Search results for: clinical care

Authors: Arsyam Mawardi, Sony Suhandono, Azzania Fibriani, Fifi Fitriyah Masduki

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Malaria is an infectious disease caused by Plasmodium sp. This disease has a high prevalence in Indonesia, especially in Jayapura. The vaccine that is currently being developed has not been effective in overcoming malaria. This is due to the high polymorphism in the Plasmodium genome especially in areas that encode Plasmodium surface proteins. Merozoite Surface Protein 1 (MSP1) Plasmodium falciparum is a surface protein that plays a role in the invasion process in human erythrocytes through the interaction of Glycophorin A protein receptors and sialic acid in erythrocytes with Reticulocyte Binding Proteins (RBP) and Duffy Adhesion Protein (DAP) ligands in merozoites. MSP1 can be targeted to be a specific antigen and predicted epitope area which will be used for the development of diagnostic and malaria vaccine therapy. MSP1 consists of 17 blocks, each block is dimorphic, and has been marked as the K1 and MAD20 alleles. Exceptions only in block 2, because it has 3 alleles, among others K1, MAD20 and RO33. These polymorphisms cause allelic variations and implicate the severity of patients infected P. falciparum. In addition, polymorphism of MSP1 in Jayapura isolates has not been reported so it is interesting to be further identified and projected as a specific antigen. Therefore, in this study, we analyzed the allele polymorphism as well as detected the MSP1 epitope antigen candidate on block 2 P. falciparum. Clinical samples of selected malaria patients followed the consecutive sampling method, examining malaria parasites with blood preparations on glass objects observed through a microscope. Plasmodium DNA was isolated from the blood of malarial positive patients. The block 2 MSP1 gene was amplified using PCR method and cloned using the pGEM-T easy vector then transformed to TOP'10 E.coli. Positive colonies selection was performed with blue-white screening. The existence of target DNA was confirmed by PCR colonies and DNA sequencing methods. Furthermore, DNA sequence analysis was done through alignment and formation of a phylogenetic tree using MEGA 6 software and insilico analysis using IEDB software to predict epitope candidate for P. falciparum. A total of 15 patient samples have been isolated from Plasmodium DNA. PCR amplification results show the target gene size about ± 1049 bp. The results of MSP1 nucleotide alignment analysis reveal that block 2 MSP1 genes derived from the sample of malarial patients were distributed in four different allele family groups, K1 (7), MAD20 (1), RO33 (0) and MSP1_Jayapura (10) alleles. The most commonly appears of the detected allele is MSP1_Jayapura single allele. There was no significant association between sex variables, age, the density of parasitemia and alel variation (Mann Whitney, U > 0.05), while symptomatic signs have a significant difference as a trigger of detectable allele variation (U < 0.05). In this research, insilico study shows that there is a new epitope antigen candidate from the MSP1_Jayapura allele and it is predicted to be recognized by B cells with 17 amino acid lengths in the amino acid sequence 187 to 203.

Keywords: epitope candidate, insilico analysis, MSP1 P. falciparum, polymorphism

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Authors: Salima R. Rajwani, Tazeen Ali, Rubina Barolia, Yasmin Parpio, Nasreen Alwani, Salima B. Virani

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Introduction: Nurses and physicians have a critical role in initiating lifesaving interventions during cardiac arrest. It is important that timely delivery of high quality Cardio Pulmonary Resuscitation (CPR) with advanced resuscitation skills and management of cardiac arrhythmias is a key dimension of code during cardiac arrest. It will decrease the chances of patient survival if the healthcare professionals are unable to initiate CPR timely. Moreover, traditional training will not prepare physicians and nurses at a competent level and their knowledge level declines over a period of time. In this regard, simulation training has been proven to be effective in promoting resuscitation skills. Simulation teaching learning strategy improves knowledge level, and skills performance during resuscitation through experiential learning without compromising patient safety in real clinical situations. The purpose of the study is to evaluate the effectiveness of simulation training in Advanced Cardiac Life Support Courses by using the selfefficacy tool. Methods: The study design is a quantitative research design and non-randomized quasi-experimental study design. The study examined the effectiveness of simulation through self-efficacy in two instructional methods; one is Medium Fidelity Simulation (MFS) and second is Traditional Training Method (TTM). The sample size was 220. Data was compiled by using the SPSS tool. The standardized simulation based training increases self-efficacy, knowledge, and skills and improves the management of patients in actual resuscitation. Results: 153 students participated in study; CG: n = 77 and EG: n = 77. The comparison was done between arms in pre and post-test. (F value was 1.69, p value is <0.195 and df was 1). There was no significant difference between arms in the pre and post-test. The interaction between arms was observed and there was no significant difference in interaction between arms in the pre and post-test. (F value was 0.298, p value is <0.586 and df is 1. However, the results showed self-efficacy scores were significantly higher within experimental group in post-test in advanced cardiac life support resuscitation courses as compared to Traditional Training Method (TTM) and had overall (p <0.0001) and F value was 143.316 (mean score was 45.01 and SD was 9.29) verses pre-test result showed (mean score was 31.15 and SD was 12.76) as compared to TTM in post-test (mean score was 29.68 and SD was 14.12) verses pre-test result showed (mean score was 42.33 and SD was 11.39). Conclusion: The standardized simulation-based training was conducted in the safe learning environment in Advanced Cardiac Life Suport Courses and physicians and nurses benefited from self-confidence, early identification of life-threatening scenarios, early initiation of CPR, and provides high-quality CPR, timely administration of medication and defibrillation, appropriate airway management, rhythm analysis and interpretation, and Return of Spontaneous Circulation (ROSC), team dynamics, debriefing, and teaching and learning strategies that will improve the patient survival in actual resuscitation.

Keywords: advanced cardiac life support, cardio pulmonary resuscitation, return of spontaneous circulation, simulation

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Authors: Miriam I. Jimenez-Perez, Mariana C. Orellana-Haro, Carolina Guzman-Brambila

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As part of microbiology and dietetics courses, students of medicine and nutrition analyze the main pathogenic microorganisms and perform dietary analyzes. The course of microbiology describes in a general way the main pathogens including bacteria, viruses, fungi, and parasites, as well as their interaction with the human species. We hypothesize that lack of practical application of the course causes the students not to find the value and the clinical application of it when in reality it is a matter of great importance for healthcare in our country. The courses of the medical microbiology and dietetics are mostly theoretical and only a few hours of laboratory practices. Therefore, it is necessary the incorporation of new innovative techniques that involve more practices and community fieldwork, real cases analysis and real-life situations. The purpose of this intervention was to incorporate real-world learning experiences in the instruction of medical microbiology and dietetics courses, in order to improve the learning process, understanding and the application in the field. During a period of 6 months, medicine and nutrition students worked in a community of urban poverty. We worked with 90 children between 4 and 6 years of age from low-income families with no access to medical services, to give an infectious diagnosis related to nutritional status in these children. We expect that this intervention would give a different kind of context to medical microbiology and dietetics students improving their learning process, applying their knowledge and laboratory practices to help a needed community. First, students learned basic skills in microbiology diagnosis test during laboratory sessions. Once, students acquired abilities to make biochemical probes and handle biological samples, they went to the community and took stool samples from children (with the corresponding informed consent). Students processed the samples in the laboratory, searching for enteropathogenic microorganism with RapID™ ONE system (Thermo Scientific™) and parasites using Willis and Malloy modified technique. Finally, they compared the results with the nutritional status of the children, previously measured by anthropometric indicators. The anthropometric results were interpreted by the OMS Anthro software (WHO, 2011). The microbiological result was interpreted by ERIC® Electronic RapID™ Code Compendium software and validated by a physician. The results were analyses of infectious outcomes and nutritional status. Related to fieldwork community learning experiences, our students improved their knowledge in microbiology and were capable of applying this knowledge in a real-life situation. They found this kind of learning useful when they translate theory to a real-life situation. For most of our students, this is their first contact as health caregivers with real population, and this contact is very important to help them understand the reality of many people in Mexico. In conclusion, real-world or fieldwork learning experiences empower our students to have a real and better understanding of how they can apply their knowledge in microbiology and dietetics and help a much- needed population, this is the kind of reality that many people live in our country.

Keywords: real-world learning experiences, medical microbiology, dietetics, nutritional status, infectious status.

