Search results for: renal insufficiency chronic

Authors: Alvarez M., Chapela M. J., Balboa E., Rubianes D., Sinde E., Fernandez de Ana C., Rodríguez-Blanco A.

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The gut microbiota plays an important role as gut inflammation could contribute to colorectal cancer development; however, this role is still not fully understood, and tools able to prevent this progression are yet to be developed. The main objective of this study was to monitor the effects of a mushroom extracts formulation in gut microbial community composition of an Azoxymethane (AOM)/Dextran sodium sulfate (DSS) mice model of inflammation-linked carcinogenesis. For the in vivo study, 41 adult male mice of the C57BL / 6 strain were obtained. 36 of them have been induced in a state of colon carcinogenesis by a single intraperitoneal administration of AOM at a dose of 12.5 mg/kg; the control group animals received instead of the same volume of 0.9% saline. DSS is an extremely toxic polysaccharide sulfate that causes chronic inflammation of the colon mucosa, favoring the appearance of severe colitis and the production of tumors induced by AOM. Induction by AOM/DSS is an interesting platform for chemopreventive intervention studies. This time the model was used to monitor gut microbiota changes as a result of supplementation with a specific mushroom extracts formulation previously shown to have prebiotic activity. The animals have been divided into three groups: (i) Cancer + mushroom extracts formulation experimental group: to which the MicoDigest2.0 mushroom extracts formulation developed by Hifas da Terra S.L has been administered dissolved in drinking water at an estimated concentration of 100 mg / ml. (ii) Control group of animals with Cancer: to which normal water has been administered without any type of treatment. (iii) Control group of healthy animals: these are the animals that have not been induced cancer or have not received any treatment in drinking water. This treatment has been maintained for a period of 3 months, after which the animals were sacrificed to obtain tissues that were subsequently analyzed to verify the effects of the mushroom extract formulation. A microbiological analysis has been carried out to compare the microbial communities present in the intestines of the mice belonging to each of the study groups. For this, the methodology of massive sequencing by molecular analysis of the 16S gene has been used (Ion Torrent technology). Initially, DNA extraction and metagenomics libraries were prepared using the 16S Metagenomics kit, always following the manufacturer's instructions. This kit amplifies 7 of the 9 hypervariable regions of the 16S gene that will then be sequenced. Finally, the data obtained will be compared with a database that makes it possible to determine the degree of similarity of the sequences obtained with a wide range of bacterial genomes. Results obtained showed that, similarly to certain natural compounds preventing colorectal tumorigenesis, a mushroom formulation enriched the Firmicutes and Proteobacteria phyla and depleted Bacteroidetes. Therefore, it was demonstrated that the consumption of the mushroom extracts’ formulation developed could promote the recovery of the microbial balance that is disrupted in the mice model of carcinogenesis. More preclinical and clinical studies are needed to validate this promising approach.

Keywords: carcinogenesis, microbiota, mushroom extracts, inflammation

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Authors: Jason M. Hegenauer, Nicholas Fucci

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In the late 1990s, a major deinstitutionalization movement of elderly patients took place, since which, the design of long-term care facilities has not been adequately analyzed in the United States. Over the course of the last 25 years, major innovations in construction methods, technology, and medicine have been developed, drastically changing the landscape of healthcare architecture. In light of recent events, and the expected increase in elderly populations with the aging of the baby-boomer generation, it is evident that reconsideration of these facilities is essential for the proper care of aging populations. The global response has been effective in stifling this pandemic; however, widespread disease still poses an imminent threat to the human race. Having witnessed the devastation Covid-19 has reaped throughout nursing homes and long-term care facilities, it is evident that the current strategies for protecting our most vulnerable populations are not enough. Light renovation of existing facilities and previously overlooked considerations for new construction projects can drastically lower the risk at nursing homes and long-term care facilities. A reconfigured entry sequence supplements several of the features which have been long-standing essentials of the design of these facilities. This research focuses on several aspects identified as needing improvement, including indoor environment quality, security measures incorporated into healthcare architecture and design, and architectural mitigation strategies for sick building syndrome. The results of this study have been compiled as 'best practices' for the design of future healthcare construction projects focused on the health, safety, and quality of life of the residents of these facilities. These design strategies, which can easily be implemented through renovation of existing facilities and new construction projects, minimize risk of infection and spread of disease while allowing routine functions to continue with minimal impact, should the need for future lockdowns arise. Through the current lockdown procedures, which were implemented during the Covid-19 pandemic, isolation of residents has caused great unrest and worry for family members and friends as they are cut off from their loved ones. At this time, data is still being reported, leaving infection and death rates inconclusive; however, recent projections in some states list long-term care facility deaths as high as 60% of all deaths in the state. The population of these facilities consists of residents who are elderly, immunocompromised, and have underlying chronic medical conditions. According to the Centers for Disease Control, these populations are particularly susceptible to infection and serious illness. The obligation to protect our most vulnerable population cannot be overlooked, and the harsh measures recently taken as a response to the Covid-19 pandemic prove that the design strategies currently utilized for doing so are inadequate.

Keywords: building security, healthcare architecture and design, indoor environment quality, new construction, sick building syndrome, renovation

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Authors: Shagufta Jabeen, Faez Jesse Firdaus Abdullah, Zunita Zakaria, Nurulfiza Mat Isa, Yung Chie Tan, Wai Yan Yee, Abdul Rahman Omar

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Pasteurella multocida is associated with acute, as well as, chronic infections in avian and bovine such as pasteurellosis and hemorrhagic septicemia (HS) in cattle and buffaloes. Iron is one of the most important nutrients for pathogenic bacteria including Pasteurella and acts as a cofactor or prosthetic group in several essential enzymes and is needed for amino acid, pyrimidine, and DNA biosynthesis. In our recent study, we showed that 2% of Pasteurella multocida serotype A strain PMTB2.1 encode for iron regulating genes (Accession number CP007205.1). Genome sequencing of other Pasteurella multocida serotypes namely PM70 and HB01 also indicated up to 2.5% of the respective genome encode for iron regulating genes, suggesting that Pasteurella multocida genome comprises of multiple systems for iron uptake. Since P. multocida PMTB2.1 has more than 40 CDs out of 2097 CDs (approximately 2%), encode for iron-regulated. The gene expression profiling of four iron-regulating genes namely fbpb, yfea, fece and fur were characterized under iron-restricted environment. The P. multocida strain PMTB2.1 was grown in broth with and without iron chelating agent and samples were collected at different time points. Relative mRNA expression profile of these genes was determined using Taqman probe based real-time PCR assay. The data analysis, normalization with two house-keeping genes and the quantification of fold changes were carried out using Bio-Rad CFX manager software version 3.1. Results of this study reflect that iron reduced environment has significant effect on expression profile of iron regulating genes (p < 0.05) when compared to control (normal broth) and all evaluated genes act differently with response to iron reduction in media. The highest relative fold change of fece gene was observed at early stage of treatment indicating that PMTB2.1 may utilize its periplasmic protein at early stage to acquire iron. Furthermore, down-regulation expression of fece with the elevated expression of other genes at later time points suggests that PMTB2.1 control their iron requirements in response to iron availability by down-regulating the expression of iron proteins. Moreover, significantly high relative fold change (p ≤ 0.05) of fbpb gene is probably associated with the ability of P. multocida to directly use host iron complex such as hem, hemoglobin. In addition, the significant increase (p ≤ 0.05) in fbpb and yfea expressions also reflects the utilization of multiple iron systems in P. multocida strain PMTB2.1. The findings of this study are very much important as relative scarcity of free iron within hosts creates a major barrier to microbial growth inside host and utilization of outer-membrane proteins system in iron acquisition probably occurred at early stage of infection with P. multocida. In conclusion, the presence and utilization of multiple iron system in P. multocida strain PMTB2.1 revealed the importance of iron in the survival of P. multocida.

Keywords: iron-related genes, real-time PCR, gene expression profiling, fold changes

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Authors: Sukalyan Chakraborty

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Arsenic contamination in groundwater has been a matter of serious concern worldwide. Globally, arsenic contaminated water has caused serious chronic human diseases and in the last few decades the transfer of arsenic to human beings via food chain has gained much attention because food represents a further potential exposure pathway to arsenic in instances where crops are irrigated with high arsenic groundwater, grown in contaminated fields or cooked with arsenic laden water. In the present study, the groundwater of Sahibganj district of Jharkhand has been analysed to find the degree of contamination and its probable associated risk due to direct consumption or irrigation. The present study area comprising of three blocks, namely Sahibganj, Rajmahal and Udhwa in Sahibganj district of Jharkhand state, India, situated in the western bank of river Ganga has been investigated for arsenic contamination in groundwater, soil and crops predominantly growing in the region. Associated physicochemical parameters of groundwater including pH, temperature, electrical conductivity (EC), total dissolved solids (TDS), dissolved oxygen (DO), oxidation reduction potential (ORP), ammonium, nitrate and chloride were assessed to understand the mobilisation mechanism and chances of arsenic exposure from soil to crops and further into the food chain. Results suggested the groundwater to be dominantly Ca-HCO3- type with low redox potential and high total dissolved solids load. Major cations followed the order of Ca ˃ Na ˃ Mg ˃ K. The concentration of major anions was found in the order of HCO3− > Cl− > SO42− > NO3− > PO43− varied between 0.009 to 0.20 mg L-1. Fe concentrations of the groundwater samples were below WHO permissible limit varying between 54 to 344 µg L-1. Phosphate concentration was high and showed a significant positive correlation with arsenic. As concentrations ranged from 7 to 115 µg L-1 in premonsoon, between 2 and 98 µg L-1 in monsoon and 1 to 133µg L-1 in postmonsoon season. Arsenic concentration was found to be much higher than the WHO or BIS permissible limit in majority of the villages in the study area. Arsenic was also seen to be positively correlated with iron and phosphate. PCA results demonstrated the role of both geological condition and anthropogenic inputs to influence the water quality. Arsenic was also found to increase with depth up to 100 m from the surface. Calculation of carcinogenic and non-carcinogenic effects of the arsenic concentration in the communities exposed to the groundwater for drinking and other purpose indicated high risk with an average of more than 1 in a 1000 population. Health risk analysis revealed high to very high carcinogenic and non-carcinogenic risk for adults and children in the communities dependent on groundwater of the study area. Observation suggested the groundwater to be considerably polluted with arsenic and posing significant health risk for the exposed communities. The mobilisation mechanism of arsenic also could be identified from the results suggesting reductive dissolution of Fe oxyhydroxides due to high phosphate concentration from agricultural input arsenic release from the sediments along river Ganges.

