without pre-conditioning, the membrane will show variations in feed pressure operations and salt rejection. The paper will discuss the critical variables of pre-conditioning steps that can affect the overall performance of the HSRO membrane and demonstrate the data to support the need for pre-conditioning of HSRO elements. Our preliminary data suggests that there can be up to 35 % reduction in flow due to initial heat treatment, which also positively affects the increase in salt rejection. The paper will go into detail about the fundamental understanding of the performance change of HSRO after the pre-conditioning step and its effect on the quality of medical water produced. The paper will also discuss another critical point, “regular hot water sanitization” of these HSRO membranes. Regular hot water sanitization (at 80°C-85°C) is necessary to keep the membrane bioburden free; however, it can negatively impact the performance of the membrane over time. We will demonstrate several data points on hot water sanitization using FilmTec HSRO elements and challenge its robustness to produce quality medical water. The last part of this paper will discuss the construction details of the FilmTec HSRO membrane and features that make it suitable to pre-condition and sanitize at high temperatures.

Keywords: heat sanitizable reverse osmosis, HSRO, medical water, hemodialysis water, water for Injection, pre-conditioning, heat sanitization

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95 Approximate-Based Estimation of Single Event Upset Effect on Statistic Random-Access Memory-Based Field-Programmable Gate Arrays

Authors: Mahsa Mousavi, Hamid Reza Pourshaghaghi, Mohammad Tahghighi, Henk Corporaal

Abstract:

Recently, Statistic Random-Access Memory-based (SRAM-based) Field-Programmable Gate Arrays (FPGAs) are widely used in aeronautics and space systems where high dependability is demanded and considered as a mandatory requirement. Since design’s circuit is stored in configuration memory in SRAM-based FPGAs; they are very sensitive to Single Event Upsets (SEUs). In addition, the adverse effects of SEUs on the electronics used in space are much higher than in the Earth. Thus, developing fault tolerant techniques play crucial roles for the use of SRAM-based FPGAs in space. However, fault tolerance techniques introduce additional penalties in system parameters, e.g., area, power, performance and design time. In this paper, an accurate estimation of configuration memory vulnerability to SEUs is proposed for approximate-tolerant applications. This vulnerability estimation is highly required for compromising between the overhead introduced by fault tolerance techniques and system robustness. In this paper, we study applications in which the exact final output value is not necessarily always a concern meaning that some of the SEU-induced changes in output values are negligible. We therefore define and propose Approximate-based Configuration Memory Vulnerability Factor (ACMVF) estimation to avoid overestimating configuration memory vulnerability to SEUs. In this paper, we assess the vulnerability of configuration memory by injecting SEUs in configuration memory bits and comparing the output values of a given circuit in presence of SEUs with expected correct output. In spite of conventional vulnerability factor calculation methods, which accounts any deviations from the expected value as failures, in our proposed method a threshold margin is considered depending on user-case applications. Given the proposed threshold margin in our model, a failure occurs only when the difference between the erroneous output value and the expected output value is more than this margin. The ACMVF is subsequently calculated by acquiring the ratio of failures with respect to the total number of SEU injections. In our paper, a test-bench for emulating SEUs and calculating ACMVF is implemented on Zynq-7000 FPGA platform. This system makes use of the Single Event Mitigation (SEM) IP core to inject SEUs into configuration memory bits of the target design implemented in Zynq-7000 FPGA. Experimental results for 32-bit adder show that, when 1% to 10% deviation from correct output is considered, the counted failures number is reduced 41% to 59% compared with the failures number counted by conventional vulnerability factor calculation. It means that estimation accuracy of the configuration memory vulnerability to SEUs is improved up to 58% in the case that 10% deviation is acceptable in output results. Note that less than 10% deviation in addition result is reasonably tolerable for many applications in approximate computing domain such as Convolutional Neural Network (CNN).

Keywords: fault tolerance, FPGA, single event upset, approximate computing

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94 Scoring System for the Prognosis of Sepsis Patients in Intensive Care Units

Authors: Javier E. García-Gallo, Nelson J. Fonseca-Ruiz, John F. Duitama-Munoz

Abstract:

Sepsis is a syndrome that occurs with physiological and biochemical abnormalities induced by severe infection and carries a high mortality and morbidity, therefore the severity of its condition must be interpreted quickly. After patient admission in an intensive care unit (ICU), it is necessary to synthesize the large volume of information that is collected from patients in a value that represents the severity of their condition. Traditional severity of illness scores seeks to be applicable to all patient populations, and usually assess in-hospital mortality. However, the use of machine learning techniques and the data of a population that shares a common characteristic could lead to the development of customized mortality prediction scores with better performance. This study presents the development of a score for the one-year mortality prediction of the patients that are admitted to an ICU with a sepsis diagnosis. 5650 ICU admissions extracted from the MIMICIII database were evaluated, divided into two groups: 70% to develop the score and 30% to validate it. Comorbidities, demographics and clinical information of the first 24 hours after the ICU admission were used to develop a mortality prediction score. LASSO (least absolute shrinkage and selection operator) and SGB (Stochastic Gradient Boosting) variable importance methodologies were used to select the set of variables that make up the developed score; each of this variables was dichotomized and a cut-off point that divides the population into two groups with different mean mortalities was found; if the patient is in the group that presents a higher mortality a one is assigned to the particular variable, otherwise a zero is assigned. These binary variables are used in a logistic regression (LR) model, and its coefficients were rounded to the nearest integer. The resulting integers are the point values that make up the score when multiplied with each binary variables and summed. The one-year mortality probability was estimated using the score as the only variable in a LR model. Predictive power of the score, was evaluated using the 1695 admissions of the validation subset obtaining an area under the receiver operating characteristic curve of 0.7528, which outperforms the results obtained with Sequential Organ Failure Assessment (SOFA), Oxford Acute Severity of Illness Score (OASIS) and Simplified Acute Physiology Score II (SAPSII) scores on the same validation subset. Observed and predicted mortality rates within estimated probabilities deciles were compared graphically and found to be similar, indicating that the risk estimate obtained with the score is close to the observed mortality, it is also observed that the number of events (deaths) is indeed increasing as the outcome go from the decile with the lowest probabilities to the decile with the highest probabilities. Sepsis is a syndrome that carries a high mortality, 43.3% for the patients included in this study; therefore, tools that help clinicians to quickly and accurately predict a worse prognosis are needed. This work demonstrates the importance of customization of mortality prediction scores since the developed score provides better performance than traditional scoring systems.

Keywords: intensive care, logistic regression model, mortality prediction, sepsis, severity of illness, stochastic gradient boosting

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93 Analysis of Potential Associations of Single Nucleotide Polymorphisms in Patients with Schizophrenia Spectrum Disorders

Authors: Tatiana Butkova, Nikolai Kibrik, Kristina Malsagova, Alexander Izotov, Alexander Stepanov, Anna Kaysheva

Abstract:

Relevance. The genetic risk of developing schizophrenia is determined by two factors: single nucleotide polymorphisms and gene copy number variations. The search for serological markers for early diagnosis of schizophrenia is driven by the fact that the first five years of the disease are accompanied by significant biological, psychological, and social changes. It is during this period that pathological processes are most amenable to correction. The aim of this study was to analyze single nucleotide polymorphisms (SNPs) that are hypothesized to potentially influence the onset and development of the endogenous process. Materials and Methods It was analyzed 73 single nucleotide polymorphism variants. The study included 48 patients undergoing inpatient treatment at "Psychiatric Clinical Hospital No. 1" in Moscow, comprising 23 females and 25 males. Inclusion criteria: - Patients aged 18 and above. - Diagnosis according to ICD-10: F20.0, F20.2, F20.8, F21.8, F25.1, F25.2. - Voluntary informed consent from patients. Exclusion criteria included: - The presence of concurrent somatic or neurological pathology, neuroinfections, epilepsy, organic central nervous system damage of any etiology, and regular use of medication. - Substance abuse and alcohol dependence. - Women who were pregnant or breastfeeding. Clinical and psychopathological assessment was complemented by psychometric evaluation using the PANSS scale at the beginning and end of treatment. The duration of observation during therapy was 4-6 weeks. Total DNA extraction was performed using QIAamp DNA. Blood samples were processed on Illumina HiScan and genotyped for 652,297 markers on the Infinium Global Chips Screening Array-24v2.0 using the IMPUTE2 program with parameters Ne=20,000 and k=90. Additional filtration was performed based on INFO>0.5 and genotype probability>0.5. Quality control of the obtained DNA was conducted using agarose gel electrophoresis, with each tested sample having a volume of 100 µL. Results. It was observed that several SNPs exhibited gender dependence. We identified groups of single nucleotide polymorphisms with a membership of 80% or more in either the female or male gender. These SNPs included rs2661319, rs2842030, rs4606, rs11868035, rs518147, rs5993883, and rs6269.Another noteworthy finding was the limited combination of SNPs sufficient to manifest clinical symptoms leading to hospitalization. Among all 48 patients, each of whom was analyzed for deviations in 73 SNPs, it was discovered that the combination of involved SNPs in the manifestation of pronounced clinical symptoms of schizophrenia was 19±3 out of 73 possible. In study, the frequency of occurrence of single nucleotide polymorphisms also varied. The most frequently observed SNPs were rs4849127 (in 90% of cases), rs1150226 (86%), rs1414334 (75%), rs10170310 (73%), rs2857657, and rs4436578 (71%). Conclusion. Thus, the results of this study provide additional evidence that these genes may be associated with the development of schizophrenia spectrum disorders. However, it's impossible cannot rule out the hypothesis that these polymorphisms may be in linkage disequilibrium with other functionally significant polymorphisms that may actually be involved in schizophrenia spectrum disorders. It has been shown that missense SNPs by themselves are likely not causative of the disease but are in strong linkage disequilibrium with non-functional SNPs that may indeed contribute to disease predisposition.

Keywords: gene polymorphisms, genotyping, single nucleotide polymorphisms, schizophrenia.