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Authors: Sahar Nasr, Lin Li, Edwin Wang

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Bladder cancer (BLCA) is known as the 13th cause of death among cancer patients worldwide, and ~575,000 new BLCA cases are diagnosed each year. Urothelial carcinoma (UC) is the most prevalent subtype among BLCA patients, which can be categorized into muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). Currently, various therapeutic options are available for UC patients, including (1) transurethral resection followed by intravesical instillation of chemotherapeutics or Bacillus Calmette-Guérin for NMIBC patients, (2) neoadjuvant platinum-based chemotherapy (NAC) plus radical cystectomy is the standard of care for localized MIBC patients, and (3) systematic chemotherapy for metastatic UC. However, conventional treatments may lead to several challenges for treating patients. As an illustration, some patients may suffer from recurrence of the disease after the first line of treatment. Recently, immune checkpoint therapy (ICT) has been introduced as an alternative treatment strategy for the first or second line of treatment in advanced or metastatic BLCA patients. Although ICT showed lucrative results for a fraction of BLCA patients, ~80% of patients were not responsive to it. Therefore, novel treatment methods are required to augment the ICI response rate within BLCA patients. It has been shown that the infiltration of T-cells into the tumor microenvironment (TME) is positively correlated with the response to ICT within cancerous patients. Therefore, the goal of this study is to enhance the infiltration of cytotoxic T-cells into TME through the identification of target genes within the tumor that are responsible for the non-T-cell inflamed TME and their inhibition. BLCA bulk RNA-sequencing data from The Cancer Genome Atlas (TCGA) and immune score for TCGA samples were used to determine the Pearson correlation score between the expression of different genes and immune score for each sample. The genes with strong negative correlations were selected (r < -0.2). Thereafter, the correlation between the expression of each gene and survival in BLCA patients was calculated using the TCGA data and Cox regression method. The genes that are common in both selected gene lists were chosen for further analysis. Afterward, BLCA bulk and single-cell RNA-sequencing data were ranked based on the expression of each selected gene and the top and bottom 25% samples were used for pathway enrichment analysis. If the pathways related to the T-cell infiltration (e.g., antigen presentation, interferon, or chemokine pathways) were enriched within the low-expression group, the gene was included for downstream analysis. Finally, the selected genes will be used to calculate the correlation between their expression and the infiltration rate of the activated CD+8 T-cells, natural killer cells and the activated dendric cells. A list of potential target genes has been identified and ranked based on the above-mentioned analysis and criteria. SUN-1 got the highest score within the gene list and other identified genes in the literature as benchmarks. In conclusion, inhibition of SUN1 may increase the tumor-infiltrating lymphocytes and the efficacy of ICI in BLCA patients. BLCA tumor cells with and without SUN-1 CRISPR/Cas9 knockout will be injected into the syngeneic mouse model to validate the predicted SUN-1 effect on increasing tumor-infiltrating lymphocytes.

Keywords: data analysis, gene expression analysis, gene identification, immunoinformatic, functional genomics, transcriptomics

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Authors: Al. Tsertsvadze. L. Ebralidze, I. Matchutadze. D. Berashvili, A. Bakuridze

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Peatlands are landscape elements, they are formed over a very long period by physical, chemical, biologic, and geologic processes. In the moderate zone of Caucasus, the Kolkheti lowlands are distinguished by the diversity of relictual plants, a high degree of endemism, orographic, climate, landscape, and other characteristics of high levels of biodiversity. The unique properties of the Kolkheti region lead to the formation of special, so-called, endemic peat peloids. The composition and properties of peloids strongly depend on peat-forming plants. Peat is considered a unique complex of raw materials, which can be used in different fields of the industry: agriculture, metallurgy, energy, biotechnology, chemical industry, health care. They are formed in permanent wetland areas. As a result of decay, higher plants remain in the anaerobic area, with the participation of microorganisms. Peat mass absorbs soil and groundwater. Peloids are predominantly rich with humic substances, which are characterized by high biological activity. Humic acids stimulate enzymatic activity, regenerative processes, and have anti-inflammatory activity. Objects of the research were Kolkheti peat peloids (Ispani, Anaklia, Churia, Chirukhi, Peranga) possessing different formation phases. Due to specific physical and chemical properties of research objects, the aim of the research was to develop analytical methods in order to study the chemical composition of the objects. The research was held using modern instrumental methods of analysis: Ultraviolet-visible spectroscopy and Infrared spectroscopy, Scanning Electron Microscopy, Centrifuge, dry oven, Ultraturax, pH meter, fluorescence spectrometer, Gas chromatography-mass spectrometry (GC-MS/MS), Gas chromatography. Based on the research ration between organic and inorganic substances, the spectrum of micro and macro elements, also the content of minerals was determined. The content of organic nitrogen was determined using the Kjeldahl method. The total composition of amino acids was studied by a spectrophotometric method using standard solutions of glutamic and aspartic acids. Fatty acid was determined using GC (Gas chromatography). Based on the obtained results, we can conclude that the method is valid to identify fatty acids in the research objects. The content of organic substances in the research objects was held using GC-MS. Using modern instrumental methods of analysis, the chemical composition of research objects was studied. Each research object is predominantly reached with a broad spectrum of organic (fatty acids, amino acids, carbocyclic and heterocyclic compounds, organic acids and their esters, steroids) and inorganic (micro and macro elements, minerals) substances. Modified methods used in the presented research may be utilized for the evaluation of cosmetological balneological and pharmaceutical means prepared on the base of Kolkheti's Sphagnum Peat Peloids.

Keywords: modern analytical methods, natural resources, peat, chemistry

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Authors: Khachen Kongpakwattana, Nathorn Chaiyakunapruk

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Background: Decision-analytic models for Alzheimer’s disease (AD) have been advanced to discrete-event simulation (DES), in which individual-level modelling of disease progression across continuous severity spectra and incorporation of key parameters such as treatment persistence into the model become feasible. This study aimed to apply the DES to perform a cost-effectiveness analysis of treatment for AD in Thailand. Methods: A dataset of Thai patients with AD, representing unique demographic and clinical characteristics, was bootstrapped to generate a baseline cohort of patients. Each patient was cloned and assigned to donepezil, galantamine, rivastigmine, memantine or no treatment. Throughout the simulation period, the model randomly assigned each patient to discrete events including hospital visits, treatment discontinuation and death. Correlated changes in cognitive and behavioral status over time were developed using patient-level data. Treatment effects were obtained from the most recent network meta-analysis. Treatment persistence, mortality and predictive equations for functional status, costs (Thai baht (THB) in 2017) and quality-adjusted life year (QALY) were derived from country-specific real-world data. The time horizon was 10 years, with a discount rate of 3% per annum. Cost-effectiveness was evaluated based on the willingness-to-pay (WTP) threshold of 160,000 THB/QALY gained (4,994 US$/QALY gained) in Thailand. Results: Under a societal perspective, only was the prescription of donepezil to AD patients with all disease-severity levels found to be cost-effective. Compared to untreated patients, although the patients receiving donepezil incurred a discounted additional costs of 2,161 THB, they experienced a discounted gain in QALY of 0.021, resulting in an incremental cost-effectiveness ratio (ICER) of 138,524 THB/QALY (4,062 US$/QALY). Besides, providing early treatment with donepezil to mild AD patients further reduced the ICER to 61,652 THB/QALY (1,808 US$/QALY). However, the dominance of donepezil appeared to wane when delayed treatment was given to a subgroup of moderate and severe AD patients [ICER: 284,388 THB/QALY (8,340 US$/QALY)]. Introduction of a treatment stopping rule when the Mini-Mental State Exam (MMSE) score goes below 10 to a mild AD cohort did not deteriorate the cost-effectiveness of donepezil at the current treatment persistence level. On the other hand, none of the AD medications was cost-effective when being considered under a healthcare perspective. Conclusions: The DES greatly enhances real-world representativeness of decision-analytic models for AD. Under a societal perspective, treatment with donepezil improves patient’s quality of life and is considered cost-effective when used to treat AD patients with all disease-severity levels in Thailand. The optimal treatment benefits are observed when donepezil is prescribed since the early course of AD. With healthcare budget constraints in Thailand, the implementation of donepezil coverage may be most likely possible when being considered starting with mild AD patients, along with the stopping rule introduced.

Keywords: Alzheimer's disease, cost-effectiveness analysis, discrete event simulation, health technology assessment

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Authors: Oyvind Nordvik, Peder O. L. Heggdal, Jonas Brannstrom, Flemming Vassbotn, Anne Kari Aarstad, Hans Jorgen Aarstad

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Background: Hearing Loss (HL) is a condition that may affect people in all stages of life, but the prevalence increases with age, mostly because of age-related HL, generally referred to as presbyacusis. As human speech is related to relatively high frequencies, even a limited hearing loss at high frequencies may cause impaired speech intelligibility. Being diagnosed with, treated for and living with a chronic condition such as HL, must for many be a disabling and stressful condition that put ones coping resources to test. Stress is a natural part of life and most people will experience stressful events or periods. Chronic diseases, such as HL, are risk factor for distress in individuals, causing anxiety and lowered mood. How an individual cope with HL may be closely connected to the level of distress he or she is experiencing and to personality, which can be defined as those characteristics of a person that account for consistent patterns of feelings, thinking, and behavior. Thus, as to distress in life, such as illness or disease, available coping strategies may be more important than the challenge itself. The same line of arguments applies to level of experienced health-related quality of life (HRQoL). Aim: The aim of this study was to investigate the relationship between distress, HRQoL, reported hearing loss, personality and coping in patients with HL. Method: 158 adult (aged 18-78 years) patients with HL, referred for hearing aid (HA) fitting at Haukeland University Hospital in western Norway, participated in the study. Both first-time users, as well as patients referred for HA renewals were included. First-time users had been pre-examined by an ENT-specialist. The questionnaires were answered before the actual HA fitting procedure. The pure-tone average (PTA; frequencies 0.5, 1, 2, and 4 kHz) was determined for each ear. The Eysenck personality inventory, neuroticism and lie scales, the Theoretically Originated Measure of the Cognitive Activation Theory of Stress (TOMCATS) measuring active coping, hopelessness and helplessness, as well as distress (General Health Questionnaire (GHQ) - 12 items) and the EORTC Quality of Life Questionnaire general part were answered. In addition, we used a revised and shortened version of the Abbreviated Profile of Hearing Aid Benefit (APHAB) as a measure of patient-reported hearing loss. Results: Significant correlations were determined between APHAB (weak), HRQoL scores (strong), distress scores (strong) on the one side and personality and choice of coping scores on the other side. As measured by stepwise regression analyses, the distress and HRQoL scores were scored secondary to the obtained personality and coping scores. The APHAB scores were as determined by regression analyses scored secondary to PTA (best ear), level of neuroticism and lie score. Conclusion: We found that reported employed coping style, distress/HRQoL and personality are closely connected to each other in this patient group. Patient-reported HL was associated to hearing level and personality. There is need for further investigations on these questions, and how these associations may influence the clinical context.