Keywords: arsenic, physicochemical parameters, mobilisation, health effects

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Authors: Karolina Wieczorek, Sophie Wiliams

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Introduction: Patient data is often collected in Electronic Health Record Systems (EHR) for purposes such as providing care as well as reporting data. This information can be re-used to validate data models in clinical trials or in epidemiological studies. Manual validation of automated tools is vital to pick up errors in processing and to provide confidence in the output. Mentioning a disease in a discharge letter does not necessarily mean that a patient suffers from this disease. Many of them discuss a diagnostic process, different tests, or discuss whether a patient has a certain disease. The COVID-19 dataset in this study used natural language processing (NLP), an automated algorithm which extracts information related to COVID-19 symptoms, complications, and medications prescribed within the hospital. Free-text patient clinical patient notes are rich sources of information which contain patient data not captured in a structured form, hence the use of named entity recognition (NER) to capture additional information. Methods: Patient data (discharge summary letters) were exported and screened by an algorithm to pick up relevant terms related to COVID-19. Manual validation of automated tools is vital to pick up errors in processing and to provide confidence in the output. A list of 124 Systematized Nomenclature of Medicine (SNOMED) Clinical Terms has been provided in Excel with corresponding IDs. Two independent medical student researchers were provided with a dictionary of SNOMED list of terms to refer to when screening the notes. They worked on two separate datasets called "A” and "B”, respectively. Notes were screened to check if the correct term had been picked-up by the algorithm to ensure that negated terms were not picked up. Results: Its implementation in the hospital began on March 31, 2020, and the first EHR-derived extract was generated for use in an audit study on June 04, 2020. The dataset has contributed to large, priority clinical trials (including International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) by bulk upload to REDcap research databases) and local research and audit studies. Successful sharing of EHR-extracted datasets requires communicating the provenance and quality, including completeness and accuracy of this data. The results of the validation of the algorithm were the following: precision (0.907), recall (0.416), and F-score test (0.570). Percentage enhancement with NLP extracted terms compared to regular data extraction alone was low (0.3%) for relatively well-documented data such as previous medical history but higher (16.6%, 29.53%, 30.3%, 45.1%) for complications, presenting illness, chronic procedures, acute procedures respectively. Conclusions: This automated NLP algorithm is shown to be useful in facilitating patient data analysis and has the potential to be used in more large-scale clinical trials to assess potential study exclusion criteria for participants in the development of vaccines.

Keywords: automated, algorithm, NLP, COVID-19

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Authors: Sandra Cardoso, Gaspar Pais, Judite Neves, Sandra Cavaca, Fernando Araújo

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In 2021, Portugal has 63 emergency department (ED) visits per 100 people annually, the highest numbers in Europe. While EDs provide a critical service, high use is indicative of inappropriate and inefficient healthcare. In Portugal, all ED have the Manchester Triage System (MTS), a clinical risk management tool to enable that patients are seen in order of clinical priority. In 2023, more than 40% of the ED visits were of non-urgent conditions (blue and green), that could be better managed in primary health care (PHC), meaning wrong use of resources and lack of health literacy. From 2017, the country has a phone line, SNS24 (Contact Centre of the National Health Service), for triage, counseling, and referral service, 24 hours/7 days a week. The pilot project ‘Call before, save lives’ was implemented in the municipalities of Póvoa de Varzim and Vila do Conde (around 150.000 residents), in May 2023, by the executive board of the Portuguese Health Service, with the support of the Shared Services of the Ministry of Health, and local authorities. This geographical area has short travel times, 99% of the population a family doctor and the region is organized in a health local unit (HLU), integrating PHC and the local hospital. The purposes of this project included to increase awareness to contact SNS 24, before going to an ED, and non-urgent conditions oriented to a family doctor, reducing ED visits. The implementation of the project involved two phases, beginning with: i) development of campaigns using local influencers (fishmonger, model, fireman) through local institutions and media; ii) provision of telephone installed on site to contact SNS24; iii) establishment of open consultation in PHC; iv) promotion of the use of SNS24; v) creation of acute consultations at the hospital for complex chronic patients; and vi) direct referral for home hospitalization by PHC. The results of this project showed an excellent level of access to SNS24, an increase in the number of users referred to ED, with great satisfaction of users and professionals. The second phase, initiated in January 2024, for access to the ED, the need for prior referral was established as an admission rule, except for certain situations, as trauma patients. If the patient refuses, their registration in the ED and subsequent screening in accordance with the MTS must be ensured. When the patient is non-urgent, shall not be observed in the ED, provided that, according to his clinical condition, is guaranteed to be referred to PHC or to consultation/day hospital, through effective scheduling of an appointment for the same or the following day. In terms of results, 8 weeks after beginning of phase 2, we assist of a decrease in self-reported patients to ED from 59% to 15%, and a reduction of around 7% of ED visits. The key for this success was an effective public campaign that increases the knowledge of the right use of the health system, and capable of changing behaviors.

Keywords: contact centre of the national health service, emergency department visits, public campaign, health literacy, SNS24

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Authors: Priyoth Kittiteerasack, Alana Steffen, Alicia K. Matthews

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Depression is a leading cause of the worldwide burden of disability and disease burden. Notably, lesbian, gay, bisexual, and transgender (LGBT) populations are more likely to be a high-risk group for depression compared to their heterosexual and cisgender counterparts. To date, little is known about the rates and predictors of depression among Thai LGBT populations. As such, the purpose of this study was to: 1) measure the prevalence of depression among a diverse sample of Thai LGBT adults and 2) determine the influence of minority stress variables (discrimination, victimization, internalized homophobia, and identity concealment), general stress (stress and loneliness), and coping strategies (problem-focused, avoidance, and seeking social support) on depression outcomes. This study was guided by the Minority Stress Model (MSM). The MSM posits that elevated rates of mental health problems among LGBT populations stem from increased exposures to social stigma due to their membership in a stigmatized minority group. Social stigma, including discrimination and violence, represents unique sources of stress for LGBT individuals and have a direct impact on mental health. This study was conducted as part of a larger descriptive study of mental health among Thai LGBT adults. Standardized measures consistent with the MSM were selected and translated into the Thai language by a panel of LGBT experts using the forward and backward translation technique. The psychometric properties of translated instruments were tested and acceptable (Cronbach’s alpha > .8 and Content Validity Index = 1). Study participants were recruited using convenience and snowball sampling methods. Self-administered survey data were collected via an online survey and via in-person data collection conducted at a leading Thai LGBT organization. Descriptive statistics and multivariate analyses using multiple linear regression models were conducted to analyze study data. The mean age of participants (n = 411) was 29.5 years (S.D. = 7.4). Participants were primarily male (90.5%), homosexual (79.3%), and cisgender (76.6%). The mean score for depression of study participant was 9.46 (SD = 8.43). Forty-three percent of LGBT participants reported clinically significant levels of depression as measured by the Beck Depression Inventory. In multivariate models, the combined influence of demographic, stress, coping, and minority stressors explained 47.2% of the variance in depression scores (F(16,367) = 20.48, p < .001). Minority stressors independently associated with depression included discrimination (β = .43, p < .01) victimization (β = 1.53, p < .05), and identity concealment (β = -.54, p < .05). In addition, stress (β = .81, p < .001), history of a chronic disease (β = 1.20, p < .05), and coping strategies (problem-focused coping β = -1.88, p < .01, seeking social support β = -1.12, p < .05, and avoidance coping β = 2.85, p < .001) predicted depression scores. The study outcomes emphasized that minority stressors uniquely contributed to depression levels among Thai LGBT participants over and above typical non-minority stressors. Study findings have important implications for nursing practice and the development of intervention research.

Keywords: depression, LGBT, minority stress, sexual and gender minority, Thailand

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Authors: Sandhya Parameswaran, Prajakta Dhuri

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Despite great improvements in health care, the world oral health report states that dental problems still persist, particularly among underprivileged groups in both developing and developed countries. Dental caries and periodontal diseases are identified as the most important oral health problems globally. Acidic foods and beverages can affect natural teeth, and chronic exposure often leads to the development of dental erosion, abrasion, and decay. In recent years, there has been an increased interest toward essential oils. These are secondary metabolites and possess antibacterial, antifungal and antioxidant properties. Essential oils are volatile and chemically unstable in the presence of air, light, moisture and high temperature. Hence many novel methods like a liposomal encapsulation of oils have been introduced to enhance the stability and bioavailability. This research paper focuses on two essential oils, clove and cinnamon oil. Clove oil was obtained from Syzygium aromaticum Linn using clavengers apparatus. It contains eugenol and β caryophyllene. Cinnamon oil, from the barks of Cinnamomum cassia, contains cinnamaldehyde, The objective of the current research was to develop a liposomal carrier system containing clove and cinnamon oil and study their synergistic activity against dental pathogens when formulated as a gel. Methodology: The essential oil were first tested for their antimicrobial activity against dental pathogens, Lactobacillus acidophillus (MTCC No. 10307, MRS broth) and Streptococcus Mutans (MTCC No .890, Brain Heart Infusion agar). The oils were analysed by UV spectroscopy for eugenol and cinnamaldehyde content. Standard eugenol was linear between 5ppm to 25ppm at 282nm and standard cinnamaldehde from 1ppm to 5pmm at 284nm. The concentration of eugenol in clove oil was found to be 62.65 % w/w, and that of cinnamaldehyde was found to be 5.15%s w/w. The oils were then formulated into liposomes. Liposomes were prepared by thin film hydration method using Phospholipid, Cholesterol, and other oils dissolved in a chloroform methanol (3:1) mixture. The organic solvent was evaporated in a rotary evaporator above lipid transition temperature. The film was hydrated with phosphate buffer (pH 5.5).The various batches of liposomes were characterized and compared for their size, loading rate, encapsulation efficiency and morphology. The prepared liposomes when evaluated for entrapment efficiency showed 65% entrapment for clove and 85% for cinnamon oil. They were also tested for their antimicrobial activity against dental pathogens and their synergistic activity studied. Based on the activity and the entrapment efficiency the amount of liposomes required to prepare 1gm of the gel was calculated. The gel was prepared using a simple ointment base and contained 0.56% of cinnamon and clove liposomes. A simultaneous method of analysis for eugenol and cinnamaldehyde.was then developed using HPLC. The prepared gels were then studied for their stability as per ICH guidelines. Conclusion: It was found that liposomes exhibited spherical shaped vesicles and protected the essential oil from degradation. Liposomes, therefore, constitute a suitable system for encapsulation of volatile, unstable essential oil constituents.

Keywords: cinnamon oil, clove oil, dental caries, liposomes

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Authors: Jaci Marie Mastrandrea, Rosario Haro

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Background: The National Comprehensive Cancer Network (NCCN) recommends that healthcare institutions have established processes for integrating palliative care (PC) into cancer treatment and that all cancer patients be screened for PC needs upon initial diagnosis as well as throughout the entire continuum of care (National Comprehensive Cancer Network, 2021). Early PC screening and intervention is directly associated with improved patient outcomes. The Sky Lakes Cancer Treatment Center (SLCTC) is an institution that has access to PC services yet does not have protocols in place for identifying patients with palliative needs or a standardized referral process. The aim of this quality improvement project was to improve early access to PC services by establishing a standardized screening and referral process for outpatient oncology patients. Method: The sample population included all adult patients with an oncology diagnosis who presented to the SLCTC for treatment during the project timeline. The “Palliative and Supportive Needs Assessment'' (PSNA) screening tool was developed from validated, evidence-based PC referral criteria. The tool was initially implemented using paper forms, and data was collected over a period of eight weeks. Patients were screened by nurses on the SLCTC oncology treatment team. Nurses responsible for screening patients received an educational inservice prior to implementation. Patients with a PSNA score of three or higher received an educational handout on the topic of PC and education about PC and symptom management. A score of five or higher indicates that PC referral is strongly recommended, and the patient’s EHR is flagged for the oncology provider to review orders for PC referral. The PSNA tool was approved by Sky Lakes administration for full integration into Epic-Beacon. The project lead collaborated with the Sky Lakes’ information systems team and representatives from Epic on the tool’s aesthetic and functionality within the Epic system. SLCTC nurses and physicians were educated on how to document the PSNA within Epic and where to view results. Results: Prior to the implementation of the PSNA screening tool, the SLCTC had zero referrals to PC in the past year, excluding referrals to hospice. Data was collected from the completed screening assessments of 100 patients under active treatment at the SLCTC. Seventy-three percent of patients met criteria for PC referral with a score greater than or equal to three. Of those patients who met referral criteria, 53.4% (39 patients) were referred for a palliative and supportive care consultation. Patients that were not referred to PC upon meeting criteria were flagged in EPIC for re-screening within one to three months. Patients with lung cancer, chronic hematologic malignancies, breast cancer, and gastrointestinal malignancy most frequently met the criteria for PC referral and scored highest overall on the scale of 0-12. Conclusion: The implementation of a standardized PC screening tool at the SLCTC significantly increased awareness of PC needs among cancer patients in the outpatient setting. Additionally, data derived from this quality improvement project supports the national recommendation for PC to be an integral component of cancer treatment across the entire continuum of care.

Keywords: oncology, palliative and supportive care, symptom management, outpatient oncology, palliative screening tool

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Authors: Margarita Ivanova, Julia Dao, Andrew Friedman, Neil Kasaci, Rekha Gopal, Ozlem Goker-Alpan

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In Fabry disease (FD), α-galactosidase A (α-Gal A) deficiency leads to the accumulation of globotriaosylceramide (Lyso-Gb3 and Gb3), triggering a pathologic cascade that causes the severity of organs damage. The heart is one of the several organs with high sensitivity to the α-Gal A deficiency. A subgroup of patients with significant residual of α-Gal A activity with primary cardiac involvement is occasionally referred to as “cardiac variant.” The cardiovascular complications are most frequently encountered, contributing substantially to morbidity, and are the leading cause of premature death in male and female patients with FD. The deposition of Lyso-Gb-3 and Gb-3 within the myocardium affects cardiac function with resultant progressive cardiovascular pathology. Gb-3 and Lyso-Gb-3 accumulation at the cellular level trigger a cascade of events leading to end-stage fibrosis. In the cardiac tissue, Lyso-Gb-3 deposition is associated with the increased release of inflammatory factors and transforming growth factors. Infiltration of lymphocytes and macrophages into endomyocardial tissue indicates that inflammation plays a significant role in cardiac damage. Moreover, accumulated data suggest that chronic inflammation leads to multisystemic FD pathology even under enzyme replacement therapy (ERT). NF-κB activation plays a subsequent role in the inflammatory response to cardiac dysfunction and advanced heart failure in the general population. TNFalpha/NF-κB signaling protects the myocardial evoking by ischemic preconditioning; however, this protective effect depends on the concentration of TNF-α. Thus, we hypothesize that TNF-α is a critical factor in determining the grade of cardio-pathology. Cardiac hypertrophy corresponds to the expansion of the coronary vasculature to maintain a sufficient supply of nutrients and oxygen. Coronary activation of angiogenesis and fibrosis plays a vital role in cardiac vascularization, hypertrophy, and tissue remodeling. We suggest that the interaction between the inflammatory pathways and cardiac vascularization is a bi-directional process controlled by secreted cytokines and growth factors. The co-coordination of these two processes has never been explored in FD. In a cohort of 40 patients with FD, biomarkers associated with inflammation and cardio hypertrophic remodeling were studied. FD patients were categorized into three groups based on LVmass/DSA, LVEF, and ECG abnormalities: FD with no cardio complication, FD with moderate cardio complication, and severe cardio complication. Serum levels of NF-kB, TNFalpha, Il-6, Il-2, MCP1, ING-gamma, VEGF, IGF-1, TGFβ, and FGF2 were quantified by enzyme-linked immunosorbent assays (ELISA). Among the biomarkers, MCP-1, INF-gamma, VEGF, TNF-alpha, and TGF-beta were elevated in FD patients. Some of these biomarkers also have the potential to correlate with cardio pathology in FD. Conclusion: The study provides information about the role of inflammatory pathways and biomarkers of cardio hypertrophic remodeling in FD patients. This study will also reveal the mechanisms that link intracellular accumulation of Lyso-GB-3 and Gb3 to the development of cardiomyopathy with myocardial thickening and resultant fibrosis.

Keywords: biomarkers, Fabry disease, inflammation, growth factors

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Authors: Chee Wai Ku, Pui See Chin

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As an emerging alternative to hysterectomy, uterine artery embolization (UAE) has been widely used in the management of fibroids and in controlling postpartum hemorrhage (PPH) unresponsive to other therapies. Research has shown UAE to be a safe, minimally invasive procedure with few complications and minimal effects on future fertility. We present two cases highlighting the use of UAE in preventing PPH in a patient with a large fibroid at the time of cesarean section and in the treatment of secondary PPH refractory to other therapies in another patient. We present a 36-year primiparous woman who booked at 18+6 weeks gestation with a 13.7 cm subserosal fibroid at the lower anterior wall of the uterus near the cervix and a 10.8 cm subserosal fibroid in the left wall. Prophylactic internal iliac artery occlusion balloons were placed prior to the planned classical midline cesarean section. The balloons were inflated once the baby was delivered. Bilateral uterine arteries were embolized subsequently. The estimated blood loss (EBL) was 400 mls and hemoglobin (Hb) remained stable at 10 g/DL. Ultrasound scan 2 years postnatally showed stable uterine fibroids 10.4 and 7.1 cm, which was significantly smaller than before. We present the second case of a 40-year-old G2P1 with a previous cesarean section for failure to progress. There were no antenatal problems, and the placenta was not previa. She presented with term labour and underwent an emergency cesarean section for failed vaginal birth after cesarean. Intraoperatively extensive adhesions were noted with bladder drawn high, and EBL was 300 mls. Postpartum recovery was uneventful. She presented with secondary PPH 3 weeks later complicated by hypovolemic shock. She underwent an emergency examination under anesthesia and evacuation of the uterus, with EBL 2500mls. Histology showed decidua with chronic inflammation. She was discharged well with no further PPH. She subsequently returned one week later for secondary PPH. Bedside ultrasound showed that the endometrium was thin with no evidence of retained products of conception. Uterotonics were administered, and examination under anesthesia was performed, with uterine Bakri balloon and vaginal pack insertion after. EBL was 1000 mls. There was no definite cause of PPH with no uterine atony or products of conception. To evaluate a potential cause, pelvic angiogram and super selective left uterine arteriogram was performed which showed profuse contrast extravasation and acute bleeding from the left uterine artery. Superselective embolization of the left uterine artery was performed. No gross contrast extravasation from the right uterine artery was seen. These two cases demonstrated the superior efficacy of UAE. Firstly, the prophylactic use of intra-arterial balloon catheters in pregnant patients with large fibroids, and secondly, in the diagnosis and management of secondary PPH refractory to uterotonics and uterine tamponade. In both cases, the need for laparotomy hysterectomy was avoided, resulting in the preservation of future fertility. UAE should be a consideration for hemodynamically stable patients in centres with access to interventional radiology.

Keywords: fertility preservation, secondary postpartum hemorrhage, uterine embolization, uterine fibroids

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Authors: Ifeyinwa Victor-Uadiale, Georgina Pearson, Sophie Witter, D. Reidpath

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Introduction: Smoking, alcohol misuse, unhealthy diet, and physical inactivity are the primary drivers of noncommunicable diseases (NCD), including cardiovascular diseases, cancers, respiratory diseases, and diabetes, worldwide. Collectively, these diseases are the leading cause of all global deaths, most of which are premature, affecting people between 30 and 70 years. Empirical evidence suggests that these risk behaviors can be modified by community-based interventions (CBI). However, there is little insight into the mechanisms and contextual factors of successful community interventions that impact risk behaviours for chronic diseases. This study examined “Under what circumstances, for whom, and how, do community-based interventions modify smoking, alcohol use, unhealthy diet, and physical inactivity among adults”. Adopting the Capability (C), Opportunity (O), Motivation (M), Behavior (B) (COM-B) framework for behaviour change, it sought to: (1) identify the mechanisms through which CBIs could reduce tobacco use and alcohol consumption and increase physical activity and the consumption of healthy diets and (2) examine the contextual factors that trigger the impact of these mechanisms on these risk behaviours among adults. Methods: Pawson’s realist review method was used to examine the literature. Empirical evidence and theoretical understanding were combined to develop a realist program theory that explains how CBIs influence NCD risk behaviours. Documents published between 2002 and 2020 were systematically searched in five electronic databases (CINAHL, Cochrane Library, Medline, ProQuest Central, and PsycINFO). They were included if they reported on community-based interventions aimed at cardiovascular diseases, cancers, respiratory diseases, and diabetes in a global context; and had an outcome targeted at smoking, alcohol, physical activity, and diet. Findings: Twenty-nine scientific documents were retrieved and included in the review. Over half of them (n = 18; 62%) focused on three of the four risk behaviours investigated in this review. The review identified four mechanisms: capability, opportunity, motivation, and social support that are likely to change the dietary and physical activity behaviours in adults given certain contexts. There were weak explanations of how the identified mechanisms could likely change smoking and alcohol consumption habits. In addition, eight contextual factors that may affect how these mechanisms impact physical activity and dietary behaviours were identified: suitability to work and family obligations, risk status awareness, socioeconomic status, literacy level, perceived need, availability and access to resources, culture, and group format. Conclusion: The findings suggest that CBIs are likely to improve the physical activity and dietary habits of adults if the intervention function seeks to educate, incentivize, change the environment, and model the right behaviours. The review applies and advances theory, realist research, and the design and implementation of community-based interventions for NCD prevention.

Keywords: community-based interventions, noncommunicable disease, realist program theory, risk behaviors

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Authors: Sahar El Shair, Laura Greco, William Reay, Murray Cairns

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Background: Rheumatoid arthritis (RA) is a chronic, systematic, inflammatory, autoimmune disease that involves damages to joints and erosions to the associated bones and cartilage, resulting in reduced physical function and disability. RA is a multifactorial disorder influenced by heterogenous genetic and environmental factors. Whilst different medications have proven successful in reducing inflammation associated with RA, they often come with significant side effects and limited efficacy. To address this, the novel pharmagenic enrichment score (PES) algorithm was tested in self-reported RA patients from the UK Biobank (UKBB), which is a cohort of predominantly European ancestry, and identified individuals with a high genetic risk in clinically actionable biological pathways to identify novel opportunities for precision interventions and drug repurposing to treat RA. Methods and materials: Genetic association data for rheumatoid arthritis was derived from publicly available genome-wide association studies (GWAS) summary statistics (N=97173). The PES framework exploits competitive gene set enrichment to identify pathways that are associated with RA to explore novel treatment opportunities. This data is then integrated into WebGestalt, Drug Interaction database (DGIdb) and DrugBank databases to identify existing compounds with existing use or potential for repurposed use. The PES for each of these candidates was then profiled in individuals with RA in the UKBB (Ncases = 3,719, Ncontrols = 333,160). Results A total of 209 pathways with known drug targets after multiple testing correction were identified. Several pathways, including interferon gamma signaling and TID pathway (which relates to a chaperone that modulates interferon signaling), were significantly associated with self-reported RA in the UKBB when adjusting for age, sex, assessment centre month and location, RA polygenic risk and 10 principal components. These pathways have a major role in RA pathogenesis, including autoimmune attacks against certain citrullinated proteins, synovial inflammation, and bone loss. Encouragingly, many also relate to the mechanism of action of existing RA medications. The analyses also revealed statistically significant association between RA polygenic scores and self-reported RA with individual PES scorings, highlighting the potential utility of the PES algorithm in uncovering additional genetic insights that could aid in the identification of individuals at risk for RA and provide opportunities for more targeted interventions. Conclusions In this study, pharmacologically annotated genetic risk was explored through the PES framework to overcome inter-individual heterogeneity and enable precision drug repurposing in RA. The results showed a statistically significant association between RA polygenic scores and self-reported RA and individual PES scorings for 3,719 RA patients. Interestingly, several enriched PES pathways were targeted by already approved RA drugs. In addition, the analysis revealed genetically supported drug repurposing opportunities for future treatment of RA with a relatively safe profile.

Keywords: rheumatoid arthritis, precision medicine, drug repurposing, system biology, bioinformatics

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Authors: Mustafa Metin Donma, Orkide Donma

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Childhood obesity is an important clinical problem because it may lead to chronic diseases during the adulthood period of the individual. Obesity is a metabolic disease associated with low-grade inflammation. The liver occurs at the center of metabolic pathways. Adropin, fibroblast growth factor-21 (FGF-21), and fetuin-A are hepatokines. Due to the immense participation of the liver in glucose metabolism, these liver-derived factors may be associated with insulin resistance (IR), which is a phenomenon discussed within the scope of obesity problems. The aim of this study is to determine the concentrations of adropin, FGF-21, and fetuin-A in childhood obesity, to point out possible differences between the obesity groups, and to investigate possible associations among these three hepatokines in obese and morbidly obese children. A total of one hundred and thirty-two children were included in the study. Two obese groups were constituted. The groups were matched in terms of mean ± SD values of ages. Body mass index values of obese and morbidly obese groups were 25.0 ± 3.5 kg/m² and 29.8 ± 5.7 kg/m², respectively. Anthropometric measurements including waist circumference, hip circumference, head circumference, and neck circumference were recorded. Informed consent forms were taken from the parents of the participants. The ethics committee of the institution approved the study protocol. Blood samples were obtained after overnight fasting. Routine biochemical tests, including glucose- and lipid-related parameters, were performed. Concentrations of the hepatokines (adropin, FGF-21, fetuin A) were determined by enzyme-linked immunosorbent assay. Insulin resistance indices such as homeostasis model assessment for IR (HOMA-IR), alanine transaminase-to aspartate transaminase ratio (ALT/AST), diagnostic obesity notation model assessment laboratory index, diagnostic obesity notation model assessment metabolic syndrome index as well as obesity indices such as diagnostic obesity notation model assessment-II index, and fat mass index were calculated using the previously derived formulas. Statistical evaluation of the study data as well as findings of the study was performed by SPSS for Windows. Statistical difference was accepted significant when p is smaller than 0.05. Statistically significant differences were found for insulin, triglyceride, high-density lipoprotein cholesterol levels of the groups. A significant increase was observed for FGF-21 concentrations in the morbidly obese group. Higher adropin and fetuin-A concentrations were observed in the same group in comparison with the values detected in the obese group (p > 0.05). There was no statistically significant difference between the ALT/AST values of the groups. In all of the remaining IR and obesity indices, significantly increased values were calculated for morbidly obese children. Significant correlations were detected between HOMA-IR and each of the hepatokines. The highest one was the association with fetuin-A (r=0.373, p=0.001). In conclusion, increased levels observed in adropin, FGF-21, and fetuin-A have shown that these hepatokines possess increasing potential going from obese to morbid obese state. Out of the correlations found with the IR index, the most affected hepatokine was fetuin-A, the parameter possibly used as the indicator of the advanced obesity stage.

Keywords: adropin, fetuin A, fibroblast growth factor-21, insulin resistance, pediatric obesity

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Authors: Innocent Atuhe, Babra Nalwadda, Grace Mulyowa, Annabella Habinka Ejiri

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Background: Atopic Dermatitis (AD) is one of the most prevalent and growing chronic inflammatory skin diseases in African prisons. AD care is limited in African due to a lack of information about the disease amongst primary care workers, limited access to dermatologists, lack of proper training of healthcare workers, and shortage of appropriate treatments. We designed and implemented the Prisons Telederma project based on the recommendations of the International Society of Atopic Dermatitis. We aimed at; i) increase awareness and understanding of teledermatology among prison health workers and ii) improve treatment outcomes of prisoners with atopic dermatitis through increased access to and utilization of consultant dermatologists through teledermatology in Uganda prisons. Approach: We used Store-and-forward Teledermatology (SAF-TD) to increase access to dermatologist-led care for prisoners and prison staff with AD. We conducted five days of training for prison health workers using an adapted WHO training guide on recognizing neglected tropical diseases through changes on the skin together with an adapted American Academy of Dermatology (AAD) Childhood AD Basic Dermatology Curriculum designed to help trainees develop a clinical approach to the evaluation and initial management of patients with AD. This training was followed by blended e-learning, webinars facilitated by consultant Dermatologists with local knowledge of medication and local practices, apps adjusted for pigmented skin, WhatsApp group discussions, and sharing pigmented skin AD pictures and treatment via zoom meetings. We hired a team of Ugandan Senior Consultant dermatologists to draft an iconographic atlas of the main dermatoses in pigmented African skin and shared this atlas with prison health staff for use as a job aid. We had planned to use MySkinSelfie mobile phone application to take and share skin pictures of prisoners with AD with Consultant Dermatologists, who would review the pictures and prescribe appropriate treatment. Unfortunately, the National Health Service withdrew the app from the market due to technical issues. We monitored and evaluated treatment outcomes using the Patient-Oriented Eczema Measure (POEM) tool. We held four advocacy meetings to persuade relevant stakeholders to increase supplies and availability of first-line AD treatments such as emollients in prison health facilities. Results: We have the very first iconographic atlas of the main dermatoses in pigmented African skin. We increased; i) the proportion of prison health staff with adequate knowledge of AD and teledermatology from 20% to 80%; ii) the proportion of prisoners with AD reporting improvement in disease severity (POEM scores) from 25% to 35% in one year; iii) increased proportion of prisoners with AD seen by consultant dermatologist through teledermatology from 0% to 20% in one year and iv)Increased the availability of AD recommended treatments in prisons health facilities from 5% to 10% in one year. Our study contributes to the use, evaluation, and verification of the use of teledermatology to increase access to specialist dermatology services to the most hard to reach areas and vulnerable populations such as that of prisoners.

Keywords: teledermatology, prisoners, reaching, un-reachable

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Authors: Christabel Ihedike, John Mooney, Monica Price

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Summary: This study aims to critically evaluate effect of photochemical smog on respiratory health in Nigeria. Cohort of chronic obstructive pulmonary disease (COPD) patients was recruited from two large hospitals in Abuja Nigeria. Respiratory health questionnaires, daily diaries, dyspnoea scale and lung function measurement were used to obtain health data and investigate the relationship with air quality data (principally ozone, NOx and particulate pollution). Concentrations of air pollutants were higher than WHO and Nigerian air quality standard. The result suggests a correlation between measured air quality and exacerbation of respiratory illness. Introduction: Photochemical smog is a significant health challenge in most cities and its effect on respiratory health is well acknowledged. This type of pollution is most harmful to the elderly, children and those with underlying respiratory disease. This study aims to investigate impact of increasing temperature and photo-chemically generated secondary air pollutants on respiratory health in Abuja Nigeria. Method and Result: Health data was collected using spirometry to measure lung function on routine attendance at the clinic, daily diaries kept by patients and information obtained using respiratory questionnaire. Questionnaire responses (obtained using an adapted and internally validated version of St George’s Hospital Respiratory Questionnaire), shows that ‘time of wheeze’ showed an association with participants activities: 30% had worse wheeze in the morning: 10% cannot shop, 15% take long-time to get washed, 25% walk slower, 15% if hurry have to stop and 5% cannot take-bath. There was also a decrease in Forced expiratory volume in the first second and Forced Vital Capacity, and daily change in the afternoon–morning may be associated with the concentration level of pollutants. Also, dyspnoea symptoms recorded that 60% of patients were on grade 3, 25% grade 2 and 15% grade 1. Daily frequency of the number of patients in the cohort that cough /brought sputum is 78%. Air pollution in the city is higher than Nigerian and WHO standards with NOx and PM10 concentrations of 693.59ug/m-3 and 748ugm-3 being measured respectively. The result shows that air pollution may increase occurrence and exacerbation of respiratory disease. Conclusion: High temperature and local climatic conditions in urban Nigeria encourages formation of Ozone, the major constituent of photochemical smog, resulting also in the formation of secondary air pollutants associated with health challenges. In this study we confirm the likely potency of the pattern of secondary air pollution in exacerbating COPD symptoms in vulnerable patient group in urban Nigeria. There is need for better regulation and measures to reduce ozone, particularly when local climatic conditions favour development of photochemical smog in such settings. Climate change and likely increasing temperatures add impetus and urgency for better air quality standards and measures (traffic-restrictions and emissions standards) in developing world settings such as Nigeria.

Keywords: Abuja-Nigeria, effect, photochemical smog, respiratory health

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Authors: Rupali Bhatia, Deepthi Nair, Geetika Khanna, Seema Singhal

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Introduction: Genital tract tuberculosis is a chronic disease (caused by reactivation of organisms from systemic distribution of Mycobacterium tuberculosis) that often presents with low grade symptoms and non-specific complaints. Patients with genital tuberculosis are usually young women seeking workup and treatment for infertility. Infertility is the commonest presentation due to involvement of the fallopian tubes, endometrium and ovarian damage with poor ovarian volume and reserve. The diagnosis of genital tuberculosis is difficult because of the fact that it is a silent invader of genital tract. Since tissue cannot be obtained from fallopian tubes, the diagnosis is made by isolation of bacilli from endometrial tissue obtained by endometrial biopsy curettage and/or aspiration. Problems are associated with sampling technique as well as diagnostic modality due to lack of adequate sample volumes and the segregation of the sample for various diagnostic tests resulting in non-uniform distribution of microorganisms. Moreover, lack of an efficient sampling technique universally applicable for all specific diagnostic tests contributes to the diagnostic challenges. Endometrial sampling plays a key role in accurate diagnosis of female genital tuberculosis. It may be done by 2 methods viz. endometrial curettage and endometrial aspiration. Both endometrial curettage and aspirate have their own limitations as curettage picks up strip of the endometrium from one of the walls of the uterine cavity including tubal osteal areas whereas aspirate obtains total tissue with exfoliated cells present in the secretory fluid of the endometrial cavity. Further, sparse and uneven distribution of the bacilli remains a major factor contributing to the limitations of the techniques. The sample that is obtained by either technique is subjected to histopathological examination, AFB staining, culture and PCR. Aim: Comparison of the sampling techniques viz. endometrial biopsy curettage and endometrial aspiration using different laboratory methods of histopathology, cytology, microbiology and molecular biology. Method: In a hospital based observational study, 75 Indian females suspected of genital tuberculosis were selected on the basis of inclusion criteria. The women underwent endometrial tissue sampling using Novaks biopsy curette and Karmans cannula. One part of the specimen obtained was sent in formalin solution for histopathological testing and another part was sent in normal saline for acid fast bacilli smear, culture and polymerase chain reaction. The results so obtained were correlated using coefficient of correlation and chi square test. Result: Concordance of results showed moderate agreement between both the sampling techniques. Among HPE, AFB and PCR, maximum sensitivity was observed for PCR, though the specificity was not as high as other techniques. Conclusion: Statistically no significant difference was observed between the results obtained by the two sampling techniques. Therefore, one may use either EA or EB to obtain endometrial samples and avoid multiple sampling as both the techniques are equally efficient in diagnosing genital tuberculosis by HPE, AFB, culture or PCR.

Keywords: acid fast bacilli (AFB), histopatholgy examination (HPE), polymerase chain reaction (PCR), endometrial biopsy curettage

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Authors: Sandy Elsayed, Aya Mohamed, Noha Nassar

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Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behavior. Multiple studies suggest that oxidative stress and neuroinflammation are key factors in the etiology of ASD and often associated with worsening of ASD-related behaviors. Nuclear factor erythroid 2-related factor 2 (NRF-2) is a transcription factor that promotes expression of antioxidant response element genes in oxidative stress. In ASD subjects, decreased expression of NRF-2 in frontal cortex shifted the redox homeostasis towards oxidative stress, and resulted in inflammation evidenced by elevation of nuclear factor kappa B (NF-κB) transcriptional activity. Dimethyl fumarate (DMF) is a NRF-2 activator that is used in the treatment of psoriasis and multiple sclerosis. It participates in the transcriptional control of inflammatory factors via inhibition of NF-κB and its downstream targets. This study aimed to investigate the role of DMF in alleviating the cognitive impairments and behavior deficits associated with ASD through mitigation of oxidative stress and inflammation in prenatal valproic acid (VPA) rat model of autism. Methods: Pregnant female Wistar rats received a single intraperitoneal injection of VPA (600 mg/kg) to induce autistic-like-behavioral and neurobiological alterations in their offspring. Chronic oral gavage of DMF (150mg/kg/day) started from postnatal day (PND) 24 till PND62 (39 days). Prenatal VPA exposure elicited autistic behaviors including decreased social interaction and stereotyped behavior. Social interaction was evaluated using three-chamber sociability test and calculation of sociability index (SI), while stereotyped repetitive behavior and anxiety associated with ASD were assessed using marble burying test (MBT). Biochemical analyses were done on prefrontal cortex homogenates including NRF-2, and NF-κB expression. Moreover, inducible nitric oxide synthase (iNOS) gene expression and tumor necrosis factor (TNF-) protein expression were evaluated as markers of inflammation. Results: Prenatal VPA elicited decreased social interaction shown by decreased SI compared to control group (p < 0.001) and DMF enhanced SI (p < 0.05). In MBT, prenatal injection of VPA manifested stereotyped behavior and enhanced number of buried marbles compared to control (p < 0.05) and DMF reduced the anxiety-related behavior in rats exhibiting ASD-like behaviors (p < 0.05). In prefrontal cortex, NRF-2 expression was downregulated in prenatal VPA model (p < 0.0001) and DMF reversed this effect (p < 0.0001). The inflammatory transcription factor NF-κB was elevated in prenatal VPA model (p < 0.0001) and reduced (p < 0.0001) upon NRF-2 activation by DMF. Prenatal VPA expressed higher levels of proinflammatory cytokine TNF- compared to control group (p < 0.0001) and DMF reduced it (p < 0.0001). Finally, the gene expression of iNOS was downregulated upon NRF-2 activation by DMF (p < 0.01). Conclusion: This study proposes that DMF is a potential agent that can be used to ameliorate autistic-like-changes through NRF-2 activation along with NF-κB downregulation and therefore, it is a promising novel therapy for ASD.

Keywords: autism spectrum disorders, dimethyl fumarate, neuroinflammation, NRF-2

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Authors: Lucile Rapin, Cynthia El Hage, Rihab Gamaoun, Maria-Fernanda Arboleda, Erin Prosk

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Introduction: Sante Cannabis (SC), a Canadian group of clinics dedicated to medical cannabis, based in Montreal and in the province of Quebec, has served more than 8000 patients seeking cannabis-based treatment over the past five years. As randomized clinical trials with natural medical cannabis are scarce, real-world evidence offers the opportunity to fill research gaps between scientific evidence and clinical practice. Data on the use of medical cannabis products from SC patients were prospectively collected, leading to a large real-world database on the use of medical cannabis. The aim of this study was to report information on the profiles of both patients and prescribed medical cannabis products at SC clinics, and to assess the safety of medical cannabis among Canadian patients. Methods: This is an observational retrospective study of 1342 adult patients who were authorized with medical cannabis products between October 2017 and September 2019. Information regarding demographic characteristics, therapeutic indications for medical cannabis use, patterns in dosing and dosage form of medical cannabis and adverse effects over one-year follow-up (initial and 4 follow-up (FUP) visits) were collected. Results: 59% of SC patients were female, with a mean age of 56.7 (SD= 15.6, range= (19-97)). Cannabis products were authorized mainly for patients with a diagnosis of chronic pain (68.8% of patients), cancer (6.7%), neurological disorders (5.6%), and mood disorders (5.4 %). At initial visit, a large majority (70%) of patients were authorized exclusively medical cannabis products, 27% were authorized a combination of pharmaceutical cannabinoids and medical cannabis and 3% were prescribed only pharmaceutical cannabinoids. This pattern was recurrent over the one-year follow-up. Overall, oil was the preferred formulation (average over visits 72.5%) followed by a combination of oil and dry (average 19%), other routes of administration accounted for less than 4%. Patients were predominantly prescribed products with a balanced THC:CBD ratio (59%-75% across visits). 28% of patients reported at least one adverse effect (AE) at the 3-month follow-up visit and 12% at the six-month FUP visit. 84.8% of total AEs were mild and transient. No serious AE was reported. Overall, the most common side effects reported were dizziness (11.95% of total AEs), drowsiness (11.4%), dry mouth (5.5%), nausea (4.8%), headaches (4.6%), cough (4.4%), anxiety (4.1%) and euphoria (3.5%). Other adverse effects accounted for less than 3% of total AE. Conclusion: Our results confirm that the primary area of clinical use for medical cannabis is in pain management. Patients in this cohort are largely utilizing plant-based cannabis oil products with a balanced ratio of THC:CBD. Reported adverse effects were mild and included dizziness and drowsiness. This real-world data confirms the tolerable safety profile of medical cannabis and suggests medical indications not yet validated in controlled clinical trials. Such data offers an important opportunity for the investigation of the long-term effects of cannabinoid exposure in real-life conditions. Real-world evidence can be used to direct clinical trial research efforts on specific indications and dosing patterns for product development.

Keywords: medical cannabis, safety, real-world data, Canada

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Authors: Noorh Albadi, Salha Khayyat

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People's moods and well-being are affected by their environment. The built environment impacts one's level of activity and health. In order to enhance users' physical health, sustainable design strategies have been developed for the physical environment to improve users' health. This study aimed to determine whether adult resorts in Saudi Arabia meet standards that ensure physical wellness to identify the needed requirements. It will be significant to the Ministry of Tourism, Sports, developers, and designers. Physical activity affects human health physically and mentally. In Saudi Arabia, the percentage of people who practiced sports in the Kingdom in 2019 was 20.04% - males and females older than 15. On the other hand, there is a lack of physical activity in Saudi Arabia; 90% of the Kingdom's population spends more than two hours sitting down without moving, which puts them at risk of contracting a non-communicable disease. The lack of physical activity and movement led to an increase in the rate of obesity among Saudis by 59% in 2020 and consequently could cause chronic diseases or death. The literature generally endorses that leading an active lifestyle improves physical health and affects mental health. Therefore, the United Nations has set 17 sustainable development goals (SDGs) to ensure healthy lives and promote well-being for all ages. One of SDG3's targets is reducing mortality, which can be achieved by raising physical activity. In order to support sustainable design, many rating systems and strategies have been developed, such as WELL building, Leadership in Energy and Environmental Design, (LEED), Active design strategies, and RIPA plan of work. The survey was used to gather qualitative and quantitative information. It was designed based on the Active Design and WELL building theories targeting beach resorts visitors, professional and beginner athletes, and non-athletics to ask them about the beach resorts they visited in the Kingdom and whether they met the criteria of sports resorts and healthy and active design theories, in addition to gathering information about the preferences of physical activities in the Saudi society in terms of the type of activities that young people prefer, where they prefer to engage in and under any thermal and light conditions. The final section asks about the design of residential units in beach sports resorts, the data collected from 127 participants. Findings revealed that participants prefer outdoor activities in moderate weather and sunlight or the evening with moderate and sufficient lighting and that no beach sports resorts in the country are constructed to support sustainable design criteria for physical activity. Participants agreed that several measures that lessen tension at beach resorts and enhance movement and activity are needed by Saudi society. The study recommends designing resorts that meet the sustainable design criteria regarding physical activity in Saudi Arabia to increase physical activity to achieve psychological and physical benefits and avoid psychological and physical diseases related to physical inactivity.

Keywords: sustainable design, SDGs, active design strategies, well building, beach resort design

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Authors: Esra Sengul, R. G. Aktas, M. E. Sitar, H. Isan

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Hepatocellular carcinoma (HCC) is a hepatocellular tumor commonly found on the surface of the chronic liver. HepG2 is the most commonly used cell type in HCC studies. The main proteins remaining in the blood serum after separation of plasma fibrinogen are albumin and globulin. The fact that the albumin showed hepatocellular damage and reflect the synthesis capacity of the liver was the main reason for our use. Alpha-Fetoprotein (AFP) is an albumin-like structural embryonic globulin found in the embryonic cortex, cord blood, and fetal liver. It has been used as a marker in the follow-up of tumor growth in various malign tumors and in the efficacy of surgical-medical treatments, so it is a good protein to look at with albumins. We have seen the morphological changes of dimethyl sulfoxide (DMSO) on HepG2 and decided to investigate its biochemical effects. We examined the effects of DMSO, which is used in cell cultures, on albumin, AFP and total protein at low doses. Material Method: Cell Culture: Medium was prepared in cell culture using Dulbecco's Modified Eagle Media (DMEM), Fetal Bovine Serum Dulbecco's (FBS), Phosphate Buffered Saline and trypsin maintained at -20 ° C. Fixation of Cells: HepG2 cells, which have been appropriately developed at the end of the first week, were fixed with acetone. We stored our cells in PBS at + 4 ° C until the fixation was completed. Area Calculation: The areas of the cells are calculated in the ImageJ (IJ). Microscope examination: The examination was performed with a Zeiss Inverted Microscope. Daytime photographs were taken at 40x, 100x 200x and 400x. Biochemical Tests: Protein (Total): Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Albumin: Serum sample was analyzed by a spectrophotometric method in autoanalyzer. Alpha-fetoprotein: Serum sample was analyzed by ECLIA method. Results: When liver cancer cells were cultured in medium with 1% DMSO for 4 weeks, a significant difference was observed when compared with the control group. As a result, we have seen that DMSO can be used as an important agent in the treatment of liver cancer. Cell areas were reduced in the DMSO group compared to the control group and the confluency ratio increased. The ability to form spheroids was also significantly higher in the DMSO group. Alpha-fetoprotein was lower than the values of an ordinary liver cancer patient and the total protein amount increased to the reference range of the normal individual. Because the albumin sample was below the specimen value, the numerical results could not be obtained on biochemical examinations. We interpret all these results as making DMSO a caretaking aid. Since each one was not enough alone we used 3 parameters and the results were positive when we refer to the values of a normal healthy individual in parallel. We hope to extend the study further by adding new parameters and genetic analyzes, by increasing the number of samples, and by using DMSO as an adjunct agent in the treatment of liver cancer.

Keywords: hepatocellular carcinoma, HepG2, dimethyl sulfoxide, cell culture, ELISA

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Authors: Nick Toossi, Joseph Hartland

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Background: Malawi is an example of a low resource setting which faces a chronic shortage of doctors and other medical staff. This shortfall is made up for by clinical officers (COs), who are para-medicals trained for 4 years. The literature suggests to improve outcomes surgical skills training specifically should be promoted for COs in district and mission hospitals. Accordingly, the primary author was tasked with developing a basic surgical skills teaching package for COs of Mulanje Mission Hospital (MMH), Malawi, as part of a 4th year medical student External Student Selected Component field trip. MMH is a hospital based in the South of Malawi near the base of Mulanje Mountain and works in an extremely isolated environment with some of the poorest communities in the country. Traveling to Malawi the medical student author performed an educational needs assessment to develop and deliver a bespoke basic surgical skills teaching package. Methodology: An initial needs assessment identified the following domains: basic surgical skills (instrument naming & handling, knot tying, suturing principles and suturing techniques) and perineal repair. Five COs took part in a teaching package involving an interactive group simulation session, overseen by senior clinical officers and surgical trainees from the UK. Non-organic and animal models were used for simulation practice. This included the use of surgical skills boards to practice knot tying and ox tongue to simulate perineal repair. All participants spoke and read English. The impact of the session was analysed in two different ways. The first was via a pre and post Single Best Answer test and the second a questionnaire including likert’s scales and free text response questions. Results: There was a positive trend in pre and post test scores on competition of the course. There was increase in the mean confidence of learners before and after the delivery of teaching in basic surgical skills and simulated perineal repair, especially in ‘instrument naming and handling’. Whilst positively received it was discovered that learners desire more frequent surgical skills teaching sessions in order to improve and revise skills. Feedback suggests that the learners were not confident in retaining the skills without regular input. Discussion: Skills and confidence were improved as a result of the teaching provided. Learner's written feedback suggested there was an overall appetite for regular surgical skills teaching in the clinical environment and further opportunities to allow for deliberate self-practice. Surgical mentorship schemes facilitating supervised theatre time among trainees and lead surgeons along with improving access to surgical models/textbooks were some of the simple suggestions to improve surgical skills and confidence among COs. Although, this study is limited by population size it is reflective of the small, isolated and low resource environment in which this healthcare is delivered. This project does suggest that current surgical skills packages used in the UK could be adapted for employment in low resource settings, but it is consistency and sustainability that staff seek above all in their on-going education.

Keywords: clinical officers, education, Malawi, surgical skills

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Authors: Ifeoma Anozie, Teka Apalata, Dominic Abaver

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Introduction: Despite use of Anti-retroviral therapy to reduce the incidence of opportunistic infections among HIV/AIDS patients, rapid episodes of re-infection after deworming are still common occurrences because pharmaceutical intervention alone does not prevent reinfection. Unsafe water and inadequate personal hygiene and parasitic infections are widely expected to accelerate the progression of HIV infection. This is because the chronic immunosuppression of HIV infection encourages susceptibility to opportunistic (including parasitic) infections which is linked to CD4+ cell count of <200 cells/μl. Intestinal parasites such as G. intestinalis and Entamoeba spp are ubiquitous protozoa that remain infectious over a long time in an environment and show resistance to standard disinfection. To control re-infection, the social factors that underpin the prevention need to be controlled. This study aims at prevention of intestinal parasites in people living with HIV/AIDS by using a treatment, hygiene education and sanitation (THEdS) bundle approach. Methods: This study was conducted in four clinics (Ngangelizwe health centre, Tsolo gateway clinic, Idutywa health centre and Nqamakwe health centre) across the seven districts in Eastern cape, South Africa. The four clinics were divided in two: experimental and control, for the purpose of intervention. Data was collected from March 2019 to February 2020. Six hundred participants were screened for intestinal parasitic infections. Stool samples were collected and analysed twice: before (Pre-test infection screening) and after (Post-test re-infection) THEdS bundle intervention. The experimental clinics received full intervention package, which include therapeutic treatment, health education on personal hygiene and sanitation training, while the control clinics received only therapeutic treatment for those found with intestinal parasitic infections. Results: Baseline prevalence of Intestinal Parasites isolated shows 12 intestinal parasites with overall frequency of 65, with Ascaris lumbricoides having most frequency (44.6%). The intervention had a cure rate of 60%, with odd ratio of 1.42, which indicates that the intervention group is 1.42 times more likely of parasite clearing as compared to the control group. The relative risk ratio of 1.17 signifies that there is 1.17 times more likelihood to clear intestinal parasite if there no intervention. Discussion and conclusion: Infection with multiple parasites can cause health defects, especially among HIV/AIDS patients. Efficiency of some HIV vaccines in HIV/AIDS patients is affected because treatment of re-infection amplifies drug resistance, affects the efficacy of the front-line drugs, and still permits transmission. In South Africa, treatment of intestinal parasites is usually offered to clinic attending HIV/AIDS patients upon suspicion but not as a mandate for patients being initiated into Antiretroviral (ART) program. The effectiveness of THEdS bundle advocates for inclusiveness of mandatory screening for intestinal parasitic infections among attendees of HIV/Aids clinics on regular basis.

Keywords: cure rate, , HIV/AIDS patients, intestinal parasites, intervention studies, reinfection rate

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Authors: Inas Raafat, Azza El Bassiouny, Waldemar L. Olszewsky, Nagui E. Mikhail, Mona Nossier, Nora E. I. El-Bassiouni, Mona Zoheiry, Houda Abou Taleb, Noha Abd El-Aal, Ali Baioumy, Shimaa Attia

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Background: Orthotopic liver transplantation is an established treatment for patients with severe acute and end-stage chronic liver disease. The shortage of donor organs continues to be the rate-limiting factor for liver transplantation throughout the world. Hepatocyte transplantation is a promising treatment for several liver diseases and can, also, be used as a "bridge" to liver transplantation in cases of liver failure. Aim of the work: This study was designed to develop a highly efficient protocol for isolation and transplantation of hepatocytes in experimental Lewis rat model to provide satisfactory guidelines for future application on humans.Materials and Methods: Hepatocytes were isolated from the liver by double perfusion technique and bone marrow cells were isolated by centrifugation of shafts of tibia and femur of donor Lewis rats. Recipient rats were subjected to sub-lethal dose of irradiation 2 days before transplantation. In a laparotomy operation the spleen was injected by freshly isolated hepatocytes and bone marrow cells were injected intravenously. The animals were sacrificed 45 day latter and splenic sections were prepared and stained with H & E, PAS AFP and Prox1. Results: The data obtained from this study showed that the double perfusion technique is successful in separation of hepatocytes regarding cell number and viability. Also the method used for bone marrow cells separation gave excellent results regarding cell number and viability. Intrasplenic engraftment of hepatocytes and live tissue formation within the splenic tissue were found in 70% of cases. Hematoxylin and eosin stained splenic sections from 7 rats showed sheets and clusters of cells among the splenic tissues. Periodic Acid Schiff stained splenic sections from 7 rats showed clusters of hepatocytes with intensely stained pink cytoplasmic granules denoting the presence of glycogen. Splenic sections from 7 rats stained with anti-α-fetoprotein antibody showed brownish cytoplasmic staining of the hepatocytes denoting positive expression of AFP. Splenic sections from 7 rats stained with anti-Prox1 showed brownish nuclear staining of the hepatocytes denoting positive expression of Prox1 gene on these cells. Also, positive expression of Prox1 gene was detected on lymphocytes aggregations in the spleens. Conclusions: Isolation of liver cells by double perfusion technique using collagenase buffer is a reliable method that has a very satisfactory yield regarding cell number and viability. The intrasplenic route of transplantation of the freshly isolated liver cells in an immunocompromised model was found to give good results regarding cell engraftment and tissue formation. Further studies are needed to assess function of engrafted hepatocytes by measuring prothrombin time, serum albumin and bilirubin levels.

Keywords: Lewis rats, hepatocytes, BMCs, transplantation, AFP, Prox1

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Authors: Anupama Singh, Papia Raj

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Though Municipal Solid Waste (MSW) is a worldwide problem, yet its implications are enormous in developing countries, as they are unable to provide proper Municipal Solid Waste Management (MSWM) for the large volume of MSW. As a result, the collected wastes are dumped in open dumping at landfilling sites while the uncollected wastes remain strewn on the roadside, many-a-time clogging drainage. Such unsafe and inadequate management of MSW causes various public health hazards. For example, MSW directly on contact or by leachate contaminate the soil, surface water, and ground water; open burning causes air pollution; anaerobic digestion between the piles of MSW enhance the greenhouse gases i.e., carbon dioxide and methane (CO2 and CH4) into the atmosphere. Moreover, open dumping can cause spread of vector borne disease like cholera, typhoid, dysentery, and so on. Patna, the capital city of Bihar, one of the most underdeveloped provinces in India, is a unique representation of this situation. Patna has been identified as the ‘garbage city’. Over the last decade there has been an exponential increase in the quantity of MSW generation in Patna. Though a large proportion of such MSW is recyclable in nature, only a negligible portion is recycled. Plastic constitutes the major chunk of the recyclable waste. The chemical composition of plastic is versatile consisting of toxic compounds, such as, plasticizers, like adipates and phthalates. Pigmented plastic is highly toxic and it contains harmful metals such as copper, lead, chromium, cobalt, selenium, and cadmium. Human population becomes vulnerable to an array of health problems as they are exposed to these toxic chemicals multiple times a day through air, water, dust, and food. Based on analysis of health data it can be emphasized that in Patna there has been an increase in the incidence of specific diseases, such as, diarrhoea, dysentry, acute respiratory infection (ARI), asthma, and other chronic respiratory diseases (CRD). This trend can be attributed to improper MSWM. The results were reiterated through a survey (N=127) conducted during 2014-15 in selected areas of Patna. Random sampling method of data collection was used to better understand the relationship between different variables affecting public health due to exposure to MSW and lack of MSWM. The results derived through bivariate and logistic regression analysis of the survey data indicate that segregation of wastes at source, segregation behavior, collection bins in the area, distance of collection bins from residential area, and transportation of MSW are the major determinants of public health issues. Sustainable recycling is a robust method for MSWM with its pioneer concerns being environment, society, and economy. It thus ensures minimal threat to environment and ecology consequently improving public health conditions. Hence, this paper concludes that sustainable recycling would be the most viable approach to manage MSW in Patna and would eventually reduce public health hazards.

Keywords: municipal solid waste, Patna, public health, sustainable recycling

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Authors: Kunal Garg, Louise Theusen Hermansan, Kanoktip Puttaraska, Oliver Hendricks, Heidi Pirttinen, Leona Gilbert

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The Germ Theory (one infectious determinant is equal to one disease) has unarguably evolved our capability to diagnose and treat infectious diseases over the years. Nevertheless, the advent of technology, climate change, and volatile human behavior has brought about drastic changes in our environment, leading us to question the relevance of the Germ Theory in our day, i.e. will vector-borne disease (VBD) sufferers produce multiple immune responses when tested for multiple microbes? Vector diseased patients producing multiple immune responses to different microbes would evidently suggest human polymicrobial infections (HPI). Ongoing diagnostic tools are exceedingly unequipped with the current research findings that would aid in diagnosing patients for polymicrobial infections. This shortcoming has caused misdiagnosis at very high rates, consequently diminishing the patient’s quality of life due to inadequate treatment. Equipped with the state-of-art scientific knowledge, PolyScan intends to address the pitfalls in current VBD diagnostics. PolyScan is a multiplex and multifunctional enzyme linked Immunosorbent assay (ELISA) platform that can test for numerous VBD microbes and allow simultaneous screening for multiple types of antibodies. To validate PolyScan, Lyme Borreliosis (LB) and spondyloarthritis (SpA) patient groups (n = 54 each) were tested for Borrelia burgdorferi, Borrelia burgdorferi Round Body (RB), Borrelia afzelii, Borrelia garinii, and Ehrlichia chaffeensis against IgM and IgG antibodies. LB serum samples were obtained from Germany and SpA serum samples were obtained from Denmark under relevant ethical approvals. The SpA group represented chronic LB stage because reactive arthritis (SpA subtype) in the form of Lyme arthritis links to LB. It was hypothesized that patients from both the groups will produce multiple immune responses that as a consequence would evidently suggest HPI. It was also hypothesized that the multiple immune response proportion in SpA patient group would be significantly larger when compared to the LB patient group across both antibodies. It was observed that 26% LB patients and 57% SpA patients produced multiple immune responses in contrast to 33% LB patients and 30% SpA patients that produced solitary immune responses when tested against IgM. Similarly, 52% LB patients and an astounding 73% SpA patients produced multiple immune responses in contrast to 30% LB patients and 8% SpA patients that produced solitary immune responses when tested against IgG. Interestingly, IgM immune dysfunction in both the patient groups was also recorded. Atypically, 6% of the unresponsive 18% LB with IgG antibody was recorded producing multiple immune responses with the IgM antibody. Similarly, 12% of the unresponsive 19% SpA with IgG antibody was recorded producing multiple immune responses with the IgM antibody. Thus, results not only supported hypothesis but also suggested that IgM may atypically prevail longer than IgG. The PolyScan concept will aid clinicians to detect patients for early, persistent, late, polymicrobial, & immune dysfunction conditions linked to different VBD. PolyScan provides a paradigm shift for the VBD diagnostic industry to follow that will drastically shorten patient’s time to receive adequate treatment.

Keywords: diagnostics, immune dysfunction, polymicrobial, TICK-TAG

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Authors: Nadeen Felemban, Hamsa Banjer, Rabaah Jaafari

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One of the most common hazards in the pharmaceutical industry is the chemical hazard, which can cause harm or develop occupational health diseases/illnesses due to chronic exposures to hazardous substances. Therefore, a chemical agent management system is required, including hazard identification, risk assessment, controls for specific hazards and inspections, to keep your workplace healthy and safe. However, routine management monitoring is also required to verify the effectiveness of the control measures. Moreover, Betamethasone Valerate and Clobetasol Propionate are some of the APIs (Active Pharmaceutical Ingredients) with highly hazardous classification-Occupational Hazard Category (OHC 4), which requires a full containment (ECA-D) during handling to avoid chemical exposure. According to Safety Data Sheet, those chemicals are reproductive toxicants (reprotoxicant H360D), which may affect female workers’ health and cause fatal damage to an unborn child, or impair fertility. In this study, qualitative (chemical Risk assessment-qCRA) was conducted to assess the chemical exposure during handling of Betamethasone Valerate and Clobetasol Propionate in pharmaceutical laboratories. The outcomes of qCRA identified that there is a risk of potential chemical exposure (risk rating 8 Amber risk). Therefore, immediate actions were taken to ensure interim controls (according to the Hierarchy of controls) are in place and in use to minimize the risk of chemical exposure. No open handlings should be done out of the Steroid Glove Box Isolator (SGB) with the required Personal Protective Equipment (PPEs). The PPEs include coverall, nitrile hand gloves, safety shoes and powered air-purifying respirators (PAPR). Furthermore, a quantitative assessment (personal air sampling) was conducted to verify the effectiveness of the engineering controls (SGB Isolator) and to confirm if there is chemical exposure, as indicated earlier by qCRA. Three personal air samples were collected using an air sampling pump and filter (IOM2 filters, 25mm glass fiber media). The collected samples were analyzed by HPLC in the BV lab, and the measured concentrations were reported in (ug/m3) with reference to Occupation Exposure Limits, 8hr OELs (8hr TWA) for each analytic. The analytical results are needed in 8hr TWA (8hr Time-weighted Average) to be analyzed using Bayesian statistics (IHDataAnalyst). The results of the Bayesian Likelihood Graph indicate (category 0), which means Exposures are de "minimus," trivial, or non-existent Employees have little to no exposure. Also, these results indicate that the 3 samplings are representative samplings with very low variations (SD=0.0014). In conclusion, the engineering controls were effective in protecting the operators from such exposure. However, routine chemical monitoring is required every 3 years unless there is a change in the processor type of chemicals. Also, frequent management monitoring (daily, weekly, and monthly) is required to ensure the control measures are in place and in use. Furthermore, a Similar Exposure Group (SEG) was identified in this activity and included in the annual health surveillance for health monitoring.

Keywords: occupational health and safety, risk assessment, chemical exposure, hierarchy of control, reproductive

Procedia PDF Downloads 173

Authors: Tatsiana Ihnatovich, Darya Nizheharodava, Mikalai Halabarodzka, Tatsiana Savitskaya, Marina Zafranskaya

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Liver fibrosis is a complex of histological changes resulting from chronic liver disease accompanied by an excessive production and deposition of extracellular matrix components in the hepatic parenchyma. Liver fibrosis is a serious medical and social problem. Hepatic stellate cells (HSCs) make a significant contribution to the extracellular matrix deposition due to liver injury. Mesenchymal stem cells (MSCs) have a pronounced anti-inflammatory, regenerative and immunomodulatory effect; they are able to differentiate into hepatocytes and induce apoptosis of activated HSCs that opens the prospect of their use for preventing the excessive fibro-formation and the development of liver cirrhosis. The aim of the study is to evaluate the effect of MSCs therapy on the expression of fibrogenesis markers genes in liver tissue and HSCs cultures of rats with experimental liver cirrhosis (ELC). Materials and methods: ELC was induced by the common bile duct ligation (CBDL) in female Wistar rats (n = 19) with an average body weight of 250 (220 ÷ 270) g. Animals from the control group (n = 10) were sham-operated. On the 56th day after the CBDL, the rats of the experimental (n = 12) and the control (n = 5) groups received intraportal MSCs in concentration of 1×106 cells/animal (previously obtained from rat’s bone marrow) or saline, respectively. The animals were taken out of the experiment on the 21st day. HSCs were isolated by sequential liver perfusion in situ with following disaggregation, enzymatic treatment and centrifugation of cell suspension on a two-stage density gradient. The expression of collagen type I (Col1a1) and type III (Col3a1), matrix metalloproteinase type 2 (MMP2) and type 9 (MMP9), tissue inhibitor of matrix metalloproteinases type 1 (TIMP1), transforming growth factor β type 1 (TGFβ1) and type 3 (TGFβ3) was determined by real-time polymerase chain reaction. Statistical analysis was performed using Statistica 10.0. Results: In ELC rats compared to sham-operated animals, a significant increase of all studied markers expression was observed. The administration of MSCs led to a significant decrease of all detectable markers in the experimental group compared to rats without cell therapy. In ELC rats, an increased MMP9/TIMP1 ratio after cell therapy was also detected. The infusion of MSCs in the sham-operated animals did not lead to any changes. In the HSCs from ELC animals, the expression of Col1a1 and Col3a1 exceeded the similar parameters of the control group (p <0.05) and statistically decreased after the MSCs administration. The correlation between Col3a1 (Rs = 0.51, p <0.05), TGFβ1 (Rs = 0.6, p <0.01), and TGFβ3 (Rs = 0.75, p <0.001) expression in HSCs cultures and liver tissue has been found. Conclusion: Intraportal administration of MSCs to rats with ELC leads to a decreased Col1a1 and Col3a1, MMP2 and MMP9, TIMP1, TGFβ1 and TGFβ3 expression. The correlation between the expression of Col3a1, TGFβ1 and TGFβ3 in liver tissue and in HSCs cultures indicates the involvement of activated HSCs in the fibrogenesis that allows considering HSCs to be the main cell therapy target in ELC.

Keywords: cell therapy, experimental liver cirrhosis, hepatic stellate cells, mesenchymal stem cells

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Authors: Prajakta Patil, Yash Huzurbazar, Abhijeet Shinde

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Aim: To develop a treatment protocol for the management of tinnitus through multi-modality brain stimulation. Methodology: Present study included 33 adults with unilateral (31 subjects) and bilateral (2 subjects) chronic tinnitus with and/or without hearing loss independent of their etiology. The Treatment protocol included 5 consecutive sessions with follow-up of 6 months. Each session was divided into 3 parts: • Pre-treatment: a) Informed consent b) Pitch and loudness matching. • Treatment: Bimanual paper pen task with tinnitus masking for 30 minutes. • Post-treatment: a) Pitch and loudness matching b) Directive counseling and obtaining feedback. Paper-pen task is to be performed bimanually that included carrying out two different writing activities in different context. The level of difficulty of the activities was increased in successive sessions. Narrowband noise of a frequency same as that of tinnitus was presented at 10 dBSL of tinnitus for 30 minutes simultaneously in the ear with tinnitus. Result: The perception of tinnitus was no longer present in 4 subjects while in remaining subjects it reduced to an intensity that its perception no longer troubled them without causing residual facilitation. In all subjects, the intensity of tinnitus decreased by an extent of 45 dB at an average. However, in few subjects, the intensity of tinnitus also decreased by more than 45 dB. The approach resulted in statistically significant reductions in Tinnitus Functional Index and Tinnitus Handicap Inventory scores. The results correlate with pre and post treatment score of Tinnitus Handicap Inventory that dropped from 90% to 0%. Discussion: Brain mapping(qEEG) Studies report that there is multiple parallel overlapping of neural subnetworks in the non-auditory areas of the brain which exhibits abnormal, constant and spontaneous neural activity involved in the perception of tinnitus with each subnetwork and area reflecting a specific aspect of tinnitus percept. The paper pen task and directive counseling are designed and delivered respectively in a way that is assumed to induce normal, rhythmically constant and premeditated neural activity and mask the abnormal, constant and spontaneous neural activity in the above-mentioned subnetworks and the specific non-auditory area. Counseling was focused on breaking the vicious cycle causing and maintaining the presence of tinnitus. Diverting auditory attention alone is insufficient to reduce the perception of tinnitus. Conscious awareness of tinnitus can be suppressed when individuals engage in cognitively demanding tasks of non-auditory nature as the paper pen task used in the present study. To carry out this task selective, divided, sustained, simultaneous and split attention act cumulatively. Bimanual paper pen task represents a top-down activity which underlies brain’s ability to selectively attend to the bimanual written activity as a relevant stimulus and to ignore tinnitus that is the irrelevant stimuli in the present study. Conclusion: The study suggests that this novel treatment approach is cost effective, time saving and efficient to vanish the tinnitus or to reduce the intensity of tinnitus to a negligible level and thereby eliminating the negative reactions towards tinnitus.

Keywords: multi-modality brain stimulation, neural subnetworks, non-auditory areas, paper-pen task, top-down activity

Procedia PDF Downloads 147

Authors: L. Kashyap, S. Jha, D. Shende, V. K. Mohan, P. Khanna, A. Aravindan, S. Kashyap, L. Singh, S. Aggarwal

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Obesity is associated with a chronic inflammatory state. During surgery, there is an interplay between anaesthetic and surgical stress vis-a-vis the already present complex immune state. Moreover, the postoperative period is dictated by inflammation, which is crucial for wound healing and regeneration. An excess of inflammatory response might hamper recovery besides increasing the risk for infection and complications. There is definite evidence of the immunosuppressive role of inhaled anaesthetic agents. This immune modulation may be brought into effect directly by influencing the innate and adaptive immunity cells. The effects of propofol on immune mechanisms in has been widely elucidated because of its popularity. It reduces superoxide generation, elastase release, and chemotaxis. However, there is no unequivocal proof of one’s superiority over the other. Hence, an anaesthetic regimen with lesser inflammatory potential and specific to the obese patient is needed. OBESITA trial protocol (2019) by Sousa and co-workers in progress aims to test the hypothesis that anaesthesia with sevoflurane results in a weaker proinflammatory response compared to propofol, as evidenced by lower IL-6 and other biomarkers and an increased macrophage differentiation into M2 phenotype in adipose tissue. IL-6 was used as the objective parameter to evaluate inflammation as it is regulated by both surgery and anesthesia. It is the most sensitive marker of the inflammatory response to tissue damage since it is released within minutes by blood leukocytes. We hypothesized that maintenance of anaesthesia with propofol would lead to less inflammation than that with desflurane. Aims: The effect of two anaesthetic techniques, total intravenous anaesthesia (TIVA) with propofol and desflurane, on surgical stress response was evaluated. The primary objective was to compare serum interleukin-6 (IL-6) levels before and after surgery. Methods: In this prospective single-blinded randomized controlled trial undertaken, 30 obese patients (BMI>30 kg/m2) undergoing laparoscopic bariatric surgery under general anaesthesia were recruited. Patients were randomized to receive desflurane or TIVA using a target-controlled infusion for maintenance of anaesthesia. As a marker of inflammation, pre-and post-surgery IL-6 levels were compared. Results: After surgery, IL-6 levels increased significantly in both groups. The rise in IL-6 was less with TIVA than with desflurane; however, it did not reach significance. IL-6 rise post-surgery correlated positively with the complexity of procedure and duration of surgery and anaesthesia, rather than anaesthetic technique. Both groups did not differ in terms of intra-operative hemodynamic and respiratory variables, time to awakening, postoperative pulmonary complications, and duration of hospital stay. The incidence of nausea was significantly higher with desflurane than with TIVA. Conclusion: Inflammatory response did not differ as a function of anaesthetic technique when propofol and desflurane were compared. Also, patient and surgical variables dictated post-operative inflammation more than the anaesthetic factors. Further, larger sample size is needed to confirm or refute these findings.

Keywords: bariatric, biomarkers, inflammation, laparoscopy

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