Search results for: intensive or adapted cognitive behavioral therapy

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

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

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

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Authors: Salome Schulze

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The delay of students in completing their dissertations is a worldwide problem. At the University of South Africa where this research was done, only about a third of the students complete their studies within the required period of time. This study explored the reasons why the students interrupted their studies, and why they resumed their research at a later stage. If this knowledge could be utilised to improve the throughput of doctoral students, it could have significant economic benefits for institutions of higher education while at the same time enhancing their academic prestige. To inform the investigation, attention was given to key theories concerning the learning of doctoral students, namely the situated learning theory, the social capital theory and the self-regulated learning theory, based on the social cognitive theory of learning. Ten students in the faculty of Education were purposefully selected on the grounds of their poor progress, or of having been in the system for too long. The collection of the data was in accordance with a Finnish study, since the two studies had the same aims, namely to investigate student engagement and disengagement. Graphic elicitation interviews, based on visualisations were considered appropriate to collect the data. This method could stimulate the reflection and recall of the participants’ ‘stories’ with very little input from the interviewer. The interviewees were requested to visualise, on paper, their journeys as doctoral students from the time when they first registered. They were to indicate the significant events that occurred and which facilitated their engagement or disengagement. In the interviews that followed, they were requested to elaborate on these motivating or challenging events by explaining when and why they occurred, and what prompted them to resume their studies. The interviews were tape-recorded and transcribed verbatim. Information-rich data were obtained containing visual metaphors. The data indicated that when the students suffered a period of disengagement, it was sometimes related to a lack of self-regulated learning, in particular, a lack of autonomy, and the inability to manage their time effectively. When the students felt isolated from the academic community of practice disengagement also occurred. This included poor guidance by their supervisors, which accordingly deprived them of significant social capital. The study also revealed that situational factors at home or at work were often the main reasons for the students’ procrastinating behaviour. The students, however, remained in the system. They were motivated towards a renewed engagement with their studies if they were self-regulated learners, and if they felt a connectedness with the academic community of practice because of positive relationships with their supervisors and of participation in the activities of the community (e.g., in workshops or conferences). In support of their learning, networking with significant others who were sources of information provided the students with the necessary social capital. Generally, institutions of higher education cannot address the students’ personal issues directly, but they can deal with key institutional factors in order to improve the throughput of doctoral students. It is also suggested that graphic elicitation interviews be used more often in social research that investigates the learning and development of the students.

Keywords: doctoral students, engaging and disengaging experiences, graphic elicitation interviews, student procrastination

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Authors: Pratap Chandra Pati, Prabina Rajib, Parama Barai

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The traditional finance theory neglects the role of sentiment factor in asset pricing. However, the behavioral approach to asset-pricing based on noise trader model and limit to arbitrage includes investor sentiment as a priced risk factor in the assist pricing model. Investor sentiment affects stock more that are vulnerable to speculation, hard to value and risky to arbitrage. It includes small stocks, high volatility stocks, growth stocks, distressed stocks, young stocks and non-dividend-paying stocks. Since the introduction of Chicago Board Options Exchange (CBOE) volatility index (VIX) in 1993, it is used as a measure of future volatility in the stock market and also as a measure of investor sentiment. CBOE VIX index, in particular, is often referred to as the ‘investors’ fear gauge’ by public media and prior literature. The upward spikes in the volatility index are associated with bouts of market turmoil and uncertainty. High levels of the volatility index indicate fear, anxiety and pessimistic expectations of investors about the stock market. On the contrary, low levels of the volatility index reflect confident and optimistic attitude of investors. Based on the above discussions, we investigate whether market-wide fear levels measured volatility index is priced factor in the standard asset pricing model for the Indian stock market. First, we investigate the performance and validity of Fama and French three-factor model and Carhart four-factor model in the Indian stock market. Second, we explore whether India volatility index as a proxy for fearful market-based sentiment indicators affect the cross section of stock returns after controlling for well-established risk factors such as market excess return, size, book-to-market, and momentum. Asset pricing tests are performed using monthly data on CNX 500 index constituent stocks listed on the National stock exchange of India Limited (NSE) over the sample period that extends from January 2008 to March 2017. To examine whether India volatility index, as an indicator of fear sentiment, is a priced risk factor, changes in India VIX is included as an explanatory variable in the Fama-French three-factor model as well as Carhart four-factor model. For the empirical testing, we use three different sets of test portfolios used as the dependent variable in the in asset pricing regressions. The first portfolio set is the 4x4 sorts on the size and B/M ratio. The second portfolio set is the 4x4 sort on the size and sensitivity beta of change in IVIX. The third portfolio set is the 2x3x2 independent triple-sorting on size, B/M and sensitivity beta of change in IVIX. We find evidence that size, value and momentum factors continue to exist in Indian stock market. However, VIX index does not constitute a priced risk factor in the cross-section of returns. The inseparability of volatility and jump risk in the VIX is a possible explanation of the current findings in the study.

Keywords: India VIX, Fama-French model, Carhart four-factor model, asset pricing

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Authors: Zuzana Tatarkova, Ivana Pilchova, Michal Cibulka, Martin Kolisek, Peter Racay, Peter Kaplan

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Introduction: Normal functioning of mitochondria is crucial for cardiac performance. Mitochondria undergo mitophagy and biogenesis, and mitochondrial proteins are subject to extensive post-translational modifications. The state of mitochondrial homeostasis reflects overall cellular fitness and longevity. Perturbed mitochondria produce less ATP, release greater amounts of reactive molecules, and are more prone to apoptosis. Therefore mitochondrial turnover is an integral aspect of quality control in which dysfunctional mitochondria are selectively eliminated through mitophagy. Currently, the progressive deterioration of physiological functions is seen as accumulation of modified/damaged proteins with limiting regenerative ability and disturbance of such affected protein-protein communication throughout aging in myocardial cells. Methodologies: For our study was used immunohistochemistry, biochemical methods: spectrophotometry, western blotting, immunodetection as well as more sophisticated 2D electrophoresis and mass spectrometry for evaluation protein-protein interactions and specific post-translational modification. Results and Discussion: Mitochondrial stress response to reactive species was evaluated as electron transport chain (ETC) complexes, redox-active molecules, and their possible communication. Protein-protein interactions revealed a strong linkage between age and ETC protein subunits. Redox state was strongly affected in senescent mitochondria with shift in favor of more pro-oxidizing condition within cardiomyocytes. Acute myocardial ischemia and ischemia-reperfusion (IR) injury affected ETC complexes I, II and IV with no change in complex III. Ischemia induced decrease in total antioxidant capacity, MnSOD, GSH and catalase activity with recovery in some extent during reperfusion. While MnSOD protein content was higher in IR group, activity returned to 95% of control. Nitric oxide is one of the biological molecules that can out compete MnSOD for superoxide and produce peroxynitrite. This process is faster than dismutation and led to the 10-fold higher production of nitrotyrosine after IR injury in adult with higher protection in senescent ones. 2D protein profiling revealed 140 mitochondrial proteins, 12 of them with significant changes after IR injury and 36 individual nitrotyrosine-modified proteins further identified by mass spectrometry. Linking these two groups, 5 proteins were altered after IR as well as nitrated, but only one showed massive nitration per lowering content of protein after IR injury in adult. Conclusions: Senescent cells have greater proportion of protein content, which might be modulated by several post-translational modifications. If these protein modifications are connected to functional consequences and protein-protein interactions are revealed, link may lead to the solution. Assume all together, dysfunctional proteostasis can play a causative role and restoration of protein homeostasis machinery is protective against aging and possibly age-related disorders. This work was supported by the project VEGA 1/0018/18 and by project 'Competence Center for Research and Development in the field of Diagnostics and Therapy of Oncological diseases', ITMS: 26220220153, co-financed from EU sources.

Keywords: aging heart, mitochondria, proteomics, redox state

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Authors: Mariia A. Parfenenko, Ilya S. Dantsev, Sergei V. Bochenkov, Natalia V. Vinogradova, Olga S. Groznova, Victoria Yu. Voinova

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Introduction: Autism is the most common neurodevelopmental disorder. Autism is characterized by difficulties in social interaction and adherence to stereotypic behavioral patterns and frequently co-occurs with epilepsy, intellectual disabilities, connective tissue disorders, and other conditions. CHD8 codes for chromodomain-helicase-DNA-binding protein 8 - a chromatin remodeler that regulates cellular proliferation and neurodevelopment in embryogenesis. CHD8 is one of the genes most frequently involved in autism. Patients and methods: 2 unrelated male patients, P3 and P12, aged 3 and 12 years old, underwent whole genome sequencing, which determined that they both had different likely pathogenic variants, both previously undescribed in literature. Sanger sequencing later determined that P12 inherited the variant from his affected mother. Results: P3 and P12 presented with autism, a developmental delay, ataxia, sleep disorders, overgrowth, and macrocephaly, as well as other clinical features typically present in patients with causative variants in CHD8. The mother of P12 also has autistic traits, as well as ataxia, hypotonia, sleep disorders, and other symptoms. However, P3 and P12 also have different cardiac abnormalities. P3 had signs of a repolarization disorder: a flattened T wave in the III and aVF derivations and a negative T wave in the V1-V2 derivations. He also had structural valve anomalies with associated regurgitation, local contractility impairment of the left ventricular, and diastolic dysfunction of the right ventricle. Meanwhile, P12 had Wolff-Parkinson-White syndrome and underwent radiofrequency ablation at the age of 2 years. At the time of observation, P12 had mild sinus arrhythmia and an incomplete right bundle branch block, as well as arterial hypertension. Discussion: Cardiac abnormalities were not previously reported in patients with causative variants in CHD8. The underlying mechanism for the formation of those abnormalities is currently unknown. However, the two hypotheses are either a disordered interaction with CHD7 – another chromodomain remodeler known to be directly involved in the cardiophenotype of CHARGE syndrome – a rare condition characterized by coloboma, heart defects and growth abnormalities, or the disrupted functioning of CHD8 as an A-Kinase Anchoring Protein, which are known to modulate cardiac function. Conclusion: We observed 2 unrelated autistic males with likely pathogenic variants in CHD8 that presented with typical symptoms of CHD8-related neurodevelopmental disorder, as well as cardiac abnormalities. Cardiac abnormalities have, until now, been considered uncharacteristic for patients with causative variants in CHD8. Further accumulation of data, including experimental evidence of the involvement of CHD8 in heart formation, will elucidate the mechanism underlying the cardiophenotype of those patients. Acknowledgements: Molecular genetic testing of the patients was made possible by the Charity Fund for medical and social genetic aid projects «Life Genome.»

