Search results for: disease detection

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

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

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

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Authors: Mona Isazad Mashinchi, Davood Roshan Sangachin, Francis J. Sullivan, Dietrich Rebholz-Schuhmann

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Background: Decision-making processes are nowadays driven by data, data analytics and Business Intelligence (BI). BI as a software platform can provide a wide variety of capabilities such as organization memory, information integration, insight creation and presentation capabilities. Visualizing data through dashboards is one of the BI solutions (for a variety of areas) which helps managers in the decision making processes to expose the most informative information at a glance. In the healthcare domain to date, dashboard presentations are more frequently used to track performance related metrics and less frequently used to monitor those quality parameters which relate directly to patient outcomes. Providing effective and timely care for patients and improving the health outcome are highly dependent on presenting and visualizing data and information. Objective: In this research, the focus is on the presentation capabilities of BI to design a dashboard for prostate cancer (PC) data that allows better decision making for the patients, the hospital and the healthcare system related to a cancer dataset. The aim of this research is to customize a retrospective PC dataset in a dashboard interface to give a better understanding of data in the categories (risk factors, treatment approaches, disease control and side effects) which matter most to patients as well as other stakeholders. By presenting the outcome in the dashboard we address one of the major targets of a value-based health care (VBHC) delivery model which is measuring the value and presenting the outcome to different actors in HC industry (such as patients and doctors) for a better decision making. Method: For visualizing the stored data to users, three interactive dashboards based on the PC dataset have been developed (using the Tableau Software) to provide better views to the risk factors, treatment approaches, and side effects. Results: Many benefits derived from interactive graphs and tables in dashboards which helped to easily visualize and see the patients at risk, better understanding the relationship between patient's status after treatment and their initial status before treatment, or to choose better decision about treatments with fewer side effects regarding patient status and etc. Conclusions: Building a well-designed and informative dashboard is related to three important factors including; the users, goals and the data types. Dashboard's hierarchies, drilling, and graphical features can guide doctors to better navigate through information. The features of the interactive PC dashboard not only let doctors ask specific questions and filter the results based on the key performance indicators (KPI) such as: Gleason Grade, Patient's Age and Status, but may also help patients to better understand different treatment outcomes, such as side effects during the time, and have an active role in their treatment decisions. Currently, we are extending the results to the real-time interactive dashboard that users (either patients and doctors) can easily explore the data by choosing preferred attribute and data to make better near real-time decisions.

Keywords: business intelligence, dashboard, decision making, healthcare, prostate cancer, value-based healthcare

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Authors: Vrushali Guhe, Shailza Singh

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Cutaneous leishmaniasis is neglected tropical disease present worldwide caused by the protozoan parasite Leishmania major, the therapeutic armamentarium for leishmaniasis are showing several limitations as drugs are showing toxic effects with increasing resistance by a parasite. Thus identification of novel therapeutic targets is of paramount importance. Previous studies have shown that autophagy, a cellular process, can either facilitate infection or aid in the elimination of the parasite, depending on the specific parasite species and host background in leishmaniasis. In the present study, our objective was to target the essential autophagy protein ATG8, which plays a crucial role in the survival, infection dynamics, and differentiation of the Leishmania parasite. ATG8 in Leishmania major and its homologue, LC3, in Homo sapiens, act as autophagic markers. Present study manifested the crucial role of ATG8 protein as a potential target for combating Leishmania major infection. Through bioinformatics analysis, we identified non-conserved motifs within the ATG8 protein of Leishmania major, which are not present in LC3 of Homo sapiens. Against these two non-conserved motifs, we generated a peptide library of 60 peptides on the basis of physicochemical properties. These peptides underwent a filtering process based on various parameters, including feasibility of synthesis and purification, compatibility with Selective Reaction Monitoring (SRM)/Multiple reaction monitoring (MRM), hydrophobicity, hydropathy index, average molecular weight (Mw average), monoisotopic molecular weight (Mw monoisotopic), theoretical isoelectric point (pI), and half-life. Further filtering criterion shortlisted three peptides by using molecular docking and molecular dynamics simulations. The direct interaction between ATG8 and the shortlisted peptides was confirmed through Surface Plasmon Resonance (SPR) experiments. Notably, these peptides exhibited the remarkable ability to penetrate the parasite membrane and exert profound effects on Leishmania major. The treatment with these peptides significantly impacted parasite survival, leading to alterations in the cell cycle and morphology. Furthermore, the peptides were found to modulate autophagosome formation, particularly under starved conditions, suggesting their involvement in disrupting the regulation of autophagy within Leishmania major. In vitro, studies demonstrated that the selected peptides effectively reduced the parasite load within infected host cells. Encouragingly, these findings were corroborated by in vivo experiments, which showed a reduction in parasite burden upon peptide administration. Additionally, the peptides were observed to affect the levels of LC3II within host cells. In conclusion, our findings highlight the efficacy of these novel peptides in targeting Leishmania major’s ATG8 and disrupting parasite survival. These results provide valuable insights into the development of innovative therapeutic strategies against leishmaniasis via targeting autophagy protein ATG8 of Leishmania major.

Keywords: ATG8, leishmaniasis, surface plasmon resonance, MD simulation, molecular docking, peptide designing, therapeutics

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Authors: Ibrahim Abdulla Labib, Medhat Mohamed Morsy, Gamal Hosny, Hanan Dawood Yassa, Gaber Hassan

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Amiodarone is a very effective drug, widely used for arrhythmia. Unfortunately it has many side effects involving many organs especially thyroid gland. The current work was conducted to elucidate the effect of amiodarone on the thyroid gland and the possible protective role of vitamin E. Fifty adult male albino rats weighed 200 – 250 grams were divided into five groups; ten rats each. Group I (Control): Five rats were sacrificed after three weeks and five rats were sacrificed after six weeks. Group II (Sham control): Each rat received sunflower oil orally; the solvent of vitamin E for three weeks. Group III (Amiodarone-treated): each rat received an oral dose of amiodarone; 150 mg/kg/day for three weeks. Group IV (Recovery): Each rat received amiodarone as group III then the drug was stopped for three weeks to evaluate recovery. Group V (Amiodarone + Vitamin E-treated): Each rat received amiodarone as group III followed by 100 mg/kg/day vitamin E orally for three weeks. Thyroid gland of the sacrificed animals were dissected out and prepared for light and electron microscopic studies. Amiodarone administration resulted in loss of normal follicular architecture as many follicles appeared either shrunken, empty or contained scanty pale colloid. Some follicles appeared lined by more than one layer of cells while others showed interruption of their membrane. Masson's Trichrome stained sections showed increased collagen fibers in between the thyroid follicles. Ultrastructurally, the apical border of the follicular cells showed few irregular detached microvilli. The nuclei of the follicular cells were almost irregular with chromatin condensation. The cytoplasm of most follicular cells revealed numerous dilated rough endoplasmic reticulum with numerous lysosomes. After three weeks of stopping amiodarone, the follicles were nearly regular in outline. Some follicles were filled with homogenous eosinophilic colloid and others had shrunken pale colloid or were empty. Some few follicles showed exfoliated cells in their lumina and others were still lined by more than one layer of follicular cells. Moderate amounts of collagen fibers were observed in-between thyroid follicles. Ultrastructurally, many follicular cells had rounded euchromatic nucleui, moderate number of lysosomes and moderately dilated rough endoplasmic reticulum. However, few follicular cells still showing irregular nucleui, dilated rough endoplasmic reticulum and many cytoplasmic vacuoles. Administration of vitamin E with amiodarone for three weeks resulted in obvious structural improvement. Most of the follicles were lined by a single layer of cuboidal cells and the lumina were filled with homogenous eosinophilic colloid with very few vacuolations. The majority of follicular cells had rounded nuclei with occasional detection of ballooned cells and dark nuclei. Scanty collagen fibers were detected among thyroid follicles. Ultrastructurally, most follicular cells exhibited rounded euchromatic nuclei with few short microvilli were projecting into the colloid. Few lysosomes were also noticed. It was concluded that amiodarone administration leads to many adverse histological changes in the thyroid gland. Some of these changes are reversible during the recovery period however concomitant vitamin E administration with amiodarone has a major protective role in preventing many of these changes.

Keywords: amiodarone, recovery, ultrastructure, vitamin E.

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

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

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

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Authors: Sharon Harel, Rachel Kizony, Yoram Feldman, Gabi Zeilig, Mordechai Shani

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Multiple Sclerosis (MS) is a neurological disease that may cause restriction in participation in daily activities of young adults. Main symptoms include fatigue, weakness and cognitive decline. The appearance of symptoms, their severity and deterioration rate, change between patients. The challenge of health services is to provide long-term rehabilitation services to people with MS. The objective of this presentation is to describe a course of tele-rehabilitation service of a woman with MS. Methods; R is a 48 years-old woman, diagnosed with MS when she was 22. She started to suffer from weakness of her non-dominant left upper extremity about ten years after the diagnosis. She was referred to the tele-rehabilitation service by her rehabilitation team, 16 years after diagnosis. Her goals were to improve ability to use her affected upper extremity in daily activities. On admission her score in the Mini-Mental State Exam was 30/30. Her Fugl-Meyer Assessment (FMA) score of the left upper extremity was 48/60, indicating mild weakness and she had a limitation of her shoulder abduction (90 degrees). In addition, she reported little use of her arm in daily activities as shown in her responses to the Motor Activity Log (MAL) that were equal to 1.25/5 in amount and 1.37 in quality of use. R. received two 30 minutes on-line sessions per week in the tele-rehabilitation service, with the CogniMotion system. These were complemented by self-practice with the system. The CogniMotion system provides a hybrid (synchronous-asynchronous), the home-based tele-rehabilitation program to improve the motor, cognitive and functional status of people with neurological deficits. The system consists of a computer, large monitor, and the Microsoft’s Kinect 3D sensor. This equipment is located in the client’s home and connected to a clinician’s computer setup in a remote clinic via WiFi. The client sits in front of the monitor and uses his body movements to interact with games and tasks presented on the monitor. The system provides feedback in the form of ‘knowledge of results’ (e.g., the success of a game) and ‘knowledge of performance’ (e.g., alerts for compensatory movements) to enhance motor learning. The games and tasks were adapted for R. motor abilities and level of difficulty was gradually increased according to her abilities. The results of her second assessment (after 35 on-line sessions) showed improvement in her FMA score to 52 and shoulder abduction to 140 degrees. Moreover, her responses to the MAL indicated an increased amount (2.4) and quality (2.2) of use of her left upper extremity in daily activities. She reported high level of enjoyment from the treatments (5/5), specifically the combination of cognitive challenges while moving her body. In addition, she found the system easy to use as reflected by her responses to the System Usability Scale (85/100). To-date, R. continues to receive treatments in the tele-rehabilitation service. To conclude, this case report shows the potential of using tele-rehabilitation for people with MS to provide strategies to enhance the use of the upper extremity in daily activities as well as for maintaining motor function.

