Search results for: musculoskeletal diseases

Authors: Neha Batra Bali, Monika Tomar, Vinay Gupta

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A reagentless biosensor for detection of urea based on ZnO-CuO composite thin film is presented in following work. Biosensors have immense potential for varied applications ranging from environmental to clinical testing, health care, and cell analysis. Immense growth in the field of biosensors is due to the huge requirement in today’s world to develop techniques which are both cost effective and accurate for prevention of disease manifestation. The human body comprises of numerous biomolecules which in their optimum levels are essential for functioning. However mismanaged levels of these biomolecules result in major health issues. Urea is one of the key biomolecules of interest. Its estimation is of paramount significance not only for healthcare sector but also from environmental perspectives. If level of urea in human blood/serum is abnormal, i.e., above or below physiological range (15-40mg/dl)), it may lead to diseases like renal failure, hepatic failure, nephritic syndrome, cachexia, urinary tract obstruction, dehydration, shock, burns and gastrointestinal, etc. Various metal nanoparticles, conducting polymer, metal oxide thin films, etc. have been exploited to act as matrix to immobilize urease to fabricate urea biosensor. Amongst them, Zinc Oxide (ZnO), a semiconductor metal oxide with a wide band gap is of immense interest as an efficient matrix in biosensors by virtue of its natural abundance, biocompatibility, good electron communication feature and high isoelectric point (9.5). In spite of being such an attractive candidate, ZnO does not possess a redox couple of its own which necessitates the use of electroactive mediators for electron transfer between the enzyme and the electrode, thereby causing hindrance in realization of integrated and implantable biosensor. In the present work, an effort has been made to fabricate a matrix based on ZnO-CuO composite prepared by pulsed laser deposition (PLD) technique in order to incorporate redox properties in ZnO matrix and to utilize the same for reagentless biosensing applications. The prepared bioelectrode Urs/(ZnO-CuO)/ITO/glass exhibits high sensitivity (70µAmM⁻¹cm⁻²) for detection of urea (5-200 mg/dl) with high stability (shelf life ˃ 10 weeks) and good selectivity (interference ˂ 4%). The enhanced sensing response obtained for composite matrix is attributed to the efficient electron exchange between ZnO-CuO matrix and immobilized enzymes, and subsequently fast transfer of generated electrons to the electrode via matrix. The response is encouraging for fabricating reagentless urea biosensor based on ZnO-CuO matrix.

Keywords: biosensor, reagentless, urea, ZnO-CuO composite

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Authors: Shreyas S. Hegde, Anindya Deb, Suresh Nagesh

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Computational bio-mechanics is developing rapidly as a non-invasive tool to assist the medical fraternity to help in both diagnosis and prognosis of human body related issues such as injuries, cardio-vascular dysfunction, atherosclerotic plaque etc. Any system that would help either properly diagnose such problems or assist prognosis would be a boon to the doctors and medical society in general. Recently a lot of work is being focused in this direction which includes but not limited to various finite element analysis related to dental implants, skull injuries, orthopedic problems involving bones and joints etc. Such numerical solutions are helping medical practitioners to come up with alternate solutions for such problems and in most cases have also reduced the trauma on the patients. Some work also has been done in the area related to the use of computational fluid mechanics to understand the flow of blood through the human body, an area of hemodynamics. Since cardio-vascular diseases are one of the main causes of loss of human life, understanding of the blood flow with and without constraints (such as blockages), providing alternate methods of prognosis and further solutions to take care of issues related to blood flow would help save valuable life of such patients. This project is an attempt to use computational fluid dynamics (CFD) to solve specific problems related to hemodynamics. The hemodynamics simulation is used to gain a better understanding of functional, diagnostic and theoretical aspects of the blood flow. Due to the fact that many fundamental issues of the blood flow, like phenomena associated with pressure and viscous forces fields, are still not fully understood or entirely described through mathematical formulations the characterization of blood flow is still a challenging task. The computational modeling of the blood flow and mechanical interactions that strongly affect the blood flow patterns, based on medical data and imaging represent the most accurate analysis of the blood flow complex behavior. In this project the mathematical modeling of the blood flow in the arteries in the presence of successive blockages has been analyzed using CFD technique. Different cases of blockages in terms of percentages have been modeled using commercial software CATIA V5R20 and simulated using commercial software ANSYS 15.0 to study the effect of varying wall shear stress (WSS) values and also other parameters like the effect of increase in Reynolds number. The concept of fluid structure interaction (FSI) has been used to solve such problems. The model simulation results were validated using in vivo measurement data from existing literature

Keywords: computational fluid dynamics, hemodynamics, blood flow, results validation, arteries

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Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

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Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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Authors: Ahlam Ali, Katrina Lappin, Jaine Blayney, Ken Mills