Keywords: coping, distress, hearing loss, personality

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Authors: Sheikh Mohammed Rafiul Huque

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Bangladesh since its inception has been an economy that is fuelled by agriculture and agriculture has significant contribution to the GDP of Bangladesh. The agriculture of Bangladesh predominantly and historically dependent on organic sources of raw material though the place has taken in decades by inorganic sources of raw materials due to the high demand of food for rapidly growing of population. Meanwhile, a new market segment, which is niche market, has been evolving in the urban area in favor of organic products, though 71.1% population living in rural areas is dependent mainly on conventional products. The new market segment is search of healthy and safer source of food and they could believe that organic products are the solution of that. In Bangladesh, food adulteration is very common practices among the shop-keepers to extend the shelf life of raw vegetables and fruits. The niche group of city dwellers is aware about the fact and gradually shifting their buying behavior to organic products. A recent survey on organic farming revealed that 16,200 hectares under organic farming in recent time, which was only 2,500 hectares in 2008. This study is focused on consumer awareness of organic products and tried to explore the factors affecting organic food consumption among high income group of people. The hypothesis is developed to explore the effect of gender (GENDER), ability to purchase (ABILITY) and health awareness (HEALTH) on purchase intention (INTENTION). A snowball sampling was administered among the high income group of people in Dhaka city among 150 respondents. In this sampling process the study could identify only those samples who has consume organic products. A Partial Least Square (PLS) method was used to analyze data using path analysis. It was revealed from the analysis that coefficient determination R2 is 0.829 for INTENTION endogenous latent variable. This means that three latent variables (GENDER, ABILITY, and HEALTH) significantly explain 82.9% of the variance in INTENTION of purchasing organic products. Moreover, GENDER solely explains 6.3% and 8.6% variability of ABILITY and HEALTH respectively. The inner model suggests that HEALTH has strongest negative effect on INTENTION (-0.647) followed by ABILITY (0.344) and GENDER (0.246). The hypothesized path relationship between ABILITY->INTENTION, HEALTH->INTENTION and GENDER->INTENTION are statistically significant. Furthermore, the hypothesized path relationship between GENDER->ABILITY (0.262) and GENDER->HEALTH (-0.292) also statistically significant. The purpose of the study is to demonstrate how an organic product producer can improve his participatory guarantee system (PGS) while marketing the products. The study focuses on understanding gender (GENDER), ability (ABILITY) and health (HEALTH) factors while positioning the products (INTENTION) in the mind of the consumer. In this study, the respondents are found to care about high price and ability to purchase variables with loading -0.920 and 0.898. They are good indicators of ability to purchase (ABILITY). The marketers should consider about price of organic comparing to conventional products while marketing, otherwise, that will create negative intention to buy with a loading of -0.939. Meanwhile, it is also revealed that believability of chemical free component in organic products and health awareness affects health (HEALTH) components with high loading -0.941 and 0.682. The study analyzes that low believability of chemical free component and high price of organic products affects intension to buy. The marketers should not overlook this point while targeting the consumers in Bangladesh.

Keywords: health awareness, organic products, purchase ability, purchase intention

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Authors: Maryam Fallahpoor, Biswajeet Pradhan

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Background: Artificial intelligence (AI) serves as a valuable tool in mitigating the scarcity of human resources required for the evaluation and categorization of vast quantities of medical imaging data. When AI operates with optimal precision, it minimizes the demand for human interpretations and, thereby, reduces the burden on radiologists. Among various AI approaches, deep learning (DL) stands out as it obviates the need for feature extraction, a process that can impede classification, especially with intricate datasets. The advent of DL models has ushered in a new era in medical imaging, particularly in the context of COVID-19 detection. Traditional 2D imaging techniques exhibit limitations when applied to volumetric data, such as Computed Tomography (CT) scans. Medical images predominantly exist in one of two formats: neuroimaging informatics technology initiative (NIfTI) and digital imaging and communications in medicine (DICOM). Purpose: This study aims to employ DL for the classification of COVID-19-infected pulmonary patients and normal cases based on 3D CT scans while investigating the impact of image format. Material and Methods: The dataset used for model training and testing consisted of 1245 patients from IranMehr Hospital. All scans shared a matrix size of 512 × 512, although they exhibited varying slice numbers. Consequently, after loading the DICOM CT scans, image resampling and interpolation were performed to standardize the slice count. All images underwent cropping and resampling, resulting in uniform dimensions of 128 × 128 × 60. Resolution uniformity was achieved through resampling to 1 mm × 1 mm × 1 mm, and image intensities were confined to the range of (−1000, 400) Hounsfield units (HU). For classification purposes, positive pulmonary COVID-19 involvement was designated as 1, while normal images were assigned a value of 0. Subsequently, a U-net-based lung segmentation module was applied to obtain 3D segmented lung regions. The pre-processing stage included normalization, zero-centering, and shuffling. Four distinct 3D CNN models (ResNet152, ResNet50, DensNet169, and DensNet201) were employed in this study. Results: The findings revealed that the segmentation technique yielded superior results for DICOM images, which could be attributed to the potential loss of information during the conversion of original DICOM images to NIFTI format. Notably, ResNet152 and ResNet50 exhibited the highest accuracy at 90.0%, and the same models achieved the best F1 score at 87%. ResNet152 also secured the highest Area under the Curve (AUC) at 0.932. Regarding sensitivity and specificity, DensNet201 achieved the highest values at 93% and 96%, respectively. Conclusion: This study underscores the capacity of deep learning to classify COVID-19 pulmonary involvement using real 3D hospital data. The results underscore the significance of employing DICOM format 3D CT images alongside appropriate pre-processing techniques when training DL models for COVID-19 detection. This approach enhances the accuracy and reliability of diagnostic systems for COVID-19 detection.

Keywords: deep learning, COVID-19 detection, NIFTI format, DICOM format

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Authors: Sandeep Kumar Agrawal, Aditi Bhattacharya, Janvie Manhas, Krushna Bhatt, Yatin Kholakiya, Nupur Khera, Ajoy Roychoudhury, Sudip Sen

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Autologous cultured explants of human oral mucosal epithelial cells (OMEC) are a potential therapeutic modality for limbal stem cell deficiency (LSCD). Injury or inflammation of the ocular surface in the form of burns, chemicals, Stevens Johnson syndrome, ocular cicatricial pemphigoid etc. can lead to destruction and deficiency of limbal stem cells. LSCD manifests in the form of severe ocular surface diseases (OSD) characterized by persistent and recurrent epithelial defects, conjuntivalisation and neovascularisation of the corneal surface, scarring and ultimately opacity and blindness. Most of the cases of OSD are associated with severe dry eye pertaining to diminished mucin and aqueous secretion. Mycophenolate mofetil (MMF) has been shown to upregulate the mucin expression in conjunctival goblet cells in vitro. The aim of this study was to evaluate the effects of MMF on mucin expression in primary cultures of oral mucosal epithelial cells. With institutional ethics committee approval and written informed consent, thirty oral mucosal epithelial tissue samples were obtained from patients undergoing oral surgery for non-malignant conditions. OMEC were grown on human amniotic membrane (HAM, obtained from expecting mothers undergoing elective caesarean section) scaffold for 2 weeks in growth media containing DMEM & Ham’s F12 (1:1) with 10% FBS and growth factors. In vitro dosage of MMF was standardised by MTT assay. Analysis of stem cell markers was done using RT-PCR while mucin mRNA expression was quantified using RT-PCR and q-PCR before and after treating cultured OMEC with graded concentrations of MMF for 24 hours. Protein expression was validated using immunocytochemistry. Morphological studies revealed a confluent sheet of proliferating, stratified oral mucosal epithelial cells growing over the surface of HAM scaffold. The presence of progenitor stem cell markers (p63, p75, β1-Integrin and ABCG2) and cell surface associated mucins (MUC1, MUC15 and MUC16) were elucidated by RT-PCR. The mucin mRNA expression was found to be upregulated in MMF treated primary cultures of OMEC, compared to untreated controls as quantified by q-PCR with β-actin as internal reference gene. Increased MUC1 protein expression was validated by immunocytochemistry on representative samples. Our findings conclude that OMEC have the ability to form a multi-layered confluent sheet on the surface of HAM similar to a cornea, which is important for the reconstruction of the damaged ocular surface. Cultured OMEC has stem cell properties as demonstrated by stem cell markers. MMF can be a novel enhancer of mucin production in OMEC. It has the potential to improve dry eye in patients undergoing OMEC transplantation for bilateral OSD. Further clinical trials are required to establish the role of MMF in patients undergoing OMEC transplantation.

