Search results for: family planning methods

Authors: Yana Snegireva

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Carbonate reservoirs are known for their heterogeneity, resulting from various geological processes such as diagenesis and fracturing. These complexities may cause great challenges in understanding fluid flow behavior and predicting the production performance of naturally fractured reservoirs. The investigation of carbonate reservoirs is crucial, as many petroleum reservoirs are naturally fractured, which can be difficult due to the complexity of their fracture networks. This can lead to geological uncertainties, which are important for global petroleum reserves. The problem outlines the key challenges in carbonate reservoir modeling, including the accurate representation of fractures and their connectivity, as well as capturing the impact of fractures on fluid flow and production. Traditional reservoir modeling techniques often oversimplify fracture networks, leading to inaccurate predictions. Therefore, there is a need for a modern approach that can capture the complexities of carbonate reservoirs and provide reliable predictions for effective reservoir management and production optimization. The modern approach to carbonate reservoir modeling involves the utilization of the hybrid fracture modeling approach, including the discrete fracture network (DFN) method and implicit fracture network, which offer enhanced accuracy and reliability in characterizing complex fracture systems within these reservoirs. This study focuses on the application of the hybrid method in the Nepsko-Botuobinskaya anticline of the Eastern Siberia field, aiming to prove the appropriateness of this method in these geological conditions. The DFN method is adopted to model the fracture network within the carbonate reservoir. This method considers fractures as discrete entities, capturing their geometry, orientation, and connectivity. But the method has significant disadvantages since the number of fractures in the field can be very high. Due to limitations in the amount of main memory, it is very difficult to represent these fractures explicitly. By integrating data from image logs (formation micro imager), core data, and fracture density logs, a discrete fracture network (DFN) model can be constructed to represent fracture characteristics for hydraulically relevant fractures. The results obtained from the DFN modeling approaches provide valuable insights into the East Siberia field's carbonate reservoir behavior. The DFN model accurately captures the fracture system, allowing for a better understanding of fluid flow pathways, connectivity, and potential production zones. The analysis of simulation results enables the identification of zones of increased fracturing and optimization opportunities for reservoir development with the potential application of enhanced oil recovery techniques, which were considered in further simulations on the dual porosity and dual permeability models. This approach considers fractures as separate, interconnected flow paths within the reservoir matrix, allowing for the characterization of dual-porosity media. The case study of the East Siberia field demonstrates the effectiveness of the hybrid model method in accurately representing fracture systems and predicting reservoir behavior. The findings from this study contribute to improved reservoir management and production optimization in carbonate reservoirs with the use of enhanced and improved oil recovery methods.

Keywords: carbonate reservoir, discrete fracture network, fracture modeling, dual porosity, enhanced oil recovery, implicit fracture model, hybrid fracture model

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Authors: Anzal Abbas Jaffari, Wajiha Javed, Naseem Salahuddin

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Rationale: Rabies, a vaccine preventable disease, continues to be a critical public health issue as it kills around 2000-5000 people annually in Pakistan. Along with the disease spread among animals, the dog population remains a victim of brutal culling practices by the local authorities, which adversely affects ecosystem (sinking of poison in the soil – affecting vegetation & contaminating water) and the disease spread. The dog population has been exponentially rising primarily because a lack of a consolidated nationwide Animal Birth Control program and awareness among the local communities in general and children in particular. This is reflected in Pakistan’s low SARE score - 1.5, which makes the country trails behind other developing countries like Bangladesh (2.5) and Philippines (3.5).According to an estimate, the province of Sindh alone is home to almost 2.5 million dogs. The clustering of dogs in Peri-Urban areas and inner cities localities leads to an increase of reported dog bite cases in these areas specifically. Objective: Rabies Free Pakistan (RFP), which is a joint venture of Getz Pharma Private Limited and Indus Hospital & Health Network (IHHN); it was established in 2018 to eliminate Rabies from Pakistan by 2030 using the One Health Approach. Methodology: The RFP team is actively working on advocacy and policy front with both the Federal & Provincial government to ensure that all stakeholders currently involved in dog culling in Pakistan have a paradigm shift towards humane methods of vaccination and ABC. Along with the federal government, RFP aims to declare Rabies as a notifiable disease. Whereas RFP closely works with the provincial government of Sindh to initiate a province wide Rabies Control Program.RFP program follows international standards and WHO approved protocols for this program in Pakistan.RFP team has achieved various milestones in the fight against Rabies after successfully scaling up project operations and has vaccinated more than 30,000 dogs and neutered around 7,000 dogs since 2018. Recommendations: Effective implementation of Rabies program (MDV and ABC) requires a concentrated effort to address a variety of structural and policy challenges. This essentially demands a massive shift in the attitude of individuals towards rabies. The two most significant challenges in implementing a standard policy at the structural level are lack of institutional capacity, shortage of vaccine, and absence of inter-departmental coordination among major stakeholders: federal government, provincial ministry of health, livestock, and local bodies (including local councils). The lack of capacity in health care workers to treat dog bite cases emerges as a critical challenge at the clinical level. Conclusion: Pakistan can learn from the successful international models of Sri Lanka and Mexico as they adopted the One Health Approach to eliminate rabies like RFP. The WHO advised One Health approach provides the policymakers with an interactive and cross-sectoral guide, which involves all the essential elements of the eco system (including animals, humans, and other components).

Keywords: animal birth control, dog population, mass dog vaccination, one health, rabies elimination

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Authors: Awatef Ahmed Ben Ramadan, Aqsa Arshad

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Background: There is a huge Muslim migration movement to North America and Europe for several reasons, primarily refuge from war areas and partly to search for better work and educational chances. There are always concerns regarding first-Generation Immigrant women's health and computer literacy, an adequate understanding of the health systems, and the use of the existing healthcare technology and services effectively and efficiently. Language proficiency level, preference for cultural and traditional remedies, socioeconomic factors, fear of stereotyping, limited accessibility to health services, and general unfamiliarity with the existing health services and resources are familiar variables among these women. Aims: The current study aims to assess the health and digital literacy of first-generation Muslim women in Atlanta city. Also, the study aims to examine how the COVID-19 pandemic has encouraged the use of health information technology and increased technology awareness among the targeted women. Methods: The study design is cross-sectional correlational research. The study will be conducted to produce preliminary results that the investigators want to have to supplement an NIH grant application about leveraging information technology to reduce the health inequalities amongst the first-generation immigrant Muslim women in Atlanta City. The investigators will collect the study data in two phases using different tools. Phase one was conducted in June 2022; the investigators used tools to measure health and digital literacy amongst 42 first-generation immigrant Muslim women. Phase two was conducted in November 2022; the investigators measured the Knowledge, Attitude, and Practice (KAP) of using health information technology such as telehealth from a sample of 45 first-generation Muslim immigrant women in Atlanta; in addition, the investigators measured how the current pandemic has affected their KAP to use telemedicine and telehealth services. Both phases' study participants were recruited using convenience sampling methodology. The investigators collected around 40 of 18 years old or older first-generation Muslim immigrant women for both study phases. The study excluded Immigrants who hold work visas and second-generation immigrants. Results: At the point of submitting this abstract, the investigators are still analyzing the study data to produce preliminary results to apply for an NIH grant entitled "Leveraging Health Information Technology (Health IT) to Address and Reduce Health Care Disparities (R01 Clinical Trial Optional)". This research will be the first step of a comprehensive research project to assess and measure health and digital literacy amongst a vulnerable community group. The targeted group might have different points of view from the U.S.-born inhabitants on how to: promote their health, gain healthy lifestyles and habits, screen for diseases, adhere to health treatment and follow-up plans, perceive the importance of using available and affordable technology to communicate with their providers and improve their health, and help in making serious decisions for their health. The investigators aim to develop an educational and instructional health mobile application considering the language and cultural factors that affect immigrants' ability to access different health and social support sources, know their health rights and obligations in their communities, and improve their health behavior and behavior lifestyles.