Keywords: autism spectrum disorders, chromodomain-helicase-DNA-binding protein 8, neurodevelopmental disorder, cardio phenotype

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Authors: Ireen Manase Kabembo, Patrick Chanda

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Background: Substance use disorders are among the chronic conditions that affect all age groups. Worldwide, there is an increase in young people affected by SUDs, which implies that more family members are transitioning into the caregiver role. Family caregivers play a buffering role in the formal healthcare system due to their involvement in caring for persons with acute and chronic conditions in the home setting. Family carers of youth with problematic alcohol and marijuana use experience myriad challenges in managing daily care for this medically vulnerable group. In addition, the poor health-seeking behaviours of youth with SUDs characterized by eluding treatment and runaway tendencies coupled with the effects of the pandemic made caregiving a daunting task for most family caregivers. Issues such as limited and unavailable psychotropic medications, social stigma and discrimination, financial hurdles, systemic barriers in adolescent and young adult mental healthcare services, and the lack of a perceived vulnerability to Covid-19 by youth with SUDs are experiences of family caretakers. Methods: A qualitative study with 30 family caregivers of youth aged 16-24 explored their lived experiences and subjective meanings using two in-depth semi-structured interviews, a caregiving timeline, and participant observation. Findings: Results indicate that most family caregivers had challenges managing care for treatment elusive youth, let alone having them adhere to Covid-19 regulations. However, youth who utilized healthcare services and adhered to treatment regimens had positive outcomes and sustained recovery. The effects of the pandemic, such as job losses and the closure of businesses, further exacerbated the financial challenges experienced by family caregivers, making it difficult to purchase needed medications and daily necessities for the youth. The unabated stigma and discrimination of families of substance-dependent youth in Zambian communities further isolated family caregivers, leaving them with limited support. Conclusion: Since young people with SUDs have a compromised mental capacity due to the cognitive impairments that come with continued substance abuse, they often have difficulties making sound judgements, including the need to utilize SUD recovery services. Also, their tendency to not adhere to the Covid-19 pandemic requirements places them at a higher risk for adverse health outcomes in the (post) pandemic era. This calls for urgent implementation of robust youth mental health services that address prevention and recovery for these emerging adults grappling with substance use disorders. Support for their family caregivers, often overlooked, cannot be overemphasized.

Keywords: chronic care management, Covid-19 pandemic, family caregivers, youth with substance use disorders

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Authors: Walid A. Alkeridy, Arwa Aljasser, Khalid Mohammed Alayed, Saad Alsaad, Amani S. Alqahtani, Claire Ann Lim, Sultan H. Alamri, Doaa Zainhom Mekkawy, Mohammed Al-Sofiani

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Introduction: The history of publicly funded Home Health Care (HHC) service in Saudi Arabia dates back to 1991. The first HC program was launched to provide palliative home care services for patients with terminal cancer. Thereafter, more programs launched across Saudi Arabia most remarkably was launching the national program for HHC by the Ministry Of Health (MOH) in 2008. The national HHC MOH program is mainly providing long-term care home care services for over 40,000 Saudi citizens. The scope of the HHC service program provided by the Saudi MOH is quite diverse, ranging from basic nursing care to specialized care programs, e.g., home peritoneal dialysis, home ventilation, home infusion therapy, etc. Objectives: The primary aim of our study is to report the prevalence of chronic conditions among Saudi people receiving long-term HHC services. Secondary aims include identifying the predictors of mortality among individuals receiving long-term HHC services and studying the association between frailty and poor health outcomes among HHC users. Methods: We conducted a retrospective and cross-sectional data collection from participants receiving HHC services at King Saud University Medical City, Riyadh, Saudi Arabia. Data were collected from electronic health records (EHR), patient charts, and interviewing caregivers from the year 2019 to 2022. We assessed functional performance by Katz's activity of daily living and the Bristol Activity of Daily Living Scale (BADLS). A trained health care provider assessed frailty using the Clinical Frailty Scale (CFS). Mortality was assessed by reviewing the death certificates if patients were hospitalized through discharge status ascertainment from EHR. Results: The mean age for deceased individuals in HHC was 78.3 years. Over twenty percent of individuals receiving HHC services were readmitted to the hospital. The following variables were statistically significant between deceased and alive individuals receiving HHC services; clinical frailty scale, the total number of comorbid conditions, and functional performance based on the KATZ activity of daily living scale and the BADLS. We found that the strongest predictors for mortality were pressure ulcers which had an odds ratio of 3.75 and p-value of < 0.0001, and the clinical frailty scale, which had an odds ratio of 1.69 and p-value of 0.002, using multivariate regression analysis. In conclusion, our study found that pressure ulcers and frailty are the strongest predictors of mortality for individuals receiving home health care services. Moreover, we found a high rate of annual readmission for individuals enrolled in HHC, which requires further analysis to understand the possible contributing factors for the increased rate of hospital readmission and develop strategies to address them. Future studies should focus on designing quality improvement projects aimed at improving the quality of life for individuals receiving HHC services, especially those who have pressure ulcers at the end of life.

Keywords: homecare, Saudi, prevalence, chronic

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Authors: Sami El Khatib, Agnès Leroux, Jean-Louis Merlin, François Guillemin, Marie-Ange D’Hallewin

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Photodynamic therapy (PDT) is a treatment modality based on the cytotoxic effect occurring on the target tissues by interaction of a photosensitizer with light in the presence of oxygen. One of the major advances in PDT can be attributed to the use of topical aminolevulinic (ALA) to induce Protoporphyrin IX (PpIX) for the treatment of early stage cancers as well as diagnosis. ALA is a precursor of the heme synthesis pathway. Locally delivered to the target tissue ALA overcomes the negative feedback exerted by heme and promotes the transient formation of PpIX in situ to reach critical effective levels in cells and tissue. Whereas early steps of the heme pathway occur in the cytosol, PpIX synthesis is shown to be held in the mitochondrial membranes and PpIX fluorescence is expected to accumulate in close vicinity of the initial building site and to progressively diffuse to the neighboring cytoplasmic compartment or other lipophylic organelles. PpIX is known to be highly reactive and will be degraded when irradiated with light. PpIX photobleaching is believed to be governed by a singlet oxygen mediated mechanism in the presence of oxidized amino acids and proteins. PpIX photobleaching and subsequent spectral phototransformation were described widely in tumor cells incubated in vitro with ALA solution, or ex vivo in human and porcine mucosa superfused with hexylaminolevulinate (hALA). PpIX photobleaching was also studied in vivo, using animal models such as normal or tumor mice skin and orthotopic rat bladder model. Hexyl aminolevulinate a more potent lipophilic derivative of ALA was proposed as an adjunct to standard cystoscopy in the fluorescence diagnosis of bladder cancer and other malignancies. We have previously reported the effectiveness of hALA mediated PDT of rat bladder cancer. Although normal and tumor bladder epithelium exhibit similar fluorescence intensities after intravesical instillation of two hALA concentrations (8 and 16 mM), the therapeutic response at 8mM and 20J/cm2 was completely different from the one observed at 16mM irradiated with the same light dose. Where the tumor is destroyed, leaving the underlying submucosa and muscle intact after an 8 mM instillation, 16mM sensitization and subsequent illumination results in the complete destruction of the underlying bladder wall but leaves the tumor undamaged. The object of the current study is to try to unravel the underlying mechanism for this apparent contradiction. PpIX extraction showed identical amounts of photosensitizer in tumor bearing bladders at both concentrations. Photobleaching experiments revealed mono-exponential decay curves in both situations but with a two times faster decay constant in case of 16mM bladders. Fluorescence microscopy shows an identical fluorescence pattern for normal bladders at both concentrations and tumor bladders at 8mM with bright spots. Tumor bladders at 16 mM exhibit a more diffuse cytoplasmic fluorescence distribution. The different response to PDT with regard to the initial pro-drug concentration can thus be attributed to the different cellular localization.