Keywords: limbal stem cell deficiency, mycophenolate mofetil, mucin, ocular surface disease

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Authors: Jennifer Kehinde, Claire O'donnell, Annmarie Grealish

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Introduction: Breastfeeding has been shown to provide numerous health benefits for both infants and mothers. The decision to breastfeed is influenced by physiological, psychological, and emotional factors. However, the importance of equipping mothers with the necessary knowledge for successful breastfeeding practice cannot be ruled out. The decline in global breastfeeding rate can be linked to lack of adequate breastfeeding education during prenatal stage.This systematic review examined the effectiveness of prenatal breastfeeding education on breastfeeding uptake postpartum. Method: This review was undertaken and reported in conformity with the Preferred Reporting Items for Systemic Reviews and Meta-Analysis statement (PRISMA) and was registered on the international prospective register for systematic reviews (PROSPERO: CRD42020213853). A PICO analysis (population, intervention, comparison, outcome) was undertaken to inform the choice of keywords in the search strategy to formulate the review question which was aimed at determining the effectiveness of prenatal breastfeeding educational programs at improving breastfeeding uptake following birth. A systematic search of five databases (Cumulative Index to Nursing and Allied Health Literature, Medline, Psych INFO, and Applied Social Sciences Index and Abstracts) were searched between January 2014 until July 2021 to identify eligible studies. Quality assessment and narrative synthesis were subsequently undertaken. Results: Fourteen studies were included. All 14 studies used different types of breastfeeding programs; eight used a combination of curriculum based breastfeeding education program, group prenatal breastfeeding counselling and one-to-one breastfeeding educational programs which were all delivered in person; four studies used web-based learning platforms to deliver breastfeeding education prenatally which were both delivered online and face to face over a period of 3 weeks to 2 months with follow-up periods ranging from 3 weeks to 6 months; one study delivered breastfeeding educational intervention using mother-to-mother breastfeeding support groups in promoting exclusive breastfeeding and one study disseminated breastfeeding education to participants based on the theory of planned behaviour. The most effective interventions were those that included both theory and hands-on demonstrations. Results showed an increase in breastfeeding uptake, breastfeeding knowledge, increase in positive attitude to breastfeeding and an increase in maternal breastfeeding self-efficacy among mothers who participated in breastfeeding educational programs during prenatal care. Conclusion: Prenatal breastfeeding education increases women’s knowledge of breastfeeding. Mothers who are knowledgeable about breastfeeding and hold a positive approach towards breastfeeding have the tendency to initiate breastfeeding and continue for a lengthened period. Findings demonstrates a general correlation between prenatal breastfeeding education and increased breastfeeding uptake postpartum. The high level of positive breastfeeding outcome inherent in all the studies can be attributed to prenatal breastfeeding education. This review provides rigorous contemporary evidence that healthcare professionals and policymakers can apply when developing effective strategies to improve breastfeeding rates and ultimately improve the health outcomes of mothers and infants.

Keywords: breastfeeding, breastfeeding programs, breastfeeding self-efficacy, prenatal breastfeedng education

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Authors: A. Sottomayor, M. Perez Duque, M. C. Henriques

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Introduction: Migration is not a new phenomenon; nomads often traveled, seeking better living conditions, including food and water. The increase of migrations affects all countries, rising health-related challenges. In Portugal, we have had migrant movements in the last decades, pairing with economic behavior. Irregular immigrants are detained in Santo António detention center from Portuguese Immigration and Borders Service (USHA-SEF) in Porto until court decision for a maximum of 60 days. It is the only long stay officially designated detention center for immigrants in Portugal. Immigrant health is important for public health (PH). It affects and is affected by the community. The XXVII Portuguese Government considered immigrant integration, including access to health, health promotion, protection and reduction of inequities a political priority. Many curative, psychological and legal services are provided for detainees, but until 2015, no structured health promotion or prevention actions were being held at USHA-SEF. That year, Porto Occidental PH Local Unit started to provide vaccination and health literacy on this theme for detainees and SEF workers. Our activities include a vaccine lecture, a medical consultation with vaccine prescription and administration, along with documented proof of vaccination. All vaccines are volunteer and free of charge. This action reduces the risk of importation and transmission of diseases, contributing to world eradication and elimination programs. We aimed to characterize the demography of irregular immigrant detained at UHSA-SEF and describe our activity. Methods: All data was provided by Porto Occidental Public Health Unit. All paper registers of vaccination were uploaded to MicrosoftExcel®. We included all registers and collected demographic variables, nationality, vaccination date, category, and administered vaccines. Descriptive analysis was performed using MicrosoftExcel®. Results: From 2015 to 2018, we delivered care to 256 individuals (179 immigrants; 77 workers). Considering immigrants, 72% were male, and 8 (16%) women were pregnant. 85% were between 20-54 years (ᵡ=30,8y; 2-71y), and 11 didn’t report any age. Migrants came from 48 countries, and India had the highest number (9%). MMR and Tetanus vaccines had > 90% vaccination rate and Poliomyelitis, hepatitis B and flu vaccines had around 85% vaccination rates. We had a consistent number of refusals. Conclusion: Our irregular migrant population comes from many different countries, which increases the risk of disease importation. Pregnant women are present as a particular subset of irregular migrants, and vaccination protects them and the baby. Vaccination of migrant is valuable for them and for the countries in which they pass. It contributes to universal health coverage, for eradication programmes and accomplishment of the Sustainable Development Goals. Peer influence may present as a determinant of refusals so we must consistently educate migrants before vaccination. More studies would be valuable, particularly on the migrant trajectory, duration of stay, destiny after court decision and health impact.

Keywords: migrants, public health, universal health coverage, vaccination

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Authors: Akiko Ohta, Masahiro Minami, Yusra Qadir, Jennifer York

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The Home Instruction for Parents of Preschool Youngsters (HIPPY) is a home instruction program for mothers of children 3 to 5 years old. Using role-play as a method of teaching, the participating mothers work with their home visitors and learn how to deliver the HIPPY curriculum to their children. Applying HIPPY, Reviving Hope and Home for High-risk Refugee Mothers Program (RHH) was created to provide more personalized peer support and to respond to ongoing settlement challenges for isolated and vulnerable Government Assisted Refugee (GAR) mothers. GARs often have greater needs and vulnerabilities than other refugee groups. While the support is available, they often face various challenges and barriers in starting their new lives in Canada, such as inadequate housing, low first-language literacy levels, low competency in English or French, and social isolation. The pilot project was operated by Mothers Matter Centre (MMC) from January 2019 to March 2021 in partnership with the Immigrant Services Society of BC (ISSofBC). The formative evaluation was conducted by a research team at Simon Fraser University. In order to provide more suitable support for GAR mothers, RHH intended to offer more flexibility in HIPPY delivery, supported by a home visitor, to meet the need of refugee mothers facing various conditions and challenges; to have a pool of financial resources to be used for the RHH families when necessitated during the program period; to have another designated staff member, called a community navigator, assigned to facilitate the support system for the RHH families in their settlement; to have a portable device available for each RHH mother to navigate settlement support resources; and to provide other variations of the HIPPY curriculum as an option for the RHH mothers, including a curriculum targeting pre-HIPPY age children. Reflections on each program component was collected from RHH mothers and staff members of MMC and ISSofBC, including frontline workers and management staff, through individual interviews and focus group discussions. Each of the RHH program components was analyzed and evaluated by applying Moore’s four domains framework to identify key information and generate new knowledge (data). To capture RHH mothers’ program experience more in depth based on their own reflections, the photovoice method was used. Some photos taken by the mothers will be shared to illustrate their RHH experience as part of their life stories. Over the period of the program, this evaluation observed how RHH mothers became more confident in various domains, such as communicating with others, taking public transportations alone, and teaching their own child(ren). One of the major factors behind the success was their home visitors’ flexibility and creativity to create a more meaningful and tailored approach for each mother, depending on her background and personal situation. The role of the community navigator was tested out and improved during the program period. The community navigators took the key role to assess the needs of the RHH families and connect them with community resources. Both the home visitors and community navigators were immigrant mothers themselves and owing to their dedicated care for the RHH mothers; they were able to gain trust and work closely and efficiently with RHH mothers.