Keywords: motor function, multiple-sclerosis, tele-rehabilitation, daily activities

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Authors: Antonela Matana, Dubravka Brdar, Vesela Torlak, Marijana Popovic, Ivana Gunjaca, Ozren Polasek, Vesna Boraska Perica, Maja Barbalic, Ante Punda, Caroline Hayward, Tatijana Zemunik

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Parathyroid hormone (PTH) plays a critical role in the regulation of bone mineral metabolism and calcium homeostasis. Higher PTH levels are associated with heart failure, hypertension, coronary artery disease, cardiovascular mortality and poorer bone health. A twin study estimated that 60% of the variation in PTH concentrations is genetically determined. Only one GWAS of PTH concentration has been reported to date. Identified loci explained 4.5% of the variance in circulating PTH, suggesting that additional genetic variants remain undiscovered. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels in a general population. We have performed a GWAS meta-analysis on 2596 individuals originating from three Croatian cohorts: City of Split and the Islands of Korčula and Vis, within a large-scale project of “10,001 Dalmatians”. A total of 7 411 206 variants, imputed using the 1000 Genomes reference panel, with minor allele frequency ≥ 1% and Rsq ≥ 0.5 were analyzed for the association. GWAS within each data set was performed under an additive model, controlling for age, gender and relatedness. Meta-analysis was conducted using the inverse-variance fixed-effects method. Furthermore, to identify sex-specific effects, we have conducted GWAS meta-analyses analyzing males and females separately. In addition, we have performed biological pathway analysis. Four SNPs, representing one locus, reached genome-wide significance. The most significant SNP was rs11099476 on chromosome 4 (P=1.15x10-8), which explained 1.14 % of the variance in PTH. The SNP is located near the protein-coding gene RASGEF1B. Additionally, we detected suggestive association with SNPs, rs77178854 located on chromosome 2 in the DPP10 gene (P=2.46x10-7) and rs481121 located on chromosome 1 (P=3.58x10-7) near the GRIK1 gene. One of the top hits detected in the main meta-analysis, intron variant rs77178854 located within DPP10 gene, reached genome-wide significance in females (P=2.21x10-9). No single locus was identified in the meta-analysis in males. Fifteen biological pathways were functionally enriched at a P<0.01, including muscle contraction, ion homeostasis and cardiac conduction as the most significant pathways. RASGEF1B is the guanine nucleotide exchange factor, known to be associated with height, bone density, and hip. DPP10 encodes a membrane protein that is a member of the serine proteases family, which binds specific voltage-gated potassium channels and alters their expression and biophysical properties. In conclusion, we identified 2 novel loci associated with PTH levels in a general population, providing us with further insights into the genetics of this complex trait.

Keywords: general population, genome-wide association analysis, parathyroid hormone, single nucleotide polymorphisms.

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Authors: Husham Bayazed

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Purpose of Presentation: Obesity and overweight are among the biggest health challenges of the 21st century, according to the WHO. Obviously, obese individuals suffer different courses of disease – from infections and allergies to cancer- and even respond differently to some treatment options. Of note, obesity often seems to predispose and triggers several secondary diseases such as diabetes, arteriosclerosis, or heart attacks. Since decades it seems that immunological signals gear inflammatory processes among obese individuals with the aforementioned conditions. This review aims to shed light how obesity sparks or rewire the immune system and predisposes to such unpleasant health outcomes. Moreover, lessons from the Covid-19 pandemic ascertain that people living with pre-existing conditions such as obesity can develop severe acute respiratory syndrome (SARS), which needs to be elucidated how obesity and its adjuvant inflammatory process distortion contribute to enhancing severe COVID-19 consequences. Recent Findings: In recent clinical studies, obesity was linked to alter and sparks the immune system in different ways. Adipose tissue (AT) is considered as a secondary immune organ, which is a reservoir of tissue-resident of different immune cells with mediator release, making it a secondary immune organ. Adipocytes per se secrete several pro-inflammatory cytokines (IL-6, IL-4, MCP-1, and TNF-α ) involved in activation of macrophages resulting in chronic low-grade inflammation. The correlation between obesity and T cells dysregulation is pivotal in rewiring the immune system. Of note, autophagy occurrence in adipose tissues further rewire the immune system due to flush and outburst of leptin and adiponectin, which are cytokines and influencing pro-inflammatory immune functions. These immune alterations among obese individuals are collectively incriminated in triggering several metabolic disorders and playing role in increasing cancers incidence and susceptibility to different infections. During COVID-19 pandemic, it was verified that patients with pre-existing obesity being at greater risk of suffering severe and fatal clinical outcomes. Beside obese people suffer from increased airway resistance and reduced lung volume, ACE2 expression in adipose tissue seems to be high and even higher than that in lungs, which spike infection incidence. In essence, obesity with pre-existence of pro-inflammatory cytokines such as LI-6 is a risk factor for cytokine storm and coagulopathy among COVID-19 patients. Summary: It is well documented that obesity is associated with chronic systemic low-grade inflammation, which sparks and alter different pillars of the immune system and triggers different metabolic disorders, and increases susceptibility of infections and cancer incidence. The pre-existing chronic inflammation in obese patients with the augmented inflammatory response against the viral infection seems to increase the susceptibility of these patients to developing severe COVID-19. Although the new weight loss drugs and bariatric surgery are considered as breakthrough news for obesity treatment, but preventing is easier than treating it once it has taken hold. However, obesity and immune system link new insights dispute the role of immunotherapy and regulating immune cells treating diet-induced obesity.

Keywords: immunity, metabolic disorders, cancer, COVID-19

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Authors: A. K. Tursunova, O. V. Chebonenko, A. Zh. Amirkulova, A. O. Abaildayev, O. A. Sapko, Y. M. Dyo, A. Sh. Utarbaeva

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Fusarium solani and its variants cause root and stem rot of plants. Dry rot is the most common disease of potato tubers during storage. The causative agents of fusariosis in contact with plants behave as antagonists, growth stimulants or parasites. The diversity of host-parasite relationships is explained by the parasite’s ability to produce a wide spectrum of biologically active compounds including toxins, enzymes, oligosaccharides, antibiotic substances, enniatins and gibberellins. Many of these metabolites contribute to the creation of compatible relations; others behave as elicitors, inducing various protective responses in plants. An important part of the strategy for developing plant resistance against pathogens is the activation of protein synthesis to produce protective ‘pathogenesis-related’ proteins. The family of PR-proteins known to confer the most protective response is chitinases (EC 3.2.1.14, Cht) and β-1,3-glucanases (EC 3.2.1.39, Glu). PR-proteins also include a large multigene family of peroxidases (EC 1.11.1.7, Pod), and increased activity of Pod and expression of the Pod genes leads to the development of resistance to a broad class of pathogens. Despite intensive research on the role of PR-proteins, the question of their participation in the mechanisms of formation of the F.solani–S.tuberosum pathosуstem is not sufficiently studied. Our aim was to investigate the effect of different classes of F. solani metabolites on the activity of chitinase, β-1,3-glucanases and peroxidases in tubers of Solanum tuberosum. Metabolite culture filtrate (CF) and cytoplasmic components were fractionated by extraction of the mycelium with organic solvents, salting out techniques, dialysis, column chromatography and ultrafiltration. Protein, lipid, carbohydrate and polyphenolic fractions of fungal metabolites were derived. Using enzymatic hydrolysis we obtained oligo glycans from fungal cell walls with different molecular weights. The activity of the metabolites was tested using potato tuber discs (d = 16mm, h = 5mm). The activity of PR-proteins of tubers was analyzed in a time course of 2–24 hours. The involvement of the analysed metabolites in the modulation of both early non-specific and late related to pathogenesis reactions was demonstrated. The most effective inducer was isolated from the CF (fraction of total phenolic compounds including naphtazarins). Induction of PR-activity by this fraction was: chitinase - 340-360%, glucanase - 435-450%, soluble forms of peroxidase - 400-560%, related forms of peroxidase - 215-237%. High-inducing activity was observed by the chloroform and acetonitrile extracts of the mycelium (induction of chitinase and glucanase activity was 176-240%, of soluble and bound forms of peroxidase - 190-400%). The fraction of oligo glycans mycelium cell walls of 1.2 kDa induced chitinase and β-1,3-glucanase to 239-320%; soluble forms and related peroxidase to 198-426%. Oligo glycans cell walls of 5-10 kDa had a weak suppressor effect - chitinase (21-25%) and glucanase (25-28%) activity; had no effect on soluble forms of peroxidase, but induced to 250-270% activity related forms. The CF polysaccharides of 8.5 kDa and 3.1 kDa inhibited synchronously the glucanase and chitinase specific response in step (after 24 hours at 42-50%) and the step response induced nonspecific peroxidase activity: soluble forms 4.8 -5.2 times, associated forms 1.4-1.6 times.