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92 Avoidance of Brittle Fracture in Bridge Bearings: Brittle Fracture Tests and Initial Crack Size

Authors: Natalie Hoyer

Abstract:

Bridges in both roadway and railway systems depend on bearings to ensure extended service life and functionality. These bearings enable proper load distribution from the superstructure to the substructure while permitting controlled movement of the superstructure. The design of bridge bearings, according to Eurocode DIN EN 1337 and the relevant sections of DIN EN 1993, increasingly requires the use of thick plates, especially for long-span bridges. However, these plate thicknesses exceed the limits specified in the national appendix of DIN EN 1993-2. Furthermore, compliance with DIN EN 1993-1-10 regulations regarding material toughness and through-thickness properties necessitates further modifications. Consequently, these standards cannot be directly applied to the selection of bearing materials without supplementary guidance and design rules. In this context, a recommendation was developed in 2011 to regulate the selection of appropriate steel grades for bearing components. Prior to the initiation of the research project underlying this contribution, this recommendation had only been available as a technical bulletin. Since July 2023, it has been integrated into guideline 804 of the German railway. However, recent findings indicate that certain bridge-bearing components are exposed to high fatigue loads, which necessitate consideration in structural design, material selection, and calculations. Therefore, the German Centre for Rail Traffic Research called a research project with the objective of defining a proposal to expand the current standards in order to implement a sufficient choice of steel material for bridge bearings to avoid brittle fracture, even for thick plates and components subjected to specific fatigue loads. The results obtained from theoretical considerations, such as finite element simulations and analytical calculations, are validated through large-scale component tests. Additionally, experimental observations are used to calibrate the calculation models and modify the input parameters of the design concept. Within the large-scale component tests, a brittle failure is artificially induced in a bearing component. For this purpose, an artificially generated initial defect is introduced at the previously defined hotspot into the specimen using spark erosion. Then, a dynamic load is applied until the crack initiation process occurs to achieve realistic conditions in the form of a sharp notch similar to a fatigue crack. This initiation process continues until the crack length reaches a predetermined size. Afterward, the actual test begins, which requires cooling the specimen with liquid nitrogen until a temperature is reached where brittle fracture failure is expected. In the next step, the component is subjected to a quasi-static tensile test until failure occurs in the form of a brittle failure. The proposed paper will present the latest research findings, including the results of the conducted component tests and the derived definition of the initial crack size in bridge bearings.

Keywords: bridge bearings, brittle fracture, fatigue, initial crack size, large-scale tests

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91 Smoking Elevates the Risk of Dysbiosis Associated with Dental Decay

Authors: Razia Hossaini, Maryam Hosseini

Abstract:

Background and Objective: The impact of smoking on the shift in oral microbial composition has been questioned. This study aims to compare the oral microbiome between Turkish patients with dental caries and healthy individuals. Materials and Methods: An observational case-control study was conducted from January to June 2024, involving 270 young adults (180 with dental caries and 90 healthy controls). Participants were matched by age, gender, education, sugar consumption, and tooth brushing habits. Oral samples were collected using sterilized swabs and preserved in a PBS-glycerol solution. The cultured bacterial samples were characterized based on their morphological characteristics, Gram staining properties, hemolysis patterns, and biochemical tests including methyl red, sugar fermentation, Simmons citrate utilization, coagulase production, and catalase activity. These tests were conducted to accurately identify the bacterial species present. Subsequently, the relationship between smoking and oral health was evaluated, with a particular focus on assessing the smoking-induced changes in the composition of the oral microbiota using statistical analyses. Results: The study’s results demonstrate a clear association between smoking and an increased risk of dental caries, as well as significant shifts in the oral microbiota of smokers (p=0.04). These findings emphasize the critical need for public health initiatives that target smoking cessation as a means of improving oral health outcomes. Since smokers are 1.28 times more likely to develop dental caries than non-smokers, public health campaigns should incorporate messages that highlight the direct impact of smoking on oral health, alongside the well-established risks such as lung disease and cardiovascular conditions.The observed alterations in the oral microbiota—specifically the higher prevalence of pathogens like Escherichia coli, Pseudomonas aeruginosa, Streptococcus mutans, and Lactobacillus acidophilus in patients with dental caries—suggest that smoking not only predisposes individuals to dental decay but also creates an environment conducive to the growth of harmful bacteria. Public health interventions could therefore focus on the dual benefit of smoking cessation: reducing the incidence of dental caries and restoring a healthier oral microbiome. Additionally, the reduced presence of beneficial or less pathogenic species such as Neisseria and Micrococcus luteus in smokers implies that smoking alters the protective balance of the oral microbiome. This further underscores the importance of preventive oral health strategies tailored to smokers. Conclusion: Smoking significantly impacts oral health by promoting dysbiosis, increasing cariogenic bacteria, and reducing beneficial bacteria, which contributes to the development of dental caries. These findings highlight the need for integrated public health efforts that address both smoking cessation and oral health promotion. By raising awareness of the specific oral health risks associated with smoking, public health initiatives could help reduce the burden of dental caries and other smoking-related oral diseases, ultimately improving quality of life for individuals and reducing healthcare costs.

Keywords: smoking, dysbiosis, bacteria, oral health, dental decay

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