Search results for: symptom trajectories

Authors: Soma Banerjee, Aamen Talukdar, Argha Mandal, Dipankar Chaudhuri

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Japanese Encephalitis is a major infectious disease with nearly half the world’s population living in areas where it is prevalent. Currently, treatment for it involves only supportive care and symptom management through vaccination. Due to the lack of antiviral drugs against Japanese Encephalitis Virus (JEV), the quest for such agents remains a priority. For these reasons, simulation studies of drug targets against JEV are important. Towards this purpose, docking experiments of the kinase inhibitors were done against the chosen target NS3 helicase as it is a nucleoside binding protein. Previous efforts regarding computational drug design against JEV revealed some lead molecules by virtual screening using public domain software. To be more specific and accurate regarding finding leads, in this study a proprietary software Schrödinger-GLIDE has been used. Druggability of the pockets in the NS3 helicase crystal structure was first calculated by SITEMAP. Then the sites were screened according to compatibility with ATP. The site which is most compatible with ATP was selected as target. Virtual screening was performed by acquiring ligands from databases: KinaseSARfari, KinaseKnowledgebase and Published inhibitor Set using GLIDE. The 25 ligands with best docking scores from each database were re-docked in XP mode. Protein structure alignment of NS3 was performed using VAST against MMDB, and similar human proteins were docked to all the best scoring ligands. The low scoring ligands were chosen for further studies and the high scoring ligands were screened. Seventy-three ligands were listed as the best scoring ones after performing HTVS. Protein structure alignment of NS3 revealed 3 human proteins with RMSD values lesser than 2Å. Docking results with these three proteins revealed the inhibitors that can interfere and inhibit human proteins. Those inhibitors were screened. Among the ones left, those with docking scores worse than a threshold value were also removed to get the final hits. Analysis of the docked complexes through 2D interaction diagrams revealed the amino acid residues that are essential for ligand binding within the active site. Interaction analysis will help to find a strongly interacting scaffold among the hits. This experiment yielded 21 hits with the best docking scores which could be investigated further for their drug like properties. Aside from getting suitable leads, specific NS3 helicase-inhibitor interactions were identified. Selection of Target modification strategies complementing docking methodologies which can result in choosing better lead compounds are in progress. Those enhanced leads can lead to better in vitro testing.

Keywords: antivirals, docking, glide, high-throughput virtual screening, Japanese encephalitis, ns3 helicase

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Authors: David Tennison

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In the wake of the Covid-19 pandemic, a new chronic illness emerged onto the global stage: Long Covid. Long Covid presents with several symptoms commonly seen in other poorly-understood illnesses, such as fibromyalgia (FM) and myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). However, while Long Covid has swiftly become a recognised illness, FM and ME/CFS are still seen as contested, which impacts patient care and healthcare experiences. This study aims to examine what the differences are between Long Covid and FM; and if the Long Covid case can provide guidance for how to address the healthcare challenge of contested illnesses. To address this question, this study performed comprehensive research into the history of FM; our current biomedical understanding of it; and available healthcare interventions (within the context of the UK NHS). Analysis was undertaken of the stigma and stereotypes around FM, and a comparison made between FM and the emerging Long Covid literature, along with the healthcare response to Long Covid. This study finds that healthcare for chronic contested illnesses in the UK is vastly insufficient - in terms of pharmaceutical and holistic interventions, and the provision of secondary care options. Interestingly, for Long Covid, many of the treatment suggestions are pulled directly from those used for contested illnesses. The key difference is in terms of funding and momentum – Long Covid has generated exponentially more interest and research in a short time than there has been in the last few decades of contested illness research. This stands to help people with FM and ME/CFS – for example, research has recently been funded into “brain fog”, a previously elusive and misunderstood symptom. FM is culturally regarded as a “women’s disease” and FM stigma stems from notions of “hysteria”. A key finding is that the idea of FM affecting women disproportionally is not reflected in modern population studies. Emerging data on Long Covid also suggests a slight leaning towards more female patients, however it is less feminised, potentially due to it emerging in the global historical moment of the pandemic. Another key difference is that FM is rated as an extremely low-prestige illness by healthcare professionals, while it was in large part due to the advocacy of affected healthcare professionals that Long Covid was so quickly recognised by science and medicine. In conclusion, Long Covid (and the risk of future pandemics and post-viral illnesses) highlight a crucial need for implementing new, and reinforcing existing, care networks for chronic illnesses. The difference in how contested illnesses like FM, and new ones like Long Covid are treated have a lot to do with the historical moment in which they emerge – but cultural stereotypes, from within and without medicine, need updating. Particularly as they contribute to disease stigma that causes genuine harm to patients. However, widespread understanding and acceptance of Long Covid could help fight contested illness stigma, and the attention, funding and research into Long Covid may actually help raise the profile of contested illnesses and uncover answers about their symptomatology.

Keywords: long COVID, fibromyalgia, myalgic encephalomyelitis, chronic fatigue syndrome, NHS, healthcare, contested illnesses, chronic illnesses, COVID-19 pandemic

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Authors: Qiang Guo, Ruying Qi

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This project aims to trace the developmental patterns of a child's Mandarin and English from China to Australia from age 3; 03 till 5; 06. In childhood bilingual studies, there is an assumption that age 3 is the dividing line between simultaneous bilinguals and sequential bilinguals. Determining similarities and differences between Bilingual First Language Acquisition, Early Second Language Acquisition, and Second Language Acquisition is of great theoretical significance. Studies on Bilingual First Language Acquisition, hereafter, BFLA in the past three decades have shown that the grammatical development of bilingual children progresses through the same developmental trajectories as their monolingual counterparts. Cross-linguistic interaction does not show changes of the basic grammatical knowledge, even in the weaker language. While BFLA studies show consistent results under the conditions of adequate input and meaningful interactional context, the research findings of Early Second Language Acquisition (ESLA) have demonstrated that this cohort proceeds their early English differently from both BFLA and SLA. The different development could be attributed to the age of migration, input pattern, and their Environmental Languages (Lε). In the meantime, the dynamic relationship between the two languages is an issue to invite further attention. The present study attempts to fill this gap. The child in this case study started acquiring L1 Mandarin from birth in China, where the environmental language (Lε) coincided with L1 Mandarin. When she migrated to Australia at 3;06, where the environmental language (Lε) was L2 English, her Mandarin exposure was reduced. On the other hand, she received limited English input starting from 1; 02 in China, where the environmental language (Lε) was L1 Mandarin, a non-English environment. When she relocated to Australia at 3; 06, where the environmental language (Lε) coincided with L2 English, her English exposure significantly increased. The child’s linguistic profile provides an opportunity to explore: (1) What does the child’s English developmental route look like? (2) What does the L1 Mandarin developmental pattern look like in different environmental languages? (3) How do input and environmental language interact in shaping the bilingual child’s linguistic repertoire? In order to answer these questions, two linguistic areas are selected as the focus of the investigation, namely, subject realization and wh-questions. The chosen areas are contrastive in structure but perform the same semantic functions in the two linguistically distant languages and can serve as an ideal testing ground for exploring the developmental path in the two languages. The longitudinal case study adopts a combined approach of qualitative and quantitative analysis. Two years’ Mandarin and English data are examined, and comparisons are made with age-matched monolinguals in each language in CHILDES. To the author’s best knowledge, this study is the first of this kind examining a Mandarin-English bilingual child's bilingual development at a critical age, in different input patterns, and in different environmental languages (Lε). It also expands the scope of the theory of Lε, adding empirical evidence on the relationship between input and Lε in bilingual acquisition.

Keywords: bilingual development, age, input, environmental language (Le)

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Authors: Wisam Ismail, Chole Wright, Elizabeth Baker, Cathy Tait, Mohamed Salhab, Richard Linforth

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Background: Post-mastectomy breast reconstruction is an important treatment option for women with breast cancer with psychosocial, emotional and quality of life benefits. Despite this, Asian patients are one-fifth as likely as Caucasian patients to undergo reconstruction after mastectomy. Aim: This study aimed to assess the difference in breast reconstruction rates between Asian and Caucasian patients treated at Bradford Teaching Hospitals between May 2011 – December 2015.The long-term goal is to equip healthcare professionals to improve breast cancer treatment outcome by increasing breast reconstruction rates in this sub-population. Methods: All patients undergoing mastectomy were identified using a prospectively collected departmental database. Further data was obtained via retrospective electronic case note review. Bradford city population is about 530.000 by the end of 2015, with 67.44% of the city's population was White ethnic groups and 26.83% Asian Ethnic Groups (UK population consensus). The majority of Asian population speaks Urdu, hence an Urdu speaking breast care nurse was appointed to facilitate communications and deliver a better understanding of the reconstruction options and pathways. Statistical analysis was undertaken using the SAS program. Patients were stratified by age, self-reported ethnicity, axillary surgery and reconstruction. Relative odds were calculated using univariate and multivariate logistic regression analyses with adjustment for known confounders. An Urdu speaking breast care nurse was employed throughout this period to facilitate communication and patient decision making. Results: 506 patients underwent Mastectomy over 5 years. 72 (14%) Asian v. 434 (85%) Caucasian. Overall median age is 64 years (SD1.1). Asian median age is 62 (SD0.9), versus Caucasian 65 (SD1.2). Total axillary clearance rate was 30% (42% Asian v.30% Caucasian). Overall reconstruction rate was 126 patients (28.9%).Only 6 of 72 Asian patients (<1%) underwent breast reconstruction versus 121of 434 Caucasian (28%) (p < 0.04), Odds ratio 0.68, (95% confidence interval 0.57-0.79). Conclusions: There is a significant difference in post-mastectomy reconstruction rates between Asian and Caucasian patients. This difference is likely to be multi-factorial. Higher rates of axillary clearance in Asian patients might suggest later disease presentation and/or higher rates of subsequent adjuvant therapy, both of which, can impact on the suitability of breast reconstruction. Strategies aimed at reducing racial disparities in breast reconstruction should include symptom awareness to enable earlier presentation and facilitated communication to ensure informed decision-making.

Keywords: aesthetic, Asian, breast, reconstruction

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Authors: Santhani M. Selveindran

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Background: Natural disasters are traumatic global events that are becoming increasing more common, with significant psychosocial impact on survivors. This impact results not only in psychosocial distress but, for many, can lead to psychosocial disorders and chronic psychopathology. While there are currently available interventions that seek to prevent and treat these psychosocial sequelae, their effectiveness is uncertain. The evidence-base is emerging with more primary studies evaluating the effectiveness of various psychosocial interventions for survivors of natural disasters, which remains to be synthesized. Aim of Review: To identify, critically appraise and synthesize the current evidence-base on the effectiveness of psychosocial interventions in preventing or treating Post-Traumatic Stress Disorder (PTSD), Major Depressive Disorder (MDD) and/or Generalized Anxiety Disorder (GAD) in adults and children who are survivors of natural disasters. Methods: A protocol was developed as a guide to carry out this review. A systematic search was conducted in eight international electronic databases, three grey literature databases, one dissertation and thesis repository, websites of six humanitarian and non-governmental organizations renowned for their work on natural disasters, as well as bibliographic and citation searching for eligible articles. Papers meeting the specific inclusion criteria underwent quality assessment using the Downs and Black checklist. Data were extracted from the included papers and analysed by way of narrative synthesis. Results: Database and website searching returned 3777 papers where 31 met the criteria for inclusion. Additional 2 papers were obtained through bibliographic and citation searching. Methodological quality of most papers was fair. Twenty-five studies evaluated psychological interventions, five, social interventions whereas three studies evaluated ‘mixed’ psychological and social interventions. All studies, irrespective of methodological quality, reported post-intervention reductions in symptom scores for PTSD, depression and/or anxiety and where assessed, reduced diagnosis of PTSD and MDD, and produced improvements in self-efficacy and quality of life. Statistically significant results were seen in 27 studies. However, three studies demonstrated that the evaluated interventions may not have been very beneficial. Conclusions: The overall positive results suggest that any psychosocial interventions are favourable and should be delivered to all natural disaster survivors, irrespective of age, country, and phase of disaster. Yet, heterogeneity and methodological shortcomings of the current evidence-base makes it difficult to draw definite conclusions needed to formulate categorical guidance or frameworks. Further, rigorously conducted research is needed in this area, although the feasibility of such, given the context and nature of the problem, is also recognized.

Keywords: psychosocial interventions, natural disasters, survivors, effectiveness

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Authors: Antonieta Heyden Megale

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With the advent of globalization, the social, cultural and linguistic situation of the whole world has changed. In this scenario, the teaching of English, in Brazil, has become a booming business and the belief that this language is essential to a successful life is played by the media that sees it as a commodity and spares no effort to sell it. In this context, it has become evident the growth of bilingual and international schools that have English and Portuguese as languages of instruction. According to federal legislation, all schools in the country must follow the Curriculum guidelines proposed by the Ministry of Education of Brazil. It is then mandatory that, in addition to the specific foreign curriculum an international school subscribes to, it must also teach all subjects of the official minimum curriculum and these subjects have to be taught in Portuguese. It is important to emphasize that, in these schools, English is the most prestigious language. Therefore, firstly, Brazilian teachers who teach Portuguese in such contexts find themselves in a situation in which they teach in a low-status language. Secondly, because such teachers’ actions are guided by a different cultural matrix, which differs considerably from Anglo-Saxon values and beliefs, they often experience intercultural conflict in their workplace. Taking it consideration, this research, focusing on the trajectories of a specific group of Brazilian teachers of Portuguese in international and bilingual schools located in the city of São Paulo, intends to analyze how they discursively represent their own professional identities and practices. More specifically the objectives of this research are to understand, from the perspective of the investigated teachers, how they (i) rebuilt narratively their professional careers and explain the factors that led them to an international or to an immersion bilingual school; (ii) position themselves with respect to their linguistic repertoire; (iii) interpret the intercultural practices they are involved with in school and (v) position themselves by foregrounding categories to determine their membership in the group of Portuguese teachers. We have worked with these teachers’ autobiographical narratives. The autobiographical approach assumes that the stories told by teachers are systems of meaning involved in the production of identities and subjectivities in the context of power relations. The teachers' narratives were elicited by the following trigger: "I would like you to tell me how you became a teacher in a bilingual/international school and what your impressions are about your work and about the context in which it is inserted". These narratives were produced orally, recorded, and transcribed for analysis. The teachers were also invited to draw their "linguistic portraits". The theoretical concepts of positioning and the indexical cues were taken into consideration in data analysis. The narratives produced by the teachers point to intercultural conflicts related to their expectations and representations of others, which are never neutral or objective truths but discursive constructions.

Keywords: bilingual schools, identity, interculturality, narrative

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Authors: Ruchirek Ratchaburi, W. Kevin. Hicks, Christopher S. Malley, Lisa D. Emberson

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Air pollution problems in Thailand have improved over the last few decades, but in some areas, concentrations of coarse particulate matter (PM₁₀) are above health and regulatory guidelines. It is, therefore, useful to investigate how PM₁₀ varies across Thailand, what conditions cause this variation, and how could PM₁₀ concentrations be reduced. This research uses data collected by the Thailand Pollution Control Department (PCD) from 17 monitoring sites, located across 12 provinces, and obtained between 2011 and 2015 to assess PM₁₀ concentrations and the conditions that lead to different levels of pollution. This is achieved through exploration of air mass pathways using trajectory analysis, used in conjunction with the monitoring data, to understand the contribution of different months, an hour of the day and source regions to annual PM₁₀ concentrations in Thailand. A focus is placed on locations that exceed the national standard for the protection of human health. The analysis shows how this approach can be used to explore the influence of biomass burning on annual average PM₁₀ concentration and the difference in air pollution conditions between Northern and Southern Thailand. The results demonstrate the substantial contribution that open biomass burning from agriculture and forest fires in Thailand and neighboring countries make annual average PM₁₀ concentrations. The analysis of PM₁₀ measurements at monitoring sites in Northern Thailand show that in general, high concentrations tend to occur in March and that these particularly high monthly concentrations make a substantial contribution to the overall annual average concentration. In 2011, a > 75% reduction in the extent of biomass burning in Northern Thailand and in neighboring countries resulted in a substantial reduction not only in the magnitude and frequency of peak PM₁₀ concentrations but also in annual average PM₁₀ concentrations at sites across Northern Thailand. In Southern Thailand, the annual average PM₁₀ concentrations for individual years between 2011 and 2015 did not exceed the human health standard at any site. The highest peak concentrations in Southern Thailand were much lower than for Northern Thailand for all sites. The peak concentrations at sites in Southern Thailand generally occurred between June and October and were associated with air mass back trajectories that spent a substantial proportion of time over the sea, Indonesia, Malaysia, and Thailand prior to arrival at the monitoring sites. The results show that emissions reductions from biomass burning and forest fires require action on national and international scales, in both Thailand and neighboring countries, such action could contribute to ensuring compliance with Thailand air quality standards.

Keywords: annual average concentration, long-range transport, open biomass burning, particulate matter

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Authors: Ali Saeed Alghamdi, Basel Mazen Alsolami, Basel Saeed Alghamdi, Muhanad Saleh Alzahrani Alamri, Salman Anwar Thabet, Abdulhalim J. Kinsara

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Objectives: This study measures the knowledge of the cardiovascular disease among the general population in western regions of Saudi Arabia, and it aimed to increase the level of awareness about cardiovascular diseases among the general population by providing an awareness lecture that included information about the risk factors, major symptoms, and prevention of cardiovascular diseases. The lecture has been attached at the end of the questionnaire. Setting: This study was conducted through an online questionnaire that included our aim and main objectives that targeted the general population in the Western regions of Saudi Arabia (Makkah and Madinah regions). Participants: This study participants were 460 collected through an online questionnaire. Methods: All Saudi citizens and residents who live in the western region of Saudi Arabia aged 18 years and above will be invited to participate voluntarily. A pre-structured questionnaire was designed to collect data on age, gender, marital status, education level, occupation, lifestyle habits, and history of heart diseases, with cardiac symptoms and risk factors sections. Results: The majority of respondents were females (74.8%) and Saudis. The knowledge about cardiovascular disease risk factors was weak. Only (18.5%) scores an excellent response regarding risk factors awareness. Lack of exercise, stress, and obesity were the most known risk factors. Regarding cardiovascular disease symptoms, chest pain scores the highest symptom (87.6%) among other symptoms like dyspnea, syncope, and excessive sweating. Participants revealed a poor awareness regarding cardiovascular disease symptoms also (0.9%). However, preventable factors for cardiovascular diseases were more knowledgeable than others categories in this study (60% fall into excellent knowledge). Smoking cessation, normal cholesterol level, and normal blood pressure score the highest preventable methods (92.2%), (88.6%), and (78.7%) respectively. 83.7% of the participant have attended the awareness lecture, and 99 of the attendees reported that the lecture increased their knowledge about cardiovascular disease. Conclusion: This study discussed the level of community awareness of cardiovascular disease in terms of symptoms, risk factors, and protective factors. We found a huge lack of the participant's level of knowledge about the disease and how to prevent it. Moreover, we measure the prevalence of the comorbidities among our participants (diabetes, hypertension, hypercholesterolemia/ hypertriglyceridemia) and their extent of adherence to their medication. In conclusion, this study not only demonstrates awareness of cardiovascular disease risk factors, symptoms, management, and the association between each domain but also provides educational material. Further educational material and campaigns are required to increase awareness and knowledge about cardiovascular diseases.

Keywords: awareness, cardiovascular diseases, education, prevention, risk factors

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Authors: Angela T. H. Kwan, Wenjun Liang, Jack Wellington, Mohammad Mofatteh, Thanh N. Nguyen, Pingzhong Fu, Juanmei Chen, Zile Yan, Weijuan Wu, Yongting Zhou, Shuiquan Yang, Sijie Zhou, Yimin Chen

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Background: Endovascular Therapy (EVT)—in the form of mechanical thrombectomy—following intravenous thrombolysis is the standard gold treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). It is well established that an ASPECTS ≥ 7 is associated with an increased likelihood of positive post-EVT outcomes, as compared to an ASPECTS < 7. There is also prognostic utility in coupling posterior circulation ASPECTS (pc-ASPECTS) with magnetic resonance imaging for evaluating the post-EVT functional outcome. However, the value of pc-ASPECTS applied to CT must be explored further to determine its usefulness in predicting functional outcomes following EVT. Objective: In this study, we aimed to determine whether pc-ASPECTS on CT can predict post-EVT functional outcomes among patients with AIS due to LVO. Methods: A total of 247 consecutive patients aged 18 and over receiving EVT for LVO-related AIS were recruited into a prospective database. The data were retrospectively analyzed between March 2019 to February 2022 from two comprehensive tertiary care stroke centers: Foshan Sanshui District People’s Hospital and First People's Hospital of Foshan in China. Patient parameters included EVT within 24hrs of symptom onset, premorbid modified Rankin Scale (mRS) ≤ 2, presence of distal and terminal cerebral blood vessel occlusion, and subsequent 24–72-hour post-stroke onset CT scan. Univariate comparisons were performed using the Fisher exact test or χ2 test for categorical variables and the Mann–Whitney U test for continuous variables. A p-value of ≤ 0.05 was statistically significant. Results: A total of 247 patients met the inclusion criteria; however, 3 were excluded due to the absence of post-CTs and 8 for pre-EVT ASPECTS < 7. Overall, 236 individuals were examined: 196 anterior circulation ischemic strokes and 40 posterior strokes of basilar artery occlusion. We found that both baseline post- and pc-ASPECTS ≥ 7 serve as strong positive markers of favorable outcomes at 90 days post-EVT. Moreover, lower rates of inpatient mortality/hospice discharge, 90-day mortality, and 90-day poor outcome were observed. Moreover, patients in the post-ASPECTS ≥ 7 anterior circulation group had shorter door-to-recanalization time (DRT), puncture-to-recanalization time (PRT), and last known normal-to-puncture-time (LKNPT). Conclusion: Patients of anterior and posterior circulation ischemic strokes with baseline post- and pc-ASPECTS ≥ 7 may benefit from EVT.

Keywords: endovascular therapy, thrombectomy, large vessel occlusion, cerebral ischemic stroke, ASPECTS

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Authors: Heribert R. Kaijage, Samuel N. A. Codjoe, Simon H. D. Mamuya, Mangi J. Ezekiel

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There is strong evidence that climate has changed significantly affecting various sectors including public health. The recommended feasible solution is adopting development trajectories which combine both mitigation and adaptation measures for improving resilience pathways. This approach demands a consideration for complex interactions between climate and social-ecological systems. While other sectors such as agriculture and water have developed climate resilience indices, the public health sector in Tanzania is still lagging behind. The aim of this study was to find out how can we use Demographic and Health Surveys (DHS) linked with Remote Sensing (RS) technology and metrological information as tools to inform climate change resilient development and evaluation for the health sector. Methodological review was conducted whereby a number of studies were content analyzed to find appropriate indicators and indices for climate resilience household and their integration approach. These indicators were critically reviewed, listed, filtered and their sources determined. Preliminary identification and ranking of indicators were conducted using participatory approach of pairwise weighting by selected national stakeholders from meeting/conferences on human health and climate change sciences in Tanzania. DHS datasets were retrieved from Measure Evaluation project, processed and critically analyzed for possible climate change indicators. Other sources for indicators of climate change exposure were also identified. For the purpose of preliminary reporting, operationalization of selected indicators was discussed to produce methodological approach to be used in resilience comparative analysis study. It was found that household climate resilient index depends on the combination of three indices namely Household Adaptive and Mitigation Capacity (HC), Household Health Sensitivity (HHS) and Household Exposure Status (HES). It was also found that, DHS alone cannot complement resilient evaluation unless integrated with other data sources notably flooding data as a measure of vulnerability, remote sensing image of Normalized Vegetation Index (NDVI) and Metrological data (deviation from rainfall pattern). It can be concluded that if these indices retrieved from DHS data sets are computed and scientifically integrated can produce single climate resilience index and resilience maps could be generated at different spatial and time scales to enhance targeted interventions for climate resilient development and evaluations. However, further studies are need to test for the sensitivity of index in resilience comparative analysis among selected regions.

Keywords: climate change, resilience, remote sensing, demographic and health surveys

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Authors: Valeria Panzetta, Ida Musella, Sabato Fusco, Paolo Antonio Netti

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The study of the biophysics of living cells drew attention to the pivotal role of the cytoskeleton in many cell functions, such as mechanics, adhesion, proliferation, migration, differentiation and neoplastic transformation. In particular, during the complex process of malignant transformation and invasion cell cytoskeleton devolves from a rigid and organized structure to a more compliant state, which confers to the cancer cells a great ability to migrate and adapt to the extracellular environment. In order to better understand the malignant transformation process from a mechanical point of view, it is necessary to evaluate the direct crosstalk between the cells and their surrounding extracellular matrix (ECM) in a context which is close to in vivo conditions. In this study, human biopsy tissues of lung adenocarcinoma were analyzed in order to define their mechanical phenotype at cell and ECM level, by using particle tracking microrheology (PTM) technique. Polystyrene beads (500 nm) were introduced into the sample slice. The motion of beads was obtained by tracking their displacements across cell cytoskeleton and ECM structures and mean squared displacements (MSDs) were calculated from bead trajectories. It has been already demonstrated that the amplitude of MSD is inversely related to the mechanical properties of intracellular and extracellular microenvironment. For this reason, MSDs of particles introduced in cytoplasm and ECM of healthy and tumor tissues were compared. PTM analyses showed that cancerous transformation compromises mechanical integrity of cells and extracellular matrix. In particular, the MSD amplitudes in cells of adenocarcinoma were greater as compared to cells of normal tissues. The increased motion is probably associated to a less structured cytoskeleton and consequently to an increase of deformability of cells. Further, cancer transformation is also accompanied by extracellular matrix stiffening, as confirmed by the decrease of MSDs of matrix in tumor tissue, a process that promotes tumor proliferation and invasiveness, by activating typical oncogenic signaling pathways. In addition, a clear correlation between MSDs of cells and tumor grade was found. MSDs increase when tumor grade passes from 2 to 3, indicating that cells undergo to a trans-differentiation process during tumor progression. ECM stiffening is not dependent on tumor grade, but the tumor stage resulted to be strictly correlated with both cells and ECM mechanical properties. In fact, a greater stage is assigned to tumor spread to regional lymph nodes and characterized by an up-regulation of different ECM proteins, such as collagen I fibers. These results indicate that PTM can be used to get nanomechanical characterization at different scale levels in an interpretative and diagnostic context.

Keywords: cytoskeleton, extracellular matrix, mechanical properties, particle tracking microrheology, tumor

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Authors: Natalia Banasik

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Comprehension of verbal irony is an example of pragmatic competence in understanding figurative language. The knowledge of how it develops may shed new light on the understanding of social and communicative competence that is crucial for one's effective functioning in the society. Researchers agree it is a competence that develops late in a child’s development. One of the abilities that seems crucial for irony comprehension is theory of mind (ToM), that is the ability to understand that others may have beliefs, desires and intentions different from one’s own. Although both theory of mind and irony comprehension require the ability to understand the figurative use of the false description of the reality, the exact relationship between them is still unknown. Also, even though irony comprehension in children has been studied for over thirty years, the results of the studies are inconsistent as to the age when this competence are acquired. The presented study aimed to answer questions about the developmental trajectories of irony comprehension and ascribing function to ironic utterances by preschool children. Specifically, we were interested in how it is related to the development of ToM and how comprehension of the function of irony changes with age. Data was collected from over 150 monolingual, Polish-speaking children and (so far) thirty bilingual children speaking Polish and English who live in the US. Four-, five- and six-year-olds were presented with a story comprehension task in the form of audio and visual stimuli programmed in the E-prime software (pre-recorded narrated stories, some of which included ironic utterances, and pictures accompanying the stories displayed on a touch screen). Following the presentation, the children were then asked to answer a series of questions. The questions checked the children’s understanding of the intended utterance meaning, evaluation of the degree to which it was funny and evaluation of how nice the speaker was. The children responded by touching the screen, which made it possible to measure reaction times. Additionally, the children were asked to explain why the speaker had uttered the ironic statement. Both quantitive and qualitative analyses were applied. The results of our study indicate that for irony recognition there is a significant difference among the three age groups, but what is new is that children as young as four do understand the real meaning behind the ironic statement as long as the utterance is not grammtically or lexically complex also, there is a clear correlation of ToM and irony comprehension. Although four-year olds and six-year olds understand the real meaning of the ironic utterance, it is not earlier than at the age of six when children start to explain the reason of using this marked form of expression. They talk about the speaker's intention to tell a joke, be funny, or to protect the listener's emotions. There are also some metalinguistic references, such as "mommy sometimes says things that don't make sense and this is called a metaphor".

Keywords: child's pragmatics, figurative speech, irony comprehension in children, theory of mind and irony

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Authors: Sundaresan Soundararajan, Chor Ngee Tan

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Introduction: Pyogenic spondylitis, otherwise treated conservatively with long term antibiotics, would require surgical debridement and reconstruction in about 10% to 20% of cases. The classical approach adopted many surgeons have always been anterior approach in ensuring thorough and complete debridement. This, however, comes with high rates of morbidity due to the nature of its access. Direct lateral retroperitoneal approach, which has been growing in usage in degenerative lumbar diseases, has the potential in treating pyogenic spondylitis with its ease of approach and relatively low risk of complications. Aims/Objectives: The objective of this study was to evaluate the effectiveness and clinical outcome of using lateral approach surgery in the surgical management of pyogenic spondylitis of the lumbar spine. Methods: Retrospective chart analysis was done on all patients who presented with pyogenic spondylitis (lumbar discitis/vertebral osteomyelitis) and had undergone direct lateral retroperitoneal lumbar vertebral debridement and posterior instrumentation between 2014 and 2016. Data on blood loss, surgical operating time, surgical complications, clinical outcomes and fusion rates were recorded. Results: A total of 6 patients (3 male and 3 female) underwent this procedure at a single institution by a single surgeon during the defined period. One patient presented with infected implant (PLIF) and vertebral osteomyelitis while the other five presented with single level spondylodiscitis. All patients underwent lumbar debridement, iliac strut grafting and posterior instrumentation (revision of screws for infected PLIF case). The mean operating time was 308.3 mins for all 6 cases. Mean blood loss was reported at 341cc (range from 200cc to 600cc). Presenting symptom of back pain resolved in all 6 cases while 2 cases that presented with lower limb weakness had improvement of neurological deficits. One patient had dislodged strut graft while performing posterior instrumentation and needed graft revision intraoperatively. Infective markers normalized for all patients subsequently. All subjects also showed radiological evidence of fusion on 6 months follow up. Conclusions: Lateral approach in treating pyogenic spondylitis is a viable option as it allows debridement and reconstruction without the risk that comes with other anterior approaches. It allows efficient debridement, short surgical time, moderate blood loss and low risk of vascular injuries. Clinical outcomes and fusion rates by this approach also support its use as practical MIS option surgery for such infection cases.

Keywords: lateral approach, minimally invasive, pyogenic spondylitis, XLIF

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Authors: Marc Dietrich

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Youth cultures like Punk as much as media relevant to the specific scenes associated with them offer ample opportunity for young people or juvenile adults to construct their personal identities. However, developmental psychology has largely neglected such identity construction processes during the last decades. Such was not always the case: Early developmental psychologists intensely studied youth cultures and their meaningful objects and media in the early 20th century but lost interest when cultural studies and the social sciences occupied the field after World War II. Our project Constructions of Juvenility and Generation(ality), funded by the German Federal Ministry for Education and Research, reintegrates the study of youth cultures and their meaningful objects and media in a developmental psychology perspective. We present an empirical study of the ways in which youth, juvenility, and generation (ality) are constructed and negotiated in underground media like punk fanzines (a portmanteau of fan and magazine), including both semantic and aesthetic aspects of these construction processes within punk culture. The fanzine sample was accessed by the theoretical sampling strategy typical for GTM studies. Acknowledging fanzines as artful self-produced media by scene members for scene members, we conceptualize them as authentic documents of scene norms and values. Drawing on an analysis of both text and (cover) images in Punk fanzines published in Germany (and within a sample dating from 1981 until 2015) using a novel Visual Grounded Theory approach, we found that: a) Juvenility is a highly contested concept in punk culture. Its semantic quality and valuation varies with the perspectives present within the culture (e.g. embryo punks versus older punks); b) Juvenility is constructed as having energy and being socio-critical that does not depend on biological age; c) Juvenility is regarded not an ideal per se in German Punk culture; Punk culture constructs old age in a largely positive way (e.g., as marker of being real and a historical innovator); d) Juvenility is constructed as a habit that should be kept for life as it is constantly adapted to individual biographical trajectories like specific job situations or having a family. Consequently, identity negotiation as documented in the zines attempts to balance subculturally driven perspectives on life and society with the pragmatic requirements of a bourgeois life. The proposed paper will present the main results of this large-scale study of punk fanzines and show how developmental psychology perspectives as represented in the novel methodology applied in it can advance the study of youth cultures.

Keywords: construction of juvenility, developmental psychology, visual GTM, youth culture, fanzines

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Authors: Anwesha Pathak

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With the increasing number of satellites and space debris, space traffic management (STM) becomes crucial. AI can aid in STM by predicting and preventing potential collisions, optimizing satellite trajectories, and managing orbital slots. Governance frameworks need to address the integration of AI algorithms in STM to ensure safe and sustainable satellite activities. AI and governance play significant roles in the context of satellite activities in space. Artificial intelligence (AI) technologies, such as machine learning and computer vision, can be utilized to process vast amounts of data received from satellites. AI algorithms can analyse satellite imagery, detect patterns, and extract valuable information for applications like weather forecasting, urban planning, agriculture, disaster management, and environmental monitoring. AI can assist in automating and optimizing satellite operations. Autonomous decision-making systems can be developed using AI to handle routine tasks like orbit control, collision avoidance, and antenna pointing. These systems can improve efficiency, reduce human error, and enable real-time responsiveness in satellite operations. AI technologies can be leveraged to enhance the security of satellite systems. AI algorithms can analyze satellite telemetry data to detect anomalies, identify potential cyber threats, and mitigate vulnerabilities. Governance frameworks should encompass regulations and standards for securing satellite systems against cyberattacks and ensuring data privacy. AI can optimize resource allocation and utilization in satellite constellations. By analyzing user demands, traffic patterns, and satellite performance data, AI algorithms can dynamically adjust the deployment and routing of satellites to maximize coverage and minimize latency. Governance frameworks need to address fair and efficient resource allocation among satellite operators to avoid monopolistic practices. Satellite activities involve multiple countries and organizations. Governance frameworks should encourage international cooperation, information sharing, and standardization to address common challenges, ensure interoperability, and prevent conflicts. AI can facilitate cross-border collaborations by providing data analytics and decision support tools for shared satellite missions and data sharing initiatives. AI and governance are critical aspects of satellite activities in space. They enable efficient and secure operations, ensure responsible and ethical use of AI technologies, and promote international cooperation for the benefit of all stakeholders involved in the satellite industry.

Keywords: satellite, space debris, traffic, threats, cyber security.

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Authors: Adekeye Joshua Temitope

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“Transgender” presents a complexion of ambiguity in the African context and it remains a contested topography in the discourse of sexual identity. The casts and stigmatisations towards transgender unveils vital facts and intricacies often ignored in the academic communities; the problems and oppressions of given sex/gender system, the constrain of monogamy and ignorance of fluidity of human sexuality thereby generating dual discords of “enforced heterosexual” and “unavoidable homosexual.” The African culture voids transgender movements and perceive same-sex sexual behavior as “taboo or bad habits” and this provide reasonable explanations for the failure of asserting for the sexual rights in GLBT movement in most discourse on sexuality in the African context. However, we could not deny the real existence of active flowing and fluidity of human sexuality even though its variants could be latent. The incessant consciousness of the existence of transgender practices in Africa either in form of bisexual desire or bisexual behavior with or without sexual identity, including people who identify themselves as bisexual opens up the vision for us to reconsider and reexamine what constitutes such ambiguity and controversy of transgender identity at present time. The notion of identity politics in gay, lesbian, and transgender community has its complexity and debates in its historical development. This paper analyses the representation of the historical trajectory of transgender practices by presenting the dynamic transition of how people cognize transgender practices under different historical conditions since the understanding of historical transition of bisexual practices would be very crucial and meaningful for gender/sexuality liberation movement at present time and in the future. The paper did a juxtaposition of the trajectories of bisexual practices between Anglo-American world and Africa, as it has certain similarities and differences within diverse historical complexities. The similar condition is the emergence of gay identity under the influence of capitalism but within different cultural context. Therefore, the political economy of each cultural context plays very important role in understanding the formation of sexual identities historically and its development and influence for the GLBT movement afterwards and in the future. By reexamining Kinsey’s categorization and applying Klein’s argument on individual’s sexual orientation this paper is poised to break the given and fixed connection among sexual behavior/sexual orientation/sexual identity, on the other hand to present the potential fluidity of human sexuality by reconsidering and reexamining the present given sex/gender system in our world. The paper concludes that it is obligatory for the essentialist and exclusionary trend at this historical moment since gay and lesbian communities in Africa need to clearly demonstrate and voice for themselves under the nuances of gender/sexuality liberation.

Keywords: heterosexual, homosexual, identity politics, queer politics, transgender

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Authors: Alessandra Turini Bolsoni Silva, Nilson Rogério Da Silva

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The hospitalization process for long periods and the experience of invasive and painful clinical procedures can trigger a set of stressors in children, family members and professionals, leading to stress. Mothers are, in general, the main caregivers and, therefore, have a high degree of sadness and stress with an impact on mental health. However, the father, in the face of the mother's absence, needs to assume other responsibilities such as domestic activities and healthy children in addition to work activities. In addition, he has to deal with changes in family and work relationships during the child's hospitalization, with disagreements and changes in the relationship with the partner, changes in the relationship with the children, and finding it difficult to reconcile the new tasks as a caregiver and work. A consequence of the hospitalization process is the interruption of the routine activities of both the child and the family members responsible for the care, who can go through stressful moments due to the consequences of family breakdown, attention focused only on the child and sleepless nights. In this sense, both the mother and the father can have their health affected by their child's hospitalization. The present study aims to compare the prevalence of stress and overload in mothers and fathers of hospitalized children, as well as possible associations with activities related to care. The participants were 10 fathers and 10 mothers of children hospitalized in a hospital located in a medium-sized city in the interior of São Paulo. Three instruments were used for data collection: 1) Script to characterize the participants; 2) The Lipp Stress Symptom Inventory (ISSL, 2000) 3) Zarit Burden Interview Protocol – ZBT. Contact was made with the management of the hospital in order to present the objectives of the project, then authorization was requested for the participation of the parents; after an agreement, the time and place were convenient for the participant to carry out the interview. Thus, they signed the Free and Informed Consent Term. Data were analyzed according to the instrument application manuals and organized in Figures and Tables. The results revealed that fathers and mothers have their family and professional routine affected by the hospitalization of their children, with the consequent presence of stress and overload indicators. However, the study points to a greater presence of stress and overload in mothers due to their role as the main caregiver, often interrupting their professional life to exercise care. In the case of the father, the routine is changed due to taking on household chores and taking care of the other children, with the professional life being less affected. It is hoped that the data can guide future interventions that promote and develop strategies that favor care and, at the same time, preserve the health of caregivers and that include mothers and fathers, considering that both are affected, albeit in a different way.

Keywords: stress, overload, caregivers, parents

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Authors: Tatjana Pekmezovic, Milica Jecmenica-Lukic, Igor Petrovic, Vladimir Kostic

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Background: A group of atypical parkinsonian syndromes (APS) includes a variety of rare neurodegenerative disorders characterized by reduced life expectancy, increasing disability, and considerable impact on health-related quality of life (HRQoL). Aim: In this study we wanted to answer two questions: a) which demographic and clinical factors are main contributors of HRQoL in our cohort of patients with APS, and b) how does quality of life of these patients change over 1-year follow-up period. Patients and Methods: We conducted a prospective cohort study in hospital settings. The initial study comprised all consecutive patients who were referred to the Department of Movement Disorders, Clinic of Neurology, Clinical Centre of Serbia, Faculty of Medicine, University of Belgrade (Serbia), from January 31, 2000 to July 31, 2013, with the initial diagnoses of ‘Parkinson’s disease’, ‘parkinsonism’, ‘atypical parkinsonism’ and ‘parkinsonism plus’ during the first 8 months from the appearance of first symptom(s). The patients were afterwards regularly followed in 4-6 month intervals and eventually the diagnoses were established for 46 patients fulfilling the criteria for clinically probable progressive supranuclear palsy (PSP) and 36 patients for probable multiple system atrophy (MSA). The health-related quality of life was assessed by using the SF-36 questionnaire (Serbian translation). Hierarchical multiple regression analysis was conducted to identify predictors of composite scores of SF-36. The importance of changes in quality of life scores of patients with APS between baseline and follow-up time-point were quantified using Wilcoxon Signed Ranks Test. The magnitude of any differences for the quality of life changes was calculated as an effect size (ES). Results: The final models of hierarchical regression analysis showed that apathy measured by the Apathy evaluation scale (AES) score accounted for 59% of the variance in the Physical Health Composite Score of SF-36 and 14% of the variance in the Mental Health Composite Score of SF-36 (p<0.01). The changes in HRQoL were assessed in 52 patients with APS who completed 1-year follow-up period. The analysis of magnitude for changes in HRQoL during one-year follow-up period have shown sustained medium ES (0.50-0.79) for both Physical and Mental health composite scores, total quality of life as well as for the Physical Health, Vitality, Role Emotional and Social Functioning. Conclusion: This study provides insight into new potential predictors of HRQoL and its changes over time in patients with APS. Additionally, identification of both prognostic markers of a poor HRQoL and magnitude of its changes should be considered when developing comprehensive treatment-related strategies and health care programs aimed at improving HRQoL and well-being in patients with APS.

Keywords: atypical parkinsonian syndromes, follow-up study, quality of life, APS

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Authors: Kathrina Aseanne Acapulco-Gomez, Shayne Julieane Morales, Tzar Francis Verame

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Mean platelet volume (MPV) is the most accurate measure of the size of platelets and is routinely measured by most automated hematological analyzers. Several studies have shown associations between MPV and cardiovascular risks and outcomes. Although its measurement may provide useful data, MPV remains to be a diagnostic tool that is yet to be included in routine clinical decision making. The aim of this systematic review and meta-analysis is to determine summary estimates of the diagnostic accuracy of mean platelet volume for the diagnosis of myocardial infarction among adult patients with angina and/or its equivalents in terms of sensitivity, specificity, diagnostic odds ratio, and likelihood ratios, and to determine the difference of the mean MPV values between those with MI and those in the non-MI controls. The primary search was done through search in electronic databases PubMed, Cochrane Review CENTRAL, HERDIN (Health Research and Development Information Network), Google Scholar, Philippine Journal of Pathology, and Philippine College of Physicians Philippine Journal of Internal Medicine. The reference list of original reports was also searched. Cross-sectional, cohort, and case-control articles studying the diagnostic performance of mean platelet volume in the diagnosis of acute myocardial infarction in adult patients were included in the study. Studies were included if: (1) CBC was taken upon presentation to the ER or upon admission (within 24 hours of symptom onset); (2) myocardial infarction was diagnosed with serum markers, ECG, or according to accepted guidelines by the Cardiology societies (American Heart Association (AHA), American College of Cardiology (ACC), European Society of Cardiology (ESC); and, (3) if outcomes were measured as significant difference AND/OR sensitivity and specificity. The authors independently screened for inclusion of all the identified potential studies as a result of the search. Eligible studies were appraised using well-defined criteria. Any disagreement between the reviewers was resolved through discussion and consensus. The overall mean MPV value of those with MI (9.702 fl; 95% CI 9.07 – 10.33) was higher than in those of the non-MI control group (8.85 fl; 95% CI 8.23 – 9.46). Interpretation of the calculated t-value of 2.0827 showed that there was a significant difference in the mean MPV values of those with MI and those of the non-MI controls. The summary sensitivity (Se) and specificity (Sp) for MPV were 0.66 (95% CI; 0.59 - 0.73) and 0.60 (95% CI; 0.43 – 0.75), respectively. The pooled diagnostic odds ratio (DOR) was 2.92 (95% CI; 1.90 – 4.50). The positive likelihood ratio of MPV in the diagnosis of myocardial infarction was 1.65 (95% CI; 1.20 – 22.27), and the negative likelihood ratio was 0.56 (95% CI; 0.50 – 0.64). The intended role for MPV in the diagnostic pathway of myocardial infarction would perhaps be best as a triage tool. With a DOR of 2.92, MPV values can discriminate between those who have MI and those without. For a patient with angina presenting with elevated MPV values, it is 1.65 times more likely that he has MI. Thus, it is implied that the decision to treat a patient with angina or its equivalents as a case of MI could be supported by an elevated MPV value.

Keywords: mean platelet volume, MPV, myocardial infarction, angina, chest pain

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Authors: Jurriaan Gillissen

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This work is concerned with stabilizing the numerical integration of the Navier-Stokes equation (NSE), backwards in time. Applications involve the detection of sources of, e.g., sound, heat, and pollutants. Stable reverse numerical integration of parabolic differential equations is also relevant for image de-blurring. While the literature addresses the reverse integration problem of the advection-diffusion equation, the problem of numerical reverse integration of the NSE has, to our knowledge, not yet been addressed. Owing to the presence of viscosity, the NSE is irreversible, i.e., when going backwards in time, the fluid behaves, as if it had a negative viscosity. As an effect, perturbations from the perfect solution, due to round off errors or discretization errors, grow exponentially in time, and reverse integration of the NSE is inherently unstable, regardless of using an implicit time integration scheme. Consequently, some sort of filtering is required, in order to achieve a stable, numerical, reversed integration. The challenge is to find a filter with a minimal adverse affect on the accuracy of the reversed integration. In the present work, we explore an adjoint gradient method (AGM) to achieve this goal, and we apply this technique to two-dimensional (2D), decaying turbulence. The AGM solves for the initial velocity field u0 at t = 0, that, when integrated forward in time, produces a final velocity field u1 at t = 1, that is as close as is feasibly possible to some specified target field v1. The initial field u0 defines a minimum of a cost-functional J, that measures the distance between u1 and v1. In the minimization procedure, the u0 is updated iteratively along the gradient of J w.r.t. u0, where the gradient is obtained by transporting J backwards in time from t = 1 to t = 0, using the adjoint NSE. The AGM thus effectively replaces the backward integration by multiple forward and backward adjoint integrations. Since the viscosity is negative in the adjoint NSE, each step of the AGM is numerically stable. Nevertheless, when applied to turbulence, the AGM develops instabilities, which limit the backward integration to small times. This is due to the exponential divergence of phase space trajectories in turbulent flow, which produces a multitude of local minima in J, when the integration time is large. As an effect, the AGM may select unphysical, noisy initial conditions. In order to improve this situation, we propose two remedies. First, we replace the integration by a sequence of smaller integrations, i.e., we divide the integration time into segments, where in each segment the target field v1 is taken as the initial field u0 from the previous segment. Second, we add an additional term (regularizer) to J, which is proportional to a high-order Laplacian of u0, and which dampens the gradients of u0. We show that suitable values for the segment size and for the regularizer, allow a stable reverse integration of 2D decaying turbulence, with accurate results for more then O(10) turbulent, integral time scales.

Keywords: time reversed integration, parabolic differential equations, adjoint gradient method, two dimensional turbulence

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Authors: Sourav Ray, Christoph Stein, Marcus Weber

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A new class of drug candidates, initially derived from mathematical modeling of ligand-receptor interactions, activate the μ-opioid receptor (MOR) preferentially at acidic extracellular pH-levels, as present in injured tissues. This is of commercial interest because it may preclude the adverse effects of conventional MOR agonists like fentanyl, which include but are not limited to addiction, constipation, sedation, and apnea. Animal studies indicate the importance of taking the pH value of the chemical environment of MOR into account when designing new drugs. Hydrogen bonds (HBs) play a crucial role in stabilizing protein secondary structure and molecular interaction, such as ligand-protein interaction. These bonds may depend on the pH value of the chemical environment. For the MOR, antagonist naloxone and agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) form HBs with ionizable residue HIS 297 at physiological pH to modulate signaling. However, such interactions were markedly reduced at acidic pH. Although fentanyl-induced signaling is also diminished at acidic pH, HBs with HIS 297 residue are not observed at either acidic or physiological pH for this strong agonist of the MOR. Molecular dynamics (MD) simulations can provide greater insight into the interaction between the ligand of interest and the HIS 297 residue. Amino acid protonation states are adjusted to the model difference in system acidity. Unbiased and unrestrained MD simulations were performed, with the ligand in the proximity of the HIS 297 residue. Ligand-receptor complexes were embedded in 1-palmitoyl-2-oleoyl-sn glycero-3-phosphatidylcholine (POPC) bilayer to mimic the membrane environment. The occurrence of HBs between the different ligands and the HIS 297 residue of MOR at acidic and physiological pH values were tracked across the various simulation trajectories. No HB formation was observed between fentanyl and HIS 297 residue at either acidic or physiological pH. Naloxone formed some HBs with HIS 297 at pH 5, but no such HBs were noted at pH 7. Interestingly, DAMGO displayed an opposite yet more pronounced HB formation trend compared to naloxone. Whereas a marginal number of HBs could be observed at even pH 5, HBs with HIS 297 were more stable and widely present at pH 7. The HB formation plays no and marginal role in the interaction of fentanyl and naloxone, respectively, with the HIS 297 residue of MOR. However, HBs play a significant role in the DAMGO and HIS 297 interaction. Post DAMGO administration, these HBs might be crucial for the remediation of opioid tolerance and restoration of opioid sensitivity. Although experimental studies concur with our observations regarding the influence of HB formation on the fentanyl and DAMGO interaction with HIS 297, the same could not be conclusively stated for naloxone. Therefore, some other supplementary interactions might be responsible for the modulation of the MOR activity by naloxone binding at pH 7 but not at pH 5. Further elucidation of the mechanism of naloxone action on the MOR could assist in the formulation of cost-effective naloxone-based treatment of opioid overdose or opioid-induced side effects.

Keywords: effect of system acidity, hydrogen bond formation, opioid action, receptor activation

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Authors: Ravija Gunawardana, Banuka Athuraliya

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Machine learning has emerged as a powerful tool for disease diagnosis and prediction. The use of machine learning algorithms has the potential to improve the accuracy of disease prediction, thereby enabling medical professionals to provide more effective and personalized treatments. This study focuses on developing a machine-learning model for disease prediction using symptoms and X-ray images. The importance of this study lies in its potential to assist medical professionals in accurately diagnosing diseases, thereby improving patient outcomes. Respiratory diseases are a significant cause of morbidity and mortality worldwide, and chest X-rays are commonly used in the diagnosis of these diseases. However, accurately interpreting X-ray images requires significant expertise and can be time-consuming, making it difficult to diagnose respiratory diseases in a timely manner. By incorporating machine learning algorithms, we can significantly enhance disease prediction accuracy, ultimately leading to better patient care. The study utilized the Mask R-CNN algorithm, which is a state-of-the-art method for object detection and segmentation in images, to process chest X-ray images. The model was trained and tested on a large dataset of patient information, which included both symptom data and X-ray images. The performance of the model was evaluated using a range of metrics, including accuracy, precision, recall, and F1-score. The results showed that the model achieved an accuracy rate of over 90%, indicating that it was able to accurately detect and segment regions of interest in the X-ray images. In addition to X-ray images, the study also incorporated symptoms as input data for disease prediction. The study used three different classifiers, namely Random Forest, K-Nearest Neighbor and Support Vector Machine, to predict diseases based on symptoms. These classifiers were trained and tested using the same dataset of patient information as the X-ray model. The results showed promising accuracy rates for predicting diseases using symptoms, with the ensemble learning techniques significantly improving the accuracy of disease prediction. The study's findings indicate that the use of machine learning algorithms can significantly enhance disease prediction accuracy, ultimately leading to better patient care. The model developed in this study has the potential to assist medical professionals in diagnosing respiratory diseases more accurately and efficiently. However, it is important to note that the accuracy of the model can be affected by several factors, including the quality of the X-ray images, the size of the dataset used for training, and the complexity of the disease being diagnosed. In conclusion, the study demonstrated the potential of machine learning algorithms for disease prediction using symptoms and X-ray images. The use of these algorithms can improve the accuracy of disease diagnosis, ultimately leading to better patient care. Further research is needed to validate the model's accuracy and effectiveness in a clinical setting and to expand its application to other diseases.

Keywords: K-nearest neighbor, mask R-CNN, random forest, support vector machine

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Authors: Andre C Jordaan

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The end of the Cold War and rivalry between super powers has changed the nature of military build-up in many countries. A call from international institutions like the United Nations, International Monetary Fund and the World Bank to reduce the levels of military expenditure was the order of the day. However, this bid to cut military expenditure has not been forthright. Recently, active armed conflicts occurred in at least 46 states in 2021 with 8 in the Americas, 9 in Asia and Oceania, 3 in Europe, 8 in the Middle East and North Africa and 18 in sub-Saharan Africa. Global military expenditure in 2022 was estimated to be US$2,2 trillion, representing 2.2 per cent of global gross domestic product. Particularly sharp rises in military spending have followed in African countries and the Middle East. Global military expenditure currently follows two divergent trends, either a declining trend in the West caused mainly by austerity, efforts to control budget deficits and the wrapping up of prolonged wars. However, some parts of the world shows an increasing trend on the back of security concerns, geopolitical ambitions and some internal political factors. Conflict related fatalities in sub-Saharan Africa alone increased by 19 per cent between 2020 and 2021. The interaction between military expenditure (read conflict) and international trade is generally the cause of much debate. Some argue that countries’ fear of losing trade opportunities causes political decision makers to refrain from engaging in conflict when important trading partners are involved. However, three main arguments are always present when discussing the relationship between military expenditure or conflicts and international trade: Free trade could promote peaceful cooperation, it could trigger tension between trading blocs and partners, and trade could have no effect because conflict is based on issues that are more important. Military expenditure remains an important element of the overall government expenditure in many African countries. On the other hand, numerous researchers perceive increased international trade to be one of the main factors promoting economic growth in these countries. The purpose of this paper is therefore to determine what effect, if any, exist between the level of military expenditure and international trade within a selection of 19 African countries. Applying an augmented gravity model to explore the relationship between military expenditure and international trade, evidence is found to confirm the existence of an inverse relationship between these two variables. It seems that the results are in line with the Liberal school of thought where trade is seen as an instrument of conflict prevention. Trade is therefore perceived as a symptom of peace and not a cause thereof. In general, conflict or rumors of conflict tend to reduce trade. If conflict did not impede trade, economic agents would be indifferent to risk. Many claim that trade brings peace, however, it seems that it is rather peace that brings trade. From the results, it appears that trade reduces the risk of conflict and that conflict reduces trade.

Keywords: African countries, conflict, international trade, military expenditure

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Authors: Ciro Moreno-Ramirez, Maria Tomas-Rodriguez, Simos A. Evangelou

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A motorcycle's front end links the front wheel to the motorcycle's chassis and has two main functions: the front wheel suspension and the vehicle steering. Up to this date, several suspension systems have been developed in order to achieve the best possible front end behavior, being the telescopic fork the most common one and already subjected to several years of study in terms of its kinematics, dynamics, stability and control. A motorcycle telescopic fork suspension model consists of a couple of outer tubes which contain the suspension components (coil springs and dampers) internally and two inner tubes which slide into the outer ones allowing the suspension travel. The outer tubes are attached to the frame through two triple trees which connect the front end to the main frame through the steering bearings and allow the front wheel to turn about the steering axis. This system keeps the front wheel's displacement in a straight line parallel to the steering axis. However, there exist alternative suspension designs that allow different trajectories of the front wheel with the suspension travel. In this contribution, the authors investigate an alternative front suspension system (Hossack suspension) and its influence on the motorcycle nonlinear dynamics to identify and reduce stability risks that a new suspension systems may introduce in the motorcycle dynamics. Based on an existing high-fidelity motorcycle mathematical model, the front end geometry is modified to accommodate a Hossack suspension system. It is characterized by a double wishbone design that varies the front end geometry on certain maneuverings and, consequently, the machine's behavior/response. It consists of a double wishbone structure directly attached to the chassis. In here, the kinematics of this system and its impact on the motorcycle performance/stability are analyzed and compared to the well known telescopic fork suspension system. The framework of this research is the mathematical modelling and numerical simulation. Full stability analyses are performed in order to understand how the motorcycle dynamics may be affected by the newly introduced front end design. This study is carried out by a combination of nonlinear dynamical simulation and root-loci methods. A modal analysis is performed in order to get a deeper understanding of the different modes of oscillation and how the Hossack suspension system affects them. The results show that different kinematic designs of a double wishbone suspension systems do not modify the general motorcycle's stability. The normal modes properties remain unaffected by the new geometrical configurations. However, these normal modes differ from one suspension system to the other. It is seen that the normal modes behaviour depends on various important dynamic parameters, such as the front frame flexibility, the steering damping coefficient and the centre of mass location.

Keywords: nonlinear mechanical systems, motorcycle dynamics, suspension systems, stability

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Authors: Ioanna Taouki, Marie Lallier, David Soto

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Metacognition refers to the capacity to reflect upon our own cognitive processes. Although there is an ongoing discussion in the literature on the role of metacognition in learning and academic achievement, little is known about its neurodevelopmental trajectories in early childhood, when children begin to receive formal education in reading. Here, we evaluate the metacognitive ability, estimated under a recently developed Signal Detection Theory model, of a cohort of children aged between 6 and 7 (N=60), who performed three two-alternative-forced-choice tasks (two linguistic: lexical decision task, visual attention span task, and one non-linguistic: emotion recognition task) including trial-by-trial confidence judgements. Our study has three aims. First, we investigated how metacognitive ability (i.e., how confidence ratings track accuracy in the task) relates to performance in general standardized tasks related to students' reading and general cognitive abilities using Spearman's and Bayesian correlation analysis. Second, we assessed whether or not young children recruit common mechanisms supporting metacognition across the different task domains or whether there is evidence for domain-specific metacognition at this early stage of development. This was done by examining correlations in metacognitive measures across different task domains and evaluating cross-task covariance by applying a hierarchical Bayesian model. Third, using robust linear regression and Bayesian regression models, we assessed whether metacognitive ability in this early stage is related to the longitudinal learning of children in a linguistic and a non-linguistic task. Notably, we did not observe any association between students’ reading skills and metacognitive processing in this early stage of reading acquisition. Some evidence consistent with domain-general metacognition was found, with significant positive correlations between metacognitive efficiency between lexical and emotion recognition tasks and substantial covariance indicated by the Bayesian model. However, no reliable correlations were found between metacognitive performance in the visual attention span and the remaining tasks. Remarkably, metacognitive ability significantly predicted children's learning in linguistic and non-linguistic domains a year later. These results suggest that metacognitive skill may be dissociated to some extent from general (i.e., language and attention) abilities and further stress the importance of creating educational programs that foster students’ metacognitive ability as a tool for long term learning. More research is crucial to understand whether these programs can enhance metacognitive ability as a transferable skill across distinct domains or whether unique domains should be targeted separately.

Keywords: confidence ratings, development, metacognitive efficiency, reading acquisition

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Authors: Mia Bahar, Özlem Bozkurt

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Obsessive-compulsive disorder (OCD) is a typical, persistent, and long-lasting mental health condition in which a person experiences uncontrollable, recurrent thoughts (or "obsessions") and/or activities (or "compulsions") that they feel compelled to engage in repeatedly. Obsessive-compulsive disorder is both underdiagnosed and undertreated. It frequently manifests in a variety of medical settings and is persistent, expensive, and burdensome. Obsessive-compulsive neurosis was long believed to be a condition that offered valuable insight into the inner workings of the unconscious mind. Obsessive-compulsive disorder is now recognized as a prime example of a neuropsychiatric condition susceptible to particular pharmacotherapeutic and psychotherapy therapies and mediated by pathology in particular neural circuits. An obsessive-compulsive disorder which is called OCD, usually has two components, one cognitive and the other behavioral, although either can occur alone. Obsessions are often repetitive and intrusive thoughts that invade consciousness. These obsessions are incredibly hard to control or dismiss. People who have OCD often engage in rituals to reduce anxiety associated with intrusive thoughts. Once the ritual is formed, the person may feel extreme relief and be free from anxiety until the thoughts of contamination intrude once again. These thoughts are strengthened through a manifestation of negative reinforcement because they allow the person to avoid anxiety and obscurity. These thoughts are described as autogenous, meaning they most likely come from nowhere. These unwelcome thoughts are related to actions which we can describe as Thought Action Fusion. The thought becomes equated with an action, such as if they refuse to perform the ritual, something bad might happen, and so people perform the ritual to escape the intrusive thought. In almost all cases of OCD, the person's life gets extremely disturbed by compulsions and obsessions. Studies show OCD is an estimated 1.1% prevalence, making it a challenging issue with high co-morbidities with other issues like depressive episodes, panic disorders, and specific phobias. The first to reveal brain anomalies in OCD were numerous CT investigations, although the results were inconsistent. A few studies have focused on the orbitofrontal cortex (OFC), anterior cingulate gyrus (AC), and thalamus, structures also implicated in the pathophysiology of OCD by functional neuroimaging studies, but few have found consistent results. However, some studies have found abnormalities in the basal ganglion. There have also been some discussions that OCD might be genetic. OCD has been linked to families in studies of family aggregation, and findings from twin studies show that this relationship is somewhat influenced by genetic variables. Some Research has shown that OCD is a heritable, polygenic condition that can result from de novo harmful mutations as well as common and unusual variants. Numerous studies have also presented solid evidence in favor of a significant additive genetic component to OCD risk, with distinct OCD symptom dimensions showing both common and individual genetic risks.

Keywords: compulsions, obsessions, neuropsychiatric, genetic

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Authors: Hsiao-Lin Fang

Abstract:

Every life is precious, and comprehensive care should be provided to individuals who are in the final stages of their lives. Hospice-shared care aims to provide optimal symptom control and palliative care to terminal (cancer) patients through the implementation of shared care, and to support patients and their families in making various physical and psychological adjustments in the face of death. This report examines a 10-year-boy diagnosed with Out-of-Hospital Cardiac Arrest (OHCA). The individual fainted when swimming at school and underwent 31 minutes of cardiopulmonary resuscitation (CPR). While receiving treatment at the hospital, the individual received extracorporeal membrane oxygenation(ECMO) due to unstable hemodynamics. Urgent cardiac catheterization found: Suspect acute fulminant myocarditis or underlying cardiomyopathy with acute decompensation, After the active rescue by the medical team, hemodynamics still showed only mean pressure value. With respect to the patient, interdepartmental hospice-shared care was implemented and a do-not-resuscitate (DNR) order was signed after family discussions were conducted. Assistance and instructions were provided as part of the comfort care process. A farewell gathering attended by the patient’s relatives, friends, teachers, and classmates was organized in an intensive care unit (ICU) in order to look back on the patient’s life and the beautiful memories that were created, as well as to alleviate the sorrow felt by family members, including the patient’s father and sister. For example, the patient was presented with drawings and accompanied to a garden to pick flowers. In this manner, the patient was able to say goodbye before death. Finally, the patient’s grandmother and father participated in the clinical hospice care and post-mortem care processes. A hospice-shared care clinician conducted regular follow-ups and provided care to the family of the deceased, supporting family members through the sorrowful period. Birth, old age, sickness, and death are the natural phases of human life. In recent years, growing attention has been paid to human-centered hospice care. Hospice care is individual holistic care provided by a professional team and it involves the provision of comprehensive care to a terminal patient. Hospice care aims to satisfy the physical, psychological, mental, and social needs of patients and their families. It does not involve the cessation of treatment but rather avoids the exacerbation or extension of the suffering endured by patients, thereby preserving the dignity and quality of life during the end-of-life period. Patients enjoy the company of others as they complete the last phase of their lives, and their families also receive guidance on how they can move on with their own lives after the patient’s death.

Keywords: hospice-shared care, extracorporeal membrane oxygenation (ECMO), hospice-shared care, child patient

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Authors: Hamdan Hamood Aldumaini, Amjad Hussein Meqdam, Shamsaldeen kassim Ali, Hamed Mohammed Al-Yousefi, Haron Ahmed Al-Badawi

Abstract:

Background: Autism Spectrum Disorder (ASD) is a complex developmental challenge characterized by significant impairments in social interaction, communication, and behavioral patterns. Diagnosing ASD is challenging due to the lack of definitive medical tests, making early identification crucial. Therefore, increasing people's awareness about autism leads to early diagnosis and better prognosis. Objective: Our study aims to identify the initial symptoms prompting families to seek medical advice, determine the timeline between symptom onset and formal diagnosis, and explore methods for assessing the severity of ASD. Subjects and Methods: The study design employed was a descriptive cross-sectional design, which was suitable for the nature of the research. The data collection took place from March 5, 2022, to April 5, 2022, in Autism Rehabilitation Centers in Sana'a, Yemen. The study population consisted of all children who were diagnosed with autism and visited Autism rehabilitation centers in Sana'a city. The sample size was determined using Epi info version 7, and a total population of 587 autistic children attending the treatment was calculated, but only 250 children were included in this study (176 were male vs. 74 female). Result: In terms of sociability problems, it was found that a significant proportion of Yemeni children with autism experienced difficulties in this area. Specifically, 39.6% were classified as having severe sociability problems, while 28.4% were classified as having moderate issues. Sensory-cognitive awareness problems were also prevalent among the respondents, with 29.6% exhibiting severe difficulties in this domain. Health and physical problems were identified as significant concerns for Yemeni children with autism. The results indicated that 38.4% of the participants experienced severe health and physical issues. Identifying the first symptoms of autism is crucial for early detection and intervention. According to the study, speech delay was the most commonly observed first abnormality, reported by 71.3% of parents. Communication difficulties with others were the second most noticed abnormality, reported by 54.9% of parents. Repetitive movements were the third most commonly observed abnormality, reported by 18% of parents. Regarding the awareness among parents of ASD, our study showed that a significant portion (62%) of parents lack awareness about Autism Spectrum Disorder (ASD) and its causes. Surprisingly, a majority of these parents (over 80%) believe that autism is a curable condition. Additionally, more than half (51.2%) of the parents surveyed reported insufficient knowledge about medication options available to support therapy and rehabilitation for their autistic children.

Keywords: autism characteristics, rehabilitation centres, yemen, children

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Authors: Helen J. Spray, Karina J. Linnell

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Local-global bias in adulthood is strongly dependent on environmental factors and a global bias is not the universal characteristic of adult perception it was once thought to be: whilst Western adults typically demonstrate a global bias, Namibian adults living in traditional villages possess a strong local bias. Furthermore, environmental effects on local-global bias have been shown to be highly gender-specific; whereas urbanisation promoted a global bias in urbanised Namibian women but not men, education promoted a global bias in urbanised Namibian men but not women. Adult populations, however, provide only a snapshot of the gene-environment interactions which shape perceptual bias. Yet, to date, there has been little work on the development of local-global bias across environmental settings. In the current study, local-global bias was assessed using a similarity-matching task with Navon figures in children aged between 4 and 15 years from across three populations: traditional Namibians, urban Namibians, and urban British. For the two Namibian groups, measures of urbanisation and education were obtained. Data were subjected to both between-group and within-group analyses. Between-group analyses compared developmental trajectories across population and gender. These analyses revealed a global bias from even as early as 4 in the British sample, and showed that the developmental onset of a global bias is not fixed. Urbanised Namibian children ultimately developed a global bias that was indistinguishable from British children; however, a global bias did not emerge until much later in development. For all populations, the greatest developmental effects were observed directly following the onset of formal education. No overall gender effects were observed; however, there was a significant gender by age interaction which was difficult to reconcile with existing biological-level accounts of gender differences in the development of local-global bias. Within-group analyses compared the effects of urbanisation and education on local-global bias for traditional and urban Namibian boys and girls separately. For both traditional and urban boys, education mediated all effects of age and urbanisation; however, this was not the case for girls. Traditional Namibian girls retained a local bias regardless of age, education, or urbanisation, and in urbanised girls, the development of a global bias was not attributable to any one factor specifically. These results are broadly consistent with aforementioned findings that education promoted a global bias in urbanised Namibian men but not women. The development of local-global bias does not follow a fixed trajectory but is subject to environmental control. Understanding how variability in the development of local-global bias might arise, particularly in the context of gender, may have far-reaching implications. For example, a number of educationally important cognitive functions (e.g., spatial ability) are known to show consistent gender differences in childhood and local-global bias may mediate some of these effects. With education becoming an increasingly prevalent force across much of the developing world it will be important to understand the processes that underpin its effects and their implications.

Keywords: cross-cultural, development, education, gender, local-global bias, perception, urbanisation, urbanization

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Authors: Sijie Chen, Xiaofang Chen, Juan Wang, Yingying Zhang, Yu Hong, Wanyu Zhuang, Xinxin Huang, Ping Ou, Longsheng Huang

Abstract:

Purpose: Autistic symptom improvement can be observed in children treated with acupuncture, but the mechanism is still being explored. In the present study, we used scalp acupuncture to treat autism rat model, and then their improvement in the abnormal behaviors and specific mechanisms behind were revealed by detecting animal behaviors, analyzing the RNA sequencing of the prefrontal cortex(PFC), and observing the ultrastructure of PFC neurons under the transmission electron microscope. Methods: On gestational day 12.5, Wistar rats were given valproic acid (VPA) by intraperitoneal injection, and their offspring were considered to be reliable rat models of autism. They were randomized to VPA or VPA-acupuncture group (n=8). Offspring of Wistar pregnant rats that were simultaneously injected with saline were randomly selected as the wild-type group (WT). VPA_acupuncture group rats received acupuncture intervention at 23 days of age for 4 weeks, and the other two groups followed without intervention. After the intervention, all experimental rats underwent behavioral tests. Immediately afterward, they were euthanized by cervical dislocation, and their prefrontal cortex was isolated for RNA sequencing and transmission electron microscopy. Results: The main results are as follows: 1. Animal behavioural tests: VPA group rats showed more anxiety-like behaviour and repetitive, stereotyped behaviour than WT group rats. While VPA group rats showed less spatial exploration ability, activity level, social interaction, and social novelty preference than WT group rats. It was gratifying to observe that acupuncture indeed improved these abnormal behaviors of autism rat model. 2. RNA-sequencing: The three groups of rats differed in the expression and enrichment pathways of multiple genes related to synaptic function, neural signal transduction, and circadian rhythm regulation. Our experiments indicated that acupuncture can alleviate the major symptoms of ASD by improving these neurological abnormalities. 3. Under the transmission electron microscopy, several lysosomes and mitochondrial structural abnormalities were observed in the prefrontal neurons of VPA group rats, which were manifested as atrophy of the mitochondrial membran, blurring or disappearance of the mitochondrial cristae, and even vacuolization. Moreover, the number of synapses and synaptic vesicles was relatively small. Conversely, the mitochondrial structure of rats in the WT group and VPA_acupuncture was normal, and the number of synapses and synaptic vesicles was relatively large. Conclusion: Acupuncture effectively improved the abnormal behaviors of autism rat model and the ultrastructure of the PFC neurons, which might worked by improving their abnormal synaptic function, synaptic plasticity and promoting neuronal signal transduction.

Keywords: autism spectrum disorder, acupuncture, animal behavior, RNA sequencing, transmission electron microscope

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