Keywords: bladder cancer, hexyl-aminolevulinate, photobleaching, confocal fluorescence microscopy

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Authors: Atara Shriki, Ilana Lavy

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In a rapidly changing technological society, creativity is considered as an engine of economic and social progress. No doubt the education system has a central role in nurturing all students’ creativity, however, it is normally not encouraged at school. The causes of this reality are related to a variety of circumstances, among them: external pressures to cover the curriculum and succeed in standardized tests that mostly require algorithmic thinking and implementation of rules; teachers’ tendency to teach similarly to the way they themselves were taught as school students; relating creativity to giftedness, and therefore avoid nurturing all students' creativity; lack of adequate learning materials and accessible tools for following and evaluating the development of students’ creativity; and more. Since success in academic studies requires, among other things, creativity, lecturers in higher education institutions should consider appropriate ways to nurture students’ creative thinking and assess its development. Obviously, creativity has a multifaceted nature, numerous definitions, various perspectives for studying its essence (e.g., process, personality, environment, and product), and several approaches aimed at evaluating and assessing creative expressions (e.g., cognitive, social-personal, and psychometric). In this framework, we suggest nurturing students’ creativity through engaging them in problem posing activities that are part of inquiry assignments. In order to assess the development of their creativity, we propose to employ a model that was designed for this purpose, based on the psychometric approach, viewing the posed problems as the “creative product”. The model considers four measurable aspects- fluency, flexibility, originality, and organization, as well as a total score of creativity that reflects the relative weights of each aspect. The scores given to learners are of two types: (1) Total scores- the absolute number of posed problems with respect to each of the four aspects, and a final score of creativity; (2) Relative scores- each absolute number is transformed into a number that relates to the relative infrequency of the posed problems in student’s reference group. Through converting the scores received over time into a graphical display, students can assess their progress both with respect to themselves and relative to their reference group. Course lecturers can get a picture of the strengths and weaknesses of each student as well as the class as a whole, and to track changes that occur over time in response to the learning environment they had generated. Such tracking may assist lecturers in making pedagogical decisions about emphases that should be put on one or more aspects of creativity, and about the students that should be given a special attention. Our experience indicates that schoolteachers and lecturers in higher education institutes find the combination of engaging learners in problem posing along with self-assessment of their progress through utilizing the graphical display of accumulating total and relative scores has the potential to realize most learners’ creative potential.

Keywords: creativity, problem posing, psychometric model, self-assessment

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Authors: Anne Nattembo

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Cervical cancer remains a major public health problem in developing countries, especially in Africa. Effective cervical cancer prevention communication requires identification of behaviors, attitudes and increasing awareness of a given population; thus this study focused on investigating awareness, attitudes, and behavior among female university students towards cervical cancer messages. The study objectives sought to investigate the communication behavior of young adults towards cervical cancer, to understand female students recognition of cervical cancer as a problem, to identify the frames related to cervical cancer and their impact towards audience communication and participation behaviors, to identify the factors that influence behavioral intentions and level of involvement towards cervical cancer services and to make recommendations on how to improve cervical cancer communication towards female university students. The researcher obtained data using semi-structured interviews and focus group discussions targeting 90 respondents. The semi-structured in-depth interviews were carried out through one-on-one discussions basis using a set of prepared questions among 53 respondents. All interviews were audio-tape recorded. Each interview was directly typed into Microsoft Word. 4 focus group discussions were conducted with a total of 37 respondents; 2 female only groups with 10 respondents in one and 9 respondents in another, 1 mixed with 12 participants 5 of whom were male, and 1 male only group with 6 participants. The key findings show that the participants preferred to receive and access cervical cancer information from doctors although they were mainly receiving information from the radio. In regards to the type of public the respondents represent, majority of the respondents were non-publics in the sense that they did not have knowledge about cervical cancer, had low levels of involvement and had high constraint recognition their cervical cancer knowledge levels. The researcher identified the most salient audience frames among female university students towards cervical cancer and these included; death, loss, and fear. These frames did not necessarily make cervical cancer an issue of concern among the female university students but rather an issue they distanced themselves from as they did not perceive it as a risk. The study also identified the constraints respondents face in responding to cervical cancer campaign calls-to-action which included; stigma, lack of knowledge and access to services as well as lack of recommendation from doctors. In regards to sex differences, females had more knowledge about cervical cancer than the males. In conclusion the study highlights the importance of interpersonal communication in risk or health communication with a focus on health providers proactively sharing cervical cancer prevention information with their patients. Health provider’s involvement in cervical cancer is very important in influencing behavior and compliance of cervical cancer calls-to-action. The study also provides recommendations for designing effective cervical cancer campaigns that will positively impact on the audience such as packaging cervical cancer messages that also target the males as a way of increasing their involvement and more campaigns to increase awareness of cervical cancer as well as designing positive framed messages to counter the negative audience frames towards cervical cancer.

Keywords: cervical cancer communication, health communication, university students, risk communication

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Authors: Nisa Mohan

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Clinical coding is a feasible method for estimating the national prevalence of adverse drug event (ADE) admissions. However, under-coding of ADE admissions is a limitation of this method. Whilst the under-coding will impact the accurate estimation of the actual burden of ADEs, the feasibility of the coded data in estimating the adverse drug event admissions goes much further compared to the other methods. Therefore, it is necessary to know the reasons for the under-coding in order to improve the clinical coding of ADE admissions. The ability to identify the reasons for the under-coding of ADE admissions rests on understanding the decision-making process of coding ADE admissions. Hence, the current study aimed to explore the decision-making process of clinical coders when coding cases of ADE admissions. Clinical coders from different levels of coding job such as trainee, intermediate and advanced level coders were purposefully selected for the interviews. Thirteen clinical coders were recruited from two Auckland region District Health Board hospitals for the interview study. Semi-structured, one-on-one, face-to-face interviews using open-ended questions were conducted with the selected clinical coders. Interviews were about 20 to 30 minutes long and were audio-recorded with the approval of the participants. The interview data were analysed using a general inductive approach. The interviews with the clinical coders revealed that the coders have targets to meet, and they sometimes hesitate to adhere to the coding standards. Coders deviate from the standard coding processes to make a decision. Coders avoid contacting the doctors for clarifying small doubts such as ADEs and the name of the medications because of the delay in getting a reply from the doctors. They prefer to do some research themselves or take help from their seniors and colleagues for making a decision because they can avoid a long wait to get a reply from the doctors. Coders think of ADE as a small thing. Lack of time for searching for information to confirm an ADE admission, inadequate communication with clinicians, along with coders’ belief that an ADE is a small thing may contribute to the under-coding of the ADE admissions. These findings suggest that further work is needed on interventions to improve the clinical coding of ADE admissions. Providing education to coders about the importance of ADEs, educating clinicians about the importance of clear and confirmed medical records entries, availing pharmacists’ services to improve the detection and clear documentation of ADE admissions, and including a mandatory field in the discharge summary about external causes of diseases may be useful for improving the clinical coding of ADE admissions. The findings of the research will help the policymakers to make informed decisions about the improvements. This study urges the coding policymakers, auditors, and trainers to engage with the unconscious cognitive biases and short-cuts of the clinical coders. This country-specific research conducted in New Zealand may also benefit other countries by providing insight into the clinical coding of ADE admissions and will offer guidance about where to focus changes and improvement initiatives.

Keywords: adverse drug events, clinical coders, decision making, hospital admissions

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Authors: Soraia V. M. de Sá, Miguel A. Faria, José O. Fernandes, Sara C. Cunha

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Cereals play a vital role in fulfilling the nutritional needs of children, supplying essential nutrients crucial for their growth and development. However, concerns arise due to children's heightened vulnerability due to their unique physiology, specific dietary requirements, and relatively higher intake in relation to their body weight. This vulnerability exposes them to harmful food contaminants, particularly mycotoxins, prevalent in cereals. Because of the thermal stability of mycotoxins, conventional industrial food processing often falls short of eliminating them. Children, especially those aged 4 months to 12 years, frequently encounter mycotoxins through the consumption of specialized food products, such as instant foods, breakfast cereals, bars, cookie snacks, fruit puree, and various dairy items. A close monitoring of this demographic group's exposure to mycotoxins is essential, as toxins ingestion may weaken children’s immune systems, reduce their resistance to infectious diseases, and potentially lead to cognitive impairments. The severe toxicity of mycotoxins, some of which are classified as carcinogenic, has spurred the establishment and ongoing revision of legislative limits on mycotoxin levels in food and feed globally. While EU Commission Regulation 1881/2006 addresses well-known mycotoxins in processed cereal-based foods and infant foods, the absence of regulations specifically addressing emerging mycotoxins underscores a glaring gap in the regulatory framework, necessitating immediate attention. Emerging mycotoxins have gained mounting scrutiny in recent years due to their pervasive presence in various foodstuffs, notably cereals and cereal-based products. Alarmingly, exposure to multiple mycotoxins is hypothesized to exhibit higher toxicity than isolated effects, raising particular concerns for products primarily aimed at children. This study scrutinizes the presence of 22 mycotoxins of the diverse range of chemical classes in 148 processed cereal-based foods, including 39 breakfast cereals, 25 infant formulas, 27 snacks, 25 cereal bars, and 32 cookies commercially available in Portugal. The analytical approach employed a modified QuEChERS procedure followed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. Given the paucity of information on the risk assessment of children to multiple mycotoxins in cereal and cereal-based products consumed by children of Portugal pioneers the evaluation of this critical aspect. Overall, aflatoxin B1 (AFB1) and aflatoxin G2 (AFG2) emerged as the most prevalent regulated mycotoxins, while enniatin B (ENNB) and sterigmatocystin (STG) were the most frequently detected emerging mycotoxins.