Keywords: fusarium solani, PR-proteins, peroxidase, solanum tuberosum

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Authors: Yi H. Wong, Li L. Chan, Chee O. Leong, Stephen Ambu, Joon W. Mak, Priyadashi S. Sahu

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Background: Acanthamoeba is a free-living opportunistic protist which is ubiquitously distributed in the environment. Virulent Acanthamoeba can cause fatal encephalitis in immunocompromised patients and potential blinding keratitis in immunocompetent contact lens wearers. Approximately 24 species have been identified but only the A. castellanii, A. polyphaga and A. culbertsoni are commonly associated with human infections. Until to date, the precise molecular basis for Acanthamoeba pathogenesis remains unclear. Previous studies reported that Acanthamoeba virulence can be diminished through prolonged axenic culture but revived through serial mouse passages. As no clear explanation on this reversible pathogenesis is established, hereby, we postulate that the epigenetic regulators, DNA-methyltransferases (DNMT) and histone-deacetylases (HDAC), could possibly be involved in granting the virulence plasticity of Acanthamoeba spp. Methods: Four rounds of mouse passages were conducted to revive the virulence potential of the virulence-attenuated Acanthamoeba castellanii strain (ATCC 50492). Briefly, each mouse (n=6/group) was inoculated intraperitoneally with Acanthamoebae cells (2x 105 trophozoites/mouse) and incubated for 2 months. Acanthamoebae cells were isolated from infected mouse organs by culture method and subjected to subsequent mouse passage. In vitro cytopathic, encystment and gelatinolytic assays were conducted to evaluate the virulence characteristics of Acanthamoebae isolates for each passage. PCR primers which targeted on the 2 members (DNMT1 and DNMT2) and 5 members (HDAC1 to 5) of the DNMT and HDAC gene families respectively were custom designed. Quantitative real-time PCR (qPCR) was performed to detect and quantify the relative expression of the two gene families in each Acanthamoeba isolates. Beta-tubulin of A. castellanii (Genbank accession no: XP_004353728) was included as housekeeping gene for data normalisation. PCR mixtures were also analyzed by electrophoresis for amplicons detection. All statistical analyses were performed using the paired one-tailed Student’s t test. Results: Our pathogenicity tests showed that the virulence-reactivated Acanthamoeba had a higher degree of cytopathic effect on vero cells, a better resistance to encystment challenge and a higher gelatinolytic activity which was catalysed by serine protease. qPCR assay showed that DNMT1 expression was significantly higher in the virulence-reactivated compared to the virulence-attenuated Acanthamoeba strain (p ≤ 0.01). The specificity of primers which targeted on DNMT1 was confirmed by sequence analysis of PCR amplicons, which showed a 97% similarity to the published DNA-methyltransferase gene of A. castellanii (GenBank accession no: XM_004332804.1). Out of the five primer pairs which targeted on the HDAC family genes, only HDAC4 expression was significantly difference between the two variant strains. In contrast to DNMT1, HDAC4 expression was much higher in the virulence-attenuated Acanthamoeba strain. Conclusion: Our mouse passages had successfully restored the virulence of the attenuated strain. Our findings suggested that DNA-methyltransferase (DNMT1) and histone deacetylase (HDAC4) expressions are associated with virulence potential of Acanthamoeba spp.

Keywords: acanthamoeba, DNA-methyltransferase, histone deacetylase, virulence-associated proteins

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Authors: Soumia Hammadi, Imane Nouacer, Lamine Hamida, Younes A. Hammadi, Rachid Chaibi

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Aims and objective: In the present work, we investigate the impact of both acute and chronic diabetes mellitus induced by streptozotocin (STZ) on the hypothalamus of the small gerbil (Gerbillus gerbillus). In this purpose, we aimed to study the histologic structure of the gerbil’s hypothalamic supraoptic (NSO) and paraventricular nucleus (NPV) at two distinct time points: two days and 30 days after diabetes onset. Methods: We conducted our investigation using 19 adult male gerbils weighing 25 to 28 g, divided into three groups as follow: Group I: Control gerbils (n=6) received an intraperitoneal injection of citrate buffer. Group II: STZ-diabetic gerbils (n=8) received a single intraperitoneal injection of STZ at a dose of 165 mg/kg of body weight. Diabetes onset (D0) is considered with the first hyperglycemia level exceeding 2,5 g/L. This group was further divided into two subgroups: Group II-1: Experimental Gerbils, at acute state of diabetes (n=8) sacrificed after 02 days of diabetes onset, Group II-2: Experimental Gerbils at chronic state of diabetes (n=7) sacrificed after 30 days of diabetes onset. Two and 30 days after diabetes onset, gerbils had blood drawn from the retro-orbital sinus into EDTA tubes. After centrifugation at -4°C, plasma was frozen at -80°C for later measurement of Cortisol, ACTH, and insulin. Afterward, animals were decapitated; their brain was removed, weighed, fixed in aqueous bouin, and processed and stained with Toluidine Bleu stain for histo-stereological analysis. A comparison was done with control gerbils treated with citrate buffer. Results: Compared to control gerbils, at 02 Days post diabetes onset, the neuronal somata of the paraventricular (NPV) and supraoptic nuclei (NSO) expressed numerous vacuoles of various sizes, we distinct also a neuronal juxtaposition and several unidentifiable vacuolated profiles were also seen in the neuropile. At the same time, we revealed the presence of à shrunken and condensed nuclei, which seem to touch the parvocellular neurons ( NPV); this leads us to suggest the presence of an apoptotic process in the early stage of diabetes. At 30 days of diabetes mellitus, the NPV manifests a few neurons with a distant appearance, in addition the magnocellular neurons in both NPV and NSO were hypertrophied with a rich euchromatin nucleus, a well-defined nucleolus, and a granular cytoplasm. Despite the neuronal degeneration at this stage, unexpectedly, ACTH registers a continuous significant high level compared to the early stage of diabetes mellitus and to control gerbils. Conclusion: The results suggest that the induction of diabetes mellitus using STZ in the small gerbils lead to alterations in the structure and morphology of the hypothalamus and hyper-secretion of ACTH and cortisol, possibly indicating hyperactivity of the hypothalamo-pituitary adrenal axis (HPA) during both the early and later stages of the disease. The subsequent quantitative evaluation of CRH, immunehistochemical evaluation of apoptosis, and oxidative stress assessment could corroborate our results.

Keywords: diabetes type 1., streptozotocin., small gerbil., hypothalamus., paraventricular nucleus., supraoptic nucleus.

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Authors: Rohit T. P., Sahil Athrij, Sasi Gopalan

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Currently, the content entertainment industry is dominated by mobile devices. As the trends slowly shift towards Augmented/Virtual Reality applications the computational demands on these devices are increasing exponentially and we are already reaching the limits of hardware optimizations. This paper proposes a software solution to this problem. By leveraging the capabilities of cloud computing we can offload the work from mobile devices to dedicated rendering servers that are way more powerful. But this introduces the problem of latency. This paper introduces a protocol that can achieve high-performance low latency Augmented/Virtual Reality experience. There are two parts to the protocol, 1) In-flight compression The main cause of latency in the system is the time required to transmit the camera frame from client to server. The round trip time is directly proportional to the amount of data transmitted. This can therefore be reduced by compressing the frames before sending. Using some standard compression algorithms like JPEG can result in minor size reduction only. Since the images to be compressed are consecutive camera frames there won't be a lot of changes between two consecutive images. So inter-frame compression is preferred. Inter-frame compression can be implemented efficiently using WebGL but the implementation of WebGL limits the precision of floating point numbers to 16bit in most devices. This can introduce noise to the image due to rounding errors, which will add up eventually. This can be solved using an improved interframe compression algorithm. The algorithm detects changes between frames and reuses unchanged pixels from the previous frame. This eliminates the need for floating point subtraction thereby cutting down on noise. The change detection is also improved drastically by taking the weighted average difference of pixels instead of the absolute difference. The kernel weights for this comparison can be fine-tuned to match the type of image to be compressed. 2) Dynamic Load distribution Conventional cloud computing architectures work by offloading as much work as possible to the servers, but this approach can cause a hit on bandwidth and server costs. The most optimal solution is obtained when the device utilizes 100% of its resources and the rest is done by the server. The protocol balances the load between the server and the client by doing a fraction of the computing on the device depending on the power of the device and network conditions. The protocol will be responsible for dynamically partitioning the tasks. Special flags will be used to communicate the workload fraction between the client and the server and will be updated in a constant interval of time ( or frames ). The whole of the protocol is designed so that it can be client agnostic. Flags are available to the client for resetting the frame, indicating latency, switching mode, etc. The server can react to client-side changes on the fly and adapt accordingly by switching to different pipelines. The server is designed to effectively spread the load and thereby scale horizontally. This is achieved by isolating client connections into different processes.