Keywords: refugee mothers, settlement support, program evaluation, Canada

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Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

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Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

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Authors: Lillian M. Seo, Curtis L. Petersen, Ryan J. Halter, David Kotz, John A. Batsis

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Background: Resistance-based exercises effectively enhance muscle strength, which is especially important in older populations as it reduces the risk of disability. Our group developed a Bluetooth-enabled handle for resistance exercise bands that wirelessly transmits relative force data through low-energy Bluetooth to a local smartphone or similar device. The system has the potential to measure home-based exercise interventions, allowing health professionals to monitor compliance. Its feasibility has already been demonstrated in both clinical and field-based settings, but it remained unclear whether the system’s usability persisted upon repeated use. The current study sought to assess the usability of this system and its users’ satisfaction with repeated use by deploying the device among younger adults to gather formative information that can ultimately improve the device’s design for older adults. Methods: A usability study was conducted in which 32 participants used the above system. Participants executed 10 repetitions of four commonly performed exercises: bicep flexion, shoulder abduction, elbow extension, and triceps extension. Each completed three exercise sessions, separated by at least 24 hours to minimize muscle fatigue. At its conclusion, subjects completed an adapted version of the usefulness, satisfaction, and ease (USE) questionnaire – assessing the system across four domains: usability, satisfaction, ease of use, and ease of learning. The 20-item questionnaire examined how strongly a participant agrees with positive statements about the device on a seven-point Likert scale, with one representing ‘strongly disagree’ and seven representing ‘strongly agree.’ Participants’ data were aggregated to calculate mean response values for each question and domain, effectively assessing the device’s performance across different facets of the user experience. Summary force data were visualized using a custom web application. Finally, an optional prompt at the end of the questionnaire allowed for written comments and feedback from participants to elicit qualitative indicators of usability. Results: Of the n=32 participants, 13 (41%) were female; their mean age was 32.4 ± 11.8 years, and no participants had a physical impairment. No usability questions received a mean score < 5 of seven. The four domains’ mean scores were: usefulness 5.66 ± 0.35; satisfaction 6.23 ± 0.06; ease of use 6.25 ± 0.43; and ease of learning 6.50 ± 0.19. Representative quotes of the open-ended feedback include: ‘A non-rigid strap-style handle might be useful for some exercises,’ and, ‘Would need different bands for each exercise as they use different muscle groups with different strength levels.’ General impressions were favorable, supporting the expectation that the device would be a useful tool in exercise interventions. Conclusions: A simple usability assessment of a Bluetooth-enabled resistance exercise band supports a consistent and positive user experience among young adults. This study provides adequate formative data, assuring the next steps can be taken to continue testing and development for the target population of older adults.

Keywords: Bluetooth, exercise, mobile health, mHealth, usability

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Authors: Banafsheh Nikmehr, Mohsen Bahrami, Yueqiang Song, Anuradha Koduru, Ayse K. Vuruskan, Hongkun Lu, Mallory Pitts, Tolga B. Mesen, Tamer M. Yalcinkaya

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The number of people who receive in vitro fertilization (IVF) treatment has increased on a startling trajectory over the past two decades. Despite advances in this field, particularly the introduction of intracytoplasmic sperm injection (ICSI) and the preimplantation genetic screening (PGS), the IVF success remains low. A major factor contributing to IVF failure is embryonic aneuploidy (abnormal chromosome content), which often results in miscarriage and birth defects. Although PGS is often used as the standard diagnostic tool to identify aneuploid embryos, it is an invasive approach that could affect the embryo development, and yet inaccessible to many patients due its high costs. As such, there is a clear need for a non-invasive cost-effective approach to identify euploid embryos for single embryo transfer (SET). The reported differences between morphokinetic behaviors of aneuploid and euploid embryos has shown promise to address this need. However, current literature is inconclusive and further research is urgently needed to translate current findings into clinical diagnostics. In this ongoing study, we found significant differences between morphokinetic behaviors of euploid and aneuploid embryos that provides important insights and reaffirms the promise of such behaviors for developing non-invasive methodologies. Methodology—A total of 242 embryos (euploid: 149, aneuploid: 93) from 74 patients who underwent IVF treatment in Carolinas Fertility Clinics in Winston-Salem, NC, were analyzed. All embryos were incubated in an EmbryoScope incubator. The patients were randomly selected from January 2019 to June 2021 with most patients having both euploid and aneuploid embryos. All embryos reached the blastocyst stage and had known PGS outcomes. The ploidy assessment was done by a third-party testing laboratory on day 5-7 embryo biopsies. The morphokinetic variables of each embryo were measured by the EmbryoViewer software (Uniesense FertiliTech) on time-lapse images using 7 focal depths. We compared the time to: pronuclei fading (tPNf), division to 2,3,…,9 cells (t2, t3,…,t9), start of embryo compaction (tSC), Morula formation (tM), start of blastocyst formation (tSC), blastocyst formation (tB), and blastocyst expansion (tEB), as well as intervals between them (e.g., c23 = t3 – t2). We used a mixed regression method for our statistical analyses to account for the correlation between multiple embryos per patient. Major Findings— The average age of the patients was 35.04 yrs. The average patient age associated with euploid and aneuploid embryos was not different (P = 0.6454). We found a significant difference in c45 = t5-t4 (P = 0.0298). Our results indicated this interval on average lasts significantly longer for aneuploid embryos - c45(aneuploid) = 11.93hr vs c45(euploid) = 7.97hr. In a separate analysis limited to embryos from the same patients (patients = 47, total embryos=200, euploid=112, aneuploid=88), we obtained the same results (P = 0.0316). The statistical power for this analysis exceeded 87%. No other variable was different between the two groups. Conclusion— Our results demonstrate the importance of morphokinetic variables as potential biomarkers that could aid in non-invasively characterizing euploid and aneuploid embryos. We seek to study a larger population of embryos and incorporate the embryo quality in future studies.

Keywords: IVF, embryo, euploidy, aneuploidy, morphokinteic

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Authors: Tsirekidze M., Aprasidze T.

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

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

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Authors: N. Schneider, M. Bruchhage, M. Hartweg, G. Mutungi, J. O Regan, S. Deoni

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Observational neuroimaging studies suggest differences between breast-fed and formula-fed infants in developmental myelination, a key brain process for learning and cognitive development. However, the possible effects of a nutrient formulation on myelin development in healthy term infants in an intervention study have not been investigated. Objective was, therefore, to investigate the efficacy of a nutrient formulation with higher levels of myelin-relevant nutrients as compared to a control formulation with lower levels of the same nutrients on brain myelination and cognitive development in the first 6 months of life. The study is an ongoing randomized, controlled, double-blind, two-center, parallel-group clinical trial with a nonrandomized, non-blinded arm of exclusively breastfed infants. The current findings result from a staged statistical analysis at 6 months; the recruitment and intervention period has been completed for all participants. Follow-up visits at 12, 18 and 24 months are still ongoing. N= 81 enrolled full term, neurotypical infants of both sexes were randomized into either the investigational (N= 42) or the control group (N= 39), and N= 108 children in the breast-fed arm served as a natural reference group. The effect of a blend of docosahexaenoic acid, arachidonic acid, iron, vitamin B12, folic acid as well as sphingomyelin from a uniquely proceed whey protein concentrate enriched in alpha-lactalbumin and phospholipids in an infant nutrition product matrix was investigated. The main outcomes for the staged statistical analyses at 6 months included brain myelination measures derived from MRI. Additional outcomes were brain volume, cognitive development and safety. The full analyses set at 6 months comprised N= 66 infants. Higher levels of myelin-relevant nutrients compared to lower levels resulted in significant differences in myelin structure, volume, and rate of myelination as early as 3 and 6 months of life. The cross-sectional change of means between groups for whole-brain myelin volume was 8.4% for investigational versus control formulation (3.5% versus the breastfeeding reference) group at 3 months and increased to 36.4% for investigational versus control formulation (14.1% versus breastfeeding reference) at 6 months. No statistically significant differences were detected for early cognition scores. Safety findings were largely similar across groups. This is the first pediatric nutritional neuroimaging study demonstrating the efficacy of a myelin nutrient blend on developmental myelination in well-nourished term infants. Myelination is a critical process in learning and development. The effects were demonstrated across the brain, particularly in temporal and parietal regions, known to be functionally involved in sensory, motor and language skills. These first results add to the field of nutritional neuroscience by demonstrating early life nutrition benefits for brain architecture which may be foundational for later cognitive and behavioral outcomes. ClinicalTrials.gov Identifier: NCT03111927 (Infant Nutrition and Brain Development - Full-Text View - ClinicalTrials.gov).

Keywords: brain development, infant nutrition, MRI, myelination

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Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche

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It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.

Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells

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Authors: Simone Raimondi De Souza, Glaucia Maria Moraes De Oliveira, Ronir Raggio Luiz, Glorimar Rosa

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Introduction: Obesity is among the main risk factors for cardiovascular disease (CVD). Genesis is multifactorial, including genetic, hormonal and environmental factors disorders, among which inadequate feeding pattern, for which nutritional counseling strategies have proven effective. The consumption of beta-glucans (soluble fibers that reportedly promote satiety) present in oat bran can be an effective strategy for preventing and treating obesity. Other benefits have been observed with oat bran consumption, such as reduction of hypercholesterolemia and hyperglycemia, two other risk factors for CVD. Objectives: To analyze the effect of oat bran consumption associated with nutritional counseling in reducing body mass index (BMI), blood cholesterol, glucose profile, waist and neck circumference in obese individuals, and to evaluate the change in eating pattern. Methods: clinical trial, randomized, double-blind, placebo-controlled, lasting 90 days with adults of both genders, with BMI ≥30kg/m2. The study was approved by the Ethics in Research involving human beings in a public institute of cardiology, in Rio de Janeiro, Brazil. Individuals were invited to participate and accepted formally by signing the Terms of Consent. Participants were randomized into oat bran group (gOB) or placebo group (gPCB) and received, respectively: morning prepared consisting of 40g oat bran, 30g of skimmed milk powder and 1g sweetener sucralose; refined flour 40g rice, 30g of milk powder and 1g sweetener sucralose. The Ten Steps to Healthy Eating, of Brazilian Ministry of Health were used to support the nutritional counseling. Variables analyzed: gender; age; BMI, waist circumference (WC) neck circumference (NC); systolic blood pressure (SBP); diastolic blood pressure (DBP); food consumption, total cholesterol (TC), LDL-cholesterol (LDL-c), HDL-cholesterol (HDL-c), non-HDL cholesterol (nHDLc), triglycerides (TG), fasting glucose (FG), fasting insulin (FI) and HOMA-IR. Dietary intake was assessed by 24-hour dietary recall. The Diet Quality Index revised for the Brazilian population (IQD-R) assessed quality of feeding pattern. Statistical analyzes were performed using SPSS version 21, considering statistically significant p-value less than 0.05. Results: A total of 38 participants were included, age = 50 ± 7,6years, 63% women. 19 subjects were placed in gOB and 19 in gPCB. After intervention, statistically significant reductions were observed in the following parameters: in gOB: IQD-R, TC, LDL-c, nHDL-c, FI, SBP, DBP, BMI, WC, NC; in gPCB: IQD-R, LDL-c, SBP, DBP, BMI, WC, NC. No statistically significant differences were observed in the results between groups. Conclusion: Our results reinforce nutritional counseling as important strategy for prevention and treatment of obesity and suggest that inclusion of oat bran in daily diet can bring additional benefits controlling risk factors for CVD. More studies are needed to establish all benefits of oat bran to human health as well as the ideal daily dose for consumption.

Keywords: oat bran, cardiovascular disease, nutritional counseling, obesity

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Authors: Hirseland Andreas, Kerschbaumer Lukas

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In the case of Germany, there are about one million long-term unemployed – a figure that did not vary much during the past years. These long-term unemployed did not benefit from the prospering labor market while most short-term unemployed did. Instead, they are continuously dependent on welfare and sometimes precarious short-term employment, experiencing work poverty. Long-term unemployment thus turns into a main obstacle to become employed again, especially if it is accompanied by other impediments such as low-level education (school/vocational), poor health (especially chronical illness), advanced age (older than fifty), immigrant status, motherhood or engagement in care for other relatives. As can be shown by this current research project, in these cases the chance to regain employment decreases to near nil. Almost two-thirds of all welfare recipients have multiple impediments which hinder a successful transition from welfare back to sustainable and sufficient employment. Prospective employers are unlikely to hire long-term unemployed with additional impediments because they evaluate potential employees on their negative signaling (e.g. low-level education) and the implicit assumption of unproductiveness (e.g. poor health, age). Some findings of the panel survey “Labor market and social security” (PASS) carried out by the Institute of Employment Research (the research institute of the German Federal Labor Agency) spread a ray of hope, showing that unlikely does not necessarily mean impossible. The presentation reports on current research on these very scarce “success stories” of unlikely transitions from long-term unemployment to work and how these cases were able to perform this switch against all odds. The study is based on a mixed-method design. Within the panel survey (~15,000 respondents in ~10,000 households), only 66 cases of such unlikely transitions were observed. These cases have been explored by qualitative inquiry – in depth-interviews and qualitative network techniques. There is strong evidence that sustainable transitions are influenced by certain biographical resources like habits of network use, a set of informal skills and particularly a resilient way of dealing with obstacles, combined with contextual factors rather than by job-placement procedures promoted by Job-Centers according to activation rules or by following formal paths of application. On the employer’s side small and medium-sized enterprises are often found to give job opportunities to a wider variety of applicants, often based on a slow but steadily increasing relationship leading to employment. According to these results it is possible to show and discuss some limitations of (German) activation policies targeting the labor market and their impact on welfare dependency and long-term unemployment. Based on these findings, indications for more supportive small-scale measures in the field of labor-market policies are suggested to help long-term unemployed with multiple impediments to overcome their situation (e.g. organizing small-scale-structures and low-threshold services to encounter possible employers on a more informal basis like “meet and greet”).

Keywords: against-all-odds, mixed-methods, Welfare State, long-term unemployment

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Authors: Christine Hough, Eddie Abbott-Halpin, Tariq Mahmood, Jessica Giles

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This paper draws together the findings from two research studies, each undertaken with cohorts of South Asian Muslim respondents located in the North of England between 2017 and 2019. The first study, entitled Faith Family and Crime (FFC), investigated the extent to which a Muslim family’s social and health well-being is affected by a family member’s involvement in the Criminal Justice System (CJS). This study captured a range of data through a detailed questionnaire and structured interviews. The data from the interview transcripts were analysed using open coding and an application of aspects of the grounded theory approach. The findings provide clear evidence that the respondents were neither well-informed nor supported throughout the processes of the CJS, from arrest to post-sentencing. These experiences gave rise to mental and physical stress, potentially unfair sentencing, and a significant breakdown in communication within the respondents’ families. They serve to highlight a particular aspect of complexity in the current needs of those South Asian Muslim families who find themselves involved in the CJS and is closely connected to family structure, culture, and faith. The second study, referred to throughout this paper as #ImamsBritain (that provides the majority of content for this paper), explores how Imams, in their role as community faith leaders, can best address the complex – and changing - needs of South Asian Muslims families, such as those that emerged in the findings from FFC. The changing socio-economic and political climates of the last thirty or so years have brought about significant changes to the lives of Muslim families, and these have created more complex levels of social, cultural, and faith-based needs for families and individuals. As a consequence, Imams now have much greater demands made of them, and so their role has undergone far-reaching changes in response to this. The #ImamsBritain respondents identified a pressing need to develop a wider range of pastoral and counseling skills, which they saw as extending far beyond the traditional role of the Imam as a religious teacher and spiritual guide. The #ImamsBritain project was conducted with a cohort of British Imams in the North of England. Data was collected firstly through a questionnaire that related to the respondents’ training and development needs and then analysed in depth using the Delphi approach. Through Delphi, the data were scrutinized in depth using interpretative content analysis. The findings from this project reflect the respondents’ individual perceptions of the kind of training and development they need to fulfill their role in 21st Century Britain. They also provide a unique framework for constructing a professional guide for Imams in Great Britain. The discussions and critical analyses in this paper draw on the discourses of professionalization and pastoral care and relevant reports and reviews on Imam training in Europe and Canada.

Keywords: criminal justice system, faith and culture, Imams, Muslim community leadership, professionalization, South Asian family structure

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Authors: Marina Gold, Yves Jackson, David Parrat

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The high predominance of Latin American migrants in Geneva from countries where Chagas disease is endemic (Bolivia, Brazil, Argentina, Colombia) is increasing the incidence of chronic Chagas-related problems, especially cardiovascular complications. The precarious migratory status of what are mostly undocumented migrants complicates access to health and affects patients’ and doctors’ health perceptions regarding screening, treatment and monitoring of Chagas-related health concerns. This project results from a 3 year collaboration between the Geneva University Hospital and the NGO Mundo Sano to understand the following questions: 1) how do Latin American migrants perceive their health? 2) What do they understand from Chagas disease? 3) Are patients’ and doctors’ health perceptions similar or do they have competing agendas? This paper aims to present the results of a long-term study that interrogates health perceptions among Latin American migrants in Geneva. The first phase consisted in completing surveys at three community screening events (2016, 2017. 2018), and the results of these surveys reveal the subordination of the importance of health to that of having met economic family obligation. That is, health is important only when it becomes an impediment to economic gain. The contradictory result emerged that people are aware of the importance of health prevention in order to ensure long-term health, but they do not always have agency over their life-style habits (healthy food, regular exercise, emotional stability). The second phase of the research collected open-ended interviews with selected participants, in order to explore in more detail how Latin American migrants deal with Chagas in a different socio-political and economic context to that of endemic countries. These interviews (5 in total) reveal mixed methods of managing health: social networks, access to health care transnationally (in Geneva, Spain and back in their home country), and different valuations of health problems in each situation. The third phase consisted in observations of doctor-patient consultations and further extended interviews with patients to determine doctor/patient health perceptions around Chagas disease. This phase is ongoing, but it has yielded preliminarily observations regarding the expectations that patients’ have of doctors, and the understanding of doctors’ to patients’ complex situations. Positive and complementary health perceptions include patients’ feeling that doctors in Geneva are more understanding, more knowledgeable and less racist than those in their home country, who do not provide detailed information about Chagas or its treatment and discriminate against them for being indigenous or from poor rural areas, enabling a better communication between doctors and patients. Possible conflicting health perceptions include patients addressing their health concerns more holistically and encountering the specialist’s limitations to only treating one health concern, given time limitations and lack of competition with their colleagues (the general practitioner that referred the patient, for example). The implications of this study extend the case of Chagas disease in Geneva and is relevant for all chronic concerns and migratory contexts of precarity.

Keywords: chagas disease, health perceptions, Latin American Migrants, non-endemic countries

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Authors: Demet Devrimsel Dogan, Ecem Deniz Kirkpantur, Muharrem Dogan, Ahmet Aykut, Ebru Unal Akoglu, Ozge Ecmel Onur

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Introduction: Median Arcuate Ligament Syndrome (MALS) is a rare cause of chronic abdominal pain due to external compression of the celiac trunk by a fibrous arch that unites diaphragmatic crura on each side of the aortic hiatus. While 10-24% of the population may suffer from compression of celiac trunk, it rarely causes patients to develop symptoms. The typical clinical triad of symptoms includes postprandial epigastric pain, weight loss and vomiting. The diagnosis can be made using thin section multi-detector computed tomography (CT) scans which delineate the ligament and the compressed vessel. The treatment of MALS is aimed at relieving the compression of the celiac artery to restore adequate blood flow through the vessel and neurolysis to address chronic pain. Case: A 68-year-old male presented to our clinic with acute postprandial epigastric pain. This was patients’ first attack, and the pain was the worst pain of his life. The patient did not have any other symptoms like nausea, vomiting, chest pain or dyspnea. In his medical history, the patient has had an ischemic cerebrovascular stroke 5 years ago which he recovered with no sequel, and he was using 75 mg clopidogrel and 100 mg acetylsalicylic acid. He was not using any other medication and did not have a story of cardiovascular disease. His vital signs were stable (BP:113/72 mmHg, Spo2:97, temperature:36.3°C, HR:90/bpm). In his electrocardiogram, there was ST depression in leads II, III and AVF. In his physical examination, there was only epigastric tenderness, other system examinations were normal. Physical examination through his upper gastrointestinal system showed no bleeding. His laboratory results were as follows: creatinine:1.26 mg/dL, AST:42 U/L, ALT:17 U/L, amylase:78 U/L, lipase:26 U/L, troponin:10.3 pg/ml, WBC:28.9 K/uL, Hgb:12.7 gr/dL, Plt:335 K/uL. His serial high-sensitive troponin levels were also within normal limits, his echocardiography showed no segmental wall motion abnormalities, an acute myocardial infarction was excluded. In his abdominal ultrasound, no pathology was founded. Contrast-enhanced abdominal CT and CT angiography reported ‘thickened diaphragmatic cruras are compressing and stenosing truncus celiacus superior, this is likely compatible with MALS’. The patient was consulted to general surgery, and they admitted the patient for laparoscopic ligament release. Results: MALS is a syndrome that causes postprandial pain, nausea and vomiting as its most common symptoms. Affected patients are normally young, slim women between the ages of 30 and 50 who have undergone extensive examinations to find the source of their symptoms. To diagnose MALS, other underlying pathologies should initially be excluded. The gold standard is aortic angiography. Although diagnosis and treatment of MALS are unclear, symptom resolution has been achieved with multiple surgical modalities, including open, laparoscopic or robotic ligament release as well as celiac ganglionectomy, which often requires celiac artery revascularisation.

Keywords: differential diagnosis, epigastric pain, median arcuate ligament syndrome, celiac trunk

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Authors: Fernando Martinez Soto, Gaetano Di Mino

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The application of rubber into bituminous mixtures requires attention and care during mixing and compaction. Rubber modifies the properties because it reacts in the internal structure of bitumen at high temperatures changing the performance of the mixture (interaction process of solvents with binder-rubber aggregate). The main change is the increasing of the viscosity and elasticity of the binder due to the larger sizes of the rubber particles by dry process but, this positive effect is counteracted by short mixing times, compared to wet technology, and due to the transport processes, curing time and post-compaction of the mixtures. Therefore, negative effects as swelling of rubber particles, rebounding effect of the specimens and thermal changes by different expansion of the structure inside the mixtures, can change the mechanical properties of the rubberized blends. Based on the dry technology, different asphalt-rubber binders using devulcanized or natural rubber (truck and bus tread rubber), have served to demonstrate these effects and how to solve them into two dense-gap graded rubber modified asphalt concrete mixes (RUMAC) to enhance the stability, workability and durability of the compacted samples by Superpave gyratory compactor method. This paper specifies the procedures developed in the Department of Civil Engineering of the University of Palermo during September 2016 to March 2017, for characterizing the post-compaction and mix-stability of the one conventional mixture (hot mix asphalt without rubber) and two gap-graded rubberized asphalt mixes according granulometry for rail sub-ballast layers with nominal size of Ø22.4mm of aggregates according European standard. Thus, the main purpose of this laboratory research is the application of ambient ground rubber from scrap tires processed at conventional temperature (20ºC) inside hot bituminous mixtures (160-220ºC) as a substitute for 1.5%, 2% and 3% by weight of the total aggregates (3.2%, 4.2% and, 6.2% respectively by volumetric part of the limestone aggregates of bulk density equal to 2.81g/cm³) considered, not as a part of the asphalt binder. The reference bituminous mixture was designed with 4% of binder and ± 3% of air voids, manufactured for a conventional bitumen B50/70 at 160ºC-145ºC mix-compaction temperatures to guarantee the workability of the mixes. The proportions of rubber proposed are #60-40% for mixtures with 1.5 to 2% of rubber and, #20-80% for mixture with 3% of rubber (as example, a 60% of Ø0.4-2mm and 40% of Ø2-4mm). The temperature of the asphalt cement is between 160-180 ºC for mixing and 145-160 ºC for compaction, according to the optimal values for viscosity using Brookfield viscometer and 'ring and ball' - penetration tests. These crumb rubber particles act as a rubber-aggregate into the mixture, varying sizes between 0.4mm to 2mm in a first fraction, and 2-4mm as second proportion. Ambient ground rubber with a specific gravity of 1.154g/cm³ is used. The rubber is free of loose fabric, wire, and other contaminants. It was found optimal results in real beams and cylindrical specimens with each HMA mixture reducing the swelling effect. Different factors as temperature, particle sizes of rubber, number of cycles and pressures of compaction that affect the interaction process are explained.

Keywords: crumb-rubber, gyratory compactor, rebounding effect, superpave mix-design, swelling, sub-ballast railway

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Authors: Khlood F. Salman, Richard Zoucha, Hani Nawafleh

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Introduction: Jordan ranks the fourth highest breast cancer prevalence after Lebanon, Bahrain, and Kuwait. Considerable evidence showed that cultural, ethnic, and economic differences influence a woman’s practice to early detection and prevention of breast cancer. Objectives: To understand women’s health beliefs and values in relation to early detection of breast cancer; and to explore the impact of these beliefs on their decisions regarding reluctance or acceptance of early detection measures such as mammogram screening. Design: A qualitative focused ethnography was used to collect data for this study. Settings: The study was conducted in the second largest city surrounded by a large rural area in Ma’an- Jordan. Participants: A total of twenty seven women, with no history of breast cancer, between the ages of 18 and older, who had prior health experience with health providers, and were willing to share elements of personal health beliefs related to breast health within the larger cultural context. The participants were recruited using the snowball method and words of mouth. Data collection and analysis: A short questionnaire was designed to collect data related to socio demographic status (SDQ) from all participants. A Semi-structured interviews guide was used to elicit data through interviews with the informants. Nvivo10 a data manager was utilized to assist with data analysis. Leininger’s four phases of qualitative data analysis was used as a guide for the data analysis. The phases used to analyze the data included: 1) Collecting and documenting raw data, 2) Identifying of descriptors and categories according to the domains of inquiry and research questions. Emic and etic data is coded for similarities and differences, 3) Identifying patterns and contextual analysis, discover saturation of ideas and recurrent patterns, and 4) Identifying themes and theoretical formulations and recommendations. Findings: Three major themes were emerged within the cultural and religious context; 1. Fear, denial, embarrassment and lack of knowledge were common perceptions of Ma’anis’ women regarding breast health and screening mammography, 2. Health care professionals in Jordan were not quick to offer information and education about breast cancer and screening, and 3. Willingness to learn about breast health and cancer prevention. Conclusion: The study indicated the disparities between the infrastructure and resourcing in rural and urban areas of Jordan, knowledge deficit related to breast cancer, and lack of education about breast health may impact women’s decision to go for a mammogram screening. Cultural beliefs, fear, embarrassments as well as providers lack of focus on breast health were significant contributors against practicing breast health. Health providers and policy makers should provide resources for the establishment health education programs regarding breast cancer early detection and mammography screening. Nurses should play a major role in delivering health education about breast health in general and breast cancer in particular. A culturally appropriate health awareness messages can be used in creating educational programs which can be employed at the national levels.

Keywords: breast health, beliefs, cultural context, ethnography, mammogram screening

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Authors: Fathonah Siti, Ardiana Irma

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Indonesia is currently on its track to achieve Universal Health Coverage (UHC) by 2019. The program aims to address issues on disintegration in the implementation and coverage of various health insurance schemes and fragmented fund pooling. Family planning service is covered as one of benefit packages under preventive care. However, little has been done to examine how family planning program are appropriately managed across levels of governments and how family planning services are delivered to the end user. The study is performed through focus group discussion to related policy makers and selected programmers at central and district levels. The study is also benefited from relevant studies on family planning in the UHC scheme and other supporting data. The study carefully investigates some programmatic implications when family planning is integrated in the UHC program encompassing the need to recalculate contraceptive logistics for beneficiaries (eligible couple); policy reformulation for contraceptive service provision including supply chain management; establishment of family planning standard of procedure; and a call to update Management Information System. The study confirms that there is a significant increase in the numbers of contraceptive commodities needs to be procured by the government. Holding an assumption that contraceptive prevalence rate and commodities cost will be as expected increasing at 0.5% annually, the government need to allocate almost IDR 5 billion by 2019, excluded fee for service. The government shifts its focus to maintain eligible health facilities under National Population and Family Planning Board networks. By 2019, the government has set strategies to anticipate the provision of family planning services to 45.340 health facilities distributed in 514 districts and 7 thousand sub districts. Clear division of authorities has been established among levels of governments. Three models of contraceptive supply planning have been developed and currently in the process of being institutionalized. Pre service training for family planning services has been piloted in 10 prominent universities. The position of private midwives has been appreciated as part of the system. To ensure the implementation of quality and health expenditure control, family planning standard has been established as a reference to determine set of services required to deliver to the clients properly and types of health facilities to conduct particular family planning services. Recognition to individual status of program participation has been acknowledged in the Family Enumeration since 2015. The data is precisely recorded by name by address for each family and its members. It supplies valuable information to 15.131 Family Planning Field Workers (FPFWs) to provide information and education related to family planning in an attempt to generate demand and maintain the participation of family planning acceptors who are program beneficiaries. Despite overwhelming efforts described above, some obstacles remain. The program experiences poor socialization and yet removes geographical barriers for those living in remote areas. Family planning services provided for this sub population conducted outside the scheme as a complement strategy. However, UHC program has brought remarkable improvement in access and quality of family planning services.

Keywords: beneficiary, family planning services, national population and family planning board, universal health coverage

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Authors: Pierobon Enrico, Missiaggia Marta, Castelluzzo Michele, Tommasino Francesco, Ricci Leonardo, Scifoni Emanuele, Vincezo Monaco, Boscardin Maurizio, La Tessa Chiara

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Clinical outcomes collected over the past three decades have suggested that ion therapy has the potential to be a treatment modality superior to conventional radiation for several types of cancer, including recurrences, as well as for other diseases. Although the results have been encouraging, numerous treatment uncertainties remain a major obstacle to the full exploitation of particle radiotherapy. To overcome therapy uncertainties optimizing treatment outcome, the best possible radiation quality description is of paramount importance linking radiation physical dose to biological effects. Microdosimetry was developed as a tool to improve the description of radiation quality. By recording the energy deposition at the micrometric scale (the typical size of a cell nucleus), this approach takes into account the non-deterministic nature of atomic and nuclear processes and creates a direct link between the dose deposited by radiation and the biological effect induced. Microdosimeters measure the spectrum of lineal energy y, defined as the energy deposition in the detector divided by most probable track length travelled by radiation. The latter is provided by the so-called “Mean Chord Length” (MCL) approximation, and it is related to the detector geometry. To improve the characterization of the radiation field quality, we define a new quantity replacing the MCL with the actual particle track length inside the microdosimeter. In order to measure this new quantity, we propose a two-stage detector consisting of a commercial Tissue Equivalent Proportional Counter (TEPC) and 4 layers of Low Gain Avalanche Detectors (LGADs) strips. The TEPC detector records the energy deposition in a region equivalent to 2 um of tissue, while the LGADs are very suitable for particle tracking because of the thickness thinnable down to tens of micrometers and fast response to ionizing radiation. The concept of HDM has been investigated and validated with Monte Carlo simulations. Currently, a dedicated readout is under development. This two stages detector will require two different systems to join complementary information for each event: energy deposition in the TEPC and respective track length recorded by LGADs tracker. This challenge is being addressed by implementing SoC (System on Chip) technology, relying on Field Programmable Gated Arrays (FPGAs) based on the Zynq architecture. TEPC readout consists of three different signal amplification legs and is carried out thanks to 3 ADCs mounted on a FPGA board. LGADs activated strip signal is processed thanks to dedicated chips, and finally, the activated strip is stored relying again on FPGA-based solutions. In this work, we will provide a detailed description of HDM geometry and the SoC solutions that we are implementing for the readout.

Keywords: particle tracking, ion therapy, low gain avalanche diode, tissue equivalent proportional counter, microdosimetry

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Authors: Joy Chadwick

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There is no doubt that classrooms of today are more complex and diverse than ever before. Preparing teacher candidates to meet these challenges is essential to ensure the retention of teachers within the profession and to ensure that graduates begin their teaching careers with the knowledge and understanding of how to effectively meet the diversity of students they will encounter. Creating inclusive classrooms requires teachers to have a repertoire of effective instructional skills and strategies. Teachers must also have the mindset to embrace diversity and value the uniqueness of individual students in their care. This qualitative study analyzed teacher candidates' experiences as they completed a fourteen-week teaching practicum while simultaneously completing a university course focused on inclusive pedagogy. The research investigated the challenges and successes teacher candidates had in navigating the translation of theory related to inclusive pedagogy into their teaching practice. Applying threshold concept theory as a framework, the research explored the troublesome concepts, liminal spaces, and transformative experiences as connected to inclusive practices. Threshold concept theory suggests that within all disciplinary fields, there exists particular threshold concepts that serve as gateways or portals into previously inaccessible ways of thinking and practicing. It is in these liminal spaces that conceptual shifts in thinking and understanding and deep learning can occur. The threshold concept framework provided a lens to examine teacher candidate struggles and successes with the inclusive education course content and the application of this content to their practicum experiences. A qualitative research approach was used, which included analyzing twenty-nine course reflective journals and six follow up one-to-one semi structured interviews. The journals and interview transcripts were coded and themed using NVivo software. Threshold concept theory was then applied to the data to uncover the liminal or stuck spaces of learning and the ways in which the teacher candidates navigated those challenging places of teaching. The research also sought to uncover potential transformative shifts in teacher candidate understanding as connected to teaching in an inclusive classroom. The findings suggested that teacher candidates experienced difficulties when they did not feel they had the knowledge, skill, or time to meet the needs of the students in the way they envisioned they should. To navigate the frustration of this thwarted vision, they relied on present and previous course content and experiences, collaborative work with other teacher candidates and their mentor teachers, and a proactive approach to planning for students. Transformational shifts were most evident in their ability to reframe their perceptions of children from a deficit or disability lens to a strength-based belief in the potential of students. It was evident that through their course work and practicum experiences, their beliefs regarding struggling students shifted as they saw the value of embracing neurodiversity, the importance of relationships, and planning for and teaching through a strength-based approach. Research findings have implications for teacher education programs and for understanding threshold concepts theory as connected to practice-based learning experiences.

Keywords: inclusion, inclusive education, liminal space, teacher education, threshold concepts, troublesome knowledge

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Authors: Pampita Chakraborty, Sukumar Mukherjee

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This study was done to determine the bacteriological profile and antibiotic resistance of the isolates and to find out the potential risk factors for infection with multidrug-resistant organisms. Diabetic foot ulcer is a major medical, social, economic problem and a leading cause of morbidity and mortality, especially in the developing countries like India. 25 percent of all diabetic patients develop a foot ulcer at some point in their lives which is highly susceptible to infections and that spreads rapidly, leading to overwhelming tissue destruction and subsequent amputation. Infection with multidrug resistant organisms (MDRO) may increase the cost of management and may cause additional morbidity and mortality. Proper management of these infections requires appropriate antibiotic selection based on culture and antimicrobial susceptibility testing. Early diagnosis of microbial infections is aimed to institute the appropriate antibacterial therapy initiative to avoid further complications. A total of 200 Type 2 Diabetic Mellitus patients with infection were admitted at GD Hospital and Diabetes Institute, Kolkata. 60 of them who developed ulcer during the year 2013 were included in this study. A detailed clinical history and physical examination were carried out for every subject. Specimens for microbiological studies were obtained from ulcer region. Gram-negative bacilli were tested for extended spectrum Beta-lactamase (ESBL) production by double disc diffusion method. Staphylococcal isolates were tested for susceptibility to oxacillin by screen agar method and disc diffusion. Potential risk factors for MDRO-positive samples were explored. Gram-negative aerobes were most frequently isolated, followed by gram-positive aerobes. Males were predominant in the study and majority of the patients were in the age group of 41-60 years. The presence of neuropathy was observed in 80% cases followed by peripheral vascular disease (73%). Proteus spp. (22) was the most common pathogen isolated, followed by E.coli (17). Staphylococcus aureus was predominant amongst the gram-positive isolates. S.aureus showed a high rate of resistance to antibiotic tested (63.6%). Other gram-positive isolates were found to be highly resistant to erythromycin, tetracycline and ciprofloxacin, 40% each. All isolates were found to be sensitive to Vancomycin and Linezolid. ESBL production was noted in Proteus spp and E.coli. Approximately 70 % of the patients were positive for MDRO. MDRO-infected patients had poor glycemic control (HbA1c 11± 2). Infection with MDROs is common in diabetic foot ulcers and is associated with risk factors like inadequate glycemic control, the presence of neuropathy, osteomyelitis, ulcer size and increased the requirement for surgical treatment. There is a need for continuous surveillance of resistant bacteria to provide the basis for empirical therapy and reduce the risk of complications.

Keywords: diabetic foot ulcer, bacterial infection, multidrug-resistant organism, extended spectrum beta-lactamase

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