Search results for: chronic venous disease

Authors: Najeeb Ullah Khan

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Background: The receptor activator NF-κβ ligand (RANKL) and Osteoprotegerin (OPG) polymorphisms have been associated with the progression of breast cancer to bone metastasis. Here, we aimed to investigate the association of RANKL and OPG gene polymorphism with breast to bone metastasis in the Pashtun population, Pakistan. Methods: Genomic DNA was obtained from all the study subjects (106 breast cancer, 58 breast to bone metastasis, and 51 healthy controls). RANKL (rs9533156) and OPG (rs2073618, rs3102735) polymorphisms were genotyped using Tetra-ARMS PCR. Results: Our results indicated that the frequencies of OPG (rs3102735) risk allele and genotypes carrying risk allele in breast cancer vs healthy control (C- p=0.005; CC- p=0.0208; TC- p=0.0181), bone metastasis vs healthy control (C- p=0.0211; CC- p=0.0153; TC- p=0.0775), and breast cancer vs breast to bone metastasis (C- p=0.0001; CC- p=0.0001; TC- p=0.001) were found significantly associated with disease risk. However, there was no significant association observed for OPG (rs2073618) risk allele and risk allele containing genotypes in all study groups. Similarly, RANKL (rs9533156) risk alleles and corresponding genotypes in breast cancer vs healthy control (C- p=0.0001; CC- p=0.0001; TC- p=0.0084), bone metastasis vs healthy control (C- p=0.0001; CC- p=0.0001; TC- p=0.5593), and breast cancer vs breast to bone metastasis (C- p=0.0185; CC- p=0.6077; TC- p=0.1436) showed significant association except for the risk allele carrying genotypes in breast cancer to bone metastasis (TC, p=0.1436; CC, p=0.6077). Conclusion: OPG (rs3102735) and RANKL (rs9533156) showed significant association with breast to bone metastasis, while OPG (rs2073618) didn’t show a significant association with breast to bone metastasis in Pashtun population of Pakistan. However, more investigation will be required to disseminate the results while gene sequencing or whole-exome sequencing.

Keywords: breast cancer, bone metastasis, OPG, RANKL, polymorphism

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Authors: Filip Franciszek Karuga, Szymon Turkiewicz, Marta Ditmer, Marcin Sochal, Piotr Białasiewicz, Agata Gabryelska

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Circadian rhythm, an internal coordinator of physiological processes is composed of a set of semi-autonomous clocks. Clocks are regulated through the expression of circadian clock genes which form feedback loops, creating an oscillator. The primary loop consists of activators: CLOCK, BMAL1 and repressors: CRY, PER. CLOCK can be substituted by the Neuronal PAS Domain Protein 2 (NPAS2). Orphan nuclear receptor (REV-ERB-α) is a component of the secondary major loop, modulating the expression of BMAL1. Circadian clocks might be disrupted by the obstructive sleep apnea (OSA), which has also been associated with type II diabetes mellitus (DM2). Interestingly, studies suggest that dysregulation of NPAS2 and REV-ERB-α might contribute to the pathophysiology of DM2 as well. The goal of our study was to examine the role of NPAS2 and REV-ERB-α in DM2 in OSA patients. After examination of the clinical data, all participants underwent polysomnography (PSG) to assess their apnea-hypopnea index (AHI). Based on the acquired data participants were assigned to one of 3 groups: OSA (AHI>30, no DM2; n=17 for NPAS2 and 34 for REV-ERB-α), DM2 (AHI>30 + DM2; n=7 for NPAS2 and 15 for REV-ERB-α) and control group (AHI<5, no DM2; n=16 for NPAS2 and 31 for REV-ERB-α). ELISA immunoassay was performed to assess the serum protein level of REV-ERB-α and NPAS2. The only statistically significant difference between groups was observed in NPAS2 protein level (p=0.037). Post-hoc analysis showed significant differences between the OSA and the control group (p=0.017). AHI and NPAS2 level was significantly correlated (r=-0.478, p=0.002) in all groups. A significant correlation was observed between the REV-ERB-α level and sleep efficiency (r=0.617, p=0.005) as well as sleep maintenance efficiency (r=0.645, p=0.003) in the OSA group. We conclude, that NPAS2 is associated with OSA severity and might contribute to metabolic sequelae of this disease. REV-ERB-α on the other hand can influence sleep continuity and efficiency.

Keywords: OSA, diabetes mellitus, endocrinology, chronobiology

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Authors: Jacob Medupe

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Life as we know it has changed since the global outbreak of Coronavirus Disease 2019 (COVID-19) and business as usual will not continue. The human impact of the COVID-19 crisis is already immeasurable. Moreover, COVID-19 has already negatively impacted economies, livelihoods and disrupted food systems around the world. The disruptive nature of the Corona virus has affected every sphere of life including the culture and teaching and learning. Right now the majority of education research is based around classroom management techniques that are no longer necessary with digital delivery. Instead there is a great need for new data about how to make the best use of the one-on-one attention that is now becoming possible (Diamandis & Kotler, 2014). The COVID-19 pandemic has necessitated an environment where the South African learners are focused to adhere to social distancing in order to minimise the wild spread of the Corona virus. This arrangement forces the student to utilise the online classroom technologies to continue with the lessons. The historical reality is that the country has not made much strides on the closing of the digital divide and this is particularly a common status quo in the deep rural areas. This will prove to be a toll order for most of the learners affected by the Corona Virus to be able to have a seamless access to the online learning facilities. The paper will seek to look deeply into this reality and how the Corona virus has brought us to the reality that South Africa remains a deeply unequal society in every sphere of life. The study will also explore the state of readiness for education system around the online classroom environment.

Keywords: virtual learning, virtual classroom, COVID-19, Corona virus, internet connectivity, blended learning, online learning, distance education, e-learning, self-regulated Learning, pedagogy, digital literacy

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Authors: Azza A. Ali, Hebatalla I. Ahmed, Asmaa Abdelaty