Keywords: cereal-based products, children´s nutrition, food safety, UPLC-MS/MS analysis

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Authors: Vladislav Grigorovitch, Marina Grigorovitch, David Pearlmutter, Erez Gal

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The concept of “electric island” is involved with achieving the balance between the self-power generation ability of each educational institution and energy consumption demand. Photo-Voltaic (PV) solar system installed on the roofs of educational buildings is a common way to absorb the available solar energy and generate electricity for self-consumption and even for returning to the grid. The main objective of this research is to develop and implement an “electric island” monitoring infrastructure for promoting energy efficiency in educational buildings. A microscale monitoring methodology will be developed to provide a platform to estimate energy consumption performance classified by rooms and subspaces rather than the more common macroscale monitoring of the whole building. The monitoring platform will be established on the experimental sites, enabling an estimation and further analysis of the variety of environmental and physical conditions. For each building, separate measurement configurations will be applied taking into account the specific requirements, restrictions, location and infrastructure issues. The direct results of the measurements will be analyzed to provide deeper understanding of the impact of environmental conditions and sustainability construction standards, not only on the energy demand of public building, but also on the energy consumption habits of the children that study in those schools and the educational and administrative staff that is responsible for providing the thermal comfort conditions and healthy studying atmosphere for the children. A monitoring methodology being developed in this research is providing online access to real-time data of Interferential Therapy (IFTs) from any mobile phone or computer by simply browsing the dedicated website, providing powerful tools for policy makers for better decision making while developing PV production infrastructure to achieve “electric islands” in educational buildings. A detailed measurement configuration was technically designed based on the specific conditions and restriction of each of the pilot buildings. A monitoring and analysis methodology includes a large variety of environmental parameters inside and outside the schools to investigate the impact of environmental conditions both on the energy performance of the school and educational abilities of the children. Indoor measurements are mandatory to acquire the energy consumption data, temperature, humidity, carbon dioxide and other air quality conditions in different parts of the building. In addition to that, we aim to study the awareness of the users to the energy consideration and thus the impact on their energy consumption habits. The monitoring of outdoor conditions is vital for proper design of the off-grid energy supply system and validation of its sufficient capacity. The suggested outcomes of this research include: 1. both experimental sites are designed to have PV production and storage capabilities; 2. Developing an online information feedback platform. The platform will provide consumer dedicated information to academic researchers, municipality officials and educational staff and students; 3. Designing an environmental work path for educational staff regarding optimal conditions and efficient hours for operating air conditioning, natural ventilation, closing of blinds, etc.

Keywords: sustainability, electric island, IOT, smart building

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Authors: Md Maruf Hossain Koli

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The issue of child labor is enormous and cannot be ignored in Bangladesh. The problem of child exploitation is a socio-economic reality of Bangladesh. This paper will indicate the causes, consequences, and possibilities of using microfinance as remedies of hazardous child labor in Bangladesh. Poverty is one of the main reasons for children to become child laborers. It is an indication of economic vulnerability, inadequate law, and enforcement system and cultural and social inequities along with the inaccessible and low-quality educational system. An attempt will be made in this paper to explore and analyze child labor scenario in Bangladesh and will explain holistic intervention of BRAC, the largest nongovernmental organization in the world to address child labor through promoting incubation support to youth-led enterprises. A combination of research methods were used to write this paper. These include non-reactive observation in the form of literature review, desk studies as well as reactive observation like site visits and, semi-structured interviews. Hazardous Child labor is a multi-dimensional and complex issue. This paper was guided by the answer following research questions to better understand the current context of hazardous child labor in Bangladesh, especially in Dhaka city. The author attempted to figure out why child labor should be considered as a development issue? Further, it also encountered why child labor in Bangladesh is not being reduced at an expected pace? And finally what could be a sustainable solution to eradicate this situation. One of the most challenging characteristics of child labor is that it interrupts a child’s education and cognitive development hence limiting the building of human capital and fostering intergenerational reproduction of poverty and social exclusion. Children who are working full-time and do not attend school, cannot develop the necessary skills. This leads them and their future generation to remain in poor socio-economic condition as they do not get a better paying job. The vicious cycle of poverty will be reproduced and will slow down sustainable development. The outcome of the research suggests that most of the parents send their children to work to help them to increase family income. In addition, most of the youth engaged in hazardous work want to get training, mentoring and easy access to finance to start their own business. The intervention of BRAC that includes classroom and on the job training, tailored mentoring, health support, access to microfinance and insurance help them to establish startup. This intervention is working in developing business and management capacity through public-private partnerships and technical consulting. Supporting entrepreneurs, improving working conditions with micro, small and medium enterprises and strengthening value chains focusing on youth and children engaged with hazardous child labor.

Keywords: child labour, enterprise development, microfinance, youth entrepreneurship

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Authors: Iñaki Iturria, Pasquale Russo, Montserrat Nacher-Vázquez, Giuseppe Spano, Paloma López, Miguel Angel Pardo

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Introduction: It is known that some Lactic Acid Bacteria (LAB) present an interesting probiotic effect. Probiotic bacteria stimulate host resistance to microbial pathogens and thereby aid in immune response, and modulate the host's immune responses to antigens with a potential to down-regulate hypersensitivity reactions. Therefore, probiotic therapy is valuable against intestinal infections and may be beneficial in the treatment of Inflammatory Bowel Disease (IBD). Several in vitro tests are available to evaluate the probiotic potential of a LAB strain. However, an in vivo model is required to understand the interaction between the host immune system and the bacteria. During the last few years, zebrafish (Danio rerio) has gained interest as a promising vertebrate model in this field. This organism has been extensively used to study the interaction between the host and the microbiota, as well as the host immune response under several microbial infections. In this work, we report on the use of the zebrafish model to investigate in vivo the colonizing ability and the immunomodulatory effect of probiotic LAB. Methods: Lactobacillus strains belonging to different LAB species were fluorescently tagged and used to colonize germ-free zebrafish larvae gastrointestinal tract (GIT). Some of the strains had a well-documented probiotic effect (L. acidophilus LA5); while others presented an exopolysaccharide (EPS) producing phenotype, thus allowing evaluating the influence of EPS in the colonization and immunomodulatory effect. Bacteria colonization was monitored for 72 h by direct observation in real time using fluorescent microscopy. CFU count per larva was also evaluated at different times. The immunomodulatory effect was assessed analysing the differential expression of several innate immune system genes (MyD88, NF-κB, Tlr4, Il1β and Il10) by qRT- PCR. The anti-inflammatory effect was evaluated using a chemical enterocolitis zebrafish model. The protective effect against a pathogen was also studied. To that end, a challenge test was developed using a fluorescently tagged pathogen (Vibrio anguillarum-GFP+). The progression of the infection was monitored up to 3 days using a fluorescent stereomicroscope. Mortality rates and CFU counts were also registered. Results and conclusions: Larvae exposed to EPS-producing bacteria showed a higher fluorescence and CFU count than those colonized with no-EPS phenotype LAB. In the same way, qRT-PCR results revealed an immunomodulatory effect on the host after the administration of the strains with probiotic activity. A downregulation of proinflammatory cytoquines as well as other cellular mediators of inflammation was observed. The anti-inflammatory effect was found to be particularly marked following exposure to LA% strain, as well as EPS producing strains. Furthermore, the challenge test revealed a protective effect of probiotic administration. As a matter of fact, larvae fed with probiotics showed a decrease in the mortality rate ranging from 20 to 35%. Discussion: In this work, we developed a promising model, based on the use of gnotobiotic zebrafish coupled with a bacterial fluorescent tagging in order to evaluate the probiotic potential of different LAB strains. We have successfully used this system to monitor in real time the colonization and persistence of exogenous LAB within the gut of zebrafish larvae, to evaluate their immunomodulatory effect and for in vivo competition assays. This approach could bring further insights into the complex microbial-host interactions at intestinal level.

Keywords: gnotobiotic, immune system, lactic acid bacteria, probiotics, zebrafish

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Authors: Sookbin Im, Myounglyun Heo

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This study aims at analyzing composition and effects of the preliminary intervention to promote resiliency of children whose parents suffer mental illness, and considerations according to the program, and developing the resiliency promotion program for children of psychiatric patients. For participants of preliminary intervention, they were recruited through a community mental health and social welfare center in a city, and there were 10 children (eight girls and two boys) who are from second to five graders in elementary school, and whose parents suffer schizophrenia, depression, or alcoholism, etc. The program was conducted in the seminar room of the community mental illness and social welfare center from October to December 2015 and from July to September 2016. The elements of resiliency were figured out by reviewing the literature. And therapeutic activities to promote resiliency was composed, and total twice, 8 sessions(two hours, once a week) were applied. Each session consisted of playgroup activities, art activities, and role-playing with feedback for achieving goals to promote self-awareness, self-efficacy, positive outlook, ability to solve problems, empathy for others, peer group acceptance, having goals and aspirations, and assertiveness. In addition, auxiliary managers as many as children played a role as mentor and role model, and children's behaviors were collected by participatory observation. As a result of the study, four children quit the program because the schedules of their own school programs were overlapped with it. Therefore, six children completed the program. Children who completed it became active, positive, decreased compulsive actions, and increased self-expressions. The participants reacted the 8-session program is too short and regretted about it. However, recruiting the participants were difficult, and too distracting children caused negative influences in the group activities. Based on the results, the program was developed as follows: The program would consist of total 11 sessions, and the first eight sessions would be made of plays, art activities, role-plays, and presentations for promoting self-understanding, improving positiveness, providing meaning for experiences, emotional control, and interpersonal relations. In order to balance various contents, methods such as structuring environments, storytelling, emotional coaching, and group feedback would be applied, and the ninth to eleventh sessions would be booster sessions consisting of optional activities for children. This program is for children who attend school with active linguistic communications and interactions with peers. Especially, considering that effective development starts at around 10 years old, it would be for children who are third and fourth graders in elementary school. These result showed that this program was useful for improving the key elements of resiliency such as positive thinking or impulse control. It is suggested the necessary of resiliency promoting program model and practical guidance with comprehensive measuring methods(narratives, drawing, self-reported questionnaire, behavioral observation). Also, it is necessary to make a training program for the coaches or leaders to operate this program to spread out for child health.

Keywords: children, mental, parents, resilience

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Authors: Masoume Pourmohamadreza-Tajrishi, Parviz Azadfallah

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Autism spectrum disorders (ASD) involve myriad aberrant perceptual, cognitive, linguistic, and social behaviors. The term spectrum emphasizes that the disabilities associated with ASD fall on a continuum from relatively mild to severe. People with ASD may display stereotyped behaviors such as twirling, spinning objects, flapping the hands, and rocking. The individuals with ASD exhibit communication problems due to repetitive/restricted behaviors. Children with ASD who lack the motivation to learn, who do not enjoy physical challenges, or whose sensory perception results in confusing or unpleasant feedback from movement may not become sufficiently motivated to practice motor activities. As a result, they may show both a delay in developing certain motor skills. Additionally, attention is an important component of learning. As far as children with ASD have problems in joint attention, many education-based programs are needed to consider some aspects of attention and motor activities development for students with ASD. These programs focus on the basic movement skills that are crucial for the future development of the more complex skills needed in games, dance, sports, gymnastics, active play, and recreational physical activities. The purpose of the present research was to determine the effectiveness of therapeutic exercise on motor skills and attention of male students with ASD. This was an experimental study with a control group. The population consisted of 8-10 year-old male students with ASD and 30 subjects were selected randomly from an available center suitable for the children with ASD. They were evaluated by the Basic Motor Ability Test (BMAT) and Persian version of computerized Stroop color-word test and randomly assigned to an experimental and control group (15 students in per group). The experimental group participated in 16 therapeutic exercise sessions and received therapeutic exercise program (twice a week; each lasting for 45 minutes) designed based on the Spark motor program while the control group did not. All subjects were evaluated by BMAT and Stroop color-word test after the last session again. The collected data were analyzed by using multivariate analysis of covariance (MANCOVA). The results of MANCOVA showed that experimental and control groups had a significant difference in motor skills and at least one of the components of attention (correct responses, incorrect responses, no responses, the reaction time of congruent words and reaction time of incongruent words in the Stroop test). The findings showed that the therapeutic exercise had a significant effect on motor skills and all components of attention in students with ASD. We can conclude that the therapeutic exercise led to promote the motor skills and attention of students with ASD, so it is necessary to design or plan such programs for ASD students to prevent their communication or academic problems.

Keywords: Attention, autism spectrum disorder, motor skills, therapeutic exercise

Procedia PDF Downloads 130

Authors: Elena Kokkoni, Prasanna Kannappan, Ashkan Zehfroosh, Effrosyni Mavroudi, Kristina Strother-Garcia, James C. Galloway, Jeffrey Heinz, Rene Vidal, Herbert G. Tanner

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Early immobility affects the motor, cognitive, and social development. Current pediatric rehabilitation lacks the technology that will provide the dosage needed to promote mobility for young children at risk. The addition of socially assistive robots in early interventions may help increase the mobility dosage. The aim of this study is to examine the feasibility of an early intervention paradigm where non-walking infants experience independent mobility while socially interacting with robots. A dynamic environment is developed where both the child and the robot interact and learn from each other. The environment involves: 1) a range of physical activities that are goal-oriented, age-appropriate, and ability-matched for the child to perform, 2) the automatic functions that perceive the child’s actions through novel activity recognition algorithms, and decide appropriate actions for the robot, and 3) a networked visual data acquisition system that enables real-time assessment and provides the means to connect child behavior with robot decision-making in real-time. The environment was tested by bringing a two-year old boy with Down syndrome for eight sessions. The child presented delays throughout his motor development with the current being on the acquisition of walking. During the sessions, the child performed physical activities that required complex motor actions (e.g. climbing an inclined platform and/or staircase). During these activities, a (wheeled or humanoid) robot was either performing the action or was at its end point 'signaling' for interaction. From these sessions, information was gathered to develop algorithms to automate the perception of activities which the robot bases its actions on. A Markov Decision Process (MDP) is used to model the intentions of the child. A 'smoothing' technique is used to help identify the model’s parameters which are a critical step when dealing with small data sets such in this paradigm. The child engaged in all activities and socially interacted with the robot across sessions. With time, the child’s mobility was increased, and the frequency and duration of complex and independent motor actions were also increased (e.g. taking independent steps). Simulation results on the combination of the MDP and smoothing support the use of this model in human-robot interaction. Smoothing facilitates learning MDP parameters from small data sets. This paradigm is feasible and provides an insight on how social interaction may elicit mobility actions suggesting a new early intervention paradigm for very young children with motor disabilities. Acknowledgment: This work has been supported by NIH under grant #5R01HD87133.

Keywords: activity recognition, human-robot interaction, machine learning, pediatric rehabilitation

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Authors: Anna Öqvist, Malin Malmström

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Attaining a higher level of education has become an increasingly important prerequisite for people’s economic and social independence and mobility. Young people who do not pursue higher education are not as attractive as potential employees in the modern work environment. Although completing a higher education degree is not a guarantee for getting a job, it substantially increases the chances for employment and, consequently, the chances for a better life. Despite this, it’s a fact that in several regions in Sweden, fewer students are choosing to engage in higher education. Similar trends have been emphasized in, for instance, the US where high dropout patterns among young people have been noted. This is a threat to future employment and industry development in these regions because the future employment base for society is dependent upon students’ willingness to invest in higher education. Much of prior studies have focused on the role of parents’ involvement in their children’s’ school work and the positive influence parents involvement have on their children’s school performance. Parental influence on education in general has been a topic of interest among those concerned with optimal developmental and educational outcomes for children and youth in pre-, secondary- and high school. Across a range of studies, there has emerged a strong conclusion that parental influence on child and youths education generally benefits children's and youths learning and school success. Arguably then, we could expect that parents influence on whether or not to pursue a higher education would be of importance to understand young people’s choice to engage in higher education. Accordingly, understanding what drives students’ intentions to pursue higher education is an essential component of motivating students to aspire to make the most of their potential in their future work life. Drawing on the theory of planned behavior, this study examines the role of parents influence on students’ attitudes about whether higher education can be beneficial to their future work life. We used a qualitative approach by collecting interview data from 18 high school students in Sweden to capture students’ cognitive and motivational mechanisms (attitudes) to influence intentions to engage in higher education. We found that parents may positively or negatively influence students’ attitudes and subsequently a student's intention to pursue higher education. Accordingly, our results show that parents’ own attitudes and expectations on their children are keys for influencing students’ attitudes and intentions for higher education. Further, our finding illuminates the mechanisms that drive students in one direction or the other. As such, our findings show that the same categories of arguments are used for driving students’ attitudes and intentions in two opposite directions, namely; financial arguments and work life benefits arguments. Our results contribute to existing literature by showing that parents do affect young people’s intentions to engage in higher studies. The findings contribute to the theory of planned behavior and have implications for the literature on higher education and educational psychology and also provide guidance on how to inform students about facts of higher studies in school.

Keywords: higher studies, intentions, parents influence, theory of planned behavior

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Authors: N. Reza Pour, S. Chuah, T. Vo

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Background: Vertebral artery dissection (VAD) is a rare complication of pregnancy. It can occur spontaneously or following a traumatic event. The pathogenesis is unclear. Predisposing factors include chronic hypertension, Marfan’s syndrome, fibromuscular dysplasia, vasculitis and cystic medial necrosis. Physiological changes of pregnancy have also been proposed as potential mechanisms of injury to the vessel wall. The clinical presentation varies and it can present as a headache, neck pain, diplopia, transient ischaemic attack, or an ischemic stroke. Isolated cases of VAD in pregnancy and puerperium have been reported in the literature. One case was found to have posterior circulation stroke as a result of bilateral VAD and labour was induced at 37 weeks gestation for preeclampsia. Another patient at 38 weeks with severe neck pain that persisted after induction for elevated blood pressure and arteriography showed right VAD postpartum. A single case of lethal VAD in pregnancy with subsequent massive subarachnoid haemorrhage has been reported which was confirmed by the autopsy. Case Presentation: We report two cases of vertebral artery dissection in pregnancy. The first patient was a 32-year-old primigravida presented at the 38th week of pregnancy with the onset of early labour and blood pressure (BP) of 130/70 on arrival. After 2 hours, the patient developed a severe headache with blurry vision and BP was 238/120. Despite treatment with an intravenous antihypertensive, she had eclamptic fit. Magnesium solfate was started and Emergency Caesarean Section was performed under the general anaesthesia. On the second day after the operation, she developed left-sided neck pain. Magnetic Resonance Imaging (MRI) angiography confirmed a short segment left vertebral artery dissection at the level of C3. The patient was treated with aspirin and remained stable without any neurological deficit. The second patient was a 33-year-old primigavida who was admitted to the hospital at 36 weeks gestation with BP of 155/105, constant headache and visual disturbances. She was medicated with an oral antihypertensive agent. On day 4, she complained of right-sided neck pain. MRI angiogram revealed a short segment dissection of the right vertebral artery at the C2-3 level. Pregnancy was terminated on the same day with emergency Caesarean Section and anticoagulation was started subsequently. Post-operative recovery was complicated by rectus sheath haematoma requiring evacuation. She was discharged home on Aspirin without any neurological sequelae. Conclusion: Because of collateral circulation, unilateral vertebral artery dissections may go unrecognized and may be more common than suspected. The outcome for most patients is benign, reflecting the adequacy of the collateral circulation in young patients. Spontaneous VAD is usually treated with anticoagulation or antiplatelet therapy for a minimum of 3-6 months to prevent future ischaemic events, allowing the dissection to heal on its own. We had two cases of VAD in the context of hypertensive disorders of pregnancy with an acceptable outcome. A high level of vigilance is required particularly with preeclamptic patients presenting with head/neck pain to allow an early diagnosis. This is as we hypothesize, early and aggressive management of vertebral artery dissection may potentially prevent further complications.

Keywords: eclampsia, preeclampsia, pregnancy, Vertebral Artery Dissection

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Authors: Nervana Elbakary, Sami Ouanes, Sadaf Riaz, Oraib Abdallah, Islam Mahran, Noriya Al-Khuzaei, Yassin Eltorki

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Major Depressive Disorder (MDD) requires therapeutic interventions during the initial month after being diagnosed for better disease outcomes. International guidelines recommend a duration of 4–12 weeks for an initial antidepressant (IAD) trial at an optimized dose to get a response. If depressive symptoms persist after this duration, guidelines recommend switching, augmenting, or combining strategies as the next step. Most patients with MDD in the mental health setting have been labeled incorrectly as treatment-resistant where in fact they have not been subjected to an adequate trial of guideline-recommended therapy. Premature discontinuation of IAD due to ineffectiveness can cause unfavorable consequences. Avoiding irrational practices such as subtherapeutic doses of IAD, premature switching between the ADs, and refraining from unjustified polypharmacy can help the disease to go into a remission phase We aimed to determine the prevalence and the patterns of strategies applied after an IAD was changed because of a suboptimal response as a primary outcome. Secondary outcomes included the median survival time on IAD before any change; and the predictors that were associated with IAD change. This was a retrospective cross- sectional study conducted in Mental Health Services in Qatar. A dataset between January 1, 2018, and December 31, 2019, was extracted from the electronic health records. Inclusion and exclusion criteria were defined and applied. The sample size was calculated to be at least 379 patients. Descriptive statistics were reported as frequencies and percentages, in addition, to mean and standard deviation. The median time of IAD to any change strategy was calculated using survival analysis. Associated predictors were examined using two unadjusted and adjusted cox regression models. A total of 487 patients met the inclusion criteria of the study. The average age for participants was 39.1 ± 12.3 years. Patients with first experience MDD episode 255 (52%) constituted a major part of our sample comparing to the relapse group 206(42%). About 431 (88%) of the patients had an occurrence of IAD change to any strategy before end of the study. Almost half of the sample (212 (49%); 95% CI [44–53%]) had their IAD changed less than or equal to 30 days. Switching was consistently more common than combination or augmentation at any timepoint. The median time to IAD change was 43 days with 95% CI [33.2–52.7]. Five independent variables (age, bothersome side effects, un-optimization of the dose before any change, comorbid anxiety, first onset episode) were significantly associated with the likelihood of IAD change in the unadjusted analysis. The factors statistically associated with higher hazard of IAD change in the adjusted analysis were: younger age, un-optimization of the IAD dose before any change, and comorbid anxiety. Because almost half of the patients in this study changed their IAD as early as within the first month, efforts to avoid treatment failure are needed to ensure patient-treatment targets are met. The findings of this study can have direct clinical guidance for health care professionals since an optimized, evidence-based use of AD medication can improve the clinical outcomes of patients with MDD; and also, to identify high-risk factors that could worsen the survival time on IAD such as young age and comorbid anxiety

Keywords: initial antidepressant, dose optimization, major depressive disorder, comorbid anxiety, combination, augmentation, switching, premature discontinuation

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Authors: Hanan Algarni

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Background: Impairment of walking and balance skills has negative impact on functional independence and community participation after stroke. Gait recovery is considered a primary goal in rehabilitation by both patients and physiotherapists. Treadmill training coupled with virtual reality technology is a new emerging approach that offers patients with feedback, open and random skills practice while walking and interacting with virtual environmental scenes. Objectives: To synthesize the evidence around the effects of the VR treadmill training on gait speed and balance primarily, functional independence and community participation secondarily in stroke patients. Methods: Systematic review was conducted; search strategy included electronic data bases: MEDLINE, AMED, Cochrane, CINAHL, EMBASE, PEDro, Web of Science, and unpublished literature. Inclusion criteria: Participant: adult >18 years, stroke, ambulatory, without severe visual or cognitive impartments. Intervention: VR treadmill training alone or with physiotherapy. Comparator: any other interventions. Outcomes: gait speed, balance, function, community participation. Characteristics of included studies were extracted for analysis. Risk of bias assessment was performed using Cochrane's ROB tool. Narrative synthesis of findings was undertaken and summary of findings in each outcome was reported using GRADEpro. Results: Four studies were included involving 84 stroke participants with chronic hemiparesis. Interventions intensity ranged (6-12 sessions, 20 minutes-1 hour/session). Three studies investigated the effects on gait speed and balance. 2 studies investigated functional outcomes and one study assessed community participation. ROB assessment showed 50% unclear risk of selection bias and 25% of unclear risk of detection bias across the studies. Heterogeneity was identified in the intervention effects at post training and follow up. Outcome measures, training intensity and durations also varied across the studies, grade of evidence was low for balance, moderate for speed and function outcomes, and high for community participation. However, it is important to note that grading was done on few numbers of studies in each outcome. Conclusions: The summary of findings suggests positive and statistically significant effects (p<0.05) of VR treadmill training compared to other interventions on gait speed, dynamic balance skills, function and participation directly after training. However, the effects were not sustained at follow up in two studies (2 weeks-1 month) and other studies did not perform follow up measurements. More RCTs with larger sample sizes and higher methodological quality are required to examine the long term effects of VR treadmill effects on function independence and community participation after stroke, in order to draw conclusions and produce stronger robust evidence.

Keywords: virtual reality, treadmill, stroke, gait rehabilitation

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Authors: Vineeta Sirohi

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The development of critical skills and competencies becomes imperative for young people to cope with the unpredicted challenges of the time and prepare for work and life. Recognizing that education has a critical role in reaching sustainability goals as emphasized by 2030 agenda for sustainability development, educating youth in global competence, meta-cognitive competencies, and skills from the initial stages of formal education are vital. Further, educating for global competence would help in developing work readiness and boost employability. Vocational education and training in India as envisaged in various policy documents remain marginalized in practice as compared to general education. The country is still far away from the national policy goal of tracking 25% of the secondary students at grade eleven and twelve under the vocational stream. In recent years, the importance of skill development has been recognized in the present context of globalization and change in the demographic structure of the Indian population. As a result, it has become a national policy priority and taken up with renewed focus by the government, which has set the target of skilling 500 million people by 2022. This paper provides an overview of the policies, practices, and current status of vocational education and training in India supported by statistics from the National Sample Survey, the official statistics of India. The national policy documents and annual reports of the organizations actively involved in vocational education and training have also been examined to capture relevant data and information. It has also highlighted major initiatives taken by the government to promote skill development. The data indicates that in the age group 15-59 years, only 2.2 percent reported having received formal vocational training, and 8.6 percent have received non-formal vocational training, whereas 88.3 percent did not receive any vocational training. At present, the coverage of vocational education is abysmal as less than 5 percent of the students are covered by the vocational education programme. Besides, launching various schemes to address the mismatch of skills supply and demand, the government through its National Policy on Skill Development and Entrepreneurship 2015 proposes to bring about inclusivity by bridging the gender, social and sectoral divide, ensuring that the skilling needs of socially disadvantaged and marginalized groups are appropriately addressed. It is fundamental that the curriculum is aligned with the demands of the labor market, incorporating more of the entrepreneur skills. Creating nonfarm employment opportunities for educated youth will be a challenge for the country in the near future. Hence, there is a need to formulate specific skill development programs for this sector and also programs for upgrading their skills to enhance their employability. There is a need to promote female participation in work and in non-traditional courses. Moreover, rigorous research and development of a robust information base for skills are required to inform policy decisions on vocational education and training.

Keywords: policy, skill, training, vocational education

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Authors: M. D. Nirmani, K. L. N. Perera, G. H. Galhena

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Dengue has become one of the most important arbo-viral disease in all tropical and subtropical regions of the world. Aedes aegypti, is the principal vector of the virus, vary in both epidemiological and behavioral characteristics, which could be finely measured through DNA sequence comparison at their population level. Such knowledge in the population differences can assist in implementation of effective vector control strategies allowing to make estimates of the gene flow and adaptive genomic changes, which are important predictors of the spread of Wolbachia infection or insecticide resistance. As such, this study was undertaken to investigate the phylogenetic relationships of Ae. aegypti from Galle and Colombo, Sri Lanka, based on the ribosomal protein region which spans between two exons, in order to understand the geographical distribution of genetically distinct mosquito clades and its impact on mosquito control measures. A 320bp DNA region spanning from 681-930 bp, corresponding to the ribosomal protein, was sequenced in 62 Ae. aegypti larvae collected from Galle (N=30) and Colombo (N=32), Sri Lanka. The sequences were aligned using ClustalW and the haplotypes were determined with DnaSP 5.10. Phylogenetic relationships among haplotypes were constructed using the maximum likelihood method under Tamura 3 parameter model in MEGA 7.0.14 including three previously reported sequences of Australian (N=2) and Brazilian (N=1) Ae. aegypti. The bootstrap support was calculated using 1000 replicates and the tree was rooted using Aedes notoscriptus (GenBank accession No. KJ194101). Among all sequences, nineteen different haplotypes were found among which five haplotypes were shared between 80% of mosquitoes in the two populations. Seven haplotypes were unique to each of the population. Phylogenetic tree revealed two basal clades and a single derived clade. All observed haplotypes of the two Ae. aegypti populations were distributed in all the three clades, indicating a lack of genetic differentiation between populations. The Brazilian Ae. aegypti haplotype and one of the Australian haplotypes were grouped together with the Sri Lankan basal haplotype in the same basal clade, whereas the other Australian haplotype was found in the derived clade. Phylogram showed that Galle and Colombo Ae. aegypti populations are highly related to each other despite the large geographic distance (129 Km) indicating a substantial genetic similarity between them. This may have probably arisen from passive migration assisted by human travelling and trade through both land and water as the two areas are bordered by the sea. In addition, studied Sri Lankan mosquito populations were closely related to Australian and Brazilian samples. Probably this might have caused by shipping industry between the three countries as all of them are fully or partially enclosed by sea. For example, illegal fishing boats migrating to Australia by sea is perhaps a good mean of transportation of all life stages of mosquitoes from Sri Lanka. These findings indicate that extensive mosquito migrations occur between populations not only within the country, but also among other countries in the world which might be a main barrier to the successful vector control measures.

Keywords: Aedes aegypti, dengue control, extensive mosquito migration, haplotypes, phylogeny, ribosomal protein

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Authors: Aline Woine, Moïra Mikolajczak, Virginie Dardier, Isabelle Roskam

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Background information: Becoming a parent is said to be the happiest event one can ever experience in one’s life. This popular (and almost absolute) truth–which no reasonable and decent human being would ever dare question on pain of being singled out as a bad parent–contrasts with the nuances that reality offers. Indeed, while many parents do thrive in their parenting role, some others falter and become progressively overwhelmed by their parenting role, ineluctably caught in a spiral of exhaustion. Parental burnout (henceforth PB) sets in when parental demands (stressors) exceed parental resources. While it is now generally acknowledged that PB affects the parent’s behavior in terms of neglect and violence toward their offspring, little is known about the impact that the syndrome might have on the children’s internalized (anxious and depressive symptoms, somatic complaints, etc.) and/or externalized (irritability, violence, aggressiveness, conduct disorder, oppositional disorder, etc.) behaviors. Furthermore, at the time of writing, to our best knowledge, no research has yet tested the reverse effect, namely, that of the child's internalized and/or externalized behaviors on the onset and/or maintenance of parental burnout symptoms. Goals and hypotheses: The present pioneering research proposes to fill an important gap in the existing literature related to PB by investigating the bidirectional effect between PB and the child’s internalized and/or externalized behaviors. Relying on a cross-lagged longitudinal study with three waves of data collection (4 months apart), our study tests a transactional model with bidirectional and recursive relations between observed variables and at the three waves, as well as autoregressive paths and cross-sectional correlations. Methods: As we write this, wave-two data are being collected via Qualtrics, and we expect a final sample of about 600 participants composed of French-speaking (snowball sample) and English-speaking (Prolific sample) parents. Structural equation modeling is employed using Stata version 17. In order to retain as much statistical power as possible, we use all available data and therefore apply the maximum likelihood with a missing value (mlmv) as the method of estimation to compute the parameter estimates. To limit (in so far is possible) the shared method variance bias in the evaluation of the child’s behavior, the study relies on a multi-informant evaluation approach. Expected results: We expect our three-wave longitudinal study to show that PB symptoms (measured at T1) raise the occurrence/intensity of the child’s externalized and/or internalized behaviors (measured at T2 and T3). We further expect the child’s occurrence/intensity of externalized and/or internalized behaviors (measured at T1) to augment the risk for PB (measured at T2 and T3). Conclusion: Should our hypotheses be confirmed, our results will make an important contribution to the understanding of both PB and children’s behavioral issues, thereby opening interesting theoretical and clinical avenues.

Keywords: exhaustion, structural equation modeling, cross-lagged longitudinal study, violence and neglect, child-parent relationship

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Authors: Olga Smilevska Spasova, Katerina Boshkovska, Gorica Popova, Mirjana Popovska

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Introduction: Pneumonia is an infection of the pulmonary parenchyma. HPIV 3 is one of four viruses that is a member of the Paramyxoviridae family designated types 1-4 that have a nonsegmented, single-stranded RNA genome with a lipid-containing envelope. They are spread from the respiratory tract by aerosolized secretions or by direct contact with secretions. Type 3 is endemic and can cause serious illness in immunocompromised patients. Illness caused by parainfluenza occurs shortly after inoculation with the virus. The level of immunoglobulin A antibody in serum is the best predictor of susceptibility to infection. Streptococcus pneumonia or pneumococcus is a Gram-positive, spherical bacteria, usually found in pairs and it is a member of the genus Streptococcus. Streptococcus pneumonia resides asymptomatically in healthy carriers typically colonizing the respiratory tract, sinuses, and nasal cavity. In individuals with weaker immune systems like young infants, pneumococcal bacterium is the most common cause of community-acquired pneumonia in the world. Case Report: The aim is to present a case of lower respiratory tract infection in an infant caused by parainfluenza virus 3, S. pneumonia and undifferentiated gram-negative bacteria that was successfully treated. The infant is with a history of recurrent episodes of wheezing in the past 3mounts.Infant of 10months presents 2weeks before admittance with high fever, runny nose, and cough. The primary pediatrician prescribed oral cefpodoxime for 10days and inhaled salbutamol. Two days before admittance in hospital the infant with high fever, cough, and difficulty breathing. At admittance, infant is pale, anxious with rapid respirations, cough, wheezing and tachycardia. On auscultation: vesicular breathing sounds with high pitched wheezing and on the right coarse crackles. Investigations: Blood analysis: RBC: 4, 7 x1012L, WBC: 8,3x109L: Neut: 42.73% Lym: 41.57%, Hgb: 9.38 g/dl MCV: 62.7fl, MCH: 20.0pg MCHC: 31.8 g/dl RDW: 18.7% Plt-307.9 x109LCRP: 2,5mg/l, serum iron-7.92umol/l, O2sat-97% on blood gas analysis, puls-125/min.X-ray of chest with hyperinflationand right pericardial consolidation. Microbiological analysis of sputum sample is positive for undifferentiated gram-negative bacteria (colonizer)–resistant to cefotaxime, ampicillin, cefoxitin, sulfamet.+trimetoprim and sensitive to amikacin, gentamicin, and ciprofloxacin. Molecular multiplex RT-PCR for 19 viruses and multiplex PCR for 7 bacteria test for respiratory pathogens positive for Parainfluenza virus 3(Ct=22.73), Streptococcus pneumonia (Ct=26.75).IED: IgG-9.31g/l, IgA-0.351g/l, IgM-0.86g/l. Therapy: Treatment was started with inhaled salbutamol, intravenous antibiotic cefotaxime as well as systemic corticosteroids. On day 7 because of slow clinical resolution of chest auscultation findings and an etiologic clue with a positive sputum sample for resistant undifferentiated gram negative bacteria, a second intravenous antibiotic was administered amikacin. The infant is discharged on day 14 with resolution of clinical findings. Conclusion: Mixed co-infections with respiratory viruses and bacteria in immunocompromised infants are likely to lead to a more severe form of community acquired pneumonia that will need hospitalization.

Keywords: HPIV- 3, infant, pneumonia, S. pneumonia, x-ray chest

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Authors: Alicia Ettlin

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Amid the rise of neoliberalism to the leading economic policy model in Western societies in the 1980s, people have started to internalise a neoliberal way of thinking, whereby the human body has become an entity that can and needs to be precisely managed through free yet rational decision-making processes. The neoliberal citizen has consequently become an entrepreneur of the self who is free, independent, rational, productive and responsible for themselves, their health and wellbeing as well as their appearance. The focus on individuals as entrepreneurs who manage their bodies through the rationally thinking mind has, however, become increasingly criticised for viewing the social actor as ‘disembodied’, as a detached, social actor whose powerful mind governs over the passive body. On the other hand, the discourse around embodiment seeks to connect rational decision-making processes to the dominant neoliberal discourse which creates an embodied understanding that the body, just as other areas of people’s lives, can and should be shaped, monitored and managed through cognitive and rational thinking. This perspective offers an understanding of the body regarding its connections with the social environment that reaches beyond the debates around mind-body binary thinking. Hence, following this argument, body management should not be thought of as either solely guided by embodied discourses nor as merely falling into a mind-body dualism, but rather, simultaneously and inseparably as both at once. The descriptive, qualitative analysis of semi-structured in-depth interviews conducted with young Australian amateur athletes between the age of 18 and 24 has shown that most participants are interested in measuring and managing their body to create self-knowledge and self-improvement. The participants thereby connected self-improvement to weight loss, muscle gain or simply staying fit and healthy. Self-knowledge refers to body measurements including weight, BMI or body fat percentage. Self-management and self-knowledge that are reliant on one another to take rational and well-thought-out decisions, are both characteristic values of the neoliberal doctrine. A neoliberal way of thinking and looking after the body has also by many been connected to rewarding themselves for their discipline, hard work or achievement of specific body management goals (e.g. eating chocolate for reaching the daily step count goal). A few participants, however, have shown resistance against these neoliberal values, and in particular, against the precise monitoring and management of the body with the help of self-tracking devices. Ultimately, however, it seems that most participants have internalised the dominant discourses around self-responsibility, and by association, a sense of duty to discipline their body in normative ways. Even those who have indicated their resistance against body work and body management practices that follow neoliberal thinking and measurement systems, are aware and have internalised the concept of the rational operating mind that needs or should decide how to look after the body in terms of health but also appearance ideals. The discussion around the collected data thereby shows that embodiment and the mind/body dualism constitute two connected, rather than two separate or opposing concepts.

Keywords: dualism, embodiment, mind, neoliberalism

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Authors: Mukul Sharma, Madhusmita Das, Sundeep Chaitanya Vedithi

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Leprosy is a chronic human disease caused by Mycobacterium leprae, that cannot be cultured in vitro. Though treatable with multidrug therapy (MDT), recently, bacteria reported resistance to multiple antibiotics. Targeting DNA replication and repair pathways can serve as the foundation of developing new anti-leprosy drugs. Due to the absence of an axenic culture medium for the propagation of M. leprae, studying cellular processes, especially those belonging to DNA repair pathways, is challenging. Genomic understanding of M. Leprae harbors several protein-coding genes with no previously assigned function known as 'hypothetical proteins'. Here, we report identification and expression of known and hypothetical DNA repair genes from a human skin biopsy and mouse footpads that are involved in base excision repair, direct reversal repair, and SOS response. Initially, a bioinformatics approach was employed based on sequence similarity, identification of known protein domains to screen the hypothetical proteins in the genome of M. leprae, that are potentially related to DNA repair mechanisms. Before testing on clinical samples, pure stocks of bacterial reference DNA of M. leprae (NHDP63 strain) was used to construct standard graphs to validate and identify lower detection limit in the qPCR experiments. Primers were designed to amplify the respective transcripts, and PCR products of the predicted size were obtained. Later, excisional skin biopsies of newly diagnosed untreated, treated, and drug resistance leprosy cases from SIHR & LC hospital, Vellore, India were taken for the extraction of RNA. To determine the presence of the predicted transcripts, cDNA was generated from M. leprae mRNA isolated from clinically confirmed leprosy skin biopsy specimen across all the study groups. Melting curve analysis was performed to determine the integrity of the amplification and to rule out primer‑dimer formation. The Ct values obtained from qPCR were fitted to standard curve to determine transcript copy number. Same procedure was applied for M. leprae extracted after processing a footpad of nude mice of drug sensitive and drug resistant strains. 16S rRNA was used as positive control. Of all the 16 genes involved in BER, DR, and SOS, differential expression pattern of the genes was observed in terms of Ct values when compared to human samples; this was because of the different host and its immune response. However, no drastic variation in gene expression levels was observed in human samples except the nth gene. The higher expression of nth gene could be because of the mutations that may be associated with sequence diversity and drug resistance which suggests an important role in the repair mechanism and remains to be explored. In both human and mouse samples, SOS system – lexA and RecA, and BER genes AlkB and Ogt were expressing efficiently to deal with possible DNA damage. Together, the results of the present study suggest that DNA repair genes are constitutively expressed and may provide a reference for molecular diagnosis, therapeutic target selection, determination of treatment and prognostic judgment in M. leprae pathogenesis.

Keywords: DNA repair, human biopsy, hypothetical proteins, mouse footpads, Mycobacterium leprae, qPCR

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Authors: Mballa Abanda Serge, Henda Gnakate Biba, Romaric Guemno Kuate, Akono Rufine Nicole, Petfiang Sidonie, Bella Sidonie

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The main hypotheses proposed around the definition of the syllable and of music, of the common origin of music and language, should lead the reader to reflect on the cross-cutting questions raised by the debate on the notion of universals in linguistics and musicology. These are objects of controversy, and there lies its interest: the debate raises questions that are at the heart of theories on language. It is an inventive, original and innovative research thesis. The main hypotheses proposed around the definition of the syllable and of music, of the common origin of music and language, should lead the reader to reflect on the cross-cutting questions raised by the debate on the notion of universals in linguistics and musicology. These are objects of controversy, and there lies its interest: the debate raises questions that are at the heart of theories on language. It is an inventive, original and innovative research thesis. A contribution to the theoretical, musicological, ethno musicological and linguistic conceptualization of languages, giving rise to the practice of interlocution between the social and cognitive sciences, the activities of artistic creation and the question of modeling in the human sciences: mathematics, computer science, translation automation and artificial intelligence. When you apply this theory to any text of a folksong of a world-tone language, you do not only piece together the exact melody, rhythm, and harmonies of that song as if you knew it in advance but also the exact speaking of this language. The author believes that the issue of the disappearance of tonal languages and their preservation has been structurally resolved, as well as one of the greatest cultural equations related to the composition and creation of tonal, polytonal and random music. The experimentation confirming the theorization, It designed a semi-digital, semi-analog application which translates the tonal languages of Africa (about 2,100 languages) into blues, jazz, world music, polyphonic music, tonal and anatonal music and deterministic and random music). To test this application, I use a music reading and writing software that allows me to collect the data extracted from my mother tongue, which is already modeled in the musical staves saved in the ethnographic (semiotic) dictionary for automatic translation ( volume 2 of the book). Translation is done (from writing to writing, from writing to speech and from writing to music). Mode of operation: you type a text on your computer, a structured song (chorus-verse), and you command the machine a melody of blues, jazz and world music or variety etc. The software runs, giving you the option to choose harmonies, and then you select your melody.

Keywords: music, entanglement, langauge, science

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Authors: Tamar Lin, Nufar Buchshtab, Yifat Elharar, Julian Nicenboim, Rotem Edgar, Iddo Weiner, Lior Zelcbuch, Ariel Cohen, Sharon Kredo-Russo, Inbar Gahali-Sass, Naomi Zak, Sailaja Puttagunta, Merav Bassan

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Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder that is characterized by dry skin and flares of eczematous lesions and intense pruritus. Multiple lines of evidence suggest that AD is associated with increased colonization by Staphylococcus aureus, which contributes to disease pathogenesis through the release of virulence factors that affect both keratinocytes and immune cells, leading to disruption of the skin barrier and immune cell dysfunction. The aim of the current study is to develop a bacteriophage-based product that specifically targets S. aureus. Methods: For the discovery of phage, environmental samples were screened on 118 S. aureus strains isolated from skin samples, followed by multiple enrichment steps. Natural phages were isolated, subjected to Next-generation Sequencing (NGS), and analyzed using proprietary bioinformatics tools for undesirable genes (toxins, antibiotic resistance genes, lysogeny potential), taxonomic classification, and purity. Phage host range was determined by an efficiency of plating (EOP) value above 0.1 and the ability of the cocktail to completely lyse liquid bacterial culture under different growth conditions (e.g., temperature, bacterial stage). Results: Sequencing analysis demonstrated that the 118 S. aureus clinical strains were distributed across the phylogenetic tree of all available Refseq S. aureus (~10,750 strains). Screening environmental samples on the S. aureus isolates resulted in the isolation of 50 lytic phages from different genera, including Silviavirus, Kayvirus, Podoviridae, and a novel unidentified phage. NGS sequencing confirmed the absence of toxic elements in the phages’ genomes. The host range of the individual phages, as measured by the efficiency of plating (EOP), ranged between 41% (48/118) to 79% (93/118). Host range studies in liquid culture revealed that a subset of the phages can infect a broad range of S. aureus strains in different metabolic states, including stationary state. Combining the single-phage EOP results of selected phages resulted in a broad host range cocktail which infected 92% (109/118) of the strains. When tested in vitro in a liquid infection assay, clearance was achieved in 87% (103/118) of the strains, with no evidence of phage resistance throughout the study (24 hours). A S. aureus host was identified that can be used for the production of all the phages in the cocktail at high titers suitable for large-scale manufacturing. This host was validated for the absence of contaminating prophages using advanced NGS methods combined with multiple production cycles. The phages are produced under optimized scale-up conditions and are being used for the development of a topical formulation (BX005) that may be administered to subjects with atopic dermatitis. Conclusions: A cocktail of natural phages targeting S. aureus was effective in reducing bacterial burden across multiple assays. Phage products may offer safe and effective steroid-sparing options for atopic dermatitis.

Keywords: atopic dermatitis, bacteriophage cocktail, host range, Staphylococcus aureus

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