Keywords: 2D kernelling, augmented reality, cloud computing, dynamic load distribution, immersive experience, mobile computing, motion tracking, protocols, real-time systems, web-based augmented reality application

Procedia PDF Downloads 54

Authors: Tamam Albelwi, Robert Rogers, Hans-Peter Kubis

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Background: Exercise is widely acknowledged as a highly important health behavior, which reduces risks related to lifestyle diseases like type 2 diabetes, cardiovascular disease. However, exercise adherence is low in high-risk groups and sedentary lifestyle is more the norm than the exception. Expressed reasons for exercise participation are often based on delayed outcomes related to health threats and benefits but also enjoyment. Whether exercise is perceived as rewarding is well established in animal literature but the evidence is sparse in humans. Additionally, the question how stable any reward is perceived with time delays is an important question influencing decision-making (in favor or against a behavior). For the modality exercise, this has not been examined before. We, therefore, investigated the discounting of pre-established self-selected exercise compared with established rewards of food and money with a computer-based discounting paradigm. We hypothesized that exercise will be discounted like an established reward (food and money); however, we expect that the discounting rate is similar to a consumable reward like food. Additionally, we expected that individuals’ characteristics like preferred intensity, physical activity and body characteristics are associated with discount rates. Methods: 71 participants took part in four sessions. The sessions were designed to let participants select their preferred exercise intensity on a treadmill. Participants were asked to adjust their speed for optimizing pleasantness over an exercise period of up to 30 minutes, heart rate and pleasantness rating was measured. In further sessions, the established exercise intensity was modified and tested on perceptual validity. In the last exercise session rates of perceived exertion was measured on the preferred intensity level. Furthermore, participants filled in questionnaires related to physical activity, mood, craving, and impulsivity and answered choice questions on a bespoke computer task to establish discounting rates of their preferred exercise (kex), their favorite food (kfood) and a value-matching amount of money (kmoney). Results: Participants self-selected preferred speed was 5.5±2.24 km/h, at a heart rate of 120.7±23.5, and perceived exertion scale of 10.13±2.06. This shows that participants preferred a light exercise intensity with low to moderate cardiovascular strain based on perceived pleasantness. Computer assessment of discounting rates revealed that exercise was quickly discounted like a consumable reward, no significant difference between kfood and kex (kfood =0.322±0.263; kex=0.223±0.203). However, kmoney (kmoney=0.080±0.02) was significantly lower than the rates of exercise and food. Moreover, significant associations were found between preferred speed and kex (r=-0.302) and between physical activity levels and preferred speed (r=0.324). Outcomes show that participants perceived and discounted self-selected exercise like an established reward (food and money) but was discounted more like consumable rewards. Moreover, exercise discounting was quicker in individuals who preferred lower speeds, being less physically active. This may show that in a choice conflict between exercise and food the delay of exercise (because of distance) might disadvantage exercise as the chosen behavior particular in sedentary people. Conclusion: exercise can be perceived as a reward and is discounted quickly in time like food. Pleasant exercise experience is connected to low to moderate cardiovascular and perceptual strain.

Keywords: delay discounting, exercise, temporal discounting, time perspective

Procedia PDF Downloads 247

Authors: Aura Alejandra Burbano Patino, Mariela Agotegaray, Veronica Lassalle, Fernanda Horst

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Water pollution is of worldwide concern due to its importance as an essential resource for life. Industrial and urbanistic growth are anthropogenic activities that have caused an increase of undesirable compounds in water. In the last decade, emerging pollutants have become of great interest since, at very low concentrations (µg/L and ng/L), they exhibit a hazardous effect on wildlife, aquatic ecosystems, and human organisms. One group of emerging pollutants that are a matter of study are pharmaceuticals. Their high consumption rate and their inappropriate disposal have led to their detection in wastewater treatment plant influent, effluent, surface water, and drinking water. In consequence, numerous technologies have been developed to efficiently treat these pollutants. Adsorption appears like an easy and cost-effective technology. One of the most used adsorbents of emerging pollutants removal is carbon-based materials such as hydrochars. This study aims to use a magnetic hydrochar nanocomposite to be employed as an adsorbent for diclofenac removal. Kinetics models and the adsorption efficiency in real water samples were analyzed. For this purpose, a magnetic hydrochar nanocomposite was synthesized through the hydrothermal carbonization (HTC) technique hybridized to co-precipitation to add the magnetic component into the hydrochar, based on iron oxide nanoparticles. The hydrochar was obtained from sunflower husk residue as the precursor. TEM, TGA, FTIR, Zeta potential as a function of pH, DLS, BET technique, and elemental analysis were employed to characterize the material in terms of composition and chemical structure. Adsorption kinetics were carried out in distilled water and real water at room temperature, pH of 5.5 for distilled water and natural pH for real water samples, 1:1 adsorbent: adsorbate dosage ratio, contact times from 10-120 minutes, and 50% dosage concentration of DCF. Results have demonstrated that magnetic hydrochar presents superparamagnetic properties with a saturation magnetization value of 55.28 emu/g. Besides, it is mesoporous with a surface area of 55.52 m²/g. It is composed of magnetite nanoparticles incorporated into the hydrochar matrix, as can be proven by TEM micrographs, FTIR spectra, and zeta potential. On the other hand, kinetic studies were carried out using DCF models, finding percent removal efficiencies up to 85.34% after 80 minutes of contact time. In addition, after 120 minutes of contact time, desorption of emerging pollutants from active sites took place, which indicated that the material got saturated after that t time. In real water samples, percent removal efficiencies decrease up to 57.39%, ascribable to a possible mechanism of competitive adsorption of organic or inorganic compounds, ions for active sites of the magnetic hydrochar. The main suggested adsorption mechanism between the magnetic hydrochar and diclofenac include hydrophobic and electrostatic interactions as well as hydrogen bonds. It can be concluded that the magnetic hydrochar nanocomposite could be valorized into a by-product which appears as an efficient adsorbent for DCF removal as a model emerging pollutant. These results are being complemented by modifying experimental variables such as pollutant’s initial concentration, adsorbent: adsorbate dosage ratio, and temperature. Currently, adsorption assays of other emerging pollutants are being been carried out.

Keywords: environmental remediation, emerging pollutants, hydrochar, magnetite nanoparticles

Procedia PDF Downloads 172

Authors: Hazel James P. Agngarayngay, Arnold R. Elepaño

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Mango is the third most important export fruit in the Philippines. Despite the expanding mango trade in world market, problems on postharvest losses caused by pests and diseases are still prevalent. Many disease control and pest disinfestation methods have been studied and adopted. Heat treatment is necessary to eliminate pests and diseases to be able to pass the quarantine requirements of importing countries. During heat treatments, temperature and time are critical because fruits can easily be damaged by over-exposure to heat. Modeling the process enables researchers and engineers to study the behaviour of temperature distribution within the fruit over time. Understanding physical processes through modeling and simulation also saves time and resources because of reduced experimentation. This research aimed to simulate the heat transfer mechanism and predict the temperature distribution in ‘Carabao' mangoes during hot water treatment (HWT) and extended hot water treatment (EHWT). The simulation was performed in ANSYS CFD Software, using ANSYS CFX Solver. The simulation process involved model creation, mesh generation, defining the physics of the model, solving the problem, and visualizing the results. Boundary conditions consisted of the convective heat transfer coefficient and a constant free stream temperature. The three-dimensional energy equation for transient conditions was numerically solved to obtain heat flux and transient temperature values. The solver utilized finite volume method of discretization. To validate the simulation, actual data were obtained through experiment. The goodness of fit was evaluated using mean temperature difference (MTD). Also, t-test was used to detect significant differences between the data sets. Results showed that the simulations were able to estimate temperatures accurately with MTD of 0.50 and 0.69 °C for the HWT and EHWT, respectively. This indicates good agreement between the simulated and actual temperature values. The data included in the analysis were taken at different locations of probe punctures within the fruit. Moreover, t-tests showed no significant differences between the two data sets. Maximum heat fluxes obtained at the beginning of the treatments were 394.15 and 262.77 J.s-1 for HWT and EHWT, respectively. These values decreased abruptly at the first 10 seconds and gradual decrease was observed thereafter. Data on heat flux is necessary in the design of heaters. If underestimated, the heating component of a certain machine will not be able to provide enough heat required by certain operations. Otherwise, over-estimation will result in wasting of energy and resources. This study demonstrated that the simulation was able to estimate temperatures accurately. Thus, it can be used to evaluate the influence of various treatment conditions on the temperature-time history in mangoes. When combined with information on insect mortality and quality degradation kinetics, it could predict the efficacy of a particular treatment and guide appropriate selection of treatment conditions. The effect of various parameters on heat transfer rates, such as the boundary and initial conditions as well as the thermal properties of the material, can be systematically studied without performing experiments. Furthermore, the use of ANSYS software in modeling and simulation can be explored in modeling various systems and processes.