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Leukaemia is the most frequently (30%) occurring type of paediatric cancer. Of these, approximately 80% are acute lymphoblastic leukaemia (ALL) with acute myeloid leukaemia (AML) cases making up the remaining 20% alongside other leukaemias. Unfortunately, children with AML do not have promising prognosis with only 60% surviving 5 years or longer. It has been highlighted recently the need for age-specific therapies for AML patients, with paediatric AML cases having a different mutational landscape compared with AML diagnosed in adult patients. Drug Repurposing is a recognized strategy in drug discovery and development where an already approved drug is used for diseases other than originally indicated. We aim to identify novel combination therapies with the promise of providing alternative more effective and less toxic induction therapy options. Our in-silico analysis highlighted ‘cell death and survival’ as an aberrant, potentially targetable pathway in paediatric AML patients. On this basis, 83 apoptotic inducing compounds were screened. A preliminary single agent screen was also performed to eliminate potentially toxic chemicals, then drugs were constructed into a pooled library with 10 drugs per well over 160 wells, with 45 possible pairs and 120 triples in each well. Seven cell lines were used during this study to represent the clonality of AML in paediatric patients (Kasumi-1, CMK, CMS, MV11-14, PL21, THP1, MOLM-13). Cytotoxicity was assessed up to 72 hours using CellTox™ Green reagent. Fluorescence readings were normalized to a DMSO control. Z-Score was assigned to each well based on the mean and standard deviation of all the data. Combinations with a Z-Score <2 were eliminated and the remaining wells were taken forward for further analysis. A well was considered ‘successful’ if each drug individually demonstrated a Z-Score <2, while the combination exhibited a Z-Score >2. Each of the ten compounds in one well (155) had minimal or no effect as single agents on cell viability however, a combination of two or more of the compounds resulted in a substantial increase in cell death, therefore the ten compounds were de-convoluted to identify a possible synergistic pair/triple combinations. The screen identified two possible ‘novel’ drug pairing, with BCL2 inhibitor ABT-737, combined with either a CDK inhibitor Purvalanol A, or AKT/ PI3K inhibitor LY294002. (ABT-737- 100 nM+ Purvalanol A- 1 µM) (ABT-737- 100 nM+ LY294002- 2 µM). Three possible triple combinations were identified (LY2409881+Akti-1/2+Purvalanol A, SU9516+Akti-1/2+Purvalanol A, and ABT-737+LY2409881+Purvalanol A), which will be taken forward for examining their efficacy at varying concentrations and dosing schedules, across multiple paediatric AML cell lines for optimisation of maximum synergy. We believe that our combination screening approach has potential for future use with a larger cohort of drugs including FDA approved compounds and patient material.

Keywords: AML, drug repurposing, ABT-737, apoptosis

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Authors: George Hanna Abdelmelek Henien

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Quality and safety issues are common in Ethiopia's food processing industry, which can negatively impact consumers' health and livelihoods. The country is known for its various agricultural products that are important to the economy. However, food quality and safety policies and management practices in the food processing industry have led to many health problems, foodborne illnesses and economic losses. This article aims to show the causes and consequences of food safety and quality problems in the food processing industry in Ethiopia and discuss possible solutions to solve them. One of the main reasons for food quality and safety in Ethiopia's food processing industry is the lack of adequate regulation and enforcement mechanisms. Inadequate food safety and quality policies have led to inefficiencies in food production. Additionally, the failure to monitor and enforce existing regulations has created a good opportunity for unscrupulous companies to engage in harmful practices that endanger the lives of citizens. The impact on food quality and safety is significant due to loss of life, high medical costs, and loss of consumer confidence in the food processing industry. Foodborne diseases such as diarrhoea, typhoid and cholera are common in Ethiopia, and food quality and safety play an important role in . Additionally, food recalls due to contamination or contamination often cause significant economic losses in the food processing industry. To solve these problems, the Ethiopian government began taking measures to improve food quality and safety in the food processing industry. One of the most prominent initiatives is the Ethiopian Food and Drug Administration (EFDA), which was established in 2010 to monitor and control the quality and safety of food and beverage products in the country. EFDA has implemented many measures to improve food safety, such as carrying out routine inspections, monitoring the import of food products and implementing labeling requirements. Another solution that can improve food quality and safety in the food processing industry in Ethiopia is the implementation of food safety management system (FSMS). FSMS is a set of procedures and policies designed to identify, assess and control food safety risks during food processing. Implementing a FSMS can help companies in the food processing industry identify and address potential risks before they harm consumers. Additionally, implementing an FSMS can help companies comply with current safety and security regulations. Consequently, improving food safety policy and management system in Ethiopia's food processing industry is important to protect people's health and improve the country's economy. . Addressing the root causes of food quality and safety and implementing practical solutions that can help improve the overall food safety and quality in the country, such as establishing regulatory bodies and implementing food management systems.

Keywords: food quality, food safety, policy, management system, food processing industry food traceability, industry 4.0, internet of things, block chain, best worst method, marcos

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Authors: Mihai Palade, Gina Cecilia Pistol, Mariana Stancu, Veronica Chedea, Ionelia Taranu

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Nutrition is an important determinant of general health status, with especially focus on prevention and/or attenuation of the inflammatory-associated pathologies. People with chronic kidney disease can experience chronic inflammation that can lead to cardiovascular disease and even an increased rate of death. There are important links between chronic kidney diseases, inflammation and nutritional strategies that may prevent or protect against undesirable inflammation and oxidative stress. The grape by-products either seeds or pomace are rich in polyphenols which may be beneficial in prevention of inflammatory, antioxidant and antimicrobial processes. As a model for studying the impact of grape seeds on renal inflammation and oxidative stress, we used in this study weaned piglets. After a feeding trial of 30 days with a control diet and an experimental diet containing 5% grape seed (GS), kidney samples were collected. In renal tissues were determined the expression and activity of important markers of immune respose and oxidative stress: pro-inflammatory cytokines (TNF-alpha, IL-1 beta, IL-6, IL-8, IFN-gamma), anti-inflammatory cytokines (IL-4, IL-10), anti-oxidant enzymes (catalase CAT, superoxide dismutase SOD, glutathione peroxidise GPx) and important mediators belonging to nuclear receptors (NF-kB1, Nrf-2 and PPAR-gamma). Gene expression was evaluated by qPCR, whereas protein concentration was determined using proteomic techniques (ELISA). The activity of anti-oxidant enzymes was determined using specific kits. Our results showed that GS enriched in polyphenols does not have effect on TNF-alpha, IL-6 and IL-1 beta gene expression and protein concentration in kidney. By contrast, the gene expression and protein level of IL-8 and IFN-gamma were decreased in GS kidney. Anti-inflammatory cytokines IL-4 and IL-10 gene levels were increased in kidneys collected from GS piglets in comparison with controls, with no modification of protein levels between the two groups. The activities of anti-oxidant enzymes CAT and GPx were increased in kidney by GS, whereas SOD activity was unmodified in comparison with control samples. Also, the GS diet was associated with no modulation of mRNAs for nuclear receptors NF-kB1, Nrf-2 and PPAR-gamma gene expressions in kidneys. In conclusion, our results demonstrated that GS enriched in bioactive compounds such polyphenols could modulate inflammation and oxidative stress markers in kidney tissues. Further studies are necessary to elucidate the mechanism of action of GS compounds in case kidney inflammation associated with oxidative stress, and signalling molecules involved in these mechanisms.

