Search results for: hyperthermic intra peritoneal chemotherapy

Authors: Ved Vrat Verma, Rani Gupta, Manisha Goel

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γ-glutamyltranspeptidase (GGT: EC 2.3.2.2) is an N-terminal nucleophile hydrolase conserved in all three domains of life. GGT plays a key role in glutathione metabolism where it catalyzes the breakage of the γ-glutamyl bonds and transfer of γ-glutamyl group to water (hydrolytic activity) or amino acids or short peptides (transpeptidase activity). GGTs from bacteria, archaea, and eukaryotes (human, rat and mouse) are homologous proteins sharing >50% sequence similarity and conserved four layered αββα sandwich like three dimensional structural fold. These proteins though similar in their structure to each other, are quite diverse in their enzyme activity: some GGTs are better at hydrolysis reactions but poor in transpeptidase activity, whereas many others may show opposite behaviour. GGT is known to be involved in various diseases like asthma, parkinson, arthritis, and gastric cancer. Its inhibition prior to chemotherapy treatments has been shown to sensitize tumours to the treatment. Microbial GGT is known to be a virulence factor too, important for the colonization of bacteria in host. However, all known inhibitors (mimics of its native substrate, glutamate) are highly toxic because they interfere with other enzyme pathways. However, a few successful efforts have been reported previously in designing species specific inhibitors. We aim to leverage the diversity seen in GGT family (pathogen vs. eukaryotes) for designing specific inhibitors. Thus, in the present study, we have used DIVERGE software to identify sites in GGT proteins, which are crucial for the functional and structural divergence of these proteins. Since, type II divergence sites vary in clade specific manner, so type II divergent sites were our focus of interest throughout the study. Type II divergent sites were identified for pathogen vs. eukaryotes clusters and sites were marked on clade specific representative structures HpGGT (2QM6) and HmGGT (4ZCG) of pathogen and eukaryotes clade respectively. The crucial divergent sites within 15 A radii of the binding cavity were highlighted, and in-silico mutations were performed on these sites to delineate the role of these sites on the mechanism of catalysis and protein folding. Further, the amino acid network (AAN) analysis was also performed by Cytoscape to delineate assortative mixing for cavity divergent sites which could strengthen our hypothesis. Additionally, molecular dynamics simulations were performed for wild complexes and mutant complexes close to physiological conditions (pH 7.0, 0.1 M ionic strength and 1 atm pressure) and the role of putative divergence sites and structural integrities of the homologous proteins have been analysed. The dynamics data were scrutinized in terms of RMSD, RMSF, non-native H-bonds and salt bridges. The RMSD, RMSF fluctuations of proteins complexes are compared, and the changes at protein ligand binding sites were highlighted. The outcomes of our study highlighted some crucial divergent sites which could be used for novel inhibitors designing in a species-specific manner. Since, for drug development, it is challenging to design novel drug by targeting similar protein which exists in eukaryotes, so this study could set up an initial platform to overcome this challenge and help to deduce the more effective targets for novel drug discovery.

Keywords: γ-glutamyltranspeptidase, divergence, species-specific, drug design

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Authors: Meirav Eshkol, Miri Blaufeld, Rinat Basal

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Aim: The working environment in rural clinics is often isolated and distant from major health centers. In these circumstances, rural health care faces numerous challenges. The hope is that, in the immediate future and in the medium and long range, the rural nursing staff will realize their full professional and personal potential to their own satisfaction and to the health and welfare of their patients. Background: Rural nurses work mostly alone or with very few colleagues, and have the authority to make professional decisions, a fact which often requires them to make critical decisions in pressure situations. In addition, the expectations set for these nurses are extremely high, a fact which requires them to be extremely skilled and to fulfill their professional potential. They are required to provide high-quality and comprehensive care to the individual, the family, and the community and to maintain close interaction with the community. Work in a rural setting requires the flexibility to perform multiple tasks in an isolated setting, often far removed from major health centers. In order to maintain professional satisfaction for the rural nurse, expanded direction and training are required in professional know-how, and in the development of new and existing skills, toward the goal of treating a diverse population and to obtain a comprehensive view of the components of a diagnosis for treatment and to develop an understanding appropriate to the presented reality. Objective: To provide knowledge and to expand and develop professional skills in the prevention and advancement of health in the care of a diverse patient population. The development of strategies and skills for work under pressure alone instills expertise in performing multiple tasks in diverse disciplines. To reduce feelings of stress and burnout. Methodology: This course is the first and one of a kind in Clalit - the biggest health organisation in Israel. Observing and identifying the needs of the nurses in the field relating to the development of professional and personal skills defining goals and objectives, and determining the content of a course designed for rural nurses and kibbutz nurses who are not Clalit employees. Results: 43 nurses participated and 30 answered the feedback questionnaire. The rating of their experience was 4.33 (on a scale of 1-5, with 5 being the highest ranking). 92% indicated the importance of meeting with additional nurses to teach their colleagues. 83% of the nurses indicated an increased sense of organizational belonging. 60% indicated that the course helped to reduce feelings of stress and burnout in becoming a better rural nurse. 80% indicated that the course helped them establish intra-organizational professional cooperation and initiating processes. Conclusion: The course is an instrument which aids in increasing the feeling of organizational belonging, reducing feelings of stress and burnout, creation of relationships and cooperation both within and outside of the organization, increased the realization of the potential of the village nurse.

Keywords: rural nurse, alone, burnout, multiple tasks

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Authors: Prabhat Kashyap, Krishan Kumar

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Delhi, the capital of India, is one of the most populated and polluted city among the world. In terms of air quality, Delhi’s air is degrading day by day & becomes worst of any major city in the world. The role of biogenic volatile organic compounds (BVOCs) is not much studied in cities like Delhi as a culprit for degraded air quality. They not only play a critical role in rural areas but also determine the atmospheric chemistry of urban areas as well. Particularly, Isoprene (2-methyl 1,3-butadiene, C5H8) is the single largest emitted compound among other BVOCs globally, that influence the tropospheric ozone chemistry in urban environment as the ozone forming potential of isoprene is very high. It is mainly emitted by vegetation & a small but significant portion is also released by vehicular exhaust of petrol operated vehicles. This study investigates the spatial and temporal variations of quantitative measurements of isoprene emissions along with different traffic tracers in 2 different seasons (post-monsoon & winter) at four different locations of Delhi. For the quantification of anthropogenic and biogenic isoprene, two sites from traffic intersections (Punjabi Bagh & CRRI) and two sites from vegetative locations (JNU & Yamuna Biodiversity Park) were selected in the vicinity of isoprene emitting tree species like Ficus religiosa, Dalbergia sissoo, Eucalyptus species etc. The concentrations of traffic tracers like benzene, toluene were also determined & their robust ratios with isoprene were used to differentiate anthropogenic isoprene with biogenic portion at each site. The ozone forming potential (OFP) of all selected species along with isoprene was also estimated. For collection of intra-day samples (3 times a day) in each season, a pre-conditioned fenceline monitoring (FLM) carbopack X thermal desorption tubes were used and further analysis was done with Gas chromatography attached with mass spectrometry (GC-MS). The results of the study proposed that the ambient air isoprene is always higher in post-monsoon season as compared to winter season at all the sites because of high temperature & intense sunlight. The maximum isoprene emission flux was always observed during afternoon hours in both seasons at all sites. The maximum isoprene concentration was found to be 13.95 ppbv at Biodiversity Park during afternoon time in post monsoon season while the lower concentration was observed as low as 0.07 ppbv at the same location during morning hours in winter season. OFP of isoprene at vegetation sites is very high during post-monsoon because of high concentrations. However, OFP for other traffic tracers were high during winter seasons & at traffic locations. Furthermore, high correlation between isoprene emissions with traffic volume at traffic sites revealed that a noteworthy share of its emission also originates from road traffic.

Keywords: biogenic VOCs, isoprene emission, anthropogenic isoprene, urban vegetation

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Authors: Anthony R. Townsend, Robyn L. Fasser

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This research project provides an interpretative phenomenological analysis of a proposed conceptual model of parenting ability that has been designed to offer recommendations to guide intervention in child custody evaluations in South Africa. A recent review of the literature on child custody evaluations reveals that while there have been significant and valuable shifts in the capacity of the legal system aided by mental health professionals in understanding children and family dynamics, there remains a conceptual gap regarding the nature of parenting ability. With a view to addressing this paucity of a theoretical basis for considering parenting ability, this research project reviews a dimensional model for the assessment of parenting ability by conceiving parenting ability as a combination of good parenting and parental fitness. This model serves as a conceptual framework to guide child-custody evaluation and refine intervention in such cases to better meet the best interests of the child in a manner that bridges the professional gap between parties, legal entities, and mental health professionals. Using a model of good parenting as a point of theoretical departure, this model incorporates both intra-psychic and interpersonal attributes and behaviours of parents to form an impression of parenting ability and identify areas for potential enhancement. This research, therefore, hopes to achieve the following: (1) to provide nuanced descriptions of parents’ parenting ability; (2) to describe parents’ parenting potential; (3) to provide a parenting assessment tool for investigators in forensic family matters that will enable more useful recommendations and interventions; (4) to develop a language of consensus for investigators, attorneys, judges and parents, in forensic family matters, as to what comprises parenting ability and how this can be assessed; and (5) that all of the aforementioned will serve to advance the best interests of the children involved in such litigious matters. The evaluative promise and post-assessment prospects of this model are illustrated through three interlinking data sets: (1) the results of interviews with South African psychologists about the model, (2) retrospective analysis of care and contact evaluation reports using the model to determine if different conclusions or more specific recommendations are generated with its use and (3) the results of an interview with a psychologist who piloted this model by using it in care and contact evaluation.

Keywords: alienation, attachment, best interests of the child, care and contact evaluation, children’s act (38 of 2005), child custody evaluation, civil forensics, gatekeeping, good parenting, good-enough parenting, health professions council of South Africa, family law, forensic mental healthcare practitioners, parental fitness, parenting ability, parent management training, parenting plan, problem-determined system, psychotherapy, support of other child-parent relationship, voice of the child

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Authors: Saimir Cenameri, Arjana Tereziu, Kastriot Dallaku

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Introduction: Intra-uterine death is a common problem in obstetrical practice, and can lead to complications if left to resolve spontaneously. The cervix is unprepared, making inducing of labor difficult. Misoprostol is a synthetic prostaglandin E1 analogue, inexpensive, and is presented valid thanks to its ability to bring about changes in the cervix that lead to the induction of uterine contractions. Misoprostol is quickly absorbed when taken orally, resulting in high initial peak serum concentrations compared with the vaginal route. The vaginal misoprostol peak serum concentration is not as high and demonstrates a more gradual serum concentration decline. This is associated with many benefits for the patient; fast induction of labor; smaller doses; and fewer side effects (dose-depended). Mostly it has been used the regime of 50 μg/4 hour, with a high percentage of success and limited side effects. Objective: Evaluation of the efficiency of the use of oral and vaginal misoprostol in inducing labor, and comparing it with its use not by a previously defined protocol. Methods: Participants in this study included patients at U.H.O.G. 'Koco Gliozheni', Tirana from April 2004-July 2006, presenting with an indication for inducing labor in the third trimester for pregnancy termination. A total of 37 patients were randomly admitted for birth inducing activity, according to protocol (26), oral or vaginal protocol (10 vs. 16), and a control group (11), not subject to the protocol, was created. Oral or vaginal misoprostol was administered at a dose of 50 μg/4 h, while the fourth group participants were treated individually by the members of the medical staff. The main result of interest was the time between induction of labor to birth. Kruskal-Wallis test was used to compare the average age, parity, women weight, gestational age, Bishop's score, the size of the uterus and weight of the fetus between the four groups in the study. The Fisher exact test was used to compare day-stay and causes in the four groups. Mann-Whitney test was used to compare the time of the expulsion and the number of doses between oral and vaginal group. For all statistical tests used, the value of P ≤ 0.05 was considered statistically significant. Results: The four groups were comparable with regard to woman age and weight, parity, abortion indication, Bishop's score, fetal weight and the gestational age. There was significant difference in the percentage of deliveries within 24 hours. The average time from induction to birth per route (vaginal, oral, according to protocol and not according to the protocol) was respectively; 10.43h; 21.10h; 15.77h, 21.57h. There was no difference in maternal complications in groups. Conclusions: Use of vaginal misoprostol for inducing labor in the third trimester for termination of pregnancy appears to be more effective than the oral route, and even more to uses not according to the protocols approved before, where complications are greater and unjustified.

Keywords: inducing labor, misoprostol, pregnancy termination, third trimester

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Authors: R. Christopher, C. Brandt, N. Damons

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Background: The sequence of prevention model states that by constant assessment of injury, injury mechanisms and risk factors are identified, highlighting that collecting and recording of data is a core approach for preventing injuries. Several screening tools are available for use in the clinical setting. These screening techniques only recently received research attention, hence there is a dearth of inconsistent and controversial data regarding their applicability, validity, and reliability. Several systematic reviews related to common soccer injuries have been conducted; however, none of them addressed the screening tools for common soccer injuries. Objectives: The purpose of this study was to conduct a review of screening tools and their accuracy for common injuries in soccer. Methods: A systematic scoping review was performed based on the Joanna Briggs Institute procedure for conducting systematic reviews. Databases such as SPORT Discus, Cinahl, Medline, Science Direct, PubMed, and grey literature were used to access suitable studies. Some of the key search terms included: injury screening, screening, screening tool accuracy, injury prevalence, injury prediction, accuracy, validity, specificity, reliability, sensitivity. All types of English studies dating back to the year 2000 were included. Two blind independent reviewers selected and appraised articles on a 9-point scale for inclusion as well as for the risk of bias with the ACROBAT-NRSI tool. Data were extracted and summarized in tables. Plot data analysis was done, and sensitivity and specificity were analyzed with their respective 95% confidence intervals. I² statistic was used to determine the proportion of variation across studies. Results: The initial search yielded 95 studies, of which 21 were duplicates, and 54 excluded. A total of 10 observational studies were included for the analysis: 3 studies were analysed quantitatively while the remaining 7 were analysed qualitatively. Seven studies were graded low and three studies high risk of bias. Only high methodological studies (score > 9) were included for analysis. The pooled studies investigated tools such as the Functional Movement Screening (FMS™), the Landing Error Scoring System (LESS), the Tuck Jump Assessment, the Soccer Injury Movement Screening (SIMS), and the conventional hamstrings to quadriceps ratio. The accuracy of screening tools was of high reliability, sensitivity and specificity (calculated as ICC 0.68, 95% CI: 52-0.84; and 0.64, 95% CI: 0.61-0.66 respectively; I² = 13.2%, P=0.316). Conclusion: Based on the pooled results from the included studies, the FMS™ has a good inter-rater and intra-rater reliability. FMS™ is a screening tool capable of screening for common soccer injuries, and individual FMS™ scores are a better determinant of performance in comparison with the overall FMS™ score. Although meta-analysis could not be done for all the included screening tools, qualitative analysis also indicated good sensitivity and specificity of the individual tools. Higher levels of evidence are, however, needed for implication in evidence-based practice.

Keywords: accuracy, screening tools, sensitivity, soccer injuries, specificity

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Authors: G. Swati, D. Haranath

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Commercially available long afterglow /persistent phosphors are proprietary materials and hence the exact composition and phase responsible for their luminescent characteristics such as initial intensity and afterglow luminescence time are not known. Further to generate various emission colors, commercially available persistence phosphors are physically blended with fluorescent organic dyes such as rodhamine, kiton and methylene blue etc. Blending phosphors with organic dyes results into complete color coverage in visible spectra, however with time, such phosphors undergo thermal and photo-bleaching. This results in the loss of their true emission color. Hence, the current work is dedicated studies on inorganic based thermally and chemically stable primary color emitting nanophosphors namely SrAl2O4:Eu2+, Dy3+, (CaZn)TiO3:Pr3+, and Sr2MgSi2O7:Eu2+, Dy3+. SrAl2O4: Eu2+, Dy3+ phosphor exhibits a strong excitation in UV and visible region (280-470 nm) with a broad emission peak centered at 514 nm is the characteristic emission of parity allowed 4f65d1→4f7 transitions of Eu2+ (8S7/2→2D5/2). Sunlight excitable Sr2MgSi2O7:Eu2+,Dy3+ nanophosphors emits blue color (464 nm) with Commercial international de I’Eclairage (CIE) coordinates to be (0.15, 0.13) with a color purity of 74 % with afterglow time of > 5 hours for dark adapted human eyes. (CaZn)TiO3:Pr3+ phosphor system possess high color purity (98%) which emits intense, stable and narrow red emission at 612 nm due intra 4f transitions (1D2 → 3H4) with afterglow time of 0.5 hour. Unusual property of persistence luminescence of these nanophoshphors supersedes background effects without losing sensitive information these nanophosphors offer several advantages of visible light excitation, negligible substrate interference, high contrast bifurcation of ridge pattern, non-toxic nature revealing finger ridge details of the fingerprints. Both level 1 and level 2 features from a fingerprint can be studied which are useful for used classification, indexing, comparison and personal identification. facile methodology to extract high contrast fingerprints on non-porous and porous substrates using a chemically inert, visible light excitable, and nanosized phosphorescent label in the dark has been presented. The chemistry of non-covalent physisorption interaction between the long afterglow phosphor powder and sweat residue in fingerprints has been discussed in detail. Real-time fingerprint development on porous and non-porous substrates has also been performed. To conclude, apart from conventional dark vision applications, as prepared primary color emitting afterglow phosphors are potentional candidate for developing high contrast latent fingerprints.

Keywords: fingerprints, luminescence, persistent phosphors, rare earth

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Authors: Yuliya E. Leshchenko, Tatyana S. Ostapenko

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Language variation is a widespread linguistic phenomenon which can affect different levels of a language system: phonological, morphological, lexical, syntactic, etc. It is obvious that the scope of possible standard alternations within a particular language is limited by a variety of its norms and regulations which set more or less clear boundaries for what is possible and what is not possible for the speakers. The possibility of lexical variation (alternate usage of lexical items within the same contexts) is based on the fact that the meanings of words are not clearly and rigidly defined in the consciousness of the speakers. Therefore, lexical variation is usually connected with unstable relationship between words and their referents: a case when a particular lexical item refers to different types of referents, or when a particular referent can be named by various lexical items. We assume that the scope of lexical variation in bilingual speech is generally wider than that observed in monolingual speech due to the fact that, besides ‘lexical item – referent’ relations it involves the possibility of cross-language variation of L1 and L2 lexical items. We use the term ‘cross-language variation’ to denote a case when two equivalent words of different languages are treated by a bilingual speaker as freely interchangeable within the common linguistic context. As distinct from code-switching which is traditionally defined as the conscious use of more than one language within one communicative act, in case of cross-language lexical variation the speaker does not perceive the alternate lexical items as belonging to different languages and, therefore, does not realize the change of language code. In the paper, the authors present research of lexical variation of adult Komi-Permyak – Russian bilingual speakers. The two languages co-exist on the territory of the Komi-Permyak District in Russia (Komi-Permyak as the ethnic language and Russian as the official state language), are usually acquired from birth in natural linguistic environment and, according to the data of sociolinguistic surveys, are both identified by the speakers as coordinate mother tongues. The experimental research demonstrated that alternation of Komi-Permyak and Russian words within one utterance/phrase is highly frequent both in speech perception and production. Moreover, our participants estimated cross-language word combinations like ‘маленькая /Russian/ нывка /Komi-Permyak/’ (‘a little girl’) or ‘мунны /Komi-Permyak/ домой /Russian/’ (‘go home’) as regular/habitual, containing no violation of any linguistic rules and being equally possible in speech as the equivalent intra-language word combinations (‘учöтик нывка’ /Komi-Permyak/ or ‘идти домой’ /Russian/). All the facts considered, we claim that constant concurrent use of the two languages results in the fact that a large number of their words tend to be intuitively interpreted by the speakers as lexical variants not only related to the same referent, but also referring to both languages or, more precisely, to none of them in particular. Consequently, we can suppose that bilingual mental lexicon includes an extensive ‘fused’ zone of lexical representations that provide the basis for cross-language variation in bilingual speech.

Keywords: bilingualism, bilingual mental lexicon, code-switching, lexical variation

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Authors: Djeddi Mabrouk

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The slow coming together between the Afro-Eurasia plates seems to be the main cause of the active deformation in the whole of North Africa which in consequence come true in Algeria with a large zone of deformation in an enough large limited band, southern through Saharan atlas and northern through tell atlas. Maghrebin and Atlassian Chain along North Africa are the consequence of this convergence. In junction zone, we have noticed a compressive regime NW-SE with a creases-faults structure and structured overthrust. From a geological point of view the north part of Algeria is younger then Saharan platform, it’s changing so unstable and constantly in movement, it’s characterized by creases openly reversed, overthrusts and reversed faults, and undergo perpetually complex movement vertically and horizontally. On structural level the north of Algeria it's a part of erogenous alpine peri-Mediterranean and essentially the tertiary age It’s spread from east to the west of Algeria over 1200 km.This oogenesis is extended from east to west on broadband of 100 km.The alpine chain is shaped by 3 domains: tell atlas in north, high plateaus in mid and Saharan atlas in the south In extreme south we find the Saharan platform which is made of Precambrian bedrock recovered by Paleozoic practically not deformed. The Algerian north and the Saharan platform are separated by an important accident along of 2000km from Agadir (Morocco) to Gabes (Tunisian). The seismic activity is localized essentially in a coastal band in the north of Algeria shaped by tell atlas, high plateaus, Saharan atlas. Earthquakes are limited in the first 20km of the earth's crust; they are caused by movements along faults of inverted orientation NE-SW or sliding tectonic plates. The center region characterizes Strong Earthquake Activity who locates mainly in the basin of Mitidja (age Neogene).The southern periphery (Atlas Blidéen) constitutes the June, more Important seism genic sources in the city of Algiers and east (Boumerdes region). The North East Region is also part of the tellian area, but it is characterized by a different strain in other parts of northern Algeria. The deformation is slow and low to moderate seismic activity. Seismic activity is related to the tectonic-slip earthquake. The most pronounced is that of 27 October 1985 (Constantine) of seismic moment magnitude Mw = 5.9. North-West region is quite active and also artificial seismic hypocenters which do not exceed 20km. The deep seismicity is concentrated mainly a narrow strip along the edge of Quaternary and Neogene basins Intra Mountains along the coast. The most violent earthquakes in this region are the earthquake of Oran in 1790 and earthquakes Orléansville (El Asnam in 1954 and 1980).

Keywords: alpine chain, seismicity north Algeria, earthquakes in Algeria, geophysics, Earth

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Authors: Beata Spilakova, Daniel J. Shaw, Radek Marecek, Milan Brazdil

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Hyperscanning affords a unique insight into the brain dynamics underlying human interaction by simultaneously scanning two or more individuals’ brain responses while they engage in dyadic exchange. This provides an opportunity to observe dynamic brain activations in all individuals participating in interaction, and possible interbrain effects among them. The present research aims to provide an experimental paradigm for hyperscanning research capable of delineating among different forms of interaction. Specifically, the goal was to distinguish between two dimensions: (1) interaction structure (concurrent vs. turn-based) and (2) goal structure (competition vs cooperation). Dual-fMRI was used to scan 22 pairs of participants - each pair matched on gender, age, education and handedness - as they played the Pattern Game. In this simple interactive task, one player attempts to recreate a pattern of tokens while the second player must either help (cooperation) or prevent the first achieving the pattern (competition). Each pair played the game iteratively, alternating their roles every round. The game was played in two consecutive sessions: first the players took sequential turns (turn-based), but in the second session they placed their tokens concurrently (concurrent). Conventional general linear model (GLM) analyses revealed activations throughout a diffuse collection of brain regions: The cooperative condition engaged medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC); in the competitive condition, significant activations were observed in frontal and prefrontal areas, insula cortices and the thalamus. Comparisons between the turn-based and concurrent conditions revealed greater precuneus engagement in the former. Interestingly, mPFC, PCC and insulae are linked repeatedly to social cognitive processes. Similarly, the thalamus is often associated with a cognitive empathy, thus its activation may reflect the need to predict the opponent’s upcoming moves. Frontal and prefrontal activation most likely represent the higher attentional and executive demands of the concurrent condition, whereby subjects must simultaneously observe their co-player and place his own tokens accordingly. The activation of precuneus in the turn-based condition may be linked to self-other distinction processes. Finally, by performing intra-pair correlations of brain responses we demonstrate condition-specific patterns of brain-to-brain coupling in mPFC and PCC. Moreover, the degree of synchronicity in these neural signals related to performance on the game. The present results, then, show that different types of interaction recruit different brain systems implicated in social cognition, and the degree of inter-player synchrony within these brain systems is related to nature of the social interaction.

Keywords: brain-to-brain coupling, hyperscanning, pattern game, social interaction

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Authors: Ahmed Mohammed Omer Alghamdi

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Since the COVID-19 pandemic started, a rapid, unexpected transition from face-to-face to virtual classroom (VC) teaching has involved several challenges and obstacles. However, there are also opportunities and thoughts that need to be examined and discussed. In addition, the entire world is witnessing that the teaching system and, more particularly, higher education institutes have been interrupted. To maintain the learning and teaching practices as usual, countries were forced to transition from traditional to virtual classes using various technology-based devices. In this regard, the Kingdom of Saudi Arabia (KSA) is no exception. Focusing on how the current situation has forced many higher education institutes to change to virtual classes may possibly provide a clear insight into adopted practices and implications. The main purpose of this study, therefore, was to investigate how both Saudi English as a foreign language (EFL) teachers and students perceived the implementation of virtual classes as a key factor for useful language teaching and learning process during the COVID-19 pandemic period at a Saudi university. The impetus for the research was, therefore, the need to find ways of identifying the deficiencies in this application and to suggest possible solutions that might rectify those deficiencies. This study seeks to answer the following overarching research question: “How do Saudi EFL instructors and students perceive the use of virtual classes during the COVID-19 pandemic period in their language teaching and learning context?” The following sub-questions are also used to guide the design of the study to answer the main research question: (1) To what extent are virtual classes important intra-pandemic from Saudi EFL instructors’ and students’ perspectives? (2) How effective are virtual classes for fostering English language students’ achievement? (3) What are the challenges and obstacles that instructors and students may face during the implementation of virtual teaching? A mixed method approach was employed in this study; the questionnaire data collection represented the quantitative method approach for this study, whereas the transcripts of recorded interviews represented the qualitative method approach. The participants included EFL teachers (N = 4) and male and female EFL students (N = 36). Based on the findings of this study, various aspects from teachers' and students’ perspectives were examined to determine the use of the virtual classroom applications in terms of fulfilling the students’ English language learning needs. The major findings of the study revealed that the virtual classroom applications during the current pandemic situation encountered three major challenges, among which the existence of the following essential aspects, namely lack of technology and an internet connection, having a large number of students in a virtual classroom and lack of students’ and teachers’ interactions during the virtual classroom applications. Finally, the findings indicated that although Saudi EFL students and teachers view the virtual classrooms in a positive light during the pandemic period, they reported that for long and post-pandemic period, they preferred the traditional face-to-face teaching procedure.

Keywords: virtual classes, English as a foreign language, COVID-19, Internet, pandemic

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Authors: T. Arkle, D. Pournaras, S. Lam, B. Kumar

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Introduction: Fundoplication is widely recognised as the best surgical option for gastro-oesophageal reflux disease (GORD) in the general population. However, there is controversy surrounding the use of conventional fundoplication in obese patients. Whilst the intra-operative failure of fundoplication, including wrap disruption, is reportedly higher in obese individuals, the more significant issue surrounds symptom recurrence post-surgery. Could a bariatric procedure be considered in obese patients for weight management, to treat the GORD, and to also reduce the risk of recurrence? Roux-en-Y gastric bypass, a widely performed bariatric procedure, has been shown to be highly successful both in controlling GORD symptoms and in weight management in obese patients. Furthermore, NICE has published clear guidelines on eligibility for bariatric surgery, with the main criteria being type 3 obesity or type 2 obesity with the presence of significant co-morbidities that would improve with weight loss. This study aims to identify the proportion of patients who undergo conventional fundoplication for GORD and/or hiatus hernia, which would have been eligible for bariatric surgery referral according to NICE guidelines. Methods: All patients who underwent fundoplication procedures for GORD and/or hiatus hernia repair at a single NHS foundation trust over a 10-year period will be identified using the Trust’s health records database. Pre-operative patient records will be used to find BMI and the presence of significant co-morbidities at the time of consideration for surgery. This information will be compared to NICE guidelines to determine potential eligibility for the bariatric surgical referral at the time of initial surgical intervention. Results: A total of 321 patients underwent fundoplication procedures between January 2011 and December 2020; 133 (41.4%) had available data for BMI or to allow BMI to be estimated. Of those 133, 40 patients (30%) had a BMI greater than 30kg/m², and 7 (5.3%) had BMI >35kg/m². One patient (0.75%) had a BMI >40 and would therefore be automatically eligible according to NICE guidelines. 4 further patients had significant co-morbidities, such as hypertension and osteoarthritis, which likely be improved by weight management surgery and therefore also indicated eligibility for referral. Overall, 3.75% (5/133) of patients undergoing conventional fundoplication procedures would have been eligible for bariatric surgical referral, these patients were all female, and the average age was 60.4 years. Conclusions: Based on this Trust’s experience, around 4% of obese patients undergoing fundoplication would have been eligible for bariatric surgical intervention. Based on current evidence, in class 2/3 obese patients, there is likely to have been a notable proportion with recurrent disease, potentially requiring further intervention. These patient’s may have benefitted more through undergoing bariatric surgery, for example a Roux-en-Y gastric bypass, addressing both their obesity and GORD. Use of patient written notes to obtain BMI data for the 188 patients with missing BMI data and further analysis to determine outcomes following fundoplication in all patients, assessing for incidence of recurrent disease, will be undertaken to strengthen conclusions.