Keywords: heat transfer, heat treatment, mango, modeling and simulation

Procedia PDF Downloads 233

Authors: Afolabi K. Esther, Kuye Tolulope, Babafemi, L. Olayemi, Omikunle Yemisi

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Background: Cervical cancer is a potentially preventable disease of public significance. All sexually active women are at risk of cervical cancer; however, the uptake and coverage are low in low-middle resource countries. Hence, the programme explored the feasibility of demonstrating an innovative and low-cost system approach to cervical cancer screening service delivery among reproductive-aged women in low–resource settings in Southwestern Nigeria. This was to promote the uptake and quality improvement of cervical cancer screening services. Methods: This study was an intervention project in three senatorial districts in Osun State that have primary, secondary and tertiary health facilities. The project was in three phases; Pre-intervention, Intervention, and Post-intervention. The study utilised the existing infrastructure, facilities and staff in project settings. The study population was nurse-midwives, community health workers and reproductive-aged women (30-49 years). The intervention phase entailed using innovative, culturally appropriate strategies to create awareness of cervical cancer and preventive health-seeking behaviour among women in the reproductive-aged group (30-49) years. Also, the service providers (community health workers, Nurses, and Midwives) were trained on screening methods and treatment of pre-cancerous lesions, and there was the provision of essential equipment and supplies for cervical cancer screening services at health facilities. Besides, advocacy and engagement were made with relevant stakeholders to integrate the cervical cancer screening services into related reproductive health services and greater allocation of resources. The expected results compared the pre and post-intervention using the baseline and process indicators and the effect of the intervention phase on screening coverage using a plausibility assessment design. The project lasted 12 months; visual Inspection with Acetic acid (VIA) screening for the women for six months and follow-up in 6 months for women receiving treatment. Results: The pre-intervention phase assessed baseline service delivery statistics in the previous 12 months drawn from the retrospective data collected as part of the routine monitoring and reporting systems. The uptake of cervical cancer screening services was low as the number of women screened in the previous 12 months was 156. Service personnel's competency level was fair (54%), and limited availability of essential equipment and supplies for cervical cancer screening services. At the post-intervention phase, the level of uptake had increased as the number of women screened was 1586 within six months in the study settings. This showed about a 100-%increase in the uptake of cervical cancer screening services compared with the baseline assessment. Also, the post-intervention level of competency of service delivery personnel had increased to 86.3%, which indicates quality improvement of the cervical cancer screening service delivery. Conclusion: the findings from the study have shown an effective approach to strengthening and improving cervical cancer screening service delivery in Southwestern Nigeria. Hence, the intervention promoted a positive attitude and health-seeking behaviour among the target population, significantly influencing the uptake of cervical cancer screening services.

Keywords: cervical cancer, screening, nigeria, health system strengthening

Procedia PDF Downloads 78

Authors: Pampita Chakraborty, Sukumar Mukherjee

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

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

Procedia PDF Downloads 319

Authors: K. A.Veselova, N. V.Gromova, I. N.Antonova, I. N. Kalakutskii

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There are many diseases and incidents that may result facial defects and deformities: cancer, trauma, burns, congenital anomalies, and autoimmune diseases. In some cases, patient may acquire atypically extensive facial defect, including more than one anatomical region or, by contrast, atypically small defect (e.g. partial auricular defect). The anaplastology gives us opportunity to help patient with facial disfigurement in cases when plastic surgery is contraindicated. Using of implant retention for facial prosthesis is strongly recommended because improves both aesthetic and functional results and makes using of the prosthesis more comfortable. Prostheticly oriented fixture position is extremely important for aesthetic and functional long-term result; however, the optimal site for fixture placement is not clear in cases with atypical configuration of facial defect. The objective of this report is to demonstrate challenges in fixture position determination we have faced with and offer the solution. In this report, four cases of implant-supported facial prosthesis are described. Extra-oral implants with four millimeter length were used in all cases. The decision regarding the quantity of surgical stages was based on anamnesis of disease. Facial prostheses were manufactured according to conventional technique. Clinical and technological difficulties and mistakes are described, and prostheticly oriented approach for determination of fixture position is demonstrated. The case with atypically large combined orbital and nasal defect resulting after arteriovenous malformation is described: the correct positioning of artificial eye was impossible due to wrong position of the fixture (with suprastructure) located in medial aspect of supraorbital rim. The suprastructure was unfixed and this fixture wasn`t used for retention in order to achieve appropriate artificial eye placement and better aesthetic result. In other case with small partial auricular defect (only helix and antihelix were absent) caused by squamoized cell carcinoma T1N0M0 surgical template was used to avoid the difficulties. To achieve the prostheticly oriented fixture position in case of extremely small defect the template was made on preliminary cast using vacuum thermoforming method. Two radiopaque markers were incorporated into template in preferable for fixture placement positions taking into account future prosthesis configuration. The template was put on remaining ear and cone-beam CT was performed to insure, that the amount of bone is enough for implant insertion in preferable position. Before the surgery radiopaque markers were extracted and template was holed for guide drill. Fabrication of implant-retained facial prostheses gives us opportunity to improve aesthetics, retention and patients’ quality of life. But every inaccuracy in planning leads to challenges on surgery and prosthetic stages. Moreover, in cases with atypically small or extended facial defects prostheticly oriented approach for determination of fixture position is strongly required. The approach including surgical template fabrication is effective, easy and cheap way to avoid mistakes and unpredictable result.

Keywords: anaplastology, facial prosthesis, implant-retained facial prosthesis., maxillofacil prosthese

Procedia PDF Downloads 80

Authors: Priyanka Sharma, Ranjita Das, Mohan C. Kalita, Debajit Thakur

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Background: Actinomycetes are the richest source of novel bioactive secondary metabolites such as antibiotics, enzymes and other therapeutically useful metabolites with diverse biological activities. The present study aims at the antimicrobial potential and genetic diversity of culturable Actinomycetes isolated from protected forest ecosystems of Assam which includes Kaziranga National Park (26°30˝-26°45˝N and 93°08˝-93°36˝E), Pobitora Wildlife Sanctuary (26º12˝-26º16˝N and 91º58˝-92º05˝E) and Gibbon Wildlife Sanctuary (26˚40˝-26˚45˝N and 94˚20˝-94˚25˝E) which are located in the North-eastern part of India. Northeast India is a part of the Indo-Burma mega biodiversity hotspot and most of the protected forests of this region are still unexplored for the isolation of effective antibiotic-producing Actinomycetes. Thus, there is tremendous possibility that these virgin forests could be a potential storehouse of novel microorganisms, particularly Actinomycetes, exhibiting diverse biological properties. Methodology: Soil samples were collected from different ecological niches of the protected forest ecosystems of Assam and Actinomycetes were isolated by serial dilution spread plate technique using five selective isolation media. Preliminary screening of Actinomycetes for an antimicrobial activity was done by spot inoculation method and the secondary screening by disc diffusion method against several test pathogens, including multidrug resistant Staphylococcus aureus (MRSA). The strains were further screened for the presence of antibiotic synthetic genes such as type I polyketide synthases (PKS-I), type II polyketide synthases (PKS-II) and non-ribosomal peptide synthetases (NRPS) genes. Genetic diversity of the Actinomycetes producing antimicrobial metabolites was analyzed through 16S rDNA-RFLP using Hinf1 restriction endonuclease. Results: Based on the phenotypic characterization, a total of 172 morphologically distinct Actinomycetes were isolated and screened for antimicrobial activity by spot inoculation method on agar medium. Among the strains tested, 102 (59.3%) strains showed activity against Gram-positive bacteria, 98 (56.97%) against Gram-negative bacteria, 92 (53.48%) against Candida albicans MTCC 227 and 130 (75.58%) strains showed activity against at least one of the test pathogens. Twelve Actinomycetes exhibited broad spectrum antimicrobial activity in the secondary screening. The taxonomic identification of these twelve strains by 16S rDNA sequencing revealed that Streptomyces was found to be the predominant genus. The PKS-I, PKS-II and NRPS genes detection indicated diverse bioactive products of these twelve Actinomycetes. Genetic diversity by 16S rDNA-RFLP indicated that Streptomyces was the dominant genus amongst the antimicrobial metabolite producing Actinomycetes. Conclusion: These findings imply that Actinomycetes from the protected forest ecosystems of Assam, India, are a potential source of bioactive secondary metabolites. These areas are as yet poorly studied and represent diverse and largely unscreened ecosystem for the isolation of potent Actinomycetes producing antimicrobial secondary metabolites. Detailed characterization of the bioactive Actinomycetes as well as purification and structure elucidation of the bioactive compounds from the potent Actinomycetes is the subject of ongoing investigation. Thus, to exploit Actinomycetes from such unexplored forest ecosystems is a way to develop bioactive products.

Keywords: Actinomycetes, antimicrobial activity, forest ecosystems, RFLP

Procedia PDF Downloads 365

Authors: Solanki Ravirajsinh, Kudo Kuniaki, Sharma Ankit, Devi Sherine, Kuboshima Misaki, Tachi Shuntaro

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In software development life cycles, the absence of scalable CI/CD significantly impacts organizations, leading to increased overall maintenance costs, prolonged release delivery times, heightened manual efforts, and difficulties in meeting tight deadlines. Implementing CI/CD with standard serverless technologies using cloud services overcomes all the above-mentioned issues and helps organizations improve efficiency and faster delivery without the need to manage server maintenance and capacity. By integrating scalable CI/CD with scalable automation testing, productivity, quality, and agility are enhanced while reducing the need for repetitive work and manual efforts. Implementing scalable CI/CD for development using cloud services like ECS (Container Management Service), AWS Fargate, ECR (to store Docker images with all dependencies), Serverless Computing (serverless virtual machines), Cloud Log (for monitoring errors and logs), Security Groups (for inside/outside access to the application), Docker Containerization (Docker-based images and container techniques), Jenkins (CI/CD build management tool), and code management tools (GitHub, Bitbucket, AWS CodeCommit) can efficiently handle the demands of diverse development environments and are capable of accommodating dynamic workloads, increasing efficiency for faster delivery with good quality. CI/CD pipelines encourage collaboration among development, operations, and quality assurance teams by providing a centralized platform for automated testing, deployment, and monitoring. Scalable CI/CD streamlines the development process by automatically fetching the latest code from the repository every time the process starts, building the application based on the branches, testing the application using a scalable automation testing framework, and deploying the builds. Developers can focus more on writing code and less on managing infrastructure as it scales based on the need. Serverless CI/CD eliminates the need to manage and maintain traditional CI/CD infrastructure, such as servers and build agents, reducing operational overhead and allowing teams to allocate resources more efficiently. Scalable CI/CD adjusts the application's scale according to usage, thereby alleviating concerns about scalability, maintenance costs, and resource needs. Creating scalable automation testing using cloud services (ECR, ECS Fargate, Docker, EFS, Serverless Computing) helps organizations run more than 500 test cases in parallel, aiding in the detection of race conditions, performance issues, and reducing execution time. Scalable CI/CD offers flexibility, dynamically adjusting to varying workloads and demands, allowing teams to scale resources up or down as needed. It optimizes costs by only paying for the resources as they are used and increases reliability. Scalable CI/CD pipelines employ automated testing and validation processes to detect and prevent errors early in the development cycle.