Keywords: animal model, kidney inflammation, oxidative stress, grape seed

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Authors: Edna Negron-Martinez

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Our time's global challenges and trends —like those associated with climate change, demographics displacements, growing health inequalities, and increasing burden of diseases— have complex connections to the determinants of health. Information on the burden of disease causes and prevention is fundamental for public health actions, like preparedness and responses for disasters, and recovery resources after the event. For instance, there is an increasing consensus about key findings of the effects and connections of the global burden of disease, as it generates substantial healthcare costs, consumes essential resources and prevents the attainment of optimal health and well-being. The goal of this research endeavor is to promote a comprehensive understanding of the connections between social, environmental, and economic influences on health. These connections are illustrated by pulling from clearly the core curriculum of multidisciplinary areas —as urban design, energy, housing, and economy— as well as in the health system itself. A systematic review of primary and secondary data included a variety of issues as global health, natural disasters, and critical pollution impacts on people's health and the ecosystems. Environmental health is challenged by the unsustainable consumption patterns and the resulting contaminants that abound in many cities and urban settings around the world. Poverty, inadequate housing, and poor health are usually linked. The house is a primary environmental health context for any individual and especially for more vulnerable groups; such as children, older adults and those who are sick. Nevertheless, very few countries show strong decoupling of environmental degradation from economic growth, as indicated by a recent 2017 Report of the World Bank. Worth noting, the environmental fraction of the global burden of disease in a 2016 World Health Organization (WHO) report estimated that 12.6 million global deaths, accounting for 23% (95% CI: 13-34%) of all deaths were attributable to the environment. Among the environmental contaminants include heavy metals, noise pollution, light pollution, and urban sprawl. Those key findings make a call to the significance to urgently adopt in a global scale the United Nations post-2015 Sustainable Development Goals (SDGs). The SDGs address the social, environmental, and economic factors that influence health and health inequalities, advising how these sectors, in turn, benefit from a healthy population. Consequently, more actions are necessary from an inter-sectoral and systemic paradigm to enforce an integrated sustainability policy implementation aimed at the environmental, social, and economic determinants of health.

Keywords: building capacity for workforce development, ecological and environmental health effects of pollution, public health education, sustainability

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Authors: Leila Fozouni, Anahita Mazandarani

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Background: Maternal infections are the most common cause of infections in infants, and the level of infection and its severity highly depends on the degree of colonization of the bacteria in the mother; so, the occurrence of aggressive diseases is not unpredictable in mothers with very high colonization. Group B Streptococcus is part of the normal flora of the gastrointestinal and genital tracts in women and is the leading cause of septicemia and meningitis in newborns. Today Zinc oxide nanoparticle is regarded as one of the most commonly used and safest nanoparticles for defeating Gram-positive and Gram-negative bacteria. This study aims to determine the antibacterial effects of Zinc oxide on the growth of drug-resistant group B Streptococcus strains isolated from pregnant women. Materials and Methods: This cross-sectional study was conducted on 150 pregnant women of 28–37 weeks admitted to seven hospitals and maternity wards in Golestan province, northeast of Iran. For bacterial identification, rectovaginal swabs were firstly inoculated to the Todd-Hewitt Broth and cultured in blood agar (containing 5% sheep blood). Then microbiologic and PCR methods were performed to detect group B Streptococci. Disk diffusion and broth microdilution tests were used to determine the bacterial susceptibility to antibiotics according to CLSI M100(2021) criteria. The antibacterial properties of Zinc oxide nanoparticles were evaluated using the agar well-diffusion method. Results: The prevalence of group B Streptococcus was 18% in pregnant women. Out of twenty-seven positive cultures, 62.96% were higher than thirty years old. Ninety percent and 45% of isolates were resistant to clindamycin and erythromycin, respectively, and susceptibility to cefazolin was 71%. In addition, susceptibility to ampicillin and penicillin were 74% and 55%, respectively. The results showed that 82% of erythromycin-resistant, 92% clindamycin-resistant, and 78% of cefazolin-resistant isolates were eliminated by zinc oxide nanoparticles at a concentration of 100 mg/L of the nanoparticle. Furthermore, ZnONPs could inhibit all drug-resistant isolates at a concentration of 200 mg/mL (MIC90 ≥ 200). Conclusion: Since the drug resistance of group B streptococci against various antibiotics is increasing, determining and investigating the drug-resistance pattern of this bacterium to different antibiotics in order to prevent arbitrary consumption of antibiotics by pregnant women and ultimately prevent Infant mortality seems necessary. Generally, ZnONPs showed a high antimicrobial effect, and it was revealed that the bactericide effect increases upon the increase in the concentration of the nanoparticle.