Keywords: bariatric surgery, GORD, Nissen fundoplication, nice guidelines

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Authors: Geanderson Eduardo Ambrósio, Dênis Antônio Da Cunha, Marcel Viana Pires

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Historically, human development has been based on economic gains associated with intensive energy activities, which often are exhaustive in the emission of Greenhouse Gases (GHGs). It requires the establishment of targets for mitigation of GHGs in order to disassociate the human development from emissions and prevent further climate change. Brazil presents itself as one of the most GHGs emitters and it is of critical importance to discuss such reductions in intra-national framework with the objective of distributional equity to explore its full mitigation potential without compromising the development of less developed societies. This research displays some incipient considerations about which Brazil’s micro-regions should reduce, when the reductions should be initiated and what its magnitude should be. We started with the methodological assumption that human development and GHGs emissions arise in the future as their behavior was observed in the past. Furthermore, we assume that once a micro-region became developed, it is able to maintain gains in human development without the need of keep growing GHGs emissions rates. The human development index and the carbon dioxide equivalent emissions (CO2e) were extrapolated to the year 2050, which allowed us to calculate when the micro-regions will become developed and the mass of GHG’s emitted. The results indicate that Brazil must throw 300 GT CO2e in the atmosphere between 2011 and 2050, of which only 50 GT will be issued by micro-regions before it’s develop and 250 GT will be released after development. We also determined national mitigation targets and structured reduction schemes where only the developed micro-regions would be required to reduce. The micro-region of São Paulo, the most developed of the country, should be also the one that reduces emissions at most, emitting, in 2050, 90% less than the value observed in 2010. On the other hand, less developed micro-regions will be responsible for less impactful reductions, i.e. Vale do Ipanema will issue in 2050 only 10% below the value observed in 2010. Such methodological assumption would lead the country to issue, in 2050, 56.5% lower than that observed in 2010, so that the cumulative emissions between 2011 and 2050 would reduce by 130 GT CO2e over the initial projection. The fact of associating the magnitude of the reductions to the level of human development of the micro-regions encourages the adoption of policies that favor both variables as the governmental planner will have to deal with both the increasing demand for higher standards of living and with the increasing magnitude of reducing emissions. However, if economic agents do not act proactively in local and national level, the country is closer to the scenario in which emits more than the one in which mitigates emissions. The research highlighted the importance of considering the heterogeneity in determining individual mitigation targets and also ratified the theoretical and methodological feasibility to allocate larger share of contribution for those who historically emitted more. It is understood that the proposals and discussions presented should be considered in mitigation policy formulation in Brazil regardless of the adopted reduction target.

Keywords: greenhouse gases, human development, mitigation, intensive energy activities

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Authors: Kaushiki Sanyal, Rajesh Chakrabarti

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In India, on average, about 60 Bills are passed every year in both Houses of Parliament – Lok Sabha and Rajya Sabha (calculated from information on websites of both Houses). These are debated in both Lok Sabha (House of Commons) and Rajya Sabha (Council of States) before they are passed. However, lawmakers rarely use empirical evidence to make a case for a law. Most of the time, they support a law on the basis of anecdote, intuition, and common sense. While these do play a role in law-making, without the necessary empirical evidence, laws often fail to achieve their desired results. The quality of legislative debates is an indicator of the efficacy of the legislative process through which a Bill is enacted. However, the study of legislative debates has not received much attention either in India or worldwide due to the difficulty of objectively measuring the quality of a debate. Broadly, three approaches have emerged in the study of legislative debates. The rational-choice or formal approach shows that speeches vary based on different institutional arrangements, intra-party politics, and the political culture of a country. The discourse approach focuses on the underlying rules and conventions and how they impact the content of the debates. The deliberative approach posits that legislative speech can be reasoned, respectful, and informed. This paper aims to (a) develop a framework to judge the quality of debates by using the deliberative approach; (b) examine the legislative debates of three Bills passed in different periods as a demonstration of the framework, and (c) examine the broader structural issues that disincentive MPs from scrutinizing Bills. The framework would include qualitative and quantitative indicators to judge a debate. The idea is that the framework would provide useful insights into the legislators’ knowledge of the subject, the depth of their scrutiny of Bills, and their inclination toward evidence-based research. The three Bills that the paper plans to examine are as follows: 1. The Narcotics Drugs and Psychotropic Substances Act, 1985: This act was passed to curb drug trafficking and abuse. However, it mostly failed to fulfill its purpose. Consequently, it was amended thrice but without much impact on the ground. 2. The Criminal Laws (Amendment) Act, 2013: This act amended the Indian Penal Code to add a section on human trafficking. The purpose was to curb trafficking and penalise traffickers, pimps, and middlemen. However, the crime rate remains high while the conviction rate is low. 3. The Surrogacy (Regulation) Act, 2021: This act bans commercial surrogacy allowing only relatives to act as surrogates as long as there is no monetary payment. Experts fear that instead of preventing commercial surrogacy, it would drive the activity underground. The consequences would be borne by the surrogate, who would not be protected by law. The purpose of the paper is to objectively analyse the quality of parliamentary debates, get insights into how MPs understand the evidence and deliberate on steps to incentivise them to use empirical evidence.

Keywords: legislature, debates, empirical, India

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Authors: Seyedeh Nasim Mirbahari, Taha Azad, Mehdi Totonchi

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Oncolytic viruses, which only replicate in tumor cells, are being extensively studied for their use in cancer therapy. A particular virus known as the vaccinia virus, a member of the poxvirus family, has demonstrated oncolytic abilities glioma. Treating Glioma with traditional methods such as chemotherapy and radiotherapy is quite challenging. Even though oncolytic viruses have shown immense potential in cancer treatment, their effectiveness in glioblastoma treatment is still low. Therefore, there is a need to improve and optimize immunotherapies for better results. In this study, we have designed oncoVV-TT, which can more effectively target tumor cells while minimizing replication in normal cells by replacing the thymidine kinase gene with a luc-p2a-GFP gene expression cassette. Human glioblastoma cell line U251 MG, rat glioblastoma cell line C6, and non-tumor cell line HFF were plated at 105 cells in a 12-well plates in 2 mL of DMEM-F2 medium with 10% FBS added to each well. Then incubated at 37°C. After 16 hours, the cells were treated with oncoVV-TT at an MOI of 0.01, 0.1 and left in the incubator for a further 24, 48, 72 and 96 hours. Viral replication assay, fluorescence imaging and viability tests, including trypan blue and crystal violet, were conducted to evaluate the cytotoxic effect of oncoVV-TT. The finding shows that oncoVV-TT had significantly higher cytotoxic activity and proliferation rates in tumor cells in a dose and time-dependent manner, with the strongest effect observed in U251 MG. To conclude, oncoVV-TT has the potential to be a promising oncolytic virus for cancer treatment, with a more cytotoxic effect in human glioblastoma cells versus rat glioma cells. To assess the effectiveness of vaccinia virus-mediated viral therapy, we have tested U251mg and C6 tumor cell lines taken from human and rat gliomas, respectively. The study evaluated oncoVV-TT's ability to replicate and lyse cells and analyzed the survival rates of the tested cell lines when treated with different doses of oncoVV-TT. Additionally, we compared the sensitivity of human and mouse glioma cell lines to the oncolytic vaccinia virus. All experiments regarding viruses were conducted under biosafety level 2. We engineered a Vaccinia-based oncolytic virus called oncoVV-TT to replicate specifically in tumor cells. To propagate the oncoVV-TT virus, HeLa cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 10 MOI virus was added. After 48 h, cells were harvested by scraping, and viruses were collected by 3 sequential freezing and thawing cycles followed by removal of cell debris by centrifugation (1500 rpm, 5 min). The supernatant was stored at −80 ◦C for the following experiments. To measure the replication of the virus in Hela, cells (5 × 104/well) were plated in 24-well plates and incubated overnight to attach to the bottom of the wells. Subsequently, 5 MOI virus or equal dilution of PBS was added. At the treatment time of 0 h, 24 h, 48 h, 72 h and 96 h, the viral titers were determined under the fluorescence microscope (BZ-X700; Keyence, Osaka, Japan). Fluorescence intensity was quantified using the imagej software according to the manufacturer’s protocol. For the isolation of single-virus clones, HeLa cells seeded in six-well plates (5×105 cells/well). After 24 h (100% confluent), the cells were infected with a 10-fold dilution series of TianTan green fluorescent protein (GFP)virus and incubated for 4 h. To examine the cytotoxic effect of oncoVV-TT virus ofn U251mg and C6 cell, trypan blue and crystal violet assay was used.

Keywords: oncolytic virus, immune therapy, glioma, vaccinia virus

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Authors: Mitsuhiro Hirai, Satoshi Ajito, Nobutaka Shimizu, Noriyuki Igarashi, Hiroki Iwase, Shinichi Takata

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Sugars and polyols are known to be bioprotectants preventing such as protein denaturation and enzyme deactivation and widely used as a nontoxic additive in various industrial and medical products. The mechanism of their protective actions has been explained by specific bindings between biological components and additives, changes in solvent viscosities, and surface tension and free energy changes upon transfer of those components into additive solutions. On the other hand, some organisms having tolerances against extreme environment produce stress proteins and/or accumulate sugars in cells, which is called cryptobiosis. In particular, trehalose has been drawing attention relevant to cryptobiosis under external stress such as high or low temperature, drying, osmotic pressure, and so on. The function of cryptobiosis by trehalose has been explained relevant to the restriction of the intra-and/or-inter-molecular movement by vitrification or from the replacement of water molecule by trehalose. Previous results suggest that the structure and interaction between sugar and water are a key determinant for understanding cryptobiosis. Recently, we have shown direct evidence that the protein hydration (solvation) and structural stability against chemical and thermal denaturation significantly depend on sugar species and glycerol. Sugar and glycerol molecules tend to be preferentially or weakly excluded from the protein surface and preserved the native protein hydration shell. Due to the protective action of the protein hydration shell by those molecules, the protein structure is stabilized against chemical (guanidinium chloride) and thermal denaturation. The protective action depends on sugar species. To understand the above trend and difference in detail, it is essentially important to clarify the characteristics of solutions containing those additives. In this study, by using wide-angle X-ray scattering technique covering a wide spatial region (~3-120 Å), we have clarified structures of sugar solutions with the concentration from 5% w/w to 65% w/w. The sugars measured in the present study were monosaccharides (glucose, fructose, mannose) and disaccharides (sucrose, trehalose, maltose). Due to observed scattering data with a wide spatial resolution, we have succeeded in obtaining information on the internal structure of individual sugar molecules and on the correlation between them. Every sugar gradually shortened the average inter-molecular distance as the concentration increased. The inter-molecular interaction between sugar molecules was essentially showed an exclusive tendency for every sugar, which appeared as the presence of a repulsive correlation hole. This trend was more weakly seen for trehalose compared to other sugars. The intermolecular distance and spread of individual molecule clearly showed the dependence of sugar species. We will discuss the relation between the characteristic of sugar solution and its protective action of biological materials.

Keywords: hydration, protein, sugar, X-ray scattering

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Authors: M. Cardenas-Garcia, P. P. Gonzalez-Perez

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Intercellular communication is a necessary condition for cellular functions and it allows a group of cells to survive as a population. Throughout this interaction, the cells work in a coordinated and collaborative way which facilitates their survival. In the case of cancerous cells, these take advantage of intercellular communication to preserve their malignancy, since through these physical unions they can send signs of malignancy. The Wnt/β-catenin signaling pathway plays an important role in the formation of intercellular communications, being also involved in a large number of cellular processes such as proliferation, differentiation, adhesion, cell survival, and cell death. The modeling and simulation of cellular signaling systems have found valuable support in a wide range of modeling approaches, which cover a wide spectrum ranging from mathematical models; e.g., ordinary differential equations, statistical methods, and numerical methods– to computational models; e.g., process algebra for modeling behavior and variation in molecular systems. Based on these models, different simulation tools have been developed from mathematical ones to computational ones. Regarding cellular and molecular processes in cancer, its study has also found a valuable support in different simulation tools that, covering a spectrum as mentioned above, have allowed the in silico experimentation of this phenomenon at the cellular and molecular level. In this work, we simulate and explore the complex interaction patterns of intercellular communication in cancer cells using the Cellulat bioinformatics tool, a computational simulation tool developed by us and motivated by two key elements: 1) a biochemically inspired model of self-organizing coordination in tuple spaces, and 2) the Gillespie’s algorithm, a stochastic simulation algorithm typically used to mimic systems of chemical/biochemical reactions in an efficient and accurate way. The main idea behind the Cellulat simulation tool is to provide an in silico experimentation environment that complements and guides in vitro experimentation in intra and intercellular signaling networks. Unlike most of the cell signaling simulation tools, such as E-Cell, BetaWB and Cell Illustrator which provides abstractions to model only intracellular behavior, Cellulat is appropriate for modeling both intracellular signaling and intercellular communication, providing the abstractions required to model –and as a result, simulate– the interaction mechanisms that involve two or more cells, that is essential in the scenario discussed in this work. During the development of this work we made evident the application of our computational simulation tool (Cellulat) for the modeling and simulation of intercellular communication between normal and cancerous cells, and in this way, propose key molecules that may prevent the arrival of malignant signals to the cells that surround the tumor cells. In this manner, we could identify the significant role that has the Wnt/β-catenin signaling pathway in cellular communication, and therefore, in the dissemination of cancer cells. We verified, using in silico experiments, how the inhibition of this signaling pathway prevents that the cells that surround a cancerous cell are transformed.

Keywords: cancer cells, in silico approach, intercellular communication, key molecules, modeling and simulation

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Authors: Enrico Gugliandolo, Salvatore Cuzzocrea, Rosalia Crupi

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Osteoarthritis (OA) is one of the most common chronic pain conditions in dogs and cats. OA pain is currently viewed as a mixed phenomenon involving both inflammatory and neuropathic mechanisms at the peripheral (joint) and central (spinal and supraspinal) levels. Oxidative stress has been implicated in OA pain. Although nonsteroidal anti-inflammatory drugs are commonly prescribed for OA pain, they should be used with caution in pets because of adverse effects in the long term and controversial efficacy on neuropathic pain. An unmet need remains for safe and effective long-term treatments for OA pain. Palmitoyl-glucosamine (PGA) is an analogue of the ALIAamide palmitoylethanolamide, i.e., a body’s own endocannabinoid-like compound playing a sentinel role in nociception. PGA, especially in the micronized formulation, was shown safe and effective in OA pain. The aim of this study was to investigate the effect of a co-micronized formulation of PGA with the natural antioxidant curcumin (PGA-cur) on OA pain. Ten Sprague-Dawley male rats were used for each treatment group. The University of Messina Review Board for the care and use of animals authorized the study. On day 0, rats were anesthetized (5.0% isoflurane in 100% O2) and received intra-articular injection of MIA (3 mg in 25 μl saline) in the right knee joint, with the left being injected an equal volume of saline. Starting the third day after MIA injection, treatments were administered orally three times per week for 21 days, at the following doses: PGA 20 mg/kg, curcumin 10 mg/kg, PGA-cur (2:1 ratio) 30 mg/kg. On day 0 and 3, 7, 14 and 21 days post-injection, mechanical allodynia was measured using a dynamic plantar Von Frey hair aesthesiometer and expressed as paw withdrawal threshold (PWT) and latency (PWL). Motor functional recovery of the rear limb was evaluated on the same time points by walking track analysis using the sciatic functional index. On day 21 post-MIA injection, the concentration of the following inflammatory and nociceptive mediators was measured in serum using commercial ELISA kits: tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), nerve growth factor (NGF) and matrix metalloproteinase-1-3-9 (MMP-1, MMP-3, MMP-9). The results were analyzed by ANOVA followed by Bonferroni post-hoc test for multiple comparisons. Micronized PGA reduced neuropathic pain, as shown by the significant higher PWT and PWL values compared to vehicle group (p < 0.0001 for all the evaluated time points). The effect of PGA-cur was superior at all time points (p < 0.005). PGA-cur restored motor function already on day 14 (p < 0.005), while micronized PGA was effective a week later (D21). MIA-induced increase in the serum levels of all the investigated mediators was inhibited by PGA-cur (p < 0.01). PGA was also effective, except on IL-1 and MMP-3. Curcumin alone was inactive in all the experiments at any time point. The encouraging results suggest that PGA-cur may represent a valuable option in OA pain management and warrant further confirmation in well-powered clinical trials.

Keywords: ALIAmides, curcumin, osteoarthritis, palmitoyl-glucosamine

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Authors: Moustafa Osman Mohammed

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This paper introduces Luhmann’s autopoietic social systems starting with the original concept of autopoiesis by biologists and scientists, including the modification of general systems based on socialized medicine. A specific type of autopoietic system is explained in the three existing groups of the ecological phenomena: interaction, social and medical sciences. This hypothesis model, nevertheless, has a nonlinear interaction with its natural environment ‘interactional cycle’ for the exchange of photon energy with molecular without any changes in topology. The external forces in the systems environment might be concomitant with the natural fluctuations’ influence (e.g. radioactive radiation, electromagnetic waves). The cantilever sensor deploys insights to the future chip processor for prevention of social metabolic systems. Thus, the circuits with resonant electric and optical properties are prototyped on board as an intra–chip inter–chip transmission for producing electromagnetic energy approximately ranges from 1.7 mA at 3.3 V to service the detection in locomotion with the least significant power losses. Nowadays, therapeutic systems are assimilated materials from embryonic stem cells to aggregate multiple functions of the vessels nature de-cellular structure for replenishment. While, the interior actuators deploy base-pair complementarity of nucleotides for the symmetric arrangement in particular bacterial nanonetworks of the sequence cycle creating double-stranded DNA strings. The DNA strands must be sequenced, assembled, and decoded in order to reconstruct the original source reliably. The design of exterior actuators have the ability in sensing different variations in the corresponding patterns regarding beat-to-beat heart rate variability (HRV) for spatial autocorrelation of molecular communication, which consists of human electromagnetic, piezoelectric, electrostatic and electrothermal energy to monitor and transfer the dynamic changes of all the cantilevers simultaneously in real-time workspace with high precision. A prototype-enabled dynamic energy sensor has been investigated in the laboratory for inclusion of nanoscale devices in the architecture with a fuzzy logic control for detection of thermal and electrostatic changes with optoelectronic devices to interpret uncertainty associated with signal interference. Ultimately, the controversial aspect of molecular frictional properties is adjusted to each other and forms its unique spatial structure modules for providing the environment mutual contribution in the investigation of mass temperature changes due to pathogenic archival architecture of clusters.

Keywords: autopoiesis, nanoparticles, quantum photonics, portable energy, photonic structure, photodynamic therapeutic system

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Authors: Priyanka Manghani, Manthan Patel, Rahul Peddawad

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Cervical Cancer is a major public health hurdle in the area of women’s health. The most common cause of Cervical Cancer is the Human Papilloma Virus (HPV). Human papilloma virus has various genotypes, with HPV 16 and HPV 18 being the major etiological factor causing carcinoma of the Cervix. Early screening and detection by Papanicolaou Smears (PAP) is an effective method for identifying premalignant and malignant lesions. In case of existing pre- malignant lesions /cervical dysplasia’s found with HPV 16 or 18, appropriate follow up can be done to prevent it from developing into a neoplasm. Aims and Objectives: Primary Aim; To study various abnormal cervical cytology reports as detected by Pap Smear Tests, using the Bethesda System in women at a Tertiary Care Hospital. Secondary Aim; To discuss the importance of Pap smear in Cervical Cancer Screening Program. Materials and Methods: Our study is a prospective study, based on 101 women who attended the Out-patient department of Obstetrics and Gynecology at a tertiary care hospital in age group 20-40 years with chief complaints of white/foul vaginal discharge, post-coital Bleeding, low back pain, irregular menstruation, etc. 60 women, who were tested, of the total no of women, were commercial sex workers, thus being a high-risk group for HPV infection. All women underwent conventional cytology. For all the abnormal smears, further cervical biopsies were done, and the final diagnosis was done on the basis of histopathology (gold standard). Results: In all these patients, 16 patients presented with normal smears out of which 2 belonged to the category of commercial sex workers (3.33%) and 14 being from the normal/control group (34.15%). 44 women presented with inflammatory smears out of which 30 were commercial sex workers (50%) and 14 from the control Group (34.15%). A total of 11 women presented with infectious etiology with 6 being commercial sex workers (10%) and 5 (12.2%) being in the control group. A total of 8 patients presented with low-grade squamous intra epithelial lesion (LSIL) with 7 (11.7%) being commercial sex workers and 1(2.44%) patient belonging to the control group. A Total of 7 patients presented with high-grade squamous intraepithelial lesion (HSIL) with 6 (10%) being commercial sex workers and 1 (2.44%) belonging to the control group. 9 patients in total presented with atypical squamous cells of undetermined significance (ASCUS) with 6(10%) being commercial sex workers and 3 (7.32%) belonging to the control group. Squamous cell carcinoma(SCC) presence was found only in 1(1.7%) commercial sex worker. Conclusion – We conclude that HSIL, LSIL, SCC and sexually related infections are comparatively more common in vulnerable groups such as sex workers due to a variety of factors such as multiple sexual partners and poor genital hygiene. Early screening and follow up interventions are highly needed for them along with Health education for risk factors and to emphasize on the importance of Pap smear screening.

Keywords: cervical cancer, papanicolaou (pap) smear, bethesda system, neoplasm

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Authors: Mohamed M. Zaki, Maha M. Hady

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Salmonella spp. have been categorized as the world’s biggest threats to human health and poultry products are mostly incriminated sources. In Egypt, it was found that S. enteritidis and S. typhimurium are the most prevalent ones in poultry farms. It is recommended to eliminate salmonella from living bird by competing for salmonella contamination in feed in order to establish a healthy gut. The Feed acidifiers are the group of feed additives containing low-molecular-weight organic acids and/ or their salts which act as performance promoters by lowering the pH in the gut, optimizes digestion and inhibit bacterial growth. The inclusion of organic acid in pure form nonetheless effective in feed, yet, it is difficult to handle in feed mills as it is corrosive and produce more losses during pelleting process. The current study aimed at to evaluate the impact of incorporation of sodium diformate (SDF) and a commercial acidifier, CA (a mixture of butyric and propionic acids and their ammonium salts) at 0.4% dietary levels on broilers performance and the control S. enteritidis infection. Two hundreds and seventy unsexed cobb chickens were allotted in one of three treatments (90/ group) which were, the control (no acidifier, C- &C+), the 0.4% SDF (SDF- & SDF +) and the 0.4% CA (CA- & CA +) dietary levels for 35 days. Before the allocation of the groups, ten extra birds and a diet sample were bacteriologically examined to ensure negative contamination with salmonella. The birds were raised on deep-litter separated pens and had free access to feed and water all the time. The experimentally formulated diets were kept at 40C. After 24h access to the different dietary treatments, all the birds in the positive groups (n=15/ replicate) were inoculated intra-crop with 0.2 ml of 24 h broth culture of S. entertidis containing 1X 107 organisms while the negative-treated groups were inoculated with the same amount of the negative broth and second inoculation was done at 22 d of age. Colocal swabs were collected individually from all birds 2 h pre-inoculation to assure the absence of salmonella, then 1, 3, 5, 7, 21 days post-inoculation to recover salmonella. Performance parameter (body weight gain and feed efficiency) were calculated. Mortalities were recorded and reisolation of the salmonella was adopted to ensure it was the inoculated ones. The results revealed that the dietary acidification with sodium diformate significantly improved broilers performance and tends to produce heavier birds as compared to the negative control and CA groups. Moreover, the dietary inclusion of both acidifiers at level of 0.4% was able to eliminate mortalities completely at the relevant inoculation time. Regarding the shedding of S. enteritidius in positive groups, the SDF treatment resulted in significant (p<0.05) cessation of the shedding at 3 days post-inoculation compared to 7 days post-inoculation for the CA-group. In conclusion, sodium diformate at 0.4% dietary level in broiler diets has a valuable effect not only on broilers performance but also by eliminating S. enteritidis the main source of salmonella contamination in poultry farms which is feed.

Keywords: acidifier, broilers, Salmonalla spp, sodium diformate

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Authors: Ashok Kumar, Shiv Brat Singh, Kalyan Kumar Ray

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There is growing awareness to design steels against fatigue damage Ferrite martensite dual-phase steels are known to exhibit favourable mechanical properties like good strength, ductility, toughness, continuous yielding, and high work hardening rate. However, dual-phase steels containing bainite as second phase are potential alternatives for ferrite martensite steels for certain applications where good fatigue property is required. Fatigue properties of dual phase steels are popularly assessed by the nature of variation of crack growth rate (da/dN) with stress intensity factor range (∆K), and the magnitude of fatigue threshold (∆Kth) for long cracks. There exists an increased emphasis to understand not only the long crack fatigue behavior but also short crack growth behavior of ferrite bainite dual phase steels. The major objective of this report is to examine the influence of microstructures on the short and long crack growth behavior of a series of developed dual-phase steels with varying amounts of bainite and. Three low carbon steels containing Nb, Cr and Mo as microalloying elements steels were selected for making ferrite-bainite dual-phase microstructures by suitable heat treatments. The heat treatment consisted of austenitizing the steel at 1100°C for 20 min, cooling at different rates in air prior to soaking these in a salt bath at 500°C for one hour, and finally quenching in water. Tensile tests were carried out on 25 mm gauge length specimens with 5 mm diameter using nominal strain rate 0.6x10⁻³ s⁻¹ at room temperature. Fatigue crack growth studies were made on a recently developed specimen configuration using a rotating bending machine. The crack growth was monitored by interrupting the test and observing the specimens under an optical microscope connected to an Image analyzer. The estimated crack lengths (a) at varying number of cycles (N) in different fatigue experiments were analyzed to obtain log da/dN vs. log °∆K curves for determining ∆Kthsc. The microstructural features of these steels have been characterized and their influence on the near threshold crack growth has been examined. This investigation, in brief, involves (i) the estimation of ∆Kthsc and (ii) the examination of the influence of microstructure on short and long crack fatigue threshold. The maximum fatigue threshold values obtained from short crack growth experiments on various specimens of dual-phase steels containing different amounts of bainite are found to increase with increasing bainite content in all the investigated steels. The variations of fatigue behavior of the selected steel samples have been explained with the consideration of varying amounts of the constituent phases and their interactions with the generated microstructures during cyclic loading. Quantitative estimation of the different types of fatigue crack paths indicates that the propensity of a crack to pass through the interfaces depends on the relative amount of the microstructural constituents. The fatigue crack path is found to be predominantly intra-granular except for the ones containing > 70% bainite in which it is predominantly inter-granular.

Keywords: bainite, dual phase steel, fatigue crack growth rate, long crack fatigue threshold, short crack fatigue threshold

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Authors: Yazan S. Khaled, Shazana Shamsuddin, Jim Tiernan, Mike McPherson, Thomas Hughes, Paul Millner, David G. Jayne

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Introduction: There is a need for real-time imaging of colorectal cancer (CRC) to allow tailored surgery to the disease stage. Fluorescence guided laparoscopic imaging of primary colorectal cancer and the draining lymphatics would potentially bring stratified surgery into clinical practice and realign future CRC management to the needs of patients. Fluorescent nanoparticles can offer many advantages in terms of intra-operative imaging and therapy (theranostic) in comparison with traditional soluble reagents. Nanoparticles can be functionalised with diverse reagents and then targeted to the correct tissue using an antibody or Affimer (artificial binding protein). We aimed to develop and test fluorescent silica nanoparticles and targeted against CRC using an anti-carcinoembryonic antigen (CEA) Affimer (Aff). Methods: Anti-CEA and control Myoglobin Affimer binders were subcloned into the expressing vector pET11 followed by transformation into BL21 Star™ (DE3) E.coli. The expression of Affimer binders was induced using 0.1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG). Cells were harvested, lysed and purified using nickle chelating affinity chromatography. The photosensitiser Foslip (soluble analogue of 5,10,15,20-Tetra(m-hydroxyphenyl) chlorin) was incorporated into the core of silica nanoparticles using water-in-oil microemulsion technique. Anti-CEA or control Affs were conjugated to silica nanoparticles surface using sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo SMCC) chemical linker. Binding of CEA-Aff or control nanoparticles to colorectal cancer cells (LoVo, LS174T and HC116) was quantified in vitro using confocal microscopy. Results: The molecular weights of the obtained band of Affimers were ~12.5KDa while the diameter of functionalised silica nanoparticles was ~80nm. CEA-Affimer targeted nanoparticles demonstrated 9.4, 5.8 and 2.5 fold greater fluorescence than control in, LoVo, LS174T and HCT116 cells respectively (p < 0.002) for the single slice analysis. A similar pattern of successful CEA-targeted fluorescence was observed in the maximum image projection analysis, with CEA-targeted nanoparticles demonstrating 4.1, 2.9 and 2.4 fold greater fluorescence than control particles in LoVo, LS174T, and HCT116 cells respectively (p < 0.0002). There was no significant difference in fluorescence for CEA-Affimer vs. CEA-Antibody targeted nanoparticles. Conclusion: We are the first to demonstrate that Foslip-doped silica nanoparticles conjugated to anti-CEA Affimers via SMCC allowed tumour cell-specific fluorescent targeting in vitro, and had shown sufficient promise to justify testing in an animal model of colorectal cancer. CEA-Affimer appears to be a suitable targeting molecule to replace CEA-Antibody. Targeted silica nanoparticles loaded with Foslip photosensitiser is now being optimised to drive photodynamic killing, via reactive oxygen generation.

Keywords: colorectal cancer, silica nanoparticles, Affimers, antibodies, imaging

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Authors: S. D. Zalepugin, A. E. Murzich, D. G. Satskevich, A. B. Palivanov

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Introduction. The incidence of spinal injuries in patients under 18 years of age has increased significantly in recent years, which represents a significant economic, social and medical problem. The most common method of surgical stabilization of spinal fractures in pediatric patients is transpedicular posterior spinal fusion, which is widely used by spinal neurosurgeons in adult patients. Purpose of the study: This study evaluates the results of treatment of thoracolumbar spine lesions in children using the transpedicular screw fixation method. Materials and methods. From 2019 to 2024, 35 children with injuries to the thoracic and lumbar spine underwent surgical treatment using the transpedicular screw fixation method. Among the injured, girls prevailed (21 cases, 60%). The age of the victims ranged from 9 to 17 years. The main causes of damage were: catatrauma (19 cases), road accident (5 cases), sports injury (6 cases), and other reasons - 5 cases. In 5 cases, suicidal attempts occurred. Co-injury was observed in most cases (20 patients, or 57%), which is natural for high-energy injury. Vertebral-spinal injury with neurological disorders was observed in 13 patients, the disorders ranged from mild inferior (4 children) to moderate/severe paraparesis (5 patients) and inferior paraplegia (4 children). 6 children had pelvic organ dysfunction in the form of urinary and fecal retention or incontinence. All thirty-five patients, within a period of 1 to 57 days after the injury, underwent several surgical interventions from the posterior surgical access using a screw fixation method (posterior decompression + spinal fusion). In 12 cases, it was necessary to perform the second stage of surgical treatment - anterior decompression of the spinal cord or its roots. Verticalization of patients was carried out within 1 to 5 days after surgery. Results. In all patients, the nearest, up to 1 year, results were evaluated. In children operated in 2019-2021, the results were studied in terms of 3 to 5 years. The procedures used, clinical results and the quality of the fixative installation were assessed. All patients managed to achieve positive results. The use of internal fixation made it possible to carry out early verticalization of children, eliminate pain syndrome and achieve a regression of neurological disorders in most patients (especially in cases when the operation was performed early after injury - from 1 to 3 days). Within the first month, the ability to self-care was fully restored. Bone fusion was observed within 6-12 months after surgery. There were no complications after surgery. The analysis of postoperative radiographs, CT and MRI images revealed the correct standing of the screws in all cases. Conclusion. The posterior spinal fusion using the new method of screw fixation in pediatric patients allows to achieve durable stabilization of damage, begins early rehabilitation of patients and reduces the duration of hospital treatment by 2-3 times. Thus, we recommend the use of a transpedicular fixator in children as a reliable, technically feasible method for restoring spinal stability with a low risk of intra- and postoperative complications.

Keywords: pediatric patients, spinal injuries, transpedicular stabilization, operative treatment

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Authors: Afentoula Mavrodi, Andreas Georgiou, Georgios Tsiotras, Vassilis Aletras

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Placing a monetary value on a quality-adjusted-life-year (QALY) is of utmost importance in economic evaluation. Identifying the population’s preferences is critical in order to understand some of the reasons driving variations in the assigned monetary value. Yet, evidence of the motives behind value assignment to a QALY by the general public is limited. Developing an instrument that would capture the population’s motives could be proven valuable to policy-makers, to guide them in allocating different values to a QALY based on users’ motivations. The aim of this study was to identify the most relevant motives and develop an appropriate instrument to assess them. To design the instrument, we employed: a) the EQ-5D-3L tool to assess participants’ current health status, and b) the Willingness-to-Pay (WTP) approach, within the Contingent Valuation (CV) Method framework, to elicit the monetary value. Advancing the open-ended approach adopted to assess solely protest bidders’ motives; a variety of follow-up item-specific statements were designed (deductive approach), aiming to evaluate motives of both protest bidders and participants willing to pay for the hypothetical treatment under consideration. The initial design of the survey instrument was the outcome of an extensive literature review. This instrument was revised based on 15 semi-structured interviews that took place in September 2018 and a pilot study held during two months (October-November) in 2018. Individuals with different educational, occupational and economical backgrounds and adequate verbal skills were recruited to complete the semi-structured interviews. The follow-up motivation statements of both protest bidders and those willing to pay were revised and rephrased after the semi-structured interviews. In total 4 statements for protest bidders and 3 statements for those willing to pay for the treatment were chosen to be included in the survey tool. Using the CATI (Computer Assisted Telephone Interview) method, a randomly selected sample of 97 persons living in Thessaloniki, Greece, completed the questionnaire on two occasions over a period of 4 weeks. Based on pilot study results, a test-retest reliability assessment was performed using the intra-class correlation coefficient (ICC). All statements formulated for protest bidders showed acceptable reliability (ICC values of 0.84 (95% CI: 0.67, 0.92) and above). Similarly, all statements for those willing to pay for the treatment showed high reliability (ICC values of 0.86 (95% CI: 0.78, 0.91) and above). Overall, the instrument designed in this study was reliable with regards to the item-specific statements assessing participants’ motivation. Validation of the instrument will take place in a future study. For a holistic WTP per QALY instrument, participants’ motivation must be addressed broadly. The instrument developed in this study captured a variety of motives and provided insight with regards to the method through which the latter are evaluated. Last but not least, it extended motive assessment to all study participants and not only protest bidders.

Keywords: contingent valuation method, instrument, motives, quality-adjusted life-year, willingness-to-pay

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Authors: Elizabeth M. Annoni, Elena G. Tolkacheva

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Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia that is a known prognostic marker for stroke, heart failure and death. Reentrant mechanisms of rotor formation, which are stable electrical sources of cardiac excitation, are believed to cause AF. No existing commercial mapping systems have been demonstrated to consistently and accurately predict rotor locations outside of the pulmonary veins in patients with persistent AF. There is a clear need for robust spatio-temporal techniques that can consistently identify rotors using unique characteristics of the electrical recordings at the pivot point that can be applied to clinical intracardiac mapping. Recently, we have developed four new signal analysis approaches – Shannon entropy (SE), Kurtosis (Kt), multi-scale frequency (MSF), and multi-scale entropy (MSE) – to identify the pivot points of rotors. These proposed techniques utilize different cardiac signal characteristics (other than local activation) to uncover the intrinsic complexity of the electrical activity in the rotors, which are not taken into account in current mapping methods. We validated these techniques using high-resolution optical mapping experiments in which direct visualization and identification of rotors in ex-vivo Langendorff-perfused hearts were possible. Episodes of ventricular tachycardia (VT) were induced using burst pacing, and two examples of rotors were used showing 3-sec episodes of a single stationary rotor and figure-8 reentry with one rotor being stationary and one meandering. Movies were captured at a rate of 600 frames per second for 3 sec. with 64x64 pixel resolution. These optical mapping movies were used to evaluate the performance and robustness of SE, Kt, MSF and MSE techniques with respect to the following clinical limitations: different time of recordings, different spatial resolution, and the presence of meandering rotors. To quantitatively compare the results, SE, Kt, MSF and MSE techniques were compared to the “true” rotor(s) identified using the phase map. Accuracy was calculated for each approach as the duration of the time series and spatial resolution were reduced. The time series duration was decreased from its original length of 3 sec, down to 2, 1, and 0.5 sec. The spatial resolution of the original VT episodes was decreased from 64x64 pixels to 32x32, 16x16, and 8x8 pixels by uniformly removing pixels from the optical mapping video.. Our results demonstrate that Kt, MSF and MSE were able to accurately identify the pivot point of the rotor under all three clinical limitations. The MSE approach demonstrated the best overall performance, but Kt was the best in identifying the pivot point of the meandering rotor. Artifacts mildly affect the performance of Kt, MSF and MSE techniques, but had a strong negative impact of the performance of SE. The results of our study motivate further validation of SE, Kt, MSF and MSE techniques using intra-atrial electrograms from paroxysmal and persistent AF patients to see if these approaches can identify pivot points in a clinical setting. More accurate rotor localization could significantly increase the efficacy of catheter ablation to treat AF, resulting in a higher success rate for single procedures.

Keywords: Atrial Fibrillation, Optical Mapping, Signal Processing, Rotors

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Authors: Lucia Liu, Matthew Koziol

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Obsessive-compulsive disorder (OCD), a long-lasting anxiety disorder involving recurrent, intrusive thoughts, affects over 2 million adults in the United States. Transcranial magnetic stimulation (TMS) stands out as a noninvasive, cutting-edge therapy that has been shown to reduce symptoms in patients with treatment-resistant OCD. The Food and Drug Administration (FDA) approved protocol pairs TMS sessions with individualized symptom provocation, aiming to improve the susceptibility of brain circuits to stimulation. However, limited standardization or guidance exists on how to conduct symptom provocation and which methods are most effective. This study aims to compare the effect of internal versus external techniques to induce obsessional stress in a clinical setting during TMS therapy. Two symptom provocation methods, (i) Asking patients thought-provoking questions about their obsessions (internal) and (ii) Requesting patients to perform obsession-related tasks (external), were employed in a crossover design with repeated measurement. Thirty-six treatments of NeuroStar TMS were administered to each of two patients over 8 weeks in an outpatient clinic. Patient One received 18 sessions of internal provocation followed by 18 sessions of external provocation, while Patient Two received 18 sessions of external provocation followed by 18 sessions of internal provocation. The primary outcome was the level of self-reported obsessional stress on a visual analog scale from 1 to 10. The secondary outcome was self-reported OCD severity, collected biweekly in a four-level Likert-scale (1 to 4) of bad, fair, good and excellent. Outcomes were compared and tested between provocation arms through repeated measures ANOVA, accounting for intra-patient correlations. Ages were 42 for Patient One (male, White) and 57 for Patient Two (male, White). Both patients had similar moderate symptoms at baseline, as determined through the Yale-Brown Obsessive Compulsive Scale (YBOCS). When comparing obsessional stress induced across the two arms of internal and external provocation methods, the mean (SD) was 6.03 (1.18) for internal and 4.01 (1.28) for external strategies (P=0.0019); ranges were 3 to 8 for internal and 2 to 8 for external strategies. Internal provocation yielded 5 (31.25%) bad, 6 (33.33%) fair, 3 (18.75%) good, and 2 (12.5%) excellent responses for OCD status, while external provocation yielded 5 (31.25%) bad, 9 (56.25%) fair, 1 (6.25%) good, and 1 (6.25%) excellent responses (P=0.58). Internal symptom provocation tactics had a significantly stronger impact on inducing obsessional stress and led to better OCD status (non-significant). This could be attributed to the fact that answering questions may prompt patients to reflect more on their lived experiences and struggles with OCD. In the future, clinical trials with larger sample sizes are warranted to validate this finding. Results support the increased integration of internal methods into structured provocation protocols, potentially reducing the time required for provocation and achieving greater treatment response to TMS.

Keywords: obsessive-compulsive disorder, transcranial magnetic stimulation, mental health, symptom provocation

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Authors: Hyunjoo Park, Taehyun Kim, Taehyun Kim

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Human life, activity, and culture depend on the wider environment. Cities offer economic opportunities for goods and services, but cannot exist in environments without food, energy, and water supply. Technological innovation in energy supply and transport speeds up the expansion of urban areas and the physical separation from agricultural land. As a result, division of urban agricultural areas causes more energy demand for food and goods transport between the regions. As the energy resources are leaking all over the world, the impact on the environment crossing the boundaries of cities is also growing. While advances in energy and other technologies can reduce the environmental impact of consumption, there is still a gap between energy supply and demand by current technology, even in technically advanced countries. Therefore, reducing energy demand is more realistic than relying solely on the development of technology for sustainable development. The purpose of this study is to introduce the application of carbon footprint assessment in fields of urban planning and geography. In urban studies, carbon footprint has been assessed at different geographical scales, such as nation, city, region, household, and individual. Carbon footprint assessment for a nation and a city is available by using national or city level statistics of energy consumption categories. By means of carbon footprint calculation, it is possible to compare the ecological capacity and deficit among nations and cities. Carbon footprint also offers great insight on the geographical distribution of carbon intensity at a regional level in the agricultural field. The study shows the background of carbon footprint applications in urban planning and geography by case studies such as figuring out sustainable land-use measures in urban planning and geography. For micro level, footprint quiz or survey can be adapted to measure household and individual carbon footprint. For example, first case study collected carbon footprint data from the survey measuring home energy use and travel behavior of 2,064 households in eight cities in Gyeonggi-do, Korea. Second case study analyzed the effects of the net and gross population densities on carbon footprint of residents at an intra-urban scale in the capital city of Seoul, Korea. In this study, the individual carbon footprint of residents was calculated by converting the carbon intensities of home and travel fossil fuel use of respondents to the unit of metric ton of carbon dioxide (tCO₂) by multiplying the conversion factors equivalent to the carbon intensities of each energy source, such as electricity, natural gas, and gasoline. Carbon footprint is an important concept not only for reducing climate change but also for sustainable development. As seen in case studies carbon footprint may be measured and applied in various spatial units, including but not limited to countries and regions. These examples may provide new perspectives on carbon footprint application in planning and geography. In addition, additional concerns for consumption of food, goods, and services can be included in carbon footprint calculation in the area of urban planning and geography.

Keywords: carbon footprint, case study, geography, urban planning

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Authors: Filip Varga, Nina Jeran, Martina Biosic, Zlatko Satovic, Martina Grdisa

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Dalmatian pyrethrum (Tanacetum cinerariifolium /Trevir./ Sch. Bip.), a species endemic to the eastern Adriatic coastline, is the source of natural insecticide pyrethrin. Pyrethrin is a mixture of six compounds (pyrethrin I and II, cinerin I and II, jasmolin I and II) that exhibits high insecticidal activity with no detrimental effects to the environment. A recently optimized matrix-solid phase dispersion method (MSPD), using florisil as the sorbent, acetone-ethyl acetate (1:1, v/v) as the elution solvent, and sodium sulfate anhydrous as the drying agent was utilized to extract the pyrethrins from 10 wild populations (20 individuals per population) distributed along the Croatian coast. All six components in the extracts were qualitatively and quantitatively determined by high-performance liquid chromatography with a diode array detector (HPLC-DAD). Pearson’s correlation index was calculated between pyrethrin compounds, and differences between the populations using the analysis of variance were tested. Additionally, the correlation of each pyrethrin component with spatio-ecological variables (bioclimate, soil properties, elevation, solar radiation, and distance from the coastline) was calculated. Total pyrethrin content ranged from 0.10% to 1.35% of dry flower weight, averaging 0.58% across all individuals. Analysis of variance revealed significant differences between populations based on all six pyrethrin compounds and total pyrethrin content. On average, the lowest total pyrethrin content was found in the population from Pelješac peninsula (0.22% of dry flower weight) in which total pyrethrin content lower than 0.18% was detected in 55% of the individuals. The highest average total pyrethrin content was observed in the population from island Zlarin (0.87% of dry flower weight), in which total pyrethrin content higher than 1.00% was recorded in only 30% of the individuals. Pyrethrin I/pyrethrin II ratio as a measure of extract quality ranged from 0.21 (population from the island Čiovo) to 5.88 (population from island Mali Lošinj) with an average of 1.77 across all individuals. By far, the lowest quality of extracts was found in the population from Mt. Biokovo (pyrethrin I/II ratio lower than 0.72 in 40% of individuals) due to the high pyrethrin II content typical for this population. Pearson’s correlation index revealed a highly significant positive correlation between pyrethrin I content and total pyrethrin content and a strong negative correlation between pyrethrin I and pyrethrin II. The results of this research clearly indicate high intra- and interpopulation diversity of Dalmatian pyrethrum with regards to pyrethrin content and composition. The information obtained has potential use in plant genetic resources conservation and biodiversity monitoring. Possibly the largest potential lies in designing breeding programs aimed at increasing pyrethrin content in commercial breeding lines and reintroduction in agriculture in Croatia. Acknowledgment: This work has been fully supported by the Croatian Science Foundation under the project ‘Genetic background of Dalmatian pyrethrum (Tanacetum cinerariifolium /Trevir/ Sch. Bip.) insecticidal potential’ - (PyrDiv) (IP-06-2016-9034).

Keywords: Dalmatian pyrethrum, HPLC, MSPD, pyrethrin

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Authors: Laura O’Halloran, Zhipeng Cao, Clare M. Kelly, Hugh Garavan, Robert Whelan

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Reaction time (RT) variability on cognitive tasks provides the index of the efficiency of executive control processes (e.g. attention and inhibitory control) and is considered to be a hallmark of clinical disorders, such as attention-deficit disorder (ADHD). Increased RT variability is associated with structural and functional brain differences in children and adults with various clinical disorders, as well as poorer task performance accuracy. Furthermore, the strength of functional connectivity across various brain networks, such as the negative relationship between the task-negative default mode network and task-positive attentional networks, has been found to reflect differences in RT variability. Although RT variability may provide an index of attentional efficiency, as well as being a useful indicator of neurological impairment, the brain substrates associated with RT variability remain relatively poorly defined, particularly in a healthy sample. Method: Firstly, we used the intra-individual coefficient of variation (ICV) as an index of RT variability from “Go” responses on the Stop Signal Task. We then examined the functional and structural neural correlates of ICV in a large sample of 14-year old healthy adolescents (n=1719). Of these, a subset had elevated symptoms of ADHD (n=80) and was compared to a matched non-symptomatic control group (n=80). The relationship between brain activity during successful and unsuccessful inhibitions and gray matter volume were compared with the ICV. A mediation analysis was conducted to examine if specific brain regions mediated the relationship between ADHD symptoms and ICV. Lastly, we looked at functional connectivity across various brain networks and quantified both positive and negative correlations during “Go” responses on the Stop Signal Task. Results: The brain data revealed that higher ICV was associated with increased structural and functional brain activation in the precentral gyrus in the whole sample and in adolescents with ADHD symptoms. Lower ICV was associated with lower activation in the anterior cingulate cortex (ACC) and medial frontal gyrus in the whole sample and in the control group. Furthermore, our results indicated that activation in the precentral gyrus (Broadman Area 4) mediated the relationship between ADHD symptoms and behavioural ICV. Conclusion: This is the first study first to investigate the functional and structural correlates of ICV collectively in a large adolescent sample. Our findings demonstrate a concurrent increase in brain structure and function within task-active prefrontal networks as a function of increased RT variability. Furthermore, structural and functional brain activation patterns in the ACC, and medial frontal gyrus plays a role-optimizing top-down control in order to maintain task performance. Our results also evidenced clear differences in brain morphometry between adolescents with symptoms of ADHD but without clinical diagnosis and typically developing controls. Our findings shed light on specific functional and structural brain regions that are implicated in ICV and yield insights into effective cognitive control in healthy individuals and in clinical groups.

Keywords: ADHD, fMRI, reaction-time variability, default mode, functional connectivity

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