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Background: Manganese (Mn) is a naturally occurring element. Exposure to high levels of Mn causes neurotoxic effects and represents an environmental risk factor. Mn neurotoxicity is poorly understood but changing of AChE activity, monoamines and oxidative stress has been established. Bisphenol A (BPA) is a synthetic compound widely used in the production of polycarbonate plastics. There is considerable debate about whether its exposure represents an environmental risk. Caffeine is one of the major contributors to the dietary antioxidants which prevent oxidative damage and may reduce the risk of chronic neurodegenerative diseases. Epigallocatechin-3-gallate is another major component of green tea and has known interactions with caffeine. It also has health-promoting effects in CNS. Objective: To evaluate the potential protective effects of Caffeine and/or EGCG against Mn-induced neurotoxicity either alone or in the presence of BPA in rats. Methods: Seven groups of rats were used and received daily for 5 weeks MnCl2.4H2O (10 mg/kg, IP) except the control group which received saline, corn oil and distilled H2O. Mn was injected either alone or in combination with each of the following: BPA (50 mg/kg, PO), caffeine (10 mg/kg, PO), EGCG (5 mg/kg, IP), caffeine + EGCG and BPA +caffeine +EGCG. All rats were examined in five behavioral tests (grid, bar, swimming, open field and Y- maze tests). Biochemical changes in monoamines, caspase-3, PGE2, GSK-3B, glutamate, acetyl cholinesterase and oxidative parameters, as well as histopathological changes in the brain, were also evaluated for all groups. Results: Mn significantly increased MDA and nitrite content as well as caspase-3, GSK-3B, PGE2 and glutamate levels while significantly decreased TAC and SOD as well as cholinesterase in the striatum. It also decreased DA, NE and 5-HT levels in the striatum and frontal cortex. BPA together with Mn enhanced oxidative stress generation induced by Mn while increased monoamine content that was decreased by Mn in rat striatum. BPA abolished neuronal degeneration induced by Mn in the hippocampus but not in the substantia nigra, striatum and cerebral cortex. Behavioral examinations showed that caffeine and EGCG co-administration had more pronounced protective effect against Mn-induced neurotoxicity than each one alone. EGCG alone or in combination with caffeine prevented neuronal degeneration in the substantia nigra, striatum, hippocampus and cerebral cortex induced by Mn while caffeine alone prevented neuronal degeneration in the substantia nigra and striatum but still showed some nuclear pyknosis in cerebral cortex and hippocampus. The marked protection of caffeine and EGCG co-administration also confirmed by the significant increase in TAC, SOD, ACHE, DA, NE and 5-HT as well as the decrease in MDA, nitrite, caspase-3, PGE2, GSK-3B, the glutamic acid in the striatum. Conclusion: Neuronal degeneration induced by Mn showed some inhibition with BPA exposure despite the enhancement in oxidative stress generation. Co-administration of EGCG and caffeine can protect against neuronal degeneration induced by Mn and improve behavioral deficits associated with its neurotoxicity. The protective effect of EGCG was more pronounced than that of caffeine even with BPA co-exposure.

Keywords: manganese, bisphenol a, caffeine, epigallocatechin-3-gallate, neurotoxicity, behavioral tests, rats

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Authors: Florian Lienert, Peter Costa, Caroline Aurensan, Elaine Melander

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Introduction: Rabies pre-exposure prophylaxis (PrEP) can be given before travel and simplifies post-exposure prophylaxis (PEP). We studied the knowledge about rabies, the uptake of PrEP, and reasons for deciding for or against PrEP in at-risk travelers. We also examined how healthcare professionals (HCPs) counsel on rabies prevention. Methods: On behalf of Bavarian Nordic, Ipsos MORI conducted two online surveys in the USA. Fieldwork from February 24th to April 23rd, 2021, 689 participants aged 18-85 years, visited one of 91 endemic rabies countries in the past 3 years for at least one week, involved in at least 1 of 7 at-risk activities, heard of rabies, positive towards vaccination and chose to take part (surveyed travelers). Secondly, 76 HCPs, with responsibility for advising/ making decisions about vaccination requirements for their patients, personally recommend or prescribe vaccines for rabies, positive towards vaccination and chose to take part (surveyed HCPs). Results: A minority (36%) of surveyed travelers classified rabies as a life-threatening disease. A third of surveyed HCPs (37%) did not discuss rabies vaccination with at-risk travelers, 18% discussed only PEP, 23% only PrEP and 22% both. A minority (21%) of surveyed travelers reported having received rabies vaccination since they were 18. Among those participants (n=145), the most common reasons for deciding to get PrEP were for their own peace of mind (35%) and following an HCP recommendation (32%). Of those who decided not to receive the rabies vaccine (n=319), the most common reasons were that they did not think their risk of rabies was sufficient (23%) and that the HCP did not suggest it (23%). Conclusions: The survey demonstrated knowledge gaps around rabies and low PrEP coverage among surveyed travelers. It also highlighted the role of HCP recommendations and showed that most HCPs did not discuss PrEP with at-risk travelers.

Keywords: rabies, pre-exposure prophylaxis, travel, travel health, post-travel care, rabies treatment, vaccine, post-exposure, prophylaxis, at-risk, education, PrEP, PEP

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Authors: Omoruyi Gold Idemudia, Alexander P. Sadimenko

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The synthesis of N-heterocycles with novel properties, having broad spectrum biological activities that may become alternative medicinal drugs, have been attracting a lot of research attention due to the emergence of medicinal drug’s limitations such as disease resistance and their toxicity effects among others. Acylpyrazolones have been employed as pharmaceuticals as well as analytical reagent and their application as coordination complexes with transition metal ions have been well established. By way of a condensation reaction with amines acylpyrazolone ketones form a more chelating and superior group of compounds known as azomethines. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one was reacted with phenylhydrazine to get a new phenylhydrazone which was further reacted with aqueous solutions of palladium and platinum salts, in an effort towards the discovery of transition metal based synthetic drugs. The compounds were characterized by means of analytical, spectroscopic, thermogravimetric analysis TGA, as well as x-ray crystallography. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one phenylhydrazone crystallizes in a triclinic crystal system with a P-1 (No. 2) space group based on x-ray crystallography. The bidentate ON ligand formed a square planar geometry on coordinating with metal ions based on FTIR, electronic and NMR spectra as well as magnetic moments. Reported compounds showed antibacterial activities against the nominated bacterial isolates using the disc diffusion technique at 20 mg/ml in triplicates. The metal complexes exhibited a better antibacterial activity with platinum complex having an MIC value of 0.63 mg/ml. Similarly, ligand and complexes also showed antioxidant scavenging properties against 2, 2-diphenyl-1-picrylhydrazyl DPPH radical at 0.5mg/ml relative to ascorbic acid (standard drug).

Keywords: acylpyrazolone, antibacterial studies, metal complexes, phenylhydrazone, spectroscopy

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Authors: Fatma Koksal Çakirlar, Si̇nem Ozdemir, Selcan Akyol, Revazi̇ye Gulesen, Murat Gunaydin, Nevri̇ye Gonullu, Belkis Levent, Nuri̇ Kiraz

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Vibrio cholerae O1 and O139 are the causative agent of epidemic or pandemic cholera. V. cholerae O1 is generally accepted as a non-invasive enterotoxigenic organism causing gastroenteritis of various severities. Non-O1 V. cholerae can cause small outbreaks of diarrhea due to consumption of contaminated food and water. Particularly, the patients with achlorydria have a risk for vibrio infections. There are numerous case reports of bacteremia caused by vibrio in patients with predisposing conditions like cirrhosis, nephrotic syndrome, diabetes, hematologic malignancy, gastrectomy, and AIDS. We described in this study the first case of nontoxigenic, non-01/non-O139 V. cholerae isolated from the blood culture of a 77-year-old female patient with hipertension, diabetes, coronary artery disease, gout and about 9 years ago migrated breast cancer history. The patient with complaints of shortness of breath, fever and malaise admitted to our emergency clinic were evaluated. There was no diarrhea or abdominal symptoms in the patient. No growth in her urine culture, but blood culture (BACTEC 9120 system, Becton Dickinson, USA) was positive for non-01/non-O139 V. cholerae that was identified by conventional methods and Phoenix automated system (BD Diagnostic Systems, Sparks, MD). It does not secrete the cholera toxin. The agglutination test was negative with polyvalent O1 antisera and O139 antiserum. Empirically ceftriaxone was administered to the patient and she was discharged with improvement in general condition. In this study we report bacteremia by non-01/non-O139 V. cholerae that is rare in the worldwide and first in Turkey.