Keywords: achieve parallel execution, cloud services, scalable automation testing, scalable continuous integration and deployment

Procedia PDF Downloads 18

Authors: Sachin Mulmi Shrestha, Xin Fang, Hui Ye, Lihua Ren, Qinghua Ji, Ruihua Shi

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Background: Esophageal squamous cell carcinoma (ESCC) is a tumor arising from esophageal epithelial cells and is one of the major disease subtype in Asian countries, including China. Esophageal cancer is the 7th highest incidence based on the 2020 data of GLOBOCAN. The pathogenesis of cancer is still not well understood as many molecular and genetic basis of esophageal carcinogenesis has yet to be clearly elucidated. Circular RNAs are RNA molecules that are formed by back-splicing covalently joined 3′- and 5′-endsrather than canonical splicing, and recent data suggest circular RNAs could sponge miRNAs and are enriched with functional miRNA binding sites. Hence, we studied the mechanism of circular RNA, its biological function, and the relationship between microRNA in the carcinogenesis of ESCC. Methods: 4 pairs of normal and esophageal cancer tissues were collected in Zhongda hospital, affiliated to Southeast University, and high-throughput RNA sequencing was done. The result revealed that circ_0032746 was upregulated, and thus we selected circ_0032746 for further study. The backsplice junction of circRNA was validated by sanger sequence, and stability was determined by RNASE R assay. The binding site of circRNA and microRNA was predicted by circinteractome,mirandaand RNAhybrid database. Furthermore, circRNA was silenced by siRNA and then by lentivirus. The regulatory axis of circ0032746/miR4270 was validated by shRNA, mimic, and inhibitor transfection. Then, in vitro experiments were performed to assess the role of circ0032746 on proliferation (CCK-8 assay and colon formation assay), migration and invasion (Transewell assay), and apoptosis of ESCC. Results: The upregulated circ0032746 was validated in 9 pairs of tissues and 5 types of cell lines by qPCR, which showed high expression and was statistically significant (P<0.005) ). Upregulated circ0032746 was silenced by shRNA, which showed significant knockdown in KYSE 30 and TE-1 cell lines expression compared to control. Nuclear and cytoplasmic mRNA fraction experiment displayed the cytoplasmic location of circ0032746. The sponging of miR4270 was validated by co-transfection of sh-circ0032746 and mimic or inhibitor. Transfection with mimic showed the decreased expression of circ_0032746, whereas inhibitor inhibited the result. In vitro experiments showed that silencing of circ_0032746 inhibited the proliferation, migration, and invasion compared to the negative control group. The apoptosis was seen higher in a knockdown group than in the control group. Furthermore, 11 common mircoRNA target mRNAs were predicted by Targetscan, MirTarbase, and miRanda database, which may further play role in the pathogenesis. Conclusion: Our results showed that novel circ_0032746 is upregulated in ESCC and plays role in itsoncogenicity. Silencing of circ_0032746 inhibits the proliferation and migration of ESCC whereas increases the apoptosis of cancer cells. Hence, circ0032746 acts as an oncogene in ESCC by sponging with miR4270 and could be a potential biomarker in the diagnosis of ESCC in the future.

Keywords: circRNA, esophageal squamous cell carcinoma, microRNA, upregulated

Procedia PDF Downloads 88

Authors: Aurora Sheehy, Caitlin Prince

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Within current orthodox medical protocols, trauma and mental health issues are deemed to reside within the realm of cognitive or psychological therapists and are marginalised in these areas, in part due to limited drugs option available, mostly manipulating neurotransmitters or sedating patients to reduce symptoms. By contrast, this research presents examples from the clinical practice of how trauma can be assessed and treated physiologically. Adverse Childhood Experiences (ACEs) are a tally of different types of abuse and neglect. It has been used as a measurable and reliable predictor of the likelihood of the development of autoimmune disease. It is a direct way to demonstrate reliably the health impact of traumatic life experiences. A second assessment tool is Allostatic Load, which refers to the cumulative effects that chronic stress has on mental and physical health. It records the decline of an individual’s physiological capacity to cope with their experience. It uses a specific grouping of serum testing and physical measures. It includes an assessment of neuroendocrine, cardiovascular, immune and metabolic systems. Allostatic load demonstrates the health impact that trauma has throughout the body. It forms part of an initial intake assessment in clinical practice and could also be used in research to evaluate treatment. Examining medicinal plants for their physiological, neurological and somatic effects through the lens of Polyvagal theory offers new opportunities for trauma treatments. In situations where Polyvagal theory recommends activities and exercises to enable parasympathetic activation, many herbs that affect Effector Memory T (TEM) cells also enact these responses. Traditional or Indigenous European herbs show the potential to support the polyvagal tone, through multiple mechanisms. As the ventral vagal nerve reaches almost every major organ, plants that have actions on these tissues can be understood via their polyvagal actions, such as monoterpenes as agents to improve respiratory vagal tone, cyanogenic glycosides to reset polyvagal tone, volatile oils rich in phenyl methyl esters improve both sympathetic and parasympathetic tone, bitters activate gut function and can strongly promote parasympathetic regulation. Auricular Acupuncture uses a system of somatotopic mapping of the auricular surface overlaid with an image of an inverted foetus with each body organ and system featured. Given that the concha of the auricle is the only place on the body where the Vagus Nerve neurons reach the surface of the skin, several investigators have evaluated non-invasive, transcutaneous electrical nerve stimulation (TENS) at auricular points. Drawn from an interdisciplinary evidence base and developed through clinical practice, these assessment and treatment tools are examples of practitioners in the field innovating out of necessity for the best outcomes for patients. This paper draws on case studies to direct future research.

Keywords: polyvagal, auricular acupuncture, trauma, herbs

Procedia PDF Downloads 61

Authors: Meiling Yu, Nadia Rouatbi, Khuloud T. Al-Jamal

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Background: Treatment of neurological disorders with modern medical and surgical approaches remains difficult. Gene therapy, allowing the delivery of genetic materials that encodes potential therapeutic molecules, represents an attractive option. The treatment of brain diseases with gene therapy requires the gene-editing tool to be delivered efficiently to the central nervous system. In this study, we explored the efficiency of different delivery routes, namely intravenous (i.v.), intra-cranial (i.c.), and intra-nasal (i.n.), to deliver stable nucleic acid-lipid particles (SNALPs) containing gene-editing tools namely Cas9 mRNA and sgRNA encoding for GFP as a reporter protein. We hypothesise that SNALPs can reach the brain and perform gene-editing to different extents depending on the administration route. Intranasal administration (i.n.) offers an attractive and non-invasive way to access the brain circumventing the blood–brain barrier. Successful delivery of gene-editing tools to the brain offers a great opportunity for therapeutic target validation and nucleic acids therapeutics delivery to improve treatment options for a range of neurodegenerative diseases. In this study, we utilised Rosa26-Cas9 knock-in mice, expressing GFP, to study brain distribution and gene-editing efficiency of SNALPs after i.v.; i.c. and i.n. routes of administration. Methods: Single guide RNA (sgRNA) against GFP has been designed and validated by in vitro nuclease assay. SNALPs were formulated and characterised using dynamic light scattering. The encapsulation efficiency of nucleic acids (NA) was measured by RiboGreen™ assay. SNALPs were incubated in serum to assess their ability to protect NA from degradation. Rosa26-Cas9 knock-in mice were i.v., i.n., or i.c. administered with SNALPs to test in vivo gene-editing (GFP knockout) efficiency. SNALPs were given as three doses of 0.64 mg/kg sgGFP following i.v. and i.n. or a single dose of 0.25 mg/kg sgGFP following i.c.. knockout efficiency was assessed after seven days using Sanger Sequencing and Inference of CRISPR Edits (ICE) analysis. In vivo, the biodistribution of DiR labelled SNALPs (SNALPs-DiR) was assessed at 24h post-administration using IVIS Lumina Series III. Results: Serum-stable SNALPs produced were 130-140 nm in diameter with ~90% nucleic acid loading efficiency. SNALPs could reach and stay in the brain for up to 24h following i.v.; i.n. and i.c. administration. Decreasing GFP expression (around 50% after i.v. and i.c. and 20% following i.n.) was confirmed by optical imaging. Despite the small number of mice used, ICE analysis confirmed GFP knockout in mice brains. Additional studies are currently taking place to increase mice numbers. Conclusion: Results confirmed efficient gene knockout achieved by SNALPs in Rosa26-Cas9 knock-in mice expressing GFP following different routes of administrations in the following order i.v.= i.c.> i.n. Each of the administration routes has its pros and cons. The next stages of the project involve assessing gene-editing efficiency in wild-type mice and replacing GFP as a model target with therapeutic target genes implicated in Motor Neuron Disease pathology.

Keywords: CRISPR, nanoparticles, brain diseases, administration routes

Procedia PDF Downloads 72

Authors: Jae Won Lee, Kyung Hyun Min, Hong Jae Lee, Sang Cheon Lee

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To date, imaging techniques have attracted much attention in medicine because the detection of diseases at an early stage provides greater opportunities for successful treatment. Consequently, over the past few decades, diverse imaging modalities including magnetic resonance (MR), positron emission tomography, computed tomography, and ultrasound (US) have been developed and applied widely in the field of clinical diagnosis. However, each of the above-mentioned imaging modalities possesses unique strengths and intrinsic weaknesses, which limit their abilities to provide accurate information. Therefore, multimodal imaging systems may be a solution that can provide improved diagnostic performance. Among the current medical imaging modalities, US is a widely available real-time imaging modality. It has many advantages including safety, low cost and easy access for patients. However, its low spatial resolution precludes accurate discrimination of diseased region such as cancer sites. In contrast, MR has no tissue-penetrating limit and can provide images possessing exquisite soft tissue contrast and high spatial resolution. However, it cannot offer real-time images and needs a comparatively long imaging time. The characteristics of these imaging modalities may be considered complementary, and the modalities have been frequently combined for the clinical diagnostic process. Biominerals such as calcium carbonate (CaCO3) and calcium phosphate (CaP) exhibit pH-dependent dissolution behavior. They demonstrate pH-controlled drug release due to the dissolution of minerals in acidic pH conditions. In particular, the application of this mineralization technique to a US contrast agent has been reported recently. The CaCO3 mineral reacts with acids and decomposes to generate calcium dioxide (CO2) gas in an acidic environment. These gas-generating mineralized nanoparticles generated CO2 bubbles in the acidic environment of the tumor, thereby allowing for strong echogenic US imaging of tumor tissues. On the basis of this previous work, it was hypothesized that the loading of MR contrast agents into the CaCO3 mineralized nanoparticles may be a novel strategy in designing a contrast agent for dual imaging. Herein, CaCO3 mineralized nanoparticles that were capable of generating CO2 bubbles to trigger the release of entrapped MR contrast agents in response to tumoral acidic pH were developed for the purposes of US and MR dual-modality imaging of tumors. Gd2O3 nanoparticles were selected as an MR contrast agent. A key strategy employed in this study was to prepare Gd2O3 nanoparticle-loaded mineralized nanoparticles (Gd2O3-MNPs) using block copolymer-templated CaCO3 mineralization in the presence of calcium cations (Ca2+), carbonate anions (CO32-) and positively charged Gd2O3 nanoparticles. The CaCO3 core was considered suitable because it may effectively shield Gd2O3 nanoparticles from water molecules in the blood (pH 7.4) before decomposing to generate CO2 gas, triggering the release of Gd2O3 nanoparticles in tumor tissues (pH 6.4~7.4). The kinetics of CaCO3 dissolution and CO2 generation from the Gd2O3-MNPs were examined as a function of pH and pH-dependent in vitro magnetic relaxation; additionally, the echogenic properties were estimated to demonstrate the potential of the particles for the tumor-specific US and MR imaging.

Keywords: calcium carbonate, mineralization, ultrasound imaging, magnetic resonance imaging

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Authors: Vitaliy Petrov, Natalia Shusharina, Vitaliy Kasymov, Maksim Patrushev, Evgeny Bogdanov

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The leading worldwide death reasons are ischemic heart disease and other cardiovascular illnesses. Generally, the common symptom is high blood pressure. Long-time blood pressure control is very important for the prophylaxis, correct diagnosis and timely therapy. Non-invasive methods which are based on Korotkoff sounds are impossible to apply often and for a long time. Implantable devices can combine longtime monitoring with high accuracy of measurements. The main purpose of this work is to create a real-time monitoring system for decreasing the death rate from cardiovascular diseases. These days implantable electronic devices began to play an important role in medicine. Usually implantable devices consist of a transmitter, powering which could be wireless with a special made battery and measurement circuit. Common problems in making implantable devices are short lifetime of the battery, big size and biocompatibility. In these work, blood pressure measure will be the focus because it’s one of the main symptoms of cardiovascular diseases. Our device will consist of three parts: the implantable pressure sensor, external transmitter and automated workstation in a hospital. The Implantable part of pressure sensors could be based on piezoresistive or capacitive technologies. Both sensors have some advantages and some limitations. The Developed circuit is based on a small capacitive sensor which is made of the technology of microelectromechanical systems (MEMS). The Capacitive sensor can provide high sensitivity, low power consumption and minimum hysteresis compared to the piezoresistive sensor. For this device, it was selected the oscillator-based circuit where frequency depends from the capacitance of sensor hence from capacitance one can calculate pressure. The external device (transmitter) used for wireless charging and signal transmission. Some implant devices for these applications are passive, the external device sends radio wave signal on internal LC circuit device. The external device gets reflected the signal from the implant and from a change of frequency is possible to calculate changing of capacitance and then blood pressure. However, this method has some disadvantages, such as the patient position dependence and static using. Developed implantable device doesn’t have these disadvantages and sends blood pressure data to the external part in real-time. The external device continuously sends information about blood pressure to hospital cloud service for analysis by a physician. Doctor’s automated workstation at the hospital also acts as a dashboard, which displays actual medical data of patients (which require attention) and stores it in cloud service. Usually, critical heart conditions occur few hours before heart attack but the device is able to send an alarm signal to the hospital for an early action of medical service. The system was tested with wireless charging and data transmission. These results can be used for ASIC design for MEMS pressure sensor.

Keywords: MEMS sensor, RF power, wireless data, oscillator-based circuit

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Authors: Rahbel Rahman, Rogério Meireles Pinto, Margareth Santos Zanchetta

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Background: Existing shortcomings of current health-service delivery include poor teamwork, competencies that do not address consumer needs, and episodic rather than continuous care. Brazil’s Sistema Único de Saúde (Unified Health System, UHS) is acknowledged worldwide as a model for delivering community-based care through Estratégia Saúde da Família (FHS; Family Health Strategy) interdisciplinary teams, comprised of Community Health Agents (in Portuguese, Agentes Comunitário de Saude, ACS), nurses, and physicians. FHS teams are mandated to collectively offer clinical care, disease prevention services, vector control, health surveillance and social services. Our study compares medical providers (nurses and physicians) and community-based providers (ACS) on their perceptions of work environment, professional skills, cognitive capacities and job context. Global health administrators and policy makers can leverage on similarities and differences across care providers to develop interprofessional training for community-based primary care. Methods: Cross-sectional data were collected from 168 ACS, 62 nurses and 32 physicians in Brazil. We compared providers’ demographic characteristics (age, race, and gender) and job context variables (caseload, work experience, work proximity to community, the length of commute, and familiarity with the community). Providers perceptions were compared to their work environment (work conditions and work resources), professional skills (consumer-input, interdisciplinary collaboration, efficacy of FHS teams, work-methods and decision-making autonomy), and cognitive capacities (knowledge and skills, skill variety, confidence and perseverance). Descriptive and bi-variate analysis, such as Pearson Chi-square and Analysis of Variance (ANOVA) F-tests, were performed to draw comparisons across providers. Results: Majority of participants were ACS (64%); 24% nurses; and 12% physicians. Majority of nurses and ACS identified as mixed races (ACS, n=85; nurses, n=27); most physicians identified as males (n=16; 52%), and white (n=18; 58%). Physicians were less likely to incorporate consumer-input and demonstrated greater decision-making autonomy than nurses and ACS. ACS reported the highest levels of knowledge and skills but the least confidence compared to nurses and physicians. ACS, nurses, and physicians were efficacious that FHS teams improved the quality of health in their catchment areas, though nurses tend to disagree that interdisciplinary collaboration facilitated their work. Conclusion: To our knowledge, there has been no study comparing key demographic and cognitive variables across ACS, nurses and physicians in the context of their work environment and professional training. We suggest that global health systems can leverage upon the diverse perspectives of providers to implement a community-based primary care model grounded in interprofessional training. Our study underscores the need for in-service trainings to instill reflective skills of providers, improve communication skills of medical providers and curative skills of ACS. Greater autonomy needs to be extended to community based providers to offer care integral to addressing consumer and community needs.

Keywords: global health systems, interdisciplinary health teams, community health agents, community-based care

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Authors: Yu-Mei Hsueh, Wei-Jen Chen, Yung-Kai Huang, Cheng-Shiuan Tsai, Kuo-Cheng Yeh

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Prostate cancer occurs in men over the age of 50, and rank sixth of the top ten cancers in Taiwan, and the incidence increased gradually over the past decade in Taiwan. Arsenic is confirmed as a carcinogen by International Agency for Research on (IARC). Arsenic induces oxidative stress may be a risk factor for prostate cancer, but the mechanism is not clear. Selenium is an important antioxidant element. Whether the association between plasma selenium levels and risk of prostate cancer are modified by different genotype of selenoprotein is still unknown. Glutathione peroxidase, selenoprotein P (SEPP1) and 15 kDa selenoprotein (SEP 15) are selenoprotein and regulates selenium transport and the oxidation and reduction reaction. However, the association between gene polymorphisms of selenoprotein and prostate cancer is not yet clear. The aim of this study is to determine the relationship between plasma selenium, polymorphism of selenoprotein, urinary total arsenic concentration and prostate cancer. This study is a hospital-based case-control study. Three hundred twenty-two cases of prostate cancer and age (±5 years) 1:1 matched 322 control group were recruited from National Taiwan University Hospital, Taipei Medical University Hospital, and Wan Fang Hospital. Well-trained personnel carried out standardized personal interviews based on a structured questionnaire. Information collected included demographic and socioeconomic characteristics, lifestyle and disease history. Blood and urine samples were also collected at the same time. The Research Ethics Committee of National Taiwan University Hospital, Taipei, Taiwan, approved the study. All patients provided informed consent forms before sample and data collection. Buffy coat was to extract DNA, and the polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) was used to measure the genotypes of SEPP1 rs3797310, SEP15 rs5859, GPX1 rs1050450, GPX2 rs4902346, GPX3 rs4958872, and GPX4 rs2075710. Plasma concentrations of selenium were determined by inductively coupled plasma mass spectrometry (ICP-MS).Urinary arsenic species concentrations were measured by high-performance liquid chromatography links hydride generator and atomic absorption spectrometer (HPLC-HG-AAS). Subject with high education level compared to those with low educational level had a lower prostate cancer odds ratio (OR) Mainland Chinese and aboriginal people had a lower OR of prostate cancer compared to Fukien Taiwanese. After adjustment for age, educational level, subjects with GPX1 rs1050450 CT and TT genotype compared to the CC genotype have lower, OR of prostate cancer, the OR and 95% confidence interval (Cl) was 0.53 (0.31-0.90). SEPP1 rs3797310 CT+TT genotype compared to those with CC genotype had a marginally significantly lower OR of PC. The low levels of plasma selenium and the high urinary total arsenic concentrations had the high OR of prostate cancer in a significant dose-response manner, and SEPP1 rs3797310 genotype modified this joint association.

Keywords: prostate cancer, plasma selenium concentration, urinary total arsenic concentrations, glutathione peroxidase, selenoprotein P, selenoprotein 15, gene polymorphism

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Authors: Changhan Ouyang, Zhonglin Xie

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In response to proatherosclerotic factors such as oxidized lipids, or to therapeutic interventions such as angioplasty, stents, or bypass surgery, vascular smooth muscle cells (VSMCs) migrate from the media to the intima, resulting in intimal hyperplasia, restenosis, graft failure, or atherosclerosis. These proatherosclerotic factors also activate autophagy in VSMCs. However, the functional role of autophagy in vascular health and disease remains poorly understood. In the present study, we determined the role of autophagy in the regulation of VSMC migration. Autophagy activity in cultured human aortic smooth muscle cells (HASMCs) and mouse carotid arteries was measured by Western blot analysis of microtubule-associated protein 1 light chain 3 B (LC3B) and P62. The VSMC migration was determined by scratch wound assay and transwell migration assay. Ex vivo smooth muscle cell migration was determined using aortic ring assay. The in vivo SMC migration was examined by staining the carotid artery sections with smooth muscle alpha actin (alpha SMA) after carotid artery ligation. To examine the relationship between autophagy and neointimal hyperplasia, C57BL/6J mice were subjected to carotid artery ligation. Seven days after injury, protein levels of Atg5, Atg7, Beclin1, and LC3B drastically increased and remained higher in the injured arteries three weeks after the injury. In parallel with the activation of autophagy, vascular injury-induced neointimal hyperplasia as estimated by increased intima/media ratio. The en face staining of carotid artery showed that vascular injury enhanced alpha SMA staining in the intimal cells as compared with the sham operation. Treatment of HASMCs with platelet-derived growth factor (PDGF), one of the major factors for vascular remodeling in response to vascular injury, increased Atg7 and LC3 II protein levels and enhanced autophagosome formation. In addition, aortic ring assay demonstrated that PDGF treated aortic rings displayed an increase in neovessel formation compared with control rings. Whole mount staining for CD31 and alpha SMA in PDGF treated neovessels revealed that the neovessel structures were stained by alpha SMA but not CD31. In contrast, pharmacological and genetic suppression of autophagy inhibits VSMC migration. Especially, gene silencing of Atg7 inhibited VSMC migration induced by PDGF. Furthermore, three weeks after ligation, markedly decreased neointimal formation was found in mice treated with chloroquine, an inhibitor of autophagy. Quantitative morphometric analysis of the injured vessels revealed a marked reduction in the intima/media ratio in the mice treated with chloroquine. Conclusion: Autophagy activation increases VSMC migration while autophagy suppression inhibits VSMC migration. These findings suggest that autophagy suppression may be an important therapeutic strategy for atherosclerosis and intimal hyperplasia.

Keywords: autophagy, vascular smooth muscle cell, migration, neointimal formation

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Authors: Nurkhairul Bariyah Baharun, Afzan Adam, Reena Rahayu Md Zin

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Tumor microenvironment (TME) in breast cancer is mainly composed of cancer cells, immune cells, and stromal cells. The interaction between cancer cells and their microenvironment plays an important role in tumor development, progression, and treatment response. The TME in breast cancer includes tumor-infiltrating lymphocytes (TILs) that are implicated in killing tumor cells. TILs can be found in tumor stroma (sTILs) and within the tumor (iTILs). TILs in triple negative breast cancer (TNBC) have been demonstrated to have prognostic and potentially predictive value. The international Immune-Oncology Biomarker Working Group (TIL-WG) had developed a guideline focus on the assessment of sTILs using hematoxylin and eosin (H&E)-stained slides. According to the guideline, the pathologists use “eye balling” method on the H&E stained- slide for sTILs assessment. This method has low precision, poor interobserver reproducibility, and is time-consuming for a comprehensive evaluation, besides only counted sTILs in their assessment. The TIL-WG has therefore recommended that any algorithm for computational assessment of TILs utilizing the guidelines provided to overcome the limitations of manual assessment, thus providing highly accurate and reliable TILs detection and classification for reproducible and quantitative measurement. This study is carried out to develop a TNBC digital whole slide image (WSI) dataset from H&E-stained slides and IHC (CD4+ and CD8+) stained slides. TNBC cases were retrieved from the database of the Department of Pathology, Hospital Canselor Tuanku Muhriz (HCTM). TNBC cases diagnosed between the year 2010 and 2021 with no history of other cancer and available block tissue were included in the study (n=58). Tissue blocks were sectioned approximately 4 µm for H&E and IHC stain. The H&E staining was performed according to a well-established protocol. Indirect IHC stain was also performed on the tissue sections using protocol from Diagnostic BioSystems PolyVue™ Plus Kit, USA. The slides were stained with rabbit monoclonal, CD8 antibody (SP16) and Rabbit monoclonal, CD4 antibody (EP204). The selected and quality-checked slides were then scanned using a high-resolution whole slide scanner (Pannoramic DESK II DW- slide scanner) to digitalize the tissue image with a pixel resolution of 20x magnification. A manual TILs (sTILs and iTILs) assessment was then carried out by the appointed pathologist (2 pathologists) for manual TILs scoring from the digital WSIs following the guideline developed by TIL-WG 2014, and the result displayed as the percentage of sTILs and iTILs per mm² stromal and tumour area on the tissue. Following this, we aimed to develop an automated digital image scoring framework that incorporates key elements of manual guidelines (including both sTILs and iTILs) using manually annotated data for robust and objective quantification of TILs in TNBC. From the study, we have developed a digital dataset of TNBC H&E and IHC (CD4+ and CD8+) stained slides. We hope that an automated based scoring method can provide quantitative and interpretable TILs scoring, which correlates with the manual pathologist-derived sTILs and iTILs scoring and thus has potential prognostic implications.

Keywords: automated quantification, digital pathology, triple negative breast cancer, tumour infiltrating lymphocytes

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Authors: Mingxin Li, Liya Ni

Abstract:

Autonomous parking is a valuable feature applicable to many robotics applications such as tour guide robots, UV sanitizing robots, food delivery robots, and warehouse robots. With auto-parking, the robot will be able to park at the charging zone and charge itself without human intervention. As compared to self-driving vehicles, auto-parking is more challenging for a small-scale mobile robot only equipped with a front camera due to the camera view limited by the robot’s height and the narrow Field of View (FOV) of the inexpensive camera. In this research, auto-parking of a small-scale mobile robot with a front camera only was achieved in a four-step process: Firstly, transfer learning was performed on the AlexNet, a popular pre-trained convolutional neural network (CNN). It was trained with 150 pictures of empty parking slots and 150 pictures of occupied parking slots from the view angle of a small-scale robot. The dataset of images was divided into a group of 70% images for training and the remaining 30% images for validation. An average success rate of 95% was achieved. Secondly, the image of detected empty parking space was processed with edge detection followed by the computation of parametric representations of the boundary lines using the Hough Transform algorithm. Thirdly, the positions of the entrance point and center of available parking space were predicted based on the robot kinematic model as the robot was driving closer to the parking space because the boundary lines disappeared partially or completely from its camera view due to the height and FOV limitations. The robot used its wheel speeds to compute the positions of the parking space with respect to its changing local frame as it moved along, based on its kinematic model. Lastly, the predicted entrance point of the parking space was used as the reference for the motion control of the robot until it was replaced by the actual center when it became visible again by the robot. The linear and angular velocities of the robot chassis center were computed based on the error between the current chassis center and the reference point. Then the left and right wheel speeds were obtained using inverse kinematics and sent to the motor driver. The above-mentioned four subtasks were all successfully accomplished, with the transformed learning, image processing, and target prediction performed in MATLAB, while the motion control and image capture conducted on a self-built small scale differential drive mobile robot. The small-scale robot employs a Raspberry Pi board, a Pi camera, an L298N dual H-bridge motor driver, a USB power module, a power bank, four wheels, and a chassis. Future research includes three areas: the integration of all four subsystems into one hardware/software platform with the upgrade to an Nvidia Jetson Nano board that provides superior performance for deep learning and image processing; more testing and validation on the identification of available parking space and its boundary lines; improvement of performance after the hardware/software integration is completed.

Keywords: autonomous parking, convolutional neural network, image processing, kinematics-based prediction, transfer learning

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