Keywords: group B beta-hemolytic streptococcus, pregnant women, zinc oxide nanoparticles, drug resistance

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Authors: Pantea Salehizadeh, Martin P. Bucknall, Robert Driscoll, Jayashree Arcot, George Srzednicki

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Banana is one of the most important crops produced in large quantities in tropical and sub-tropical countries. Of the total plant material grown, approximately 40% is considered waste and left in the field to decay. This practice allows fungal diseases such as Sigatoka Leaf Spot to develop, limiting plant growth and spreading spores in the air that can cause respiratory problems in the surrounding population. The pseudostem is considered a waste residue of production (60 to 80 tonnes/ha/year), although it is a good source of dietary fiber and volatile organic compounds (VOC’s). Strategies to process banana pseudostem into palatable, nutritious and marketable food materials could provide significant social and economic benefits. Extraction of VOC’s with desirable odor from dried and fresh pseudostem could improve the smell of products from the confectionary and bakery industries. Incorporation of banana pseudostem flour into bakery products could provide cost savings and improve nutritional value. The aim of this study was to determine the effects of drying methods and different banana species on the profile of volatile aroma compounds in dried banana pseudostem. The banana species analyzed were Musa acuminata and Musa balbisiana. Fresh banana pseudostem samples were processed by either freeze-drying (FD) or heat pump drying (HPD). The extraction of VOC’s was performed at ambient temperature using vacuum distillation and the resulting, mostly aqueous, distillates were analyzed using headspace solid phase microextraction (SPME) gas chromatography – mass spectrometry (GC-MS). Optimal SPME adsorption conditions were 50 °C for 60 min using a Supelco 65 μm PDMS/DVB Stableflex fiber1. Compounds were identified by comparison of their electron impact mass spectra with those from the Wiley 9 / NIST 2011 combined mass spectral library. The results showed that the two species have notably different VOC profiles. Both species contained VOC’s that have been established in literature to have pleasant appetizing aromas. These included l-Menthone, D-Limonene, trans-linlool oxide, 1-Nonanol, CIS 6 Nonen-1ol, 2,6 Nonadien-1-ol, Benzenemethanol, 4-methyl, 1-Butanol, 3-methyl, hexanal, 1-Propanol, 2-methyl- acid، 2-Methyl-2-butanol. Results show banana pseudostem VOC’s are better preserved by FD than by HPD. This study is still in progress and should lead to the optimization of processing techniques that would promote the utilization of banana pseudostem in the food industry.

Keywords: heat pump drying, freeze drying, SPME, vacuum distillation, VOC analysis

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Authors: Pariya Sheykhmaleki, Debajyoti Pati

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Rural areas in the United States face numerous challenges in providing quality and assessable primary healthcare services, especially during emergencies such as natural disasters or pandemics. This study showcases a cutting-edge flexible module that aims to overcome these challenges by offering adaptable healthcare facilities capable of providing comprehensive health services in remote and disaster-prone regions. According to the Health Resources and Services Administration (HRSA), approximately 62 million Americans, or 1 in 5 individuals, live in areas designated as Health Professional Shortage Areas (HPSAs) for primary care. These areas are characterized by limited access to healthcare facilities, shortage of healthcare professionals, transportation barriers, inadequate healthcare infrastructure, higher rates of chronic diseases, mental health disparities, and limited availability of specialized care, including urgent circumstances like pandemics that can exacerbate this issue. To address these challenges, the literature study began by examining primary health solutions in very remote areas, e.g., spaceships, to identify the state-of-the-art technologies and the methods used to facilitate primary care needs. The literature study on flexibility in architecture and interior design was also adapted to develop a conceptual design for rural areas. The designed flexible module provides an innovative solution. This module can be prefabricated as all parts are standardized. The flexibility of the module allows the structure to be modified based on local and geographical requirements as well as the ability to expand as required. It has been designed to stand either by itself or work in tandem with public buildings. By utilizing sustainable approaches and flexible spatial configurations, the module optimizes the utilization of limited resources while ensuring efficient and effective healthcare delivery. Furthermore, the poster highlights the key features of this flexible module, including its ability to support telemedicine and telehealth services for all five levels of urgent care conditions, i.e., from facilitating fast tracks to supporting emergency room services, in two divided zones. The module's versatility enables its deployment in rural areas located far from urban centers and disaster-stricken regions, ensuring access to critical healthcare services in times of need. This module is also capable of responding in urban areas when the need for primary health becomes vastly urgent, e.g., during a pandemic. It emphasizes the module's potential to bridge the healthcare gap between rural and urban areas and mitigate the impact of rural health challenges.

Keywords: rural health, healthcare challenges, flexible modular design, telemedicine, telehealth

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Authors: Liaqat Ali, Ehsan, Muhammad Shahzad, Nasir Orakzai

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Introduction: Internal optical urethrotomy is the main stay treatment modality in management of urethral stricture. Being minimal invasive with less morbidity, it is commonly performed and favored procedure by urologists across the globe. Although short-term success rate of optical urethrotomy is promising but long-term efficacy of IOU is questionable with high recurrence rate in different studies. Numerous techniques had been adopted to reduce the recurrence after IOU like prolong catheterization and self-clean intermittent catheterization with varying success. Mitomycin C has anti-fibroblast and anti-collagen properties and has been used in trabeculectomy, myringotomy and after keloid scar excision in contemporary surgical practice. Present study according to the best of our knowledge is a pioneer pilot study in Pakistan to determine the efficacy of Mitomycin C in preventing recurrence of urethral stricture after internal optical urethrotomy. Objective: To determine the efficacy of Mitomycin C in reducing the recurrence of anterior urethral stricture after internal optical urethrotomy. Methods: It is a randomized control trial conducted in department of urology, Institute of Kidney Diseases Hayatabad Medical Complex Peshawar from March 2011 till December 2013. After approval of hospital ethical committee, we included maximum of 2 cm anterior urethral stricture irrespective of etiology. Total of 140 patients were equally divided into two groups by lottery method. Group A (Case) comprising of 70 patients in whom Mitomycin C 0.1% was injected sub mucosal in stricture area at 1,11,6 and 12 O clock position using straight working channel paediatric cystoscope after conventional optical urethrotomy. Group B (Control) 70 patients in whom only optical urethrotomy was performed. SCIC was not offered in both the groups. All the patients were regularly followed on a monthly basis for 3 months then three monthly for remaining 9 months. Recurrence was diagnosed by using diagnostic tools of retrograde urethrogram and flexible urethroscopy in selected cased. Data was collected on structured Proforma and was analyzed on SPSS. Result: The mean age in Group A was 33 ±1.5 years and Group B was 35 years. External trauma was leading cause of urethral stricture in both groups 46 (65%) Group A and 50 (71.4%) Group B. In Group A. Iatrogenic urethral trauma was 2nd etiological factor in both groups. 18(25%) Group A while 15( 21.4%) in Group B. At the end of 1 year, At the end of one year, recurrence of urethral stricture was recorded in 11 (15.71%) patient in Mitomycin C Group A and it was recorded in 27 (38.5 %) patients in group B. Significant difference p=0.001 was found in favour of group A Mitomycin group. Conclusion: Recurrence of urethral stricture is high after optical urethrotomy. Mitomycin C is found highly effective in preventing recurrence of urethral stricture after IOU.