Keywords: bacteremia, blood culture, immunocompromised patient, Non-O1 vibrio cholerae

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Authors: Alireza Jalalvand, Maryam Saleh, Somayeh Behjat Khatouni, Zahra Bahri Najafi, Foroozan Fatahinia, Narges Ismailzadeh, Behrokh Farahmand

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Object: In the last two decades, the recent outbreak of Coronavirus (SARS-CoV-2) imposed a global pandemic in the world. Despite the increasing prevalence of the disease, there are no effective drugs to treat it. A suitable and rapid way to afford an effective drug and treat the global pandemic is a computational drug study. This study used molecular docking methods to examine the potential inhibition of over 50 antiviral drugs against three fundamental proteins of SARS-CoV-2. METHODS: Through a literature review, three important proteins (a key protease, RNA-dependent RNA polymerase (RdRp), and spike) were selected as drug targets. Three-dimensional (3D) structures of protease, spike, and RdRP proteins were obtained from the Protein Data Bank. Protein had minimal energy. Over 50 antiviral drugs were considered candidates for protein inhibition and their 3D structures were obtained from drug banks. The Autodock 4.2 software was used to define the molecular docking settings and run the algorithm. RESULTS: Five drugs, including indinavir, lopinavir, saquinavir, nelfinavir, and remdesivir, exhibited the highest inhibitory potency against all three proteins based on the binding energies and drug binding positions deduced from docking and hydrogen-bonding analysis. Conclusions: According to the results, among the drugs mentioned, saquinavir and lopinavir showed the highest inhibitory potency against all three proteins compared to other drugs. It may enter laboratory phase studies as a dual-drug treatment to inhibit SARS-CoV-2.

Keywords: covid-19, drug repositioning, molecular docking, lopinavir, saquinavir

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Authors: Alyaa Farouk Ibrahim, Gehan ElSayed, Ola Mamdouh, Nazek AbdelGhany

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Background: Primary health care (PHC) can be considered the first contact between the patient and the health care system. It includes all the basic health care services to be provided to the community. Patient's satisfaction regarding health care has often improved the provision of care, also considered as one of the most important measures for evaluating the health care. Objective: This study aims to identify patient’s satisfaction with services provided at the primary health care settings in Alexandria. Setting: Seven primary health care settings representing the seven zones of Alexandria governorate were selected randomly and included in the study. Subjects: The study comprised 386 patients attended the previously selected settings at least twice before the time of the study. Tools: Two tools were utilized for data collection; sociodemographic characteristics and health status structured interview schedule and patient satisfaction scale. Reliability test for the scale was done using Cronbach's Alpha test, the result of the test ranged between 0.717 and 0.967. The overall satisfaction was computed and divided into high, medium, and low satisfaction. Results: Age of the studied sample ranged between 19 and 62 years, more than half (54.2%) of them aged 40 to less than 60 years. More than half (52.8%) of the patients included in the study were diabetics, 39.1% of them were hypertensive, 19.2% had cardiovascular diseases, the rest of the sample had tumor, liver diseases, and orthopedic/neurological disorders (6.5%, 5.2% & 3.2%, respectively). The vast majority of the study group mentioned high satisfaction with overall service cost, environmental conditions, medical staff attitude and health education given at the PHC settings (87.8%, 90.7%, 86.3% & 90.9%, respectively), however, medium satisfaction was mostly reported concerning medical checkup procedures, follow-up data and referral system (41.2%, 28.5% & 28.9%, respectively). Score level of patient satisfaction with health services provided at the assessed Primary health care settings proved to be significantly associated with patients’ social status (P=0.003, X²=14.2), occupation (P=0.011, X²=11.2), and monthly income (P=0.039, X²=6.50). In addition, a significant association was observed between score level of satisfaction and type of illness (P=0.007, X²=9.366), type of medication (P=0.014, X²=9.033), prior knowledge about the health center (P=0.050, X²=3.346), and highly significant with the administrative zone (P=0.001, X²=55.294). Conclusion: The current study revealed that overall service cost, environmental conditions, staff attitude and health education at the assessed primary health care settings gained high patient satisfaction level, while, medical checkup procedures, follow-up, and referral system caused a medium level of satisfaction among assessed patients. Nevertheless, social status, occupation, monthly income, type of illness, type of medication and administrative zones are all factors influencing patient satisfaction with services provided at the health facilities.

Keywords: patient satisfaction, chronic illness, quality of health service, quality of service indicators

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Authors: Nouira Mariem, Ennigrou Samir

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Background and aims: Healthcare-associated infections (HAI) represent a major public health problem worldwide. They represent one of the most serious adverse events in health care. The objectives of our study were to estimate the prevalence of HAI at the Charles Nicolle Hospital (CNH) and to identify the main associated factors as well as to estimate the frequency of antibiotic use. Methods: It was a cross-sectional study at the CNH with a unique passage per department (October-December 2018). All patients present at the wards for more than 48 hours were included. All patients from outpatient consultations, emergency, and dialysis departments were not included. The site definitions of infections proposed by the Centers for Disease Control and Prevention (CDC) were used. Only clinically and/or microbiologically confirmed active HAIs were included. Results: A total of 318 patients were included, with a mean age of 52 years and a sex ratio (female/male) of 1.05. A total of 41 patients had one or more active HAIs, corresponding to a prevalence of 13.1% (95% CI: 9.3%-16.9%). The most frequent site infections were urinary tract infections and pneumonia. Multivariate analysis among adult patients (>=18 years) (n=261) revealed that infection on admission (p=0.01), alcoholism (p=0.01), high blood pressure (p=0.008), having at least one invasive device inserted (p=0.004), and history of recent surgery (p=0.03), increased the risk of HAIs significantly. More than 1 of 3 patients (35.4%) were under antibiotics on the day of the survey, of which more than half (57.4%) were under two or more types of antibiotics. Conclusion: The prevalence of HAIs and antibiotic prescriptions at the CNH were considerably high. An infection prevention and control committee, as well as the development of an antibiotic stewardship program with continuous monitoring using repeated prevalence surveys, must be implemented to limit the frequency of these infections effectively.

Keywords: prevalence, healthcare associated infection, antibiotic, Tunisia

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Authors: Omar Ali, Adesh Ramsubhag, Jayaraj Jayaraman

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Seaweed extracts have been reported as plant biostimulants which could be a safer, organic alternative to harsh pesticides. The incentive to use seaweed-based biostimulants is becoming paramount in sustainable agriculture. The current study, therefore, screened a commercial extract of A. nodosum in tomatoes, cultivated in Trinidad to showcase the multiple beneficial effects. Foliar treatment with an A. nodosum commercial extract led to significant increases in fruit yield and a significant reduction of incidence of bacterial spots and early blight diseases under both greenhouse and field conditions. Investigations were carried out to reveal the possible mechanisms of action of this biostimulant through defense enzyme assays and transcriptome profiling via RNA sequencing of tomato. Studies into disease control mechanisms by A. nodosum showed that the extract stimulated the activity of enzymes such as peroxidase, phenylalanine ammonia-lyase, chitinase, polyphenol oxidase, and β-1,3-glucanase. Additionally, the transcriptome survey revealed the upregulation and enrichment of genes responsible for the biosynthesis of growth hormones, defense enzymes, PR proteins and defense-related secondary metabolites, as well as genes involved in the nutrient mobilization, photosynthesis and primary and secondary metabolic pathways. The results of the transcriptome study also demonstrated the cross-talks between growth and defense responses, confirming the bioelicitor and biostimulant value of seaweed extracts in plants. These effects could potentially implicate the benefits of seaweed extract and validate its usage in sustainable crop production.

Keywords: A. nodosum, biostimulants, elicitor, enzymes, growth responses, seaweeds, tomato, transcriptome analysis

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Authors: C. M. Williams, R. English, P. King, I. M. Brown

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Introduction: Pseudoangiomatous Stromal Hyperplasia (PASH) is a benign fibrous proliferation of breast stroma affecting predominantly premenopausal women with no significant increased risk of breast cancer. Informal recommendations for management have continued to evolve over recent years from surgical excision to observation, although there are no specific national guidelines. This study assesses the safety of a non-surgical approach to PASH management by review of cases at a single centre. Methods: Retrospective case series review (January 2011 – August 2016) was conducted on consecutive PASH cases. Diagnostic classification (clinical, radiological and histological), management outcomes, and breast cancer incidence were recorded. Results: 43 patients were followed up for median of 25 months (3-64) with 75% symptomatic at presentation. 12% of cases (n=5) had a radiological score (BIRADS MMG or US) ≥ 4 of which 3 were confirmed malignant. One further malignancy was detected and proven radiologically occult and contralateral. No patients were diagnosed with a malignancy during follow-up. Treatment evolved from 67% surgical in 2011 to 33% in 2016. Conclusions: The management of PASH has transitioned in line with other published experience. The preliminary findings suggest this appears safe with no evidence of missed malignancies; however, longer follow up is required to confirm long-term safety. Recommendations: PASH with suspicious radiological findings ( ≥ U4/R4) warrants multidisciplinary discussion for excision. In the absence of histological or radiological suspicion of malignancy, PASH can be safely managed without surgery.

Keywords: benign breast disease, conservative management, malignancy, pseudoangiomatous stromal hyperplasia, surgical excision

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Authors: Xu Yifei, Le Yining, Yang Qingluan, Tu Yanjie

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Objective: This study aims to investigate the distribution features of Traditional Chinese Medicine (TCM) syndromes and syndrome elements in Epstein-Barr virus-associated diseases and then explores the relations between TCM syndromes or syndrome elements and laboratory indicators of Epstein-Barr virus-associated diseases. Methods: A cross-sectional study of 70 patients with EBV infection was described. We assessed the diagnostic information and laboratory indicators of these patients from Huashan Hospital Affiliated to Fudan University between November 2017 and July 2019. The disease diagnosis and syndrome differentiation were based on the diagnostic criteria of EBV-associated diseases and the theory of TCM respectively. Confidence correlation analysis, logistic regression analysis, cluster analysis, and the Sankey diagram were used to analyze the correlation between the data. Results: The differentiation of the 4 primary TCM syndromes in the collected patients was correlated with the indexes of immune function, liver function, inflammation, and anemia, especially the relationship between Qifen syndrome and high lactic acid dehydrogenase level. The common 11 TCM syndrome elements were associated with the increased CD3+ T cell rate, low hemoglobin level, high procalcitonin level, high lactic acid dehydrogenase level, and low albumin level. Conclusion: The changes in immune function indexes, procalcitonin, and liver function-related indexes in patients with EBV-associated diseases were consistent with the evolution law of TCM syndromes. This study provides a reference for judging the pathological stages of these kinds of diseases, predicting their prognosis, and guiding subsequent treatment strategies based on TCM syndrome type.

Keywords: EBV-associated diseases, traditional Chinese medicine syndrome, syndrome element, diagnostics

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Authors: Vagolu S. Krishna, Shan Zheng, Estharla M. Rekha, Luke W. Guddat, Dharmarajan Sriram

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Tuberculosis (TB) remains a major threat to human health. This due to the fact that current drug treatments are less than optimal as well as the rising occurrence of multi drug-resistant and extensively drug-resistant strains of the etiological agent, Mycobacterium tuberculosis (Mt). Given the wide-spread significance of this disease, we have undertaken a design and evaluation program to discover new anti-TB drug leads. Here, our attention is focused on ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway. Importantly, this enzyme is present in bacteria but not in humans, making it an attractive proposition for drug discovery. In the present work, we used high-throughput virtual screening to identify seventeen potential inhibitors of KARI using the Birla Institute of Technology and Science in-house database. Compounds were selected based on high docking scores, which were assigned as the result of favourable interactions between the compound and the active site of KARI. The Ki values for two leads, compounds 14 and 16 are 3.71 and 3.06 µM, respectively for Mt KARI. To assess the mode of binding, 100 ns molecular dynamics simulations for these two compounds in association with Mt KARI were performed and showed that the complex was stable with an average RMSD of less than 2.5 Å for all atoms. Compound 16 showed an MIC of 2.06 ± 0.91 µM and a 1.9 fold logarithmic reduction in the growth of Mt in an infected macrophage model. The two compounds exhibited low toxicity against murine macrophage RAW 264.7 cell lines. Thus, both compounds are promising candidates for development as an anti-TB drug leads.

Keywords: ketol-acid reductoisomerase, macrophage, molecular docking and dynamics, tuberculosis

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Authors: Naoki Yamamoto, Hidenobu Ozaki, Taiichiro Ookawa, Youming Liu, Kazunori Okada, Aiping Zheng

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Rice sheath blight is one of the destructive fungal diseases in rice. We have thought that rice sheath blight resistance is a polygenic trait. Host-pathogen interactions and secondary metabolites such as lignin and phytoalexins are likely to be involved in defense against R. solani. However, to our knowledge, it is still unknown how sheath blight resistance can be enhanced in rice breeding. To seek for an alternative genetic factor that contribute to sheath blight resistance, we mined relevant allelic variations from rice core collections created in Japan. Based on disease lesion length on detached leaf sheath, we selected 30 varieties of the top tail-end and the bottom tail-end, respectively, from the core collections to perform genome-wide association mapping. Re-sequencing reads for these varieties were used for calling single nucleotide polymorphisms among the 60 varieties to create a SNP panel, which contained 1,137,131 homozygous variant sites after filitering. Association mapping highlighted a locus on the long arm of chromosome 11, which is co-localized with three sheath blight QTLs, qShB11-2-TX, qShB11, and qSBR-11-2. Based on the localization of the trait-associated alleles, we identified an ankyryn repeat-containing protein gene (ANK-M) as an uncharacterized candidate factor for rice sheath blight resistance. Allelic distributions for ANK-M in the whole rice population supported the reliability of trait-allele associations. Gene expression characteristics were checked to evaluiate the functionality of ANK-M. Since an ANK-M homolog (OsPIANK1) in rice seems a basal defense regulator against rice blast and bacterial leaf blight, ANK-M may also play a role in the rice immune system.

Keywords: allele mining, GWAS, QTL, rice sheath blight

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Authors: Agnieszka Markowska-Radomska, Ewa Dluska

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Maintaining a bioactive substances dense diet is important for the elderly, especially to prevent diseases and to support healthy ageing. Adequate bioactive substances intake can reduce the risk of developing chronic diseases (e.g. cardiovascular, osteoporosis, neurodegenerative syndromes, diseases of the oral cavity, gastrointestinal (GI) disorders, diabetes, and cancer). This can be achieved by introducing a comprehensive supplementation of components necessary for the proper functioning of the ageing body. The paper proposes the multiple emulsions of the W1/O/W2 (water-in-oil-in-water) type as carriers for effective co-encapsulation and co-delivery of bioactive substances in supplementation of the elderly. Multiple emulsions are complex structured systems ("drops in drops"). The functional structure of the W1/O/W2 emulsion enables (i) incorporation of one or more bioactive components (lipophilic and hydrophilic); (ii) enhancement of stability and bioavailability of encapsulated substances; (iii) prevention of interactions between substances, as well as with the external environment, delivery to a specific location; and (iv) release in a controlled manner. The multiple emulsions were prepared by a one-step method in the Couette-Taylor flow (CTF) contactor in a continuous manner. In general, a two-step emulsification process is used to obtain multiple emulsions. The paper contains a proposal of emulsion functionalization by introducing pH-responsive biopolymer—carboxymethylcellulose sodium salt (CMC-Na) to the external phase, which made it possible to achieve a release of components controlled by the pH of the gastrointestinal environment. The membrane phase of emulsions was soybean oil. The W1/O/W2 emulsions were evaluated for their characteristics (drops size/drop size distribution, volume packing fraction), encapsulation efficiency and stability during storage (to 30 days) at 4ºC and 25ºC. Also, the in vitro multi-substance co-release process were investigated in a simulated gastrointestinal environment (different pH and composition of release medium). Three groups of stable multiple emulsions were obtained: emulsions I with co-encapsulated vitamins B12, B6 and resveratrol; emulsions II with vitamin A and β-carotene; and emulsions III with vitamins C, E and D3. The substances were encapsulated in the appropriate emulsion phases depending on the solubility. For all emulsions, high encapsulation efficience (over 95%) and high volume packing fraction of internal droplets (0.54-0.76) were reached. In addition, due to the presence of a polymer (CMC-Na) with adhesive properties, high encapsulation stability during emulsions storage were achieved. The co-release study of encapsulated bioactive substances confirmed the possibility to modify the release profiles. It was found that the releasing process can be controlled through the composition, structure, physicochemical parameters of emulsions and pH of the release medium. The results showed that the obtained multiple emulsions might be used as potential liquid complex carriers for controlled/modified/site-specific co-delivery of bioactive substances in dietary supplementation in the elderly.

Keywords: bioactive substance co-release, co-encapsulation, elderly supplementation, multiple emulsion

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Authors: Dorcas I. Adeoye

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Disclosure experience of people living with HIV/AIDS has been a public health concern, it has also been attributed to effective way of limiting the spread of the disease. However, among working people living with HIV, it is a great issue that attracts several consequences, it is also a way of managing HIV and balancing their emotional, physical and social aspect of life. The economic, social and political aspect has been affected since the emergent of HIV. It is also not a medical problem that only needs a medical approach; it is a psychological problem that needs not to be ignored. Work attitude model and consequential theory were used to understanding the experience of disclosure or non-disclosure in the workplace. Work attitude model explains the job satisfaction and the organisational commitment of an employee that have effect on the decision and well-being in the workplace; it can also influence a decision to disclosure one’s health condition, however, consequential theory comes to play when a decision is being made, either to disclose or not, and that will attract consequences (either negative or positive) in which ever decision made. A phenomenological study was conducted among employed people that are infected with HIV/AIDS in a south-eastern region of Nigeria where unemployment rate is high. A one-to-one semi-structured interview was used to gather in-depth information about the experience of 20 working people living with HIV. Participants were recruited in a hospital and for some, hospital serves as their workplace. The outcome of the research shows that participants’ experiences vary. One thing that stood out and was found similar among all participants including participants that have disclosed, planning to disclose, or never intended to disclose, is that workplace is a place not to be trusted despite the positive outcomes disclosure could give in the workplace, and disclosure decision needs to be carefully taken. The study was concluded with recommendations that cover various aspects; however, clearer policies should be followed by all organisations to protect people living with HIV in the workplace.

Keywords: disclosure, employment, HIV/AIDS, Nigeria, workplace

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Authors: Ilana Singer, Anastasia Lučić, Julie Leclerc

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Introduction: Tics, characterized by repetitive, sudden, non-voluntary motor movements or vocalizations, are prevalent in chronic tic disorder (CT) and Tourette Syndrome (TS). These neurodevelopmental disorders often coexist with various psychiatric conditions, leading to challenges and reduced quality of life. While medication in conjunction with behavioral interventions, such as Habit Reversal Training (HRT), Exposure Response Prevention (ERP), and Comprehensive Behavioral Intervention for Tics (CBIT), has shown efficacy, a significant proportion of patients experience persistent tics. Thus, innovative treatment approaches are necessary to improve therapeutic outcomes, such as mindfulness-based approaches. Nonetheless, the effectiveness of mindfulness-based interventions in the context of CT and TS remains understudied. Objective: The objective of this scoping review is to provide an overview of the current state of research on mindfulness-based interventions for CT and TS, identify knowledge and evidence gaps, discuss the effectiveness of mindfulness-based interventions with other treatment options, and discuss implications for clinical practice and policy development. Method: Using guidelines from Peters (2020) and the PRISMA-ScR, a scoping review was conducted. Multiple electronic databases were searched from inception until June 2023, including MEDLINE, EMBASE, PsychInfo, Global Health, PubMed, Web of Science, and Érudit. Inclusion criteria were applied to select relevant studies, and data extraction was independently performed by two reviewers. Results: Five papers were included in the study. Firstly, we found that mindfulness interventions were found to be effective in reducing anxiety and depression while enhancing overall well-being in individuals with tics. Furthermore, the review highlighted the potential role of mindfulness in enhancing functional connectivity within the Default Mode Network (DMN) as a compensatory function in TS patients. This suggests that mindfulness interventions may complement and support traditional therapeutic approaches, particularly HRT, by positively influencing brain networks associated with tic regulation and control. Conclusion: This scoping review contributes to the understanding of the effectiveness of mindfulness-based interventions in managing CT and TS. By identifying research gaps, this review can guide future investigations and interventions to improve outcomes for individuals with CT or TS. Overall, these findings emphasize the potential benefits of incorporating mindfulness-based interventions as a smaller subset within comprehensive treatment strategies. However, it is essential to acknowledge the limitations of this scoping review, such as the exclusion of a pre-established protocol and the limited number of studies available for inclusion. Further research and clinical exploration are necessary to better understand the specific mechanisms and optimal integration of mindfulness-based interventions with existing behavioral interventions for this population.

Keywords: scoping reviews, Tourette Syndrome, tics, mindfulness-based, therapy, intervention

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Authors: Gokcen Akyurek, Hulya Kayihan, Deniz Yuce, Selen Yilmaz

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The stigma towards mental illness is still very rooted in our society, despite the number of studies, campaigns, and anti-stigma programs developed in recent years. Stigma represents a serious obstacle to recovery and social integration for people who experience a mental illness, affecting directly their well-being and quality of life. It implies that these persons have to deal with many other barriers apart from the disease symptoms (1-5). Convergent, recent literature suggests that less positive attitudes by mental health professionals interfere with the self-determination and recovery process (4-10).The aim of this study was to translate the Attribution Questionnaire-27 (AQ-27) to the Turkish language (AQ-27-T), and to examine the reliability and validity of this new Turkish version. Cultural adaptation was implemented according to the internationally suggested method. To determine the understandability and appropriateness of this measure for the Turkish culture, a pretest was administered and the final form was generated. Then, 424 randomly chosen people took part in the study. Participant’s mean age was 36.9±12.7 years and %52 of them female. Cronbach's alpha and intra-class coefficients were used to estimate instrument reliability. The AQ-27-T was assessed again 14 days later for test retest reliability. The AQ-27-T demonstrated acceptable internal consistency, with a Cronbach's alpha of 0.88 for the total scale and ranging between 0.86 and 0.89 for the items. The test-retest reliability was good, with Pearson correlation coefficients of 0.79 for the total scale and ranging between 0.35 and 0.77 for the items (p<0.05). Correlation between subscales was moderate-good, with Pearson correlation coefficients of 0.18-0.88 (p<0.05). Fit indices of the model supported the factor structure and paths. The AQ-27-T is a reliable measure to assess stigmatizing attitudes in Turkish.

Keywords: attribution questionnaire, validity, reliability, stigma

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Authors: Maryam Borjali

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Introduction. Mortality due to noncommunicable diseases has increased in the world today with the advent of demographic shifts, growing age, and lifestyle patterns in the world, which have been affected by economic and social crises. Congenital heart defects are one of the forms of diseases that have raised infant mortality worldwide. e objective of present study was to identify nonmedical determinants related to this abnormality from the mother’s perspectives. Methods. is research was a qualitative study and the data collection method was a semistructured interview with mothers who had children with congenital heart diseases referring to the Shahid Rajaei Heart Hospital in Tehran, Iran. A thematic analysis approach was employed to analyze transcribed documents assisted by MAXQDA Plus version 12. Results. Four general themes and ten subthemes including social contexts (social harms, social interactions, and social necessities), psychological contexts (mood disorders and mental well-being), cultural contexts (unhealthy lifestyle, family culture, and poor parental health behaviors), and environmental contexts (living area and polluted air) were extracted from interviews with mothers of children with congenital heart diseases. Conclusions. Results suggest that factors such as childhood poverty, lack of parental awareness of congenital diseases, lack of proper nutrition and health facilities, education, and lack of medical supervision during pregnancy were most related with the birth of children with congenital heart disease from mothers’ prospective. In this regard, targeted and intersectorial collaborations are proposed to address nonmedical determinants related to the incidence of congenital heart diseases.

Keywords: congenital_cou, cultural, social, platform

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Authors: Cyoung-Huei Huang, Chiu-Li Yeh, Man-Hui Pai, Sung-Ling Yeh

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This study evaluated the effect of different dietary n-6/n-3 polyunsaturated fatty acid (PUFA) ratios on modulating helper T (Th) and regulatory T (Treg) lymphocytes in mice with dextran sulfate sodium (DSS)-induced colitis. There were 3 control and 3 colitis groups in this study. Mice were fed for 24 d with an AIN-93G diet either with soybean oil (S), a mixture of soybean oil and low fish oil content (LF) or high fish oil content (HF). The ratio of n-6/n-3 PUFA in the LF diet was 4:1, and that in the HF diet was 2:1. The control groups drank distilled water while colitis groups provided 2% DSS in drinking water during day 15-19. All mice drank distilled water from day 20-24 for recovery and sacrificed on day 25. The results showed that colitis resulted in higher Th1, Th2, and Th17 and lower Treg percentages in the blood. Also, plasma haptoglobin and proinflammatory chemokines were elevated in colon lavage fluid. Colitic groups with fish oil had lower inflammatory mediators in the plasma and colon lavage fluid. Further, the percentages of Th1, Th2, and Th17 cells in the blood were lower, whereas Treg cell percentages were higher than those in the soybean oil group. The colitis group with n-6/n-3 PUFA ratio 2:1 had more pronounce effects than ratio 4:1. These results suggest that diets with an n-6/n-3 PUFA ratio of 2:1 or 4:1 regulate the Th/Treg balance and attenuate inflammatory mediator production in colitis. Compared to the n-6/n-3 PUFA ratio 4:1, the ratio of 2:1 was more effective in reducing inflammatory reactions in DSS-induced colitis.

Keywords: inflammatory bowel disease, n-3 polyunsaturated fatty acids, helper T lymphocyte, regulatory T lymphocyte

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Authors: Melanie Macgregor-Ramiasa, Isabel Hopp, Patricia Murray, Krasimir Vasilev

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Stem cells based therapies are one of the greatest promises of new-age medicine due to their potential to help curing most dreaded conditions such as cancer, diabetes and even auto-immune disease. However, establishing suitable in vitro culture materials allowing to control the fate of stem cells remain a challenge. Amongst the factor influencing stem cell behavior, substrate chemistry and nanotopogaphy are particularly critical. In this work, we used plasma assisted surface modification methods to produce model substrates with tailored nanotopography and controlled chemistry. Three different sizes of gold nanoparticles were bound to amine rich plasma polymer layers to produce homogeneous and gradient surface nanotopographies. The outer chemistry of the substrate was kept constant for all substrates by depositing a thin layer of our patented biocompatible polyoxazoline plasma polymer on top of the nanofeatures. For the first time, protein adsorption and stem cell behaviour (mouse kidney stem cells and mesenchymal stem cells) were evaluated on nanorough plasma deposited polyoxazoline thin films. Compared to other nitrogen rich coatings, polyoxazoline plasma polymer supports the covalent binding of proteins. Moderate surface nanoroughness, in both size and density, triggers cell proliferation. In association with polyoxazoline coating, cell proliferation is further enhanced on nanorough substrates. Results are discussed in term of substrates wetting properties. These findings provide valuable insights on the mechanisms governing the interactions between stem cells and their growth support.

Keywords: nanotopography, stem cells, differentiation, plasma polymer, oxazoline, gold nanoparticles

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Authors: Juni C. Kim, Anna R. Robuck, Douglas I. Walker

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The human exposome, which includes chemical exposures over the lifetime and their effects, is now recognized as an important measure for understanding human health; however, the complexity of the data makes the identification of environmental chemicals challenging. The goal of our project was to establish a computational workflow for the improved identification of environmental pollutants containing chlorine or bromine. Using the “pattern. search” function available in the R package NonTarget, we wrote a multifunctional script that searches mass spectral clusters from untargeted gas-chromatography high-resolution mass spectrometry (GC-HRMS) for the presence of spectra consistent with chlorine and bromine-containing organic compounds. The “pattern. search” function was incorporated into a different function that allows the evaluation of clusters containing multiple analyte fragments, has multi-core support, and provides a simplified output identifying listing compounds containing chlorine and/or bromine. The new function was able to process 46,000 spectral clusters in under 8 seconds and identified over 150 potential halogenated spectra. We next applied our function to a deidentified dataset from patients diagnosed with primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and healthy controls. Twenty-two spectra corresponded to potential halogenated compounds in the PSC and PBC dataset, including six significantly different in PBC patients, while four differed in PSC patients. We have developed an improved algorithm for detecting halogenated compounds in GC-HRMS data, providing a strategy for prioritizing exposures in the study of human disease.

Keywords: exposome, metabolome, computational metabolomics, high-resolution mass spectrometry, exposure, pollutants

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Authors: Ethan James

Abstract:

Over one billion people worldwide suffer from some level of vision loss or blindness as a result of progressive retinal diseases. Many patients, particularly in developing areas, are incorrectly diagnosed or undiagnosed whatsoever due to unconventional diagnostic tools and screening methods. Artificial intelligence (AI) based on deep learning (DL) convolutional neural networks (CNN) have recently gained a high interest in ophthalmology for its computer-imaging diagnosis, disease prognosis, and risk assessment. Optical coherence tomography (OCT) is a popular imaging technique used to capture high-resolution cross-sections of retinas. In ophthalmology, DL has been applied to fundus photographs, optical coherence tomography, and visual fields, achieving robust classification performance in the detection of various retinal diseases including macular degeneration, diabetic retinopathy, and retinitis pigmentosa. However, there is no complete diagnostic model to analyze these retinal images that provide a diagnostic accuracy above 90%. Thus, the purpose of this project was to develop an AI model that utilizes machine learning techniques to automatically diagnose specific retinal diseases from OCT scans. The algorithm consists of neural network architecture that was trained from a dataset of over 20,000 real-world OCT images to train the robust model to utilize residual neural networks with cyclic pooling. This DL model can ultimately aid ophthalmologists in diagnosing patients with these retinal diseases more quickly and more accurately, therefore facilitating earlier treatment, which results in improved post-treatment outcomes.

Keywords: artificial intelligence, deep learning, imaging, medical devices, ophthalmic devices, ophthalmology, retina

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Authors: Özlem Ateş Sönmezoğlu, Begüm Terzi, Ahmet Yıldırım, Leyla Gündüz

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Durum wheat quality is defined as its suitability for pasta processing, that is pasta making quality. Another factor that determines the quality of durum wheat is the nutritional value of wheat or its final products. Wheat is a basic source of calories, proteins and minerals for humans in many countries of the world. For this reason, improvement of wheat nutritional value is of great importance. In recent years, deficiencies in protein and micronutrients, particularly in iron and zinc, have seriously increased. Therefore, basic foods such as wheat must be improved for micronutrient content. The effects of some major genes for grain quality established. Gpc-B1 locus is one of the genes increased protein and micronutrients content, and used in improvement studies of durum wheat nutritional value. The aim of this study was to increase the protein content and the micronutrient (Fe, Zn ve Mn) contents of an advanced durum wheat line (TMB 1) that was previously improved for its protein quality. For this purpose, TMB1 advanced durum wheat line were used as the recurrent parent and also, UC1113-Gpc-B1 line containing the Gpc-B1 gene was used as the gene source. In all of the generations, backcrossed plants carrying the targeted gene region were selected by marker assisted selection (MAS). BC4F1 plants MAS method was employed in combination with embryo culture and rapid plant growth in a controlled greenhouse conditions in order to shorten the duration of the transition between generations in backcross breeding. The Gpc-B1 gene was selected specific molecular markers. Since Yr-36 gene associated with Gpc-B1 allele, it was also transferred to the Gpc-B1 transferred lines. Thus, the backcrossed plants selected by MAS are resistance to yellow rust disease. This research has been financially supported by TÜBİTAK (112T910).

Keywords: Durum wheat, Gpc-B1, MAS, Triticum durum, Yr-36

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Authors: Anju Joshi, C. N. Tharamani

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Diabetes is one of the leading cause of death at present and remains an important concern as the prevalence of the disease is increasing at an alarming rate. Therefore, it is crucial to diagnose the accurate levels of glucose for developing an efficient therapeutic for diabetes. Due to the availability of convenient and compact self-testing, continuous monitoring of glucose is feasible nowadays. Enzyme based electrochemical sensing of glucose is quite popular because of its high selectivity but suffers from drawbacks like complicated purification and immobilization procedures, denaturation, high cost, and low sensitivity due to indirect electron transfer. Hence, designing a robust enzyme free platform using transition metal oxides remains crucial for the efficient and sensitive determination of glucose. In the present work, manganese doped nickel oxide nanoparticles (Mn-NiO) has been synthesized onto the surface of multiwalled carbon nanotubes using a simple microwave assisted approach for non-enzymatic electrochemical sensing of glucose. The morphology and structure of the synthesized nanostructures were characterized using scanning electron microscopy (SEM) and X-Ray diffraction (XRD). We demonstrate that the synthesized nanostructures show enormous potential for electrocatalytic oxidation of glucose with high sensitivity and selectivity. Cyclic voltammetry and square wave voltammetry studies suggest superior sensitivity and selectivity of Mn-NiO decorated carbon nanotubes towards the non-enzymatic determination of glucose. A linear response between the peak current and the concentration of glucose has been found to be in the concentration range of 0.01 μM- 10000 μM which suggests the potential efficacy of Mn-NiO decorated carbon nanotubes for sensitive determination of glucose.

Keywords: diabetes, glucose, Mn-NiO decorated carbon nanotubes, non-enzymatic

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Authors: Alieh Farshbaf

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Introduction: Current anti-retroviral drugs have some restrictions for treatment of HIV-1 infection. The efficacy of retroviral drugs is not same in different infected patients and the virus rebound from latent reservoirs after stopping them. Recently, the engineering of stem cells and gene therapy provide new approaches to eliminate some drug problems by induction of resistance to HIV-1. Literature review: Up to now, AIDS-restriction genes (ARGs) were suitable candidate for gene and cell therapies, such as cc-chemokine receptor-5 (CCR5). In this manner, CCR5 provide effective cure in Berlin and Boston patients by inducing of HIV-1 resistance with allogeneic stem cell transplantation. It is showed that Zinc Finger Nuclease (ZFN) could induce HIV-1 resistance in stem cells of infected patients by homologous recombination or non-end joining mechanism and eliminate virus loading after returning the modified cells. Then, gene modification by HIV restriction factors, as TRIM5, introduced another gene candidate for HIV by interfering in infection process. These gene modifications/editing provided by stem cell futures that improve treatment in refractory disease such as HIV-1. Conclusion: Although stem cell transplantation has some complications, but in compare to retro-viral drugs demonstrated effective cure by elimination of virus loading. On the other hand, gene therapy is cost-effective for an infected patient than retroviral drugs payment in a person life-long. The results of umbilical cord blood stem cell transplantation showed that gene and cell therapy will be applied easier than previous treatment of AIDS with high efficacy.

Keywords: stem cell, AIDS, gene modification, cell engineering

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Authors: Raghavi C. Janaswamy

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In the healthcare sector, heterogenous data elements such as patients, diagnosis, symptoms, conditions, observation text from physician notes, and prescriptions form the essentials of the Electronic Health Record (EHR). The data in the form of clear text and images are stored or processed in a relational format in most systems. However, the intrinsic structure restrictions and complex joins of relational databases limit the widespread utility. In this regard, the design and development of realistic mapping and deep connections as real-time objects offer unparallel advantages. Herein, a graph neural network-based classification of EHR data has been developed. The patient conditions have been predicted as a node classification task using a graph-based open source EHR data, Synthea Database, stored in Tigergraph. The Synthea DB dataset is leveraged due to its closer representation of the real-time data and being voluminous. The graph model is built from the EHR heterogeneous data using python modules, namely, pyTigerGraph to get nodes and edges from the Tigergraph database, PyTorch to tensorize the nodes and edges, PyTorch-Geometric (PyG) to train the Graph Neural Network (GNN) and adopt the self-supervised learning techniques with the AutoEncoders to generate the node embeddings and eventually perform the node classifications using the node embeddings. The model predicts patient conditions ranging from common to rare situations. The outcome is deemed to open up opportunities for data querying toward better predictions and accuracy.

Keywords: electronic health record, graph neural network, heterogeneous data, prediction

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Authors: Karla Cautivo, Thomas Riley, Daniel Knight

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Clostridium difficile infection (CDI) is the most common cause of infectious diarrhea in hospitalised humans. C. difficile colonises the gastrointestinal tract, causes disease in a variety of animal species and can persist as a spore in diverse environments. Genetic overlap between C. difficile strains from human, animal and environmental sources suggests CDI has a zoonotic or foodborne aetiology. In Australia, C. difficile PCR ribotype RT014 (MLST clade 1) and several ST11 (MLST clade 5) RTs are found commonly in livestock. The high prevalence and diversity of ST11 strains in Australian production animals indicates Australia might be the ancestral home for this lineage. This project describes for the first time the ecology of C. difficile in Australian native animals, providing insights into the prevalence, molecular epidemiology and evolution of C. difficile in this unique environment and a possible role in CDI in humans and animals in Australia. Faecal samples were collected from wild/captive reptiles (n=37), mammals (n=104) and birds (n=102) in Western Australia in 2020/21. Anaerobic enrichment culture was performed, and C. difficile isolates were characterised by PCR ribotyping and toxin gene profiling. Seventy isolates of C. difficile were recovered (prevalence of C. difficile in faecal samples 28%, n=68/243); 27 unique RTs were identified, 5 were novel. The prevalence of C. difficile was similar for reptiles and mammals, 46% (n=17/37) and 43%(n=45/104), respectively, but significantly lower in birds (7.8%, n=8/102; p<0.00001 for both reptiles and mammals). Of the 57 isolates available for typing, RT237 (clade 5) and RT002 (clade 2) were the most prevalent, 15.8% (n=9/57) and 14% (n=8/57), respectively. The high prevalence of C. difficile in reptiles and mammals, particularly clade 5 strains, supported by previous studies of C. difficile in Australian soils, suggest that Australia might be the ancestral home of MLST clade 5.

Keywords: Clostridium difficile, zoonosis, molecular epidemiology, ecology and evolution

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Authors: Ali Taheri Mirghaed, Sara Ahani, Ashkan Zargar, Seyyed Morteza Hoseini

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Diseases are the major challenges in intensive aquaculture that cause significant annual losses. Antibiotic-therapy is a common way to control bacterial disease in fish, and oxytetracycline (OTC) is the only oral antibiotic in aquaculture approved FDA. OTC has been found to have negative effects on fish, such as oxidative stress and immune-suppression, thus, it is necessary to mitigate such effects. Medicinal herbs have various benefits on fish, including antioxidant, immunostimulant, and anti-microbial effects. Therefore, we hypothesized if dietary ginger meal (GM) interacts with dietary OTC by monitoring plasma protein fractions in rainbow trout. The study was conducted as a 2 × 2 factorial design, including diets containing 0 and 1% GM and 0 and 1.66 % OTC (corresponding to 100 mg/kg fish biomass per day). After ten days treating the fish (60 g individual weight) with these feeds, blood samples were taken from al treatments (n =3). Plasma was separated by centrifugation, and protein fractions were determined by electrophoresis. The results showed that OTC and GM had interaction effects on total protein (P<0.001), albumin (P<0.001), alpha-1 fraction (P=0.010), alpha-2 fraction (P=0.001), beta-2 fraction (P=0.014), and gamma fraction (P<0.001). Beta-1 fraction was significantly (P=0.030) affected by dietary GM. GM decreased plasma total protein, albumin, and beta-2 but increased beta-1 fraction. OTC significantly decreased total protein (P<0.001), albumin (P=0.001), alpha-2 fraction (P<0.001), beta-2 fraction (P=0.004), and gamma fraction (P<0.001) but had no significant effects on alpha-1 and beta-1 fractions. Dietary GM inhibited/suppressed the effects of dietary OTC on the plasma total protein and protein fractions. In conclusion, adding 1% GM to diet can mitigate the negative effects of dietary OTC on plasma proteins. Thus, GM may boost health of rainbow trout during the period of medication with OTC.

Keywords: ginger, plasma protein electrophoresis, dietary additive, rainbow trout

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