Keywords: first-generation immigrant Muslim women, telehealth, COVID-19 pandemic, health information technology, health and digital literacy

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Authors: Maddalena Arigoni, Maria Luisa Ratto, Raffaele A. Calogero, Luca Alessandri

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The presence of tumor heterogeneity, where distinct cancer cells exhibit diverse morphological and phenotypic profiles, including gene expression, metabolism, and proliferation, poses challenges for molecular prognostic markers and patient classification for targeted therapies. Understanding the causes and progression of cancer requires research efforts aimed at characterizing heterogeneity, which can be facilitated by evolving single-cell sequencing technologies. However, analyzing single-cell data necessitates computational methods that often lack objective validation. Therefore, the establishment of benchmarking datasets is necessary to provide a controlled environment for validating bioinformatics tools in the field of single-cell oncology. Benchmarking bioinformatics tools for single-cell experiments can be costly due to the high expense involved. Therefore, datasets used for benchmarking are typically sourced from publicly available experiments, which often lack a comprehensive cell annotation. This limitation can affect the accuracy and effectiveness of such experiments as benchmarking tools. To address this issue, we introduce omics benchmark experiments designed to evaluate bioinformatics tools to depict the heterogeneity in single-cell tumor experiments. We conducted single-cell RNA sequencing on six lung cancer tumor cell lines that display resistant clones upon treatment of EGFR mutated tumors and are characterized by driver genes, namely ROS1, ALK, HER2, MET, KRAS, and BRAF. These driver genes are associated with downstream networks controlled by EGFR mutations, such as JAK-STAT, PI3K-AKT-mTOR, and MEK-ERK. The experiment also featured an EGFR-mutated cell line. Using 10XGenomics platform with cellplex technology, we analyzed the seven cell lines together with a pseudo-immunological microenvironment consisting of PBMC cells labeled with the Biolegend TotalSeq™-B Human Universal Cocktail (CITEseq). This technology allowed for independent labeling of each cell line and single-cell analysis of the pooled seven cell lines and the pseudo-microenvironment. The data generated from the aforementioned experiments are available as part of an online tool, which allows users to define cell heterogeneity and generates count tables as an output. The tool provides the cell line derivation for each cell and cell annotations for the pseudo-microenvironment based on CITEseq data by an experienced immunologist. Additionally, we created a range of pseudo-tumor tissues using different ratios of the aforementioned cells embedded in matrigel. These tissues were analyzed using 10XGenomics (FFPE samples) and Curio Bioscience (fresh frozen samples) platforms for spatial transcriptomics, further expanding the scope of our benchmark experiments. The benchmark experiments we conducted provide a unique opportunity to evaluate the performance of bioinformatics tools for detecting and characterizing tumor heterogeneity at the single-cell level. Overall, our experiments provide a controlled and standardized environment for assessing the accuracy and robustness of bioinformatics tools for studying tumor heterogeneity at the single-cell level, which can ultimately lead to more precise and effective cancer diagnosis and treatment.

Keywords: single cell omics, benchmark, spatial transcriptomics, CITEseq

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

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

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

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Authors: Zakia Fatima, Liu Lu, Donghao Li

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The analysis of biological fluid metabolites holds significant importance in various areas, such as medical research, food science, and public health. Investigating the levels and distribution of nutrients and their metabolites in biological samples allows researchers and healthcare professionals to determine nutritional status, find hypovitaminosis or hypervitaminosis, and monitor the effectiveness of interventions such as dietary supplementation. Moreover, analysis of nutrient metabolites provides insight into their metabolism, bioavailability, and physiological processes, aiding in the clarification of their health roles. Hence, the exploration of a distinct, efficient, eco-friendly, and simpler methodology is of great importance to evaluate the metabolic content of complex biological samples. In this work, a green and rapid analytical method based on an automated online two-dimensional microscale carbon fiber/activated carbon fiber fractionation system and time-of-flight mass spectrometry (2DμCFs-TOF-MS) was used to evaluate metabolites of urine samples after oral administration of food supplements. The automated 2DμCFs instrument consisted of a microcolumn system with bare carbon fibers and modified carbon fiber coatings. Carbon fibers and modified carbon fibers exhibit different surface characteristics and retain different compounds accordingly. Three kinds of mobile-phase solvents were used to elute the compounds of varied chemical heterogeneities. The 2DμCFs separation system has the ability to effectively separate different compounds based on their polarity and solubility characteristics. No complicated sample preparation method was used prior to analysis, which makes the strategy more eco-friendly, practical, and faster than traditional analysis methods. For optimum analysis results, mobile phase composition, flow rate, and sample diluent were optimized. Water-soluble vitamins, fat-soluble vitamins, and amino acids, as well as 22 vitamin metabolites and 11 vitamin metabolic pathway-related metabolites, were found in urine samples. All water-soluble vitamins except vitamin B12 and vitamin B9 were detected in urine samples. However, no fat-soluble vitamin was detected, and only one metabolite of Vitamin A was found. The comparison with a blank urine sample showed a considerable difference in metabolite content. For example, vitamin metabolites and three related metabolites were not detected in blank urine. The complete single-run screening was carried out in 5.5 minutes with the minimum consumption of toxic organic solvent (0.5 ml). The analytical method was evaluated in terms of greenness, with an analytical greenness (AGREE) score of 0.72. The method’s practicality has been investigated using the Blue Applicability Grade Index (BAGI) tool, obtaining a score of 77. The findings in this work illustrated that the 2DµCFs-TOF-MS approach could emerge as a fast, sustainable, practical, high-throughput, and promising analytical tool for screening and accurate detection of various metabolites, pharmaceuticals, and ingredients in dietary supplements as well as biological fluids.

Keywords: metabolite analysis, sustainability, carbon fibers, urine.

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Authors: A. Newman-Tancredi, R. Depoortère, P. Gruca, E. Litwa, M. Lason, M. Papp

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The N-methyl-D-aspartic acid (NMDA) receptor antagonist, ketamine, can elicit rapid-acting antidepressant (RAAD) effects in treatment-resistant patients, but it requires parenteral co-administration with a classical antidepressant under medical supervision. In addition, ketamine can also produce serious side effects that limit its long-term use, and there is much interest in identifying RAADs based on ketamine’s mechanism of action but with safer profiles. Ketamine elicits GABAergic interneuron inhibition, glutamatergic neuron stimulation, and, notably, activation of serotonin 5-HT1A receptors in the prefrontal cortex (PFC). Direct activation of the latter receptor subpopulation with selective ‘biased agonists’ may therefore be a promising strategy to identify novel RAADs and, consistent with this hypothesis, the prototypical cortical biased agonist, NLX-101, exhibited robust RAAD-like activity in the chronic mild stress model of depression (CMS). The present study compared the effects of a novel, selective 5-HT1A receptor-biased agonist, NLX-204, with those of ketamine and NLX-101. Materials and methods: CMS procedure was conducted on Wistar rats; drugs were administered either intraperitoneally (i.p.) or by bilateral intracortical microinjection. Ketamine: 10 mg/kg i.p. or 10 µg/side in PFC; NLX-204 and NLX-101: 0.08 and 0.16 mg/kg i.p. or 16 µg/side in PFC. In addition, interaction studies were carried out with systemic NLX-204 or NLX-101 (each at 0.16 mg/kg i.p.) in combination with intracortical WAY-100635 (selective 5-HT1A receptor antagonist; 2 µg/side) or muscimol (GABA-A receptor agonist, 12.5 ng/side). Anhedonia was assessed by CMS-induced decrease in sucrose solution consumption; anxiety-like behavior was assessed using the Elevated Plus Maze (EPM), and cognitive impairment was assessed by the Novel Object Recognition (NOR) test. Results: A single administration of NLX-204 was sufficient to reverse the CMS-induced deficit in sucrose consumption, similarly to ketamine and NLX-101. NLX-204 also reduced CMS-induced anxiety in the EPM and abolished CMS-induced NOR deficits. These effects were maintained (EPM and NOR) or enhanced (sucrose consumption) over a subsequent 2-week period of treatment. The anti-anhedonic response of the drugs was also maintained for several weeks Following treatment discontinuation, suggesting that they had sustained effects on neuronal networks. A single PFC administration of NLX-204 reversed deficient sucrose consumption, similarly to ketamine and NLX-101. Moreover, the anti-anhedonic activities of systemic NLX-204 and NLX 101 were abolished by coadministration with intracortical WAY-100635 or muscimol. Conclusions: (i) The antidepressant-like activity of NLX-204 in the rat CMS model was as rapid as that of ketamine or NLX-101, supporting targeting cortical 5-HT1A receptors with selective, biased agonists to achieve RAAD effects. (ii)The anti-anhedonic activity of systemic NLX-204 was mimicked by local administration of the compound in the PFC, confirming the involvement of cortical circuits in its RAAD-like effects. (iii) Notably, the effects of systemic NLX-204 and NLX-101 were abolished by PFC administration of muscimol, indicating that they act by (indirectly) eliciting a reduction in cortical GABAergic neurotransmission. This is consistent with ketamine’s mechanism of action and suggests that there are converging NMDA and 5-HT1A receptor signaling cascades in PFC underlying the RAAD-like activities of ketamine and NLX-204. Acknowledgements: The study was financially supported by NCN grant no. 2019/35/B/NZ7/00787.

Keywords: depression, ketamine, serotonin, 5-HT1A receptor, chronic mild stress

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Authors: Silvia D. Vaca, Benjamin J. Kuo, Joao Ricardo N. Vissoci, Catherine A. Staton, Linda W. Xu, Michael Muhumuza, Hussein Ssenyonjo, John Mukasa, Joel Kiryabwire, Henry E. Rice, Gerald A. Grant, Michael M. Haglund

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Background: While delays to care exist in resource rich settings, greater delays are seen along the care continuum in low- and middle-income countries (LMICs) largely due to limited healthcare capacity to address the disproportional rates of traumatic brain injury (TBI) in Sub Saharan Africa (SSA). While many LMICs have government subsidized systems to offset surgical costs, the burden of securing funds by the patients for medications, supplies, and CT diagnostics poses a significant challenge to timely surgical interventions. In Kampala Uganda, the challenge of obtaining timely CT scans is twofold. First, due to a lack of a functional CT scanner at the tertiary hospital, patients need to arrange their own transportation to the nearby private facility for CT scans. Second, self-financing for the private CT scans ranges from $80 - $130, which is near the average monthly income in Kampala. These bottlenecks contribute significantly to the care continuum delays and are associated with poor TBI outcomes. Objective: The objectives of this study are to 1) describe the temporal delays through a modified three delays model that fits the context of neurosurgical interventions for TBI patients in Kampala and 2) investigate the association between delays and mortality. Methods: Prospective data were collected for 563 TBI patients presenting to a tertiary hospital in Kampala from 1 June – 30 November 2016. Four time intervals were constructed along five time points: injury, hospital arrival, neurosurgical evaluation, CT results, and definitive surgery. Time interval differences among mild, moderate and severe TBI and their association with mortality were analyzed. Results: The mortality rate of all TBI patients presenting to MNRH was 9.6%, which ranged from 4.7% for mild and moderate TBI patients receiving surgery to 81.8% for severe TBI patients who failed to receive surgery. The duration from injury to surgery varied considerably across TBI severity with the largest gap seen between mild TBI (174 hours) and severe TBI (69 hours) patients. Further analysis revealed care continuum differences for interval 3 (neurosurgical evaluation to CT result) and 4 (CT result to surgery) between severe TBI patients (7 hours for interval 3 and 24 hours for interval 4) and mild TBI patients (19 hours for interval 3, and 96 hours for interval 4). These post-arrival delays were associated with mortality for mild (p=0.05) and moderate TBI (p=0.03) patients. Conclusions: To our knowledge, this is the first analysis using a modified ‘three delays’ framework to analyze the care continuum of TBI patients in Uganda from injury to surgery. We found significant associations between delays and mortality for mild and moderate TBI patients. As it currently stands, poorer outcomes were observed for these mild and moderate TBI patients who were managed non-operatively or failed to receive surgery while surgical services were shunted to more severely ill patients. While well intentioned, high mortality rates were still observed for the severe TBI patients managed surgically. These results suggest the need for future research to optimize triage practices, understand delay contributors, and improve pre-hospital logistical referral systems.

Keywords: care continuum, global neurosurgery, Kampala Uganda, LMIC, Mulago, prospective registry, traumatic brain injury

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Authors: Briohny H. Spencer, Russ Chess-Williams, Catherine McDermott, Shailendra Anoopkumar-Dukie, David Christie

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Background: Prostate cancer is the second most common cancer diagnosed in men worldwide and the most prevalent in Australian men. In 2015, it was estimated that approximately 18,000 new cases of prostate cancer were diagnosed in Australia. Currently, for localised disease, androgen depravation therapy (ADT) and radiotherapy are a major part of the curative management of prostate cancer. ADT acts to reduce the levels of circulating androgens, primarily testosterone and the locally produced androgen, dihydrotestosterone (DHT), or by preventing the subsequent activation of the androgen receptor. Thus, the growth of the cancerous cells can be reduced or ceased. Radiation techniques such as brachytherapy (radiation delivered directly to the prostate by transperineal implant) or external beam radiation therapy (exposure to a sufficient dose of radiation aimed at eradicating malignant cells) are also common techniques used in the treatment of this condition. Radiotherapy (RT) has significant limitations, including reduced effectiveness in treating malignant cells present in hypoxic microenvironments leading to radio-resistance and poor clinical outcomes and also the significant side effects for the patients. Alpha1-adrenoceptor antagonists are used for many prostate cancer patients to control lower urinary tract symptoms, due to the progression of the disease itself or may arise as an adverse effect of the radiotherapy treatment. In Australia, a significant number (not a majority) of patients receive a α1-ADR antagonist and four drugs are available including prazosin, terazosin, alfuzosin and tamsulosin. There is currently limited published data on the effects of α1-ADR antagonists during radiotherapy, but it suggests these medications may improve patient outcomes by enhancing the effect of radiotherapy. Aim: To determine the impact of α1-ADR antagonists treatments on time to biochemical relapse following radiotherapy. Methods: A retrospective study of male patients receiving radiotherapy for biopsy-proven localised prostate cancer was undertaken to compare cancer outcomes for drug-naïve patients and those receiving α1-ADR antagonist treatments. Ethical approval for the collection of data at Genesis CancerCare QLD was obtained and biochemical relapse (defined by a PSA rise of >2ng/mL above the nadir) was recorded in months. Rates of biochemical relapse, prostate specific antigen doubling time (PSADT) and Kaplan-Meier survival curves were also compared. Treatment groups were those receiving α1-ADR antagonists treatment before or concurrent with their radiotherapy. Data was statistically analysed using One-way ANOVA and results expressed as mean ± standard deviation. Major findings: The mean time to biochemical relapse for tamsulosin, prazosin, alfuzosin and controls were 45.3±17.4 (n=36), 41.5±19.6 (n=11), 29.3±6.02 (n=6) and 36.5±17.6 (n=16) months respectively. Tamsulosin, prazosin but not alfuzosin delayed time to biochemical relapse although the differences were not statistically significant. Conclusion: Preliminary data for the prior and/or concurrent use of tamsulosin and prazosin showed a positive trend in delaying time to biochemical relapse although no statistical significance was shown. Larger clinical studies are indicated and with thousands of patient records yet to be analysed, it may determine if there is a significant effect of these drugs on control of prostate cancer.

Keywords: alpha1-adrenoceptor antagonists, biochemical relapse, prostate cancer, radiotherapy

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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Authors: Palak V. Patel, Jessica Pixley, Steven R. Feldman

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Introduction: Basal cell carcinoma (BCC) is the most common skin cancer worldwide and requires substantial resources to treat. When choosing between indicated therapies, providers consider their associated adverse effects, efficacy, cosmesis, and function preservation. The patient’s tumor burden, infiltrative risk, and risk of tumor recurrence are also considered. Treatment cost is often left out of these discussions. This can lead to financial toxicity, which describes the harm and quality of life reductions inflicted by high care costs. Methods: We studied the guidelines set forth by the American Academy of Dermatology for the treatment of BCC. A PubMed literature search was conducted to identify the costs of each recommended therapy. We discuss costs alongside treatment efficacy and side-effect profile. Results: Surgical treatment for BCC can be cost-effective if the appropriate treatment is selected for the presenting tumor. Curettage and electrodesiccation can be used in low-grade, low-recurrence tumors in aesthetically unimportant areas. The benefits of cost-conscious care are not likely to be outweighed by the risks of poor cosmesis or tumor return ($471 BCC of the cheek). When tumor burden is limited, MMS offers better cure rates and lower recurrence rates than surgical excision, and with comparable costs (MMS $1263; SE $949). Surgical excision with permanent sections may be indicated when tumor burden is more extensive or if molecular testing is necessary. The utility of surgical excision with frozen sections, which costs substantially more than MMS without comparable outcomes, is less clear (SE with frozen sections $2334-$3085). Less data exists on non-surgical treatments for BCC. These techniques cost less, but recurrence-risk is high. Side-effects of nonsurgical treatment are limited to local skin reactions, and cosmesis is good. Cryotherapy, 5-FU, and MAL-PDT are all more affordable than surgery, but high recurrence rates increase risk of secondary financial and psychosocial burden (recurrence rates 21-39%; cost $100-270). Radiation therapy offers better clearance rates than other nonsurgical treatments but is associated with similar recurrence rates and a significantly larger financial burden ($2591-$3460 BCC of the cheek). Treatments for advanced or metastatic BCC are extremely costly, but few patients require their use, and the societal cost burden remains low. Vismodegib and sonidegib have good response rates but substantial side effects, and therapy should be combined with multidisciplinary care and palliative measures. Expert-review has found sonidegib to be the less expensive and more efficacious option (vismodegib $128,358; sonidegib $122,579). Platinum therapy, while not FDA-approved, is also effective but expensive (~91,435). Immunotherapy offers a new line of treatment in patients intolerant of hedgehog inhibitors ($683,061). Conclusion: Dermatologists working within resource-compressed practices and with resource-limited patients must prudently manage the healthcare dollar. Surgical therapies for BCC offer the lowest risk of recurrence at the most reasonable cost. Non-surgical therapies are more affordable, but high recurrence rates increase the risk of secondary financial and psychosocial burdens. Treatments for advanced BCC are incredibly costly, but the low incidence means the overall cost to the system is low.

Keywords: nonmelanoma skin cancer, basal cell skin cancer, squamous cell skin cancer, cost of care

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Authors: Irina Mizeva, Elena Potapova, Viktor Dremin, Mikhail Mezentsev, Valeri Shupletsov

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The local tissue perfusion is regulated by the microvascular tone which is under the control of a number of physiological mechanisms. Laser Doppler flowmetry (LDF) together with wavelet analyses is the most commonly used technique to study the regulatory mechanisms of cutaneous microcirculation. External factors such as temperature, local pressure of the probe on the skin, etc. influence on the blood flow characteristics and are used as physiological tests to evaluate microvascular regulatory mechanisms. Local probe pressure influences on the microcirculation parameters measured by optical methods: diffuse reflectance spectroscopy, fluorescence spectroscopy, and LDF. Therefore, further study of probe pressure effects can be useful to improve the reliability of optical measurement. During pressure tests variation of the mean perfusion measured by means of LDF usually is estimated. An additional information concerning the physiological mechanisms of the vascular tone regulation system in response to local pressure can be obtained using spectral analyses of LDF samples. The aim of the present work was to develop protocol and algorithm of data processing appropriate for study physiological response to the local pressure test. Involving 6 subjects (20±2 years) and providing 5 measurements for every subject we estimated intersubject and-inter group variability of response of both averaged and oscillating parts of the LDF sample on external surface pressure. The final purpose of the work was to find special features which further can be used in wider clinic studies. The cutaneous perfusion measurements were carried out by LAKK-02 (SPE LAZMA Ltd., Russia), the skin loading was provided by the originally designed device which allows one to distribute the pressure around the LDF probe. The probe was installed on the dorsal part of the distal finger of the index figure. We collected measurements continuously for one hour and varied loading from 0 to 180mmHg stepwise with a step duration of 10 minutes. Further, we post-processed the samples using the wavelet transform and traced the energy of oscillations in five frequency bands over time. Weak loading leads to pressure-induced vasodilation, so one should take into account that the perfusion measured under pressure conditions will be overestimated. On the other hand, we revealed a decrease in endothelial associated fluctuations. Further loading (88 mmHg) induces amplification of pulsations in all frequency bands. We assume that such loading leads to a higher number of closed capillaries, higher input of arterioles in the LDF signal and as a consequence more vivid oscillations which mainly are formed in arterioles. External pressure higher than 144 mmHg leads to the decrease of oscillating components, after removing the loading very rapid restore of the tissue perfusion takes place. In this work, we have demonstrated that local skin loading influence on the microcirculation parameters measured by optic technique; this should be taken into account while developing portable electronic devices. The proposed protocol of local loading allows one to evaluate PIV as far as to trace dynamic of blood flow oscillations. This study was supported by the Russian Science Foundation under project N 18-15-00201.

Keywords: blood microcirculation, laser Doppler flowmetry, pressure-induced vasodilation, wavelet analyses blood

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Authors: Aileen O'loughlin

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‘Is Everybody Going WeLL?’ (IEGW?) is a 33-hour classroom-based initiative created to a) explore values and how they impact on well-being, b) encourage adolescents to connect with their community, and c) provide them with the education to encourage and maintain a lifetime love of physical activity (PA) to ensure beneficial effects on their personal well-being. This initiative is also aimed at achieving sustainable education and aligning with the United Nation’s Sustainable Development Goals numbers 3 and 4. The classroom is a unique setting in which adolescents’ PA participation can be positively influenced through fun PA policies and initiatives. The primary purpose of this research is to evaluate a range of psychosocial and PA outcomes following the 33-hour education programme. This research examined the impact of a PA and well-being programme consisting of either a 60minute or 80minute class, depending on the timetable structure of the school, delivered once a week. Participant outcomes were measured using validated questionnaires regarding Self-esteem, Mental Health Literacy (MHL) and Daily Physical Activity Participation. These questionnaires were administered at three separate time points; baseline, mid-intervention, and post intervention. Semi-structured interviews with participating teachers regarding adherence and participants’ attitudes were completed post-intervention. These teachers were randomly selected for interview. This perspective analytical cohort study included 235 post-primary school students between 11-13 years of age (100 boys and 135 girls) from five public Irish post-primary schools. Three schools received the intervention only; a 33hour interactive well-being learning unit, one school formed a control group and one school had participants in both the intervention and control group. Participating schools were a convenience sample. Data presented outlines baseline data collected pre-participation (0 hours completed). N = 18 junior certificate students returned all three questionnaires fully completed for a 56.3% return rate from 1 school, Intervention School #3. 94.4% (n = 17) of participants enjoy taking part in some form of PA, however only 5.5% (n = 1) of the participants took part in PA every day of the previous 7 days and only 5.5% (n = 1) of those surveyed participated in PA every day during a normal week. 55% (n = 11) had a low level of self-esteem, 50% (n = 9) fall within the normal range of self-esteem, and n = 0 surveyed demonstrated a high level of self-esteem. Female participants’ Mean score was higher than their male counterparts when MHL was compared. Correlation analyses revealed a small association between Self-esteem and Happiness (r = 0.549). Positive correlations were also revealed between MHL and Happiness, MHL and Self-esteem and Self-esteem and 60+ minutes of PA completed daily. IEGW? is a classroom-based with simple methods easy to implement, replicate and financially viable to both public and private schools. It’s unique dataset will allow for the evaluation of a societal approach to the psycho-social well-being and PA participation levels of adolescents. This research is a work in progress and future work is required to learn how to best support the implementation of ‘Is Everybody Going WeLL?’ as part of the school curriculum.

Keywords: education, life-long learning, physical activity, psychosocial well-being

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Authors: Tramuta Clara, Masotti Chiara, Pitti Monica, Adriano Daniela, Battistini Roberta, Serraca Laura, Decastelli Lucia

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Oysters are considered filter organisms, and their raw consumption may increase health risks for consumers: it is often associated with outbreaks of gastroenteritis or enteric illnesses. Most of these foodborne diseases are caused by Vibrio strains, enteric pathogens also involved in the diffusion of genetic determinants of antibiotic resistance and their entrance along the food chain. The European Food Safety Authority (EFSA), during the European Union report on antimicrobial resistance in 2017, focused the attention about the role of food as a possible carrier of antibiotic-resistant bacteria or antibiotic-resistance genes that determine health risks for humans. This study wants to determine antibiotic resistance and antibiotic-resistance genes in Vibrio spp. isolated from Crassostrea gigas oysters collected in the Golfo della Spezia (Liguria, Italy). A total of 47 Vibrio spp. strains were isolated (ISO21872-2:2017) during the summer of 2021 from oysters of Crassostrea gigas. The strains were identified by MALDI-TOF (Bruker, Germany) mass spectrometry and tested for antibiotic susceptibility using a broth microdiluition method (ISO20776-1:2019) using Sensititre EUVSEC plates (Thermo-Fisher Scientific) to obtain the Minimum Inhibitory Concentration (MIC). The strains were tested with PCR-based biomolecular methods, according to previous works, to define the presence of 23 resistance genes of the main classes of antibiotics used in human and veterinary medicine: tet (B), tet (C), tet (D), tet (A), tet (E), tet (G ), tet (K), tet (L), tet (M), tet (O), tet (S) (tetracycline resistance); blaCTX-M, blaTEM, blaOXA, blaSHV (β-lactam resistance); mcr-1 and mcr-2 (colistin resistance); qnrA, qnrB, and qnrS (quinolone resistance); sul1, sul2 and sul3 (sulfonamide resistance). Six different species have been identified: V. alginolyticus 34% (n=16), V. harveyi 28% (n=13), V. fortis 15% (n=7), V. pelagius 8% (n=4), V. parahaemolyticus 11% (n=5) e V. chagasii 4% (n=2). The PCR assays showed the presence of the blaTEM gene on 40% of the strains (n=19). All the other genes were not detected, except for a V. alginolyticus positive for anrS gene. The broth microdiluition method results showed an high level of resistance for ciprofloxacin (62%; n=29), ampicillin (47%; n=22), and colistin (49%; n=23). Furthermore, 32% (n=15) of strains can be considered multiresistant bacteria for the simultaneous presence of resistance for three different antibiotic classes. Susceptibility towards meropenem, azithromycin, gentamicin, ceftazidime, cefotaxime, chloramphenicol, tetracycline and sulphamethoxazole reached 100%. The Vibrio species identified in this study are widespread in marine environments and can cause gastrointerstinal infections after the ingestion of raw fish products and bivalve molluscs. The level of resistance to antibiotics such as ampicillin, ciprofloxacin and colistin can be connected to anthropic factors (industrial, agricultural and domestic wastes) that promote the spread of resistance to these antibiotics. It can be also observed a strong correlation between phenotypic (resistant MIC) and genotypic (positive blaTEM gene) resistance for ampicillin on the same strains, probably due to the transfer of genetic material between bacterial strains. Consumption of raw bivalve molluscs can represent a risk for consumers heath due to the potentially presence of foodborne pathogens, highly resistant to different antibiotics and source of transferable antibiotic-resistant genes.

Keywords: vibrio species, blaTEM genes, antimicrobial resistance, PCR

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Authors: May Bazzi, Shafik Tokmaj, Younes Saberi, Mats Geijer, Tony Jurkiewicz, Patrik Sund, Anna Bjällmark

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Mobile radiography, employing portable X-ray equipment, has become a routine procedure within hospital settings, with chest X-rays in intensive care units standing out as the most prevalent mobile X-ray examinations. This approach is not limited to hospitals alone, as it extends its benefits to imaging patients in various settings, particularly those too frail to be transported, such as elderly care residents in nursing homes. Moreover, the utility of mobile X-ray isn't confined solely to traditional healthcare recipients; it has proven to be a valuable resource for vulnerable populations, including the homeless, drug users, asylum seekers, and patients with multiple co-morbidities. Mobile X-rays reduce patient stress, minimize costly hospitalizations, and offer cost-effective imaging. While studies confirm its reliability, further research is needed, especially regarding image quality. Recent advancements in lightweight equipment with enhanced battery and detector technology provide the potential for nearly handheld radiography. The main aim of this study was to evaluate a new lightweight mobile X-ray system with two different detectors and compare the image quality with a modern stationary system. Methods: A total of 74 images of the chest (chest anterior-posterior (AP) views and chest lateral views) and pelvic/hip region (AP pelvis views, hip AP views, and hip cross-table lateral views) were acquired on a whole-body phantom (Kyotokagaku, Japan), utilizing varying image parameters. These images were obtained using a stationary system - 18 images (Mediel, Sweden), a mobile X-ray system with a second-generation detector - 28 images (FDR D-EVO II; Fujifilm, Japan) and a mobile X-ray system with a third-generation detector - 28 images (FDR D-EVO III; Fujifilm, Japan). Image quality was assessed by visual grading analysis (VGA), which is a method to measure image quality by assessing the visibility and accurate reproduction of anatomical structures within the images. A total of 33 image criteria were used in the analysis. A panel of two experienced radiologists, two experienced radiographers, and two final-term radiographer students evaluated the image quality on a 5-grade ordinal scale using the software Viewdex 3.0 (Viewer for Digital Evaluation of X-ray images, Sweden). Data were analyzed using visual grading characteristics analysis. The dose was measured by the dose-area product (DAP) reported by the respective systems. Results: The mobile X-ray equipment (both detectors) showed significantly better image quality than the stationary equipment for the pelvis, hip AP and hip cross-table lateral images with AUCVGA-values ranging from 0.64-0.92, while chest images showed mixed results. The number of images rated as having sufficient quality for diagnostic use was significantly higher for mobile X-ray generation 2 and 3 compared with the stationary X-ray system. The DAP values were higher for the stationary compared to the mobile system. Conclusions: The new lightweight radiographic equipment had an image quality at least as good as a fixed system at a lower radiation dose. Future studies should focus on clinical images and consider radiographers' viewpoints for a comprehensive assessment.

Keywords: mobile x-ray, visual grading analysis, radiographer, radiation dose

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

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

Keywords: aging heart, mitochondria, proteomics, redox state

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Authors: Keyvan Molanorouzi, Selina Khoo, Tony Morris

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In recent years, there has been a decline in physical activity among adults. Motivation has been shown to be a crucial factor in maintaining physical activity. The purpose of this study was to whether PA motives measured by the Physical Activity and Leisure Motivation Scale PALMS predicted actual amount of PA at a later time to provide evidence for the construct validity of the PALMS. A quantitative, cross-sectional descriptive research design was employed. The Demographic Form, PALMS, and International Physical Activity Questionnaire Short form (IPAQ-S) questionnaires were used to assess motives and amount for physical activity in adults on two occasions. A sample of 640 (489 male, 151 female) undergraduate students aged 18 to 25 years (mean ±SD; 22.30±8.13 years) took part in the study. Male participants were divided into three types of activities, namely exercise, racquet sport, and team sports and female participants only took part in one type of activity, namely team sports. After 14 weeks, all 640 undergraduate students who had filled in the initial questionnaire (Occasion 1) received the questionnaire via email (Occasion 2). Of the 640 students, 493 (77%; 378 males, 115 females) emailed back the completed questionnaire. The results showed that not only were pertinent sub-scales of PALMS positively related to amount of physical activity, but separate regression analyses showed the positive predictive effect of PALMS motives for amount of physical activity for each type of physical activity among participants. This study supported the construct validity of the PALMS by showing that the motives measured by PALMS did predict amount of PA. This information can be obtained to match people with specific sport or activity which in turn could potentially promote longer adherence to the specific activity.Methods: A quantitative, cross-sectional descriptive research design was employed. The Demographic Form, PALMS, and International Physical Activity Questionnaire Short form (IPAQ-S) questionnaires were used to assess motives and amount for physical activity in adults on two occasions. A sample of 640 (489 male, 151 female) undergraduate students aged 18 to 25 years (mean ±SD; 22.30±8.13 years) took part in the study. Male participants were divided into three types of activities, namely exercise, racquet sport, and team sports and female participants only took part in one type of activity, namely team sports. After 14 weeks, all 640 undergraduate students who had filled in the initial questionnaire (Occasion 1) received the questionnaire via email (Occasion 2). Of the 640 students, 493 (77%; 378 males, 115 females) emailed back the completed questionnaire. Results: The results showed that not only were pertinent sub-scales of PALMS positively related to amount of physical activity, but separate regression analyses showed the positive predictive effect of PALMS motives for amount of physical activity for each type of physical activity among participants. This study supported the construct validity of the PALMS by showing that the motives measured by PALMS did predict amount of PA. Conclusion: This information can be obtained to match people with specific sport or activity which in turn could potentially promote longer adherence to the specific activity.

Keywords: physical activity, motivation, level of physical activity, type of physical activity

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Authors: Ahmedou Moulaye Idriss, Yahya Tfeil

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Medical imaging technology has become an indispensable tool in many branches of the biomedical, health area, and research and is vitally important for the training of professionals in these fields. It is not only about the tools, technologies, and knowledge provided but also about the community that this training project proposes. In order to be able to raise the level of anatomy teaching in the medical school of Nouakchott in Mauritania, it is necessary and even urgent to facilitate access to modern technology for African countries. The role of technology as a key driver of justifiable development has long been recognized. Anatomy is an essential discipline for the training of medical students; it is a key element for the training of medical specialists. The quality and results of the work of a young surgeon depend on his better knowledge of anatomical structures. The teaching of anatomy is difficult as the discipline is being neglected by medical students in many academic institutions. However, anatomy remains a vital part of any medical education program. When anatomy is presented in various planes medical students approve of difficulties in understanding. They do not increase their ability to visualize and mentally manipulate 3D structures. They are sometimes not able to correctly identify neighbouring or associated structures. This is the case when they have to make the identification of structures related to the caudate lobe when the liver is moved to different positions. In recent decades, some modern educational tools using digital sources tend to replace old methods. One of the main reasons for this change is the lack of cadavers in laboratories with poorly qualified staff. The emergence of increasingly sophisticated mathematical models, image processing, and visualization tools in biomedical imaging research have enabled sophisticated three-dimensional (3D) representations of anatomical structures. In this paper, we report our current experience in the Faculty of Medicine in Nouakchott Mauritania. One of our main aims is to create a local learning community in the fields of anatomy. The main technological platform used in this project is called 3D Slicer. 3D Slicer platform is an open-source application available for free for viewing, analysis, and interaction with biomedical imaging data. Using the 3D Slicer platform, we created from real medical images anatomical atlases of parts of the human body, including head, thorax, abdomen, liver, and pelvis, upper and lower limbs. Data were collected from several local hospitals and also from the website. We used MRI and CT-Scan imaging data from children and adults. Many different anatomy atlases exist, both in print and digital forms. Anatomy Atlas displays three-dimensional anatomical models, image cross-sections of labelled structures and source radiological imaging, and a text-based hierarchy of structures. Open and free online anatomical atlases developed by our anatomy laboratory team will be available to our students. This will allow pedagogical autonomy and remedy the shortcomings by responding more fully to the objectives of sustainable local development of quality education and good health at the national level. To make this work a reality, our team produced several atlases available in our faculty in the form of research projects.

Keywords: anatomy, education, medical imaging, three dimensional

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

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

Keywords: homecare, Saudi, prevalence, chronic

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Authors: A. Bhatt, C. Bassi, H. Farragher, J. Musk

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Background: All medicines placed on the EU market are legally required to be accompanied by labeling and package leaflet, which provide comprehensive information, enabling its safe and appropriate use. Mock-ups with results of assessments using a target patient group must be submitted for a marketing authorisation application. Consumers need confidence in non-prescription, OTC medicines in order to manage their minor ailments and umbrella brands assist purchasing decisions by assisting easy identification within a particular therapeutic area. A number of regulatory agencies have risk management tools and guidelines to assist in developing umbrella brands for OTC medicines, however assessment and decision making is subjective and inconsistent. This study presents an evaluation in the UK following the US FDA warning concerning methaemoglobinaemia following 21 reported cases (11 children under 2 years) caused by OTC oral analgesics containing benzocaine. METHODS: A standard face to face, 25 structured task based user interview testing methodology using a standard questionnaire and rating scale in consumers aged 15-91 years, was conducted independently between June and October 2015 in their homes. Whether individuals could discriminate between the labelling, safety information and warnings on cartons and PILs between 3 different OTC medicines packs with the same umbrella name was evaluated. Each pack was presented with differing information hierarchy using, different coloured cartons, containing the 3 different active ingredients, benzocaine (oromucosal spray) and two lozenges containing 2, 4, dichlorobenzyl alcohol, amylmetacresol and hexylresorcinol respectively (for the symptomatic relief of sore throat pain). The test was designed to determine whether warnings on the carton and leaflet were prominent, accessible to alert users that one product contained benzocaine, risk of methaemoglobinaemia, and refer to the leaflet for the signs of the condition and what to do should this occur. Results: Two consumers did not locate the warnings on the side of the pack, eventually found them on the back and two suggestions to further improve accessibility of the methaemoglobinaemia warning. Using a gold pack design for the oromucosal spray, all consumers could differentiate between the 3 drugs, minimum age particulars, pharmaceutical form and the risk factor methaemoglobinaemia. The warnings for benzocaine were deemed to be clear or very clear; appearance of the 3 packs were either very well differentiated or quite well differentiated. The PIL test passed on all criteria. All consumers could use the product correctly, identify risk factors ensuring the critical information necessary for the safe use was legible and easily accessible so that confusion and errors were minimised. Conclusion: Patients with known methaemoglobinaemia are likely to be vigilant in checking for benzocaine containing products, despite similar umbrella brand names across a range of active ingredients. Despite these findings, the package design and spray format were not deemed to be sufficient to mitigate potential safety risks associated with differences in target populations and contraindications when submitted to the Regulatory Agency. Although risk management tools are increasingly being used by agencies to assist in providing objective assurance of package safety, further transparency, reduction in subjectivity and proportionate risk should be demonstrated.

Keywords: labelling, OTC, risk, user testing

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Authors: Christine Wiesenthal

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This paper asks how to read a particularly vexed and complicated life writing text. For over half a century, the wartime journals of Ruth Andreas Friedrich (1901-1977) circulated as among a handful of more or less authoritative and “authentic” first-hand accounts of German resistance under Hitler. A professional journalist, Andreas Friedrich is remembered today largely through her publications at the war’s end, which appeared in English as Berlin Underground (published by Henry Holt in 1947), just before their publication in Germany as Der Schattenmann “The Shadow Man” (also in 1947). A British edition by the now obscure Latimer House Limited (London) followed in 1948; it is based closely on but is not identical to, the Henry Holt American edition, which in turn differs significantly from its German counterpart. Both Berlin Underground and Der Schattenmann figure Andreas-Friedrich as a key figure in an anti-fascist cell that operated in Berlin under the code name “Uncle Emil,” and provide a riveting account of political terror, opportunism, and dissent under the Nazi regime. Recent scholars have, however, begun to raise fascinating and controversial questions about Andreas-Friedrich’s own writing/reconstruction process in compiling the journals and about her highly selective curatorial role and claims. The apparent absence of any surviving original manuscript for Andreas-Friedrich’s journals amplifies the questions around them. Crucially, so too does the role of the translator of the English editions of Berlin Underground, the enigmatic June Barrows Mussey, a subject that has thus far gone virtually unnoticed and which this paper will focus on. Mussey, a prolific American translator, simultaneously cultivated a career as a professional magician, publishing a number of books on that subject under the alias Henry Hay. While the record indicates that Mussey attempted to compartmentalize his professional life, research into the publishing and translation history of Berlin Underground suggests that the two roles converge in the fact of the translator’s invisibility, by effacing the traces of his own hand and leaving unmarked his own significant textual interventions, Mussey, in effect, edited, abridged, and altered Andreas Friedrich’s journals for the second time. In fact, it could be said that while the fictitious “Uncle Emil” is positioned as “the shadow man” of the German edition, Mussey himself also emerges as precisely that in the English rendering of the journals. The implications of Mussey’s translation of Andreas Friedrich’s journals are one of the most important un-examined gaps in the shadowy publishing history of Berlin Underground, a history full of “tricks” (Mussey’s words) and illusions of transparency. Based largely on archival research of unpublished materials and methods of close reading and comparative analysis, this study will seek to convey some preliminary insights and exploratory work and frame questions toward what is ultimately envisioned as an experimental project in poetic historiography. As this work is still in the early stages, it would be especially welcome to have the opportunity provided by this conference to connect with a community of life writing colleagues who might help think through some of the challenges and possibilities that lie ahead.

Keywords: women’s wartime diaries, translation studies, auto/biographical theory, politics of life writing

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Authors: Adriana Haulica

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Powered by Machine Learning, Precise medicine is tailored by now to use genetic and molecular profiling, with the aim of optimizing the therapeutic benefits for cohorts of patients. As the majority of Machine Language algorithms come from heuristics, the outputs have contextual validity. This is not very restrictive in the sense that medicine itself is not an exact science. Meanwhile, the progress made in Molecular Biology, Bioinformatics, Computational Biology, and Precise Medicine, correlated with the huge amount of human biology data and the increase in computational power, opens new healthcare challenges. A more accurate diagnosis is needed along with real-time treatments by processing as much as possible from the available information. The purpose of this paper is to present a deeper vision for the future of Artificial Intelligence in Precise medicine. In fact, actual Machine Learning algorithms use standard mathematical knowledge, mostly Euclidian metrics and standard computation rules. The loss of information arising from the classical methods prevents obtaining 100% evidence on the diagnosis process. To overcome these problems, we introduce MEDICOMPILLS, a new architectural concept tool of information processing in Precise medicine that delivers diagnosis and therapy advice. This tool processes poly-field digital resources: global knowledge related to biomedicine in a direct or indirect manner but also technical databases, Natural Language Processing algorithms, and strong class optimization functions. As the name suggests, the heart of this tool is a compiler. The approach is completely new, tailored for omics and clinical data. Firstly, the intrinsic biological intuition is different from the well-known “a needle in a haystack” approach usually used when Machine Learning algorithms have to process differential genomic or molecular data to find biomarkers. Also, even if the input is seized from various types of data, the working engine inside the MEDICOMPILLS does not search for patterns as an integrative tool. This approach deciphers the biological meaning of input data up to the metabolic and physiologic mechanisms, based on a compiler with grammars issued from bio-algebra-inspired mathematics. It translates input data into bio-semantic units with the help of contextual information iteratively until Bio-Logical operations can be performed on the base of the “common denominator “rule. The rigorousness of MEDICOMPILLS comes from the structure of the contextual information on functions, built to be analogous to mathematical “proofs”. The major impact of this architecture is expressed by the high accuracy of the diagnosis. Detected as a multiple conditions diagnostic, constituted by some main diseases along with unhealthy biological states, this format is highly suitable for therapy proposal and disease prevention. The use of MEDICOMPILLS architecture is highly beneficial for the healthcare industry. The expectation is to generate a strategic trend in Precise medicine, making medicine more like an exact science and reducing the considerable risk of errors in diagnostics and therapies. The tool can be used by pharmaceutical laboratories for the discovery of new cures. It will also contribute to better design of clinical trials and speed them up.

Keywords: bio-semantic units, multiple conditions diagnosis, NLP, omics

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Authors: Jawaad Saleem, Hannah Wright, Peter Sommerville, Adrian Hopper

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Introduction: Inpatient falls are the most commonly reported patient safety incidents, and carry a significant burden on resources, morbidity, and mortality. Ensuring adequate post falls management of patients by staff is therefore paramount to maintaining patient safety especially in out of hours and resource stretched settings. Aims: This quality improvement project aims to improve the current practice of falls management at Guys St Thomas Hospital, London as compared to our 2016 Quality Improvement Project findings. Furthermore, it looks to increase current junior doctors confidence in managing falls and their use of new guidance protocols. Methods: Multifaceted Interventions implemented included: the development of new trust wide guidelines detailing management pathways for patients post falls, available for intranet access. Furthermore, the production of 2000 lanyard cards distributed amongst junior doctors and staff which summarised these guidelines. Additionally, a ‘safety signal’ email was sent from the Trust chief medical officer to all staff raising awareness of falls and the guidelines. Formal falls teaching was also implemented for new doctors at induction. Using an established incident database, 189 consecutive falls in 2017were retrospectively analysed electronically to assess and compared to the variables measured in 2016 post interventions. A separate serious incident database was used to analyse 50 falls from May 2015 to March 2018 to ascertain the statistical significance of the impact of our interventions on serious incidents. A similar questionnaire for the 2017 cohort of foundation year one (FY1) doctors was performed and compared to 2016 results. Results: Questionnaire data demonstrated improved awareness and utility of guidelines and increased confidence as well as an increase in training. 97% of FY1 trainees felt that the interventions had increased their awareness of the impact of falls on patients in the trust. Data from the incident database demonstrated the time to review patients post fall had decreased from an average of 130 to 86 minutes. Improvement was also demonstrated in the reduced time to order and schedule X-ray and CT imaging, 3 and 5 hours respectively. Data from the serious incident database show that ‘the time from fall until harm was detected’ was statistically significantly lower (P = 0.044) post intervention. We also showed the incidence of significant delays in detecting harm ( > 10 hours) reduced post intervention. Conclusions: Our interventions have helped to significantly reduce the average time to assess, order and schedule appropriate imaging post falls. Delays of over ten hours to detect serious injuries after falls were commonplace; since the intervention, their frequency has markedly reduced. We suggest this will lead to identifying patient harm sooner, reduced clinical incidents relating to falls and thus improve overall patient safety. Our interventions have also helped increase clinical staff confidence, management, and awareness of falls in the trust. Next steps include expanding teaching sessions, improving multidisciplinary team involvement to aid this improvement.

Keywords: patient safety, quality improvement, serious incidents, falls, clinical care

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

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

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

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Authors: Andrew D. Henshaw

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The research examines the influence of familial and kinship based leadership on the resilience of politically violent organizations. Organizations of this type frequently fight in the same conflicts though are called 'terrorist' or 'insurgent' depending on political foci of the time, and thus different approaches are used to combat them. The research considers them correlated phenomena with significant overlap and identifies strengths and vulnerabilities in resilience processes. The research employs paired case studies to examine resilience in organizations under significant external pressure, and achieves this by measuring three variables. 1: Organizational robustness in terms of leadership and governance. 2. Bounce-back response efficiency to external pressures and adaptation to endogenous and exogenous shock. 3. Perpetuity of operational and attack capability, and political legitimacy. The research makes three hypotheses. First, familial/kinship leadership groups have a significant effect on organizational resilience in terms of informal operations. Second, non-familial/kinship organizations suffer in terms of heightened security transaction costs and social economics surrounding recruitment, retention, and replacement. Third, resilience in non-familial organizations likely stems from critical external supports like state sponsorship or powerful patrons, rather than organic resilience dynamics. The case studies pair familial organizations with non-familial organizations. Set 1: The Haqqani Network (HQN) - Pair: Lashkar-e-Toiba (LeT). Set 2: Jemaah Islamiyah (JI) - Pair: The Abu Sayyaf Group (ASG). Case studies were selected based on three requirements, being: contrasting governance types, exposure to significant external pressures and, geographical similarity. The case study sets were examined over 24 months following periods of significantly heightened operational activities. This enabled empirical measurement of the variables as substantial external pressures came into force. The rationale for the research is obvious. Nearly all organizations have some nexus of familial interconnectedness. Examining familial leadership networks does not provide further understanding of how terrorism and insurgency originate, however, the central focus of the research does address how they persist. The sparse attention to this in existing literature presents an unexplored yet important area of security studies. Furthermore, social capital in familial systems is largely automatic and organic, given at birth or through kinship. It reduces security vetting cost for recruits, fighters and supporters which lowers liabilities and entry costs, while raising organizational efficiency and exit costs. Better understanding of these process is needed to exploit strengths into weaknesses. Outcomes and implications of the research have critical relevance to future operational policy development. Increased clarity of internal trust dynamics, social capital and power flows are essential to fracturing and manipulating kinship nexus. This is highly valuable to external pressure mechanisms such as counter-terrorism, counterinsurgency, and strategic intelligence methods to penetrate, manipulate, degrade or destroy the resilience of politically violent organizations.

Keywords: Counterinsurgency (COIN), counter-terrorism, familial influence, insurgency, intelligence, kinship, resilience, terrorism

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Authors: Özge Çeliker Tosun, Melda Başer Secer, İsmail Düşmez, Sedat Çapar, İlkay Kozak, Melahat Aktaş, Furkan Can Şimşek, Gökhan Tosun

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Purpose: Portable innovative balance room system with digital game program; It was created to be able to be divided into small areas, such as inside the house, garden, balcony, to enable the person to enter and perform both evaluation and exercise safely, and to ensure that these results can be stored and sent to the therapist live or later when desired. The aim is to compare the effectiveness of the exercise program applied by the elderly within this system and the exercise program implemented under the supervision of a physiotherapist on balance and urinary incontinence symptoms. Materials and Methods: The study was conducted in a randomized controlled manner on 63 people with urinary incontinence (mean age: 75.5 years) at Narlıdere Nursing Home Elderly Care and Rehabilitation Center. Elderly people participating in the study were divided into 3 groups: 1. Group, an exercise program consisting of pelvic floor muscle training and OTOGA exercises, 2. Group, only pelvic floor muscle training, and 3. Group, pelvic floor muscle training and Otoga exercises in the form of a digital game program in a portable balance room system. (self-administered) for 12 weeks. Pelvic floor distress inventory (PTDE-20) and bladder diary were used to evaluate the incontinance symptoms of the cases. Pelvic floor muscle function was evaluated with superficial EMG. Berg, Fall Effectiveness Scale (FES) and Functional Status Evaluations (Chair Stand Test, Eight (8) Food Up and Go Test, Chair Sit and Reach Test, Two Minutes Step Test) were used to evaluate balance. The existence of differences between groups was analyzed using Krusskal Wallis analysis of variance, and the difference between before and after exercise was analyzed with Wilcoxon tests. Results: After treatment, PTDE-20, daily urinary incontinence and toilet visits values decreased significantly in all three groups (p < 0.001). While there was a statistically significant increase in pelvic floor muscle EMG values in the 2nd and third groups after treatment, there was no change in the other group (2nd Group PFM average EMG before-after: 5.5 (4.15-10.95) - 10.95 (8.68-13.68), P=0.05, 3 Group PFM average EMG before-after: 6.5 (4.28-11.55) - 11.75 (8.67-14.26), p=0.04). While BERG score, Chair Stand Test, Eight (8) Food Up and Go Test, and Two Minutes Step Test values increased in all groups (p<0.05), Fall Effectiveness Scale (FES) values did not change after treatment. Conclusion: Although pelvic floor muscle training combined with balance exercises reduces symptoms, it may not lead to a positive improvement in the functions of the pelvic floor muscles. For this reason, recovery lasts for a short time, and then symptoms may reoccur in the future. However, thanks to the new system, when balance exercises are combined with a game program for the pelvic floor muscles, a double effect can be achieved with a single application and both incontinence and balance problems can be treated in a safe environment where the person can do it himself. But more work needs to be done on this subject. However, thanks to the new system, a double effect can be achieved with a single application, and both incontinence and balance problems can be treated in a safe environment where the person can do it himself. But more work needs to be done on new system

Keywords: fall, urinary incontinance, balance, elderly

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Authors: Camelia Vizireanu, Daniela Istrati, Alina Georgiana Profir, Rodica Mihaela Dinica

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Globally, there is a great interest in promoting the consumption of fruit and vegetables to improve health. Due to the content of essential compounds such as antioxidants, important amounts of fruits and vegetables should be included in the daily diet. Juices are good sources of vitamins and can also help increase overall fruit and vegetable consumption. Starting from this trend (introduction into the daily diet of vegetables and fruits) as well as the desire to diversify the range of functional products for both adults and children, a fermented juice was made using probiotic microorganisms based on root vegetables, with potential beneficial effects in the diet of children, vegetarians and people with lactose intolerance. The three vegetables selected for this study, red beet, carrot, and celery bring a significant contribution to functional compounds such as carotenoids, flavonoids, betalain, vitamin B and C, minerals and fiber. By fermentation, the functional value of the vegetable juice increases due to the improved stability of these compounds. The combination of probiotic microorganisms and vegetable fibers resulted in a nutrient-rich synbiotic product. The stability of the nutritional and sensory qualities of the obtained synbiotic product has been tested throughout its shelf life. The evaluation of the physico-chemical changes of the synbiotic drink during storage confirmed that: (i) vegetable juice enriched with honey and vegetable pulp is an important source of nutritional compounds, especially carbohydrates and fiber; (ii) microwave treatment used to inhibit pathogenic microflora did not significantly affect nutritional compounds in vegetable juice, vitamin C concentration remained at baseline and beta-carotene concentration increased due to increased bioavailability; (iii) fermentation has improved the nutritional quality of vegetable juice by increasing the content of B vitamins, polyphenols and flavonoids and has a good antioxidant capacity throughout the shelf life; (iv) the FTIR and Raman spectra have highlighted the results obtained using physicochemical methods. Based on the analysis of IR absorption frequencies, the most striking bands belong to the frequencies 3330 cm⁻¹, 1636 cm⁻¹ and 1050 cm⁻¹, specific for groups of compounds such as polyphenols, carbohydrates, fatty acids, and proteins. Statistical data processing revealed a good correlation between the content of flavonoids, betalain, β-carotene, ascorbic acid and polyphenols, the fermented juice having a stable antioxidant activity. Also, principal components analysis showed that there was a negative correlation between the evolution of the concentration of B vitamins and antioxidant activity. Acknowledgment: This study has been founded by the Francophone University Agency, Project Réseau régional dans le domaine de la santé, la nutrition et la sécurité alimentaire (SaIN), No. at Dunarea de Jos University of Galati 21899/ 06.09.2017 and by the Sectorial Operational Programme Human Resources Development of the Romanian Ministry of Education, Research, Youth and Sports trough the Financial Agreement POSDRU/159/1.5/S/132397 ExcelDOC.

Keywords: bioactive compounds, fermentation, synbiotic drink from vegetables, stability during storage

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Authors: Bensaid A., Mostephaoui T., Nedjai R.

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Nowadays, wetlands are the subject of contradictory debates opposing scientific, political and administrative meanings. Indeed, given their multiple services (drinking water, irrigation, hydrological regulation, mineral, plant and animal resources...), wetlands concentrate many socio-economic and biodiversity issues. In some regions, they can cover vast areas (>100 thousand ha) of the landscape, such as the Camargue area in the south of France, inside the Rhone delta. The high biological productivity of wetlands, the strong natural selection pressures and the diversity of aquatic environments have produced many species of plants and animals that are found nowhere else. These environments are tremendous carbon sinks and biodiversity reserves depending on their age, composition and surrounding environmental conditions, wetlands play an important role in global climate projections. Covering more than 3% of the earth's surface, wetlands have experienced since the beginning of the 1990s a tremendous revival of interest, which has resulted in the multiplication of inventories, scientific studies and management experiments. The geographical and physical characteristics of the wetlands of the central region conceal a large number of natural habitats that harbour a great biological diversity. These wetlands, one of the natural habitats, are still influenced by human activities, especially agriculture, which affects its layout and functioning. In this perspective, decision-makers need to delimit spatial objects (natural habitats) in a certain way to be able to take action. Thus, wetlands are no exception to this rule even if it seems to be a difficult exercise to delimit a type of environment as whose main characteristic is often to occupy the transition between aquatic and terrestrial environment. However, it is possible to map wetlands with databases, derived from the interpretation of photos and satellite images, such as the European database Corine Land cover, which allows quantifying and characterizing for each place the characteristic wetland types. Scientific studies have shown limitations when using high spatial resolution images (SPOT, Landsat, ASTER) for the identification and characterization of small wetlands (1 hectare). To address this limitation, it is important to note that these wetlands generally represent spatially complex features. Indeed, the use of very high spatial resolution images (>3m) is necessary to map small and large areas. However, with the recent evolution of artificial intelligence (AI) and deep learning methods for satellite image processing have shown a much better performance compared to traditional processing based only on pixel structures. Our research work is also based on spectral and textural analysis on THR images (Spot and IRC orthoimage) using two object-oriented approaches, the nearest neighbour approach (k-NN) and the Super Vector Machine approach (SVM). The k-NN approach gave good results for the delineation of wetlands (wet marshes and moors, ponds, artificial wetlands water body edges, ponds, mountain wetlands, river edges and brackish marshes) with a kappa index higher than 85%.

Keywords: land development, GIS, sand dunes, segmentation, remote sensing

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Authors: Sonja Giese, Tess N. Peacock

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South African based Innovation Edge is experimenting with technology to drive positive behavior change, enable data-driven decision making, and scale quality early years services. This paper uses five case studies to illustrate how technology can be used in resource-constrained environments to first, encourage parenting practices that build early language development (using a stage-based mobile messaging pilot, ChildConnect), secondly, to improve the quality of ECD programs (using a mobile application, CareUp), thirdly, how to affordably scale services for the early detection of visual and hearing impairments (using a mobile tool, HearX), fourthly, how to build a transparent and accountable system for the registration and funding of ECD (using a blockchain enabled platform, Amply), and finally enable rapid data collection and feedback to facilitate quality enhancement of programs at scale (the Early Learning Outcomes Measure). ChildConnect and CareUp were both developed using a design based iterative research approach. The usage and uptake of ChildConnect and CareUp was evaluated with qualitative and quantitative methods. Actual child outcomes were not measured in the initial pilots. Although parents who used and engaged on either platform felt more supported and informed, parent engagement and usage remains a challenge. This is contrast to ECD practitioners whose usage and knowledge with CareUp showed both sustained engagement and knowledge improvement. HearX is an easy-to-use tool to identify hearing loss and visual impairment. The tool was tested with 10000 children in an informal settlement. The feasibility of cost-effectively decentralising screening services was demonstrated. Practical and financial barriers remain with respect to parental consent and for successful referrals. Amply uses mobile and blockchain technology to increase impact and accountability of public services. In the pilot project, Amply is being used to replace an existing paper-based system to register children for a government-funded pre-school subsidy in South Africa. Early Learning Outcomes Measure defines what it means for a child to be developmentally ‘on track’ at aged 50-69 months. ELOM administration is enabled via a tablet which allows for easy and accurate data collection, transfer, analysis, and feedback. ELOM is being used extensively to drive quality enhancement of ECD programs across multiple modalities. The nature of ECD services in South Africa is that they are in large part provided by disconnected private individuals or Non-Governmental Organizations (in contrast to basic education which is publicly provided by the government). It is a disparate sector which means that scaling successful interventions is that much harder. All five interventions show the potential of technology to support and enhance a range of ECD services, but pathways to scale are still being tested.

Keywords: assessment, behavior change, communication, data, disabilities, mobile, scale, technology, quality

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Authors: Turky Al-Qahtani, Roustem Miftahof

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Introduction: Under common assumptions of excitabi-lity, morphological (cellular) homogeneity, and spatial structural anomalies added as required, it has been shown that biological systems are able to display travelling wave dynamics. Being not self-sustainable, existence depends on the electrophysiological state of transmembrane ion channels and it requires an extrinsic/intrinsic periodic source. However, organs in the body are highly multicellular, heterogeneous, and their functionality is the outcome of electro-mechanical conjugation, rather than excitability only. Thus, peristalsis in the gut relies on spatiotemporal myoelectrical pattern formations between the mechanical, represented by smooth muscle cells (SM), and the control, comprised of a chain of primary sensory and motor neurones, components. Synaptically linked through the afferent and efferent pathways, they form a functional unit (FU) of the gut. Aims: These are: i) to study numerically the complex dynamics, and ii) to investigate the possibility of self-sustained myoelectrical activity in the FU. Methods: The FU recreates the following sequence of physiological events: deformation of mechanoreceptors of located in SM; generation and propagation of electrical waves of depolarisation - spikes - along the axon to the soma of the primary neurone; discharge of the primary neurone and spike propagation towards the motor neurone; burst of the motor neurone and transduction of spikes to SM, subsequently producing forces of contraction. These are governed by a system of nonlinear partial and ordinary differential equations being a modified version of the Hodgkin-Huxley model and SM fibre mechanics. In numerical experiments; the source of excitation is mechanical stretches of SM at a fixed amplitude and variable frequencies. Results: Low frequency (0.5 < v < 2 Hz) stimuli cause the propagation of spikes in the neuronal chain and, finally, the generation of active forces by SM. However, induced contractions are not sufficient to initiate travelling wave dynamics in the control system. At frequencies, 2 < v < 4 Hz, multiple low amplitude and short-lasting contractions are observed in SM after the termination of stretching. For frequencies (0.5 < v < 4 Hz), primary and sensory neurones demonstrate strong connectivity and coherent electrical activity. Significant qualitative and quantitative changes in dynamics of myoelectical patterns with a transition to a self-organised mode are recorded with the high degree of stretches at v = 4.5 Hz. Increased rates of deformation lead to the production of high amplitude signals at the mechanoreceptors with subsequent self-sustained excitation within the neuronal chain. Remarkably, the connection between neurones weakens resulting in incoherent firing. Further increase in a frequency of stimulation (v > 4.5 Hz) has a detrimental effect on the system. The mechanical and control systems become disconnected and exhibit uncoordinated electromechanical activity. Conclusion: To our knowledge, the existence of periodic activity in a multicellular, functionally heterogeneous biological system with mechano-electrical dynamics, such as the FU, has been demonstrated for the first time. These findings support the notion of possible peristalsis in the gut even in the absence of intrinsic sources - pacemaker cells. Results could be implicated in the pathogenesis of intestinal dysrythmia, a medical condition associated with motor dysfunction.

Keywords: complex dynamics, functional unit, the gut, dysrythmia

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