Keywords: urethral stricture, mitomycine, internal optical urethrotomy, medical and health sciences

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Authors: Norazlan Mohmad Misnan, Maizatul Hasyima Omar, Mohd Isa Wasiman

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Papaya (Carica papaya L., Caricaceae) is a tree which mainly cultivated for its fruits in many tropical regions including Australia, Brazil, China, Hawaii, and Malaysia. Beside of fruits, its leaves, seeds, and latex have also been traditionally used for treating diseases, which also reported to possess anti-cancer and anti- malaria properties. Its leaves have been reported to consist of various chemical compounds such as alkaloids, flavonoids and phenolics. Clitorin and manghaslin are among major flavonoids presence. Thus, the aim of this study is to quantify the purity of these isolated compounds (clitorin and manghsalin) by using quantitative Nuclear Magnetic Resonance (qNMR) analysis. Only fresh C. papaya leaves were used for juice extraction procedure and subsequently was freeze-dried to obtain a dark green powdered form of the extract prior to Centrifugal Partition Chromatography (CPC) separation. The CPC experiments were performed using a two-phase solvent system comprising ethyl acetate/butanol/water (1:4:5, v/v/v/v) solvent. The upper organic phase was used as the stationary phase, and the lower aqueous phase was employed as the mobile phase. Ten fractions were obtained after an hour runtime analysis. Fraction 6 and fraction 8 has been identified as clitorin (m/z 739.21 [M-H]-) and manghaslin (m/z 755.21 [M-H]-), respectively, based on LCMS data and full analysis of NMR (1H NMR, 13C NMR, HMBC, and HSQC). The 1H-qNMR measurements were carried out using a 400 MHz NMR spectrometer (JEOL ECS 400MHz, Japan) and deuterated methanol was used as a solvent. Quantification was performed using the AQARI method (Accurate Quantitative NMR) with deuterated 1,4-Bis(trimethylsilyl)benzene (BTMSB) as an internal reference substances. This AQARI protocol includes not only NMR measurement but also sample preparation that provide highest precision and accuracy than other qNMR methods. The 90° pulse length and the T1 relaxation times for compounds and BTMSB were determined prior to the quantification to give the best signal-to-noise ratio. Regions containing the two downfield signals from aromatic part (6.00–6.89 ppm), and the singlet signal, (18H) arising from BTMSB (0.63-1.05ppm) were selected for integration. The purity of clitorin and manghaslin were calculated to be 52.22% and 43.36%, respectively. Further purification is needed in order to increase its purity. This finding has demonstrated the use of qNMR for quality control and standardization of various plant extracts and which can be applied for NMR fingerprinting of other plant-based products with good reproducibility and in the case where commercial standards is not readily available.

Keywords: Carica papaya, clitorin, manghaslin, quantitative Nuclear Magnetic Resonance, Centrifugal Partition Chromatography

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Authors: Mahmood Iqbal, Khalid Nawab, Tachibana Satoshi

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Farmer Field School (FFS) is constantly aims to assist farmers to determine and learn about field ecology and integrated crop management. The study was conducted to examine the change in productivity of tomato crop in the study area; to determine increase in per acre yield of the crop, and find out reduction in per acre input cost. A study of tomato crop was conducted in ten villages namely Jabban, Bijligar Colony, Palonow, Heroshah, Zara Maira, Deghar Ghar, Sidra Jour, Anar Thangi, Miangano Korona and Wartair of district Malakand. From each village 15 respondents were selected randomly on the basis of identical allocation making sample size of 150 respondents. The research was based on primary as well as secondary data. Primary data was collected from farmers while secondary data were taken from Agriculture Extension Department Dargai, District Malakand. Interview schedule was planned and each farmer was interviewed personally. The study was based on comparison of cost, yield and income of tomato before and after FFS. Paired t-test and Statistical Package for Social Sciences (SPSS) was used for analysis; outcome of the study show that integrated pest management project has brought a positive change in the attitude of farmers of the project area through FFS approach. In district Malakand 66.0% of the respondents were between the age group of 31-50 years, 11.3% of respondents had primary level of education, 12.7% of middle level, 28.7% metric level, 3.3% of intermediate level and 2.0% of graduate level of education while 42.0% of respondents were illiterate and have no education. Average land holding size of farmers was 6.47 acres, cost of seed, crop protection from insect pest and crop protection from diseases was reduced by Rs. 210.67, Rs. 2584.43 and Rs. 3044.16 respectively, the cost of fertilizers and cost of farm yard manure was increased by Rs.1548.87 and Rs. 1151.40 respectively while tomato yield was increased by 1585.03 kg/acre from 7663.87 to 9248.90 kg/acre. The role of FFS initiate by integrated pest management project through department of agriculture extension for the development of agriculture was worth mentioning. It has brought enhancement in crop yield of tomato and their income through FFS approach. On the basis of results of the research studies, integrated pest management project should spread their developmental activities for maximum participation of the complete rural masses through participatory FFS approach.

Keywords: agriculture, Farmers field schools, extension education, tomato

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Authors: Usha S. Adiga, Sachidanada Adiga

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Introduction: Diabetes Mellitus (DM) is one of the most common non-communicable diseases which imposes a large economic burden on the global health-care system. Cost of illness studies in India have assessed the health care cost of DM, but have certain limitations due to lack of standardization of the methods used, improper documentation of data, lack of follow up, etc. The objective of the study was to estimate the cost of illness of uncomplicated versus complicated type 2 diabetes mellitus in Coastal Karnataka, India. The study also aimed to find out the trend of cost of illness of the disease over a decade. Methodology: A prevalence based bottom-up approach study was carried out in two tertiary care hospitals located in Coastal Karnataka after ethical approval. Direct Medical costs like annual laboratory costs, pharmacy cost, consultation charges, hospital bed charges, surgical /intervention costs of 238 diabetics and 340 diabetic patients respectively from two hospitals were obtained from the medical record sections. Patients were divided into six groups, uncomplicated diabetes, diabetic retinopathy(DR), nephropathy(DN), neuropathy(DNeu), diabetic foot(DF), and ischemic heart disease (IHD). Different costs incurred in 2008 and 2017 in these groups were compared, to study the trend of cost of illness. Kruskal Wallis test followed by Dunn’s test were used to compare median costs between the groups and Spearman's correlation test was used for correlation studies. Results: Uncomplicated patients had significantly lower costs (p <0.0001) compared to other groups. Patients with IHD had highest Medical expenses (p < 0.0001), followed by DN and DF (p < 0.0001 ). Annual medical costs incurred were 1.8, 2.76, 2.77, 1.76, and 4.34 times higher in retinopathy, nephropathy, diabetic foot, neuropathy and IHD patients as compared to the cost incurred in managing uncomplicated diabetics. Other costs also showed a similar pattern of rising. A positive correlation was observed between the costs incurred and duration of diabetes, a negative correlation between the glycemic status and cost incurred. The cost incurred in the management of DM in 2017 was found to be elevated 1.4 - 2.7 times when compared to that in 2008. Conclusion: It is evident from the study that the economic burden due to diabetes mellitus is substantial. It poses a significant financial burden on the healthcare system, individual and society as a whole. There is a need for the strategies to achieve optimal glycemic control and operationalize regular and early screening methods for complications so as to reduce the burden of the disease.

Keywords: COI, diabetes mellitus, a bottom up approach, economics

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Authors: Hamid Abbasi, Neda Jourabchi, Ranasadat Abedi, Kiarash Tajernarenj, Mehdi Farhoudi, Sarvin Sanaie

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Background: Alpha lipoic acid (ALA), fat- and water-soluble, coenzyme with sulfuret content, has received considerable attention for its potential therapeutic role in diabetes, cardiovascular diseases, cancers, and central nervous disease. This investigation aims to evaluate the probable protective effects of ALA in stroke patients. Methods: Based on Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, This meta-analysis was performed. The PICO criteria for this meta-analysis were as follows: Population/Patients (P: stroke patients); Intervention (I: ALA); Comparison (C: control); Outcome (O: blood glucose, lipid profile, oxidative stress, inflammatory factors).In addition, Studies that were excluded from the analysis consisted of in vitro, in vivo, and ex vivo studies, case reports, quasi-experimental studies. Scopus, PubMed, Web of Science, EMBASE databases were searched until August 2023. Results: Of 496 records that were screened in the title/abstract stage, 9 studies were included in this meta-analysis. The sample sizes in the included studies vary between 28 and 90. The result of risk of bias was performed via risk of bias (RoB) in randomized-controlled trials (RCTs) based on the second version of the Cochrane RoB assessment tool. 8 studies had a definitely high risk of bias. Discussion: To the best of our knowledge, The present meta-analysis is the first study addressing the effectiveness of ALA supplementation in enhancing post-stroke metabolic markers, including lipid profile, oxidative stress, and inflammatory indices. It is imperative to acknowledge certain potential limitations inherent in this study. First of all, type of treatment (oral or intravenous infusion) could alter the bioavailability of ALA. Our study had restricted evidence regarding the impact of ALA supplementation on included outcomes. Therefore, further research is warranted to develop into the effects of ALA specifically on inflammation and oxidative stress. Funding: The research protocol was approved and supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 72825). Registration: This study was registered in the International prospective register of systematic reviews (PROSPERO ID: CR42023461612).

Keywords: alpha-lipoic acid, lipid profile, blood glucose, inflammatory factors, oxidative stress, meta-analysis, post-stroke

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Authors: Hafsa Kamran, Asma Afreen, Zaheer Ahmed

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Internet addiction, an emerging mental health disorder from last two decades, is manifested by the inability in the controlled use of internet leading to academics, social, physiological and/or psychological difficulties. The present study aimed to assess the levels of internet addiction among university students in Lahore and to explore the effects of internet addiction on their dietary behavior and lifestyle. It was an analytical cross-sectional study. Data was collected from October to December 2016 from students of four universities selected through two-stage sampling method. The numbers of participants were 500 and 13 questionnaires were rejected due to incomplete information. Levels of Internet Addiction (IA) were calculated using Young Internet Addiction Test (YIAT). Data was also collected on students’ demographics, lifestyle factors and dietary behavior using self-reported questionnaire. Data was analyzed using SPSS (version 21). Chi-square test was applied to evaluate the relationship between variables. Results of the study revealed that 10% of the population had severe internet addiction while moderate Internet Addiction was present in 42%. High prevalence was found among males (11% vs. 8%), private sector university students (p = 0.008) and engineering students (p = 0.000). The lifestyle habits of internet addicts were significantly of poorer quality than normal users (p = 0.05). Internet addiction was found associated with lesser physically activity (p = 0.025), had shorter duration of physical activity (p = 0.016), had more disorganized sleep pattern (p = 0.023), had less duration of sleep (p = 0.019), reported being more tired and sleepy in class (p = 0.033) and spending more time on internet as compared to normal users. Severe and moderate internet addicts also found to be more overweight and obese than normal users (p = 0.000). The dietary behavior of internet addicts was significantly poorer than normal users. Internet addicts were found to skip breakfast more than a normal user (p = 0.039). Common reasons for meal skipping were lack of time and snacking between meals (p = 0.000). They also had increased meal size (p = 0.05) and habit of snacking while using the internet (p = 0.027). Fast food (p = 0.016) and fried items (p = 0.05) were most consumed snacks, while carbonated beverages (p = 0.019) were most consumed beverages among internet addicts. Internet Addicts were found to consume less than recommended daily servings of dairy (p = 0.008) and fruits (p = 0.000) and more servings of meat group (p = 0.025) than their no internet addict counterparts. In conclusion, in this study, it was demonstrated that internet addicts have unhealthy dietary behavior and inappropriate lifestyle habits. University students should be educated regarding the importance of balanced diet and healthy lifestyle, which are critical for effectual primary prevention of numerous chronic degenerative diseases. Furthermore, it is necessary to raise awareness concerning adverse effects of internet addiction among youth and their parents.

Keywords: dietary behavior, internet addiction, lifestyle, university students

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Authors: Chu-Tzu Chen, Angela S. Huang, Yu-Min Chou, Chin-Hui Yang

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Dengue is a major public health concern throughout tropical and sub-tropical regions. Taiwan is located in the Pacific Ocean and overlying the tropical and subtropical zones. The island remains humid throughout the year and receives abundant rainfall, and the temperature is very hot in summer at southern Taiwan. It is ideal for the growth of dengue vectors and would be increasing the risk on dengue outbreaks. During the first half of the 20th century, there were three island-wide dengue outbreaks (1915, 1931, and 1942). After almost forty years of dormancy, a DEN-2 outbreak occurred in Liuchiu Township, Pingtung County in 1981. Thereafter, more dengue outbreaks occurred with different scales in southern Taiwan. However, there were more than ten thousands of dengue cases in 2014 and in 2015. It did not only affect human health, but also caused widespread social disruption and economic losses. The study would like to reveal the epidemiology of dengue on Taiwan, especially the severe outbreak in 2015, and try to find the effective interventions in dengue control including dengue vaccine development for the elderly. Methods: The study applied the Notifiable Diseases Surveillance System database of the Taiwan Centers for Disease Control as data source. All cases were reported with the uniform case definition and confirmed by NS1 rapid diagnosis/laboratory diagnosis. Results: In 2014, Taiwan experienced a serious DEN-1 outbreak with 15,492 locally-acquired cases, including 136 cases of dengue hemorrhagic fever (DHF) which caused 21 deaths. However, a more serious DEN-2 outbreak occurred with 43,419 locally-acquired cases in 2015. The epidemic occurred mainly at Tainan City (22,760 cases) and Kaohsiung City (19,723 cases) in southern Taiwan. The age distribution for the cases were mainly adults. There were 228 deaths due to dengue infection, and the case fatality rate was 5.25 ‰. The average age of them was 73.66 years (range 29-96) and 86.84% of them were older than 60 years. Most of them were comorbidities. To review the clinical manifestations of the 228 death cases, 38.16% (N=87) of them were reported with warning signs, while 51.75% (N=118) were reported without warning signs. Among the 87 death cases reported to dengue with warning signs, 89.53% were diagnosed sever dengue and 84% needed the intensive care. Conclusion: The year 2015 was characterized by large dengue outbreaks worldwide. The risk of serious dengue outbreak may increase significantly in the future, and the elderly is the vulnerable group in Taiwan. However, a dengue vaccine has been licensed for use in people 9-45 years of age living in endemic settings at the end of 2015. In addition to carry out the research to find out new interventions in dengue control, developing the dengue vaccine for the elderly is very important to prevent severe dengue and deaths.

Keywords: case fatality rate, dengue, dengue vaccine, the elderly

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Authors: Lívia Pinheiro Carvalho, Luciana Di Thommazo-Luporini, Rafael Luís Luporini, José Carlos Bonjorno Junior, Renata Pedrolongo Basso Vanelli, Manoel Carneiro de Oliveira Junior, Rodolfo de Paula Vieira, Renata Trimer, Renata G. Mendes, Mylène Aubertin-Leheudre, Audrey Borghi-Silva

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Rationale: Cardiorespiratory fitness (CRF) and functional capacity in young obese and normal-weight people are associated with metabolic and cardiovascular diseases and mortality. However, it remains unclear whether their metabolically healthy (MH) or at risk (AR) phenotype influences cardiorespiratory fitness in this vulnerable population such as obese adults but also in normal-weight people. HOMA insulin resistance index (HI) and leptin-adiponectin ratio (LA) are strong markers for characterizing those phenotypes that we hypothesized to be associated with physical fitness. We also hypothesized that an easy and feasible exercise test could identify a subpopulation at risk to develop metabolic and related disorders. Methods: Thirty-nine sedentary men and women (20-45y; 18.530 kg.m-2) underwent a clinical evaluation, including the six-minute step test (ST), a well-validated and reliable test for young people. Body composition assessment was done by a tetrapolar bioimpedance in a fasting state and in the folicular phase for women. A maximal cardiopulmonary exercise testing, as well as the ST, evaluated the oxygen uptake at the peak of the test (VO2peak) by an ergospirometer Oxycon Mobile. Lipids, glucose, insulin were analysed and the ELISA method quantified the serum leptin and adiponectin from blood samples. Volunteers were divided in two groups: AR or MH according to a HI cutoff of 1.95, which was previously determined in the literature. T-test for comparison between groups, Pearson´s test to correlate main variables and ROC analysis for discriminating AR from up-and-down cycles in ST (SC) were applied (p<0.05). Results: Higher LA, fat mass (FM) and lower HDL, SC, leg lean mass (LM) and VO2peak were found in AR than in MH. Significant correlations were found between VO2peak and SC (r= 0.80) as well as between LA and FM (r=0.87), VO2peak (r=-0.73), and SC (r=-0.65). Area under de curve showed moderate accuracy (0.75) of SC <173 to discriminate AR phenotype. Conclusion: Our study found that at risk obese and normal-weight subjects showed an unhealthy metabolism as well as a poor CRF and functional daily activity capacity. Additionally, a simple and less costly functional test associated with above-mentioned aspects is able to identify ‘at risk’ subjects for primary intervention with important clinical and health implications.

Keywords: aerobic capacity, exercise, fitness, metabolism, obesity, 6MST

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Authors: Abhijit Trailokya

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Background: Cardiovascular diseases (CVD’s) are the major cause of morbidity and mortality in both developed and developing countries. Many clinical trials have demonstrated that low-density lipoprotein cholesterol (LDL-C) lowering, reduces the incidence of coronary and cerebrovascular events across a broad spectrum of patients at risk. Guidelines for the management of patients at risk have been established in Europe and North America. The guidelines have advocated progressively lower LDL-C targets and more aggressive use of statin therapy. In Indian patients, comprehensive data on dyslipidemia management and its treatment outcomes are inadequate. There is lack of information on existing treatment patterns, the patient’s profile being treated, and factors that determine treatment success or failure in achieving desired goals. Purpose: The present study was planned to determine the lipid control status in high-risk dyslipidemic patients treated with lipid-lowering therapy in India. Methods: This cross-sectional, non-interventional, single visit program was conducted across 483 sites in India where male and female patients with high-risk dyslipidemia aged 18 to 65 years who had visited for a routine health check-up to their respective physician at hospital or a healthcare center. Percentage of high-risk dyslipidemic patients achieving adequate LDL-C level (< 70 mg/dL) on lipid-lowering therapy and the association of lipid parameters with patient characteristics, comorbid conditions, and lipid lowering drugs were analysed. Results: 3089 patients were enrolled in the study; of which 64% were males. LDL-C data was available for 95.2% of the patients; only 7.7% of these patients achieved LDL-C levels < 70 mg/dL on lipid-lowering therapy, which may be due to inability to follow therapeutic plans, poor compliance, or inadequate counselling by physician. The physician’s lack of awareness about recent treatment guidelines also might contribute to patients’ poor adherence, not explaining adequately the benefit and risks of a medication, not giving consideration to the patient’s life style and the cost of medication. Statin was the most commonly used anti-dyslipidemic drug across population. The higher proportion of patients had the comorbid condition of CVD and diabetes mellitus across all dyslipidemic patients. Conclusion: As per the European Society of Cardiology guidelines the ideal LDL-C levels in high risk dyslipidemic patients should be less than 70%. In the present study, 7.7% of the patients achieved LDL-C levels < 70 mg/dL on lipid lowering therapy which is very less. Most of high risk dyslipidemic patients in India are on suboptimal dosage of statin. So more aggressive and high dosage statin therapy may be required to achieve target LDLC levels in high risk Indian dyslipidemic patients.

Keywords: cardiovascular disease, diabetes mellitus, dyslipidemia, LDL-C, lipid lowering drug, statins

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Authors: Mustafa M. Donma, Orkide Donma

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Obesity is known to be associated with many clinically important diseases including metabolic syndrome (MetS). Vitamin B₁₂ plays essential roles in fat and protein metabolisms and its cooperation with vitamin B₉ is well-known. The aim of this study is to investigate the possible contributions as well as associations of these micronutrients upon obesity and MetS during childhood. A total of 128 children admitted to Namik Kemal University, Medical Faculty, Department of Pediatrics Outpatient Clinics were included into the scope of this study. The mean age±SEM of 92 morbid obese (MO) children and 36 with MetS were 118.3±3.8 months and 129.5±6.4 months, respectively (p > 0.05). The study was approved by Namık Kemal University, Medical Faculty Ethics Committee. Written informed consent forms were obtained from the parents. Demographic features and anthropometric measurements were recorded. WHO BMI-for age percentiles were used. The values above 99 percentile were defined as MO. Components of MetS [waist circumference (WC), fasting blood glucose (FBG), triacylglycerol (TRG), high density lipoprotein cholesterol (HDL-Chol), systolic pressure (SP), diastolic pressure (DP)] were determined. Routine laboratory tests were performed. Serum vitamin B₁₂ concentrations were measured using electrochemiluminescence immunoassay. Vitamin B₉ was analyzed by an immunoassay analyzer. Values for vitamin B₁₂ < 148 pmol/L, 148-221 pmol/L, > 221 pmol/L were accepted as low, borderline and normal, respectively. Vitamin B₉ levels ≤ 4 mcg/L defined deficiency state. Statistical evaluations were performed by SPSSx Version 16.0. p≤0.05 was accepted as statistical significance level. Statistically higher body mass index (BMI), WC, hip circumference (C) and neck C were calculated in MetS group compared to children with MO. No difference was noted for head C. All MetS components differed between the groups (SP, DP p < 0.001; WC, FBG, TRG p < 0.01; HDL-Chol p < 0.05). Significantly decreased vitamin B₉ and vitamin B₁₂ levels were detected (p < 0.05) in children with MetS. In both groups percentage of folate deficiency was 5.5%. No cases were below < 148 pmol/L. However, in MO group 14.3% and in MetS group 22.2% of the cases were of borderline status. In MO group B₁₂ levels were negatively correlated with BMI, WC, hip C and head C, but not with neck C. WC, hip C, head C and neck C were all negatively correlated with HDL-Chol. None of these correlations were observed in the group of children with MetS. Strong positive correlation between FBG and insulin as well as strong negative correlation between TRG and HDL-Chol detected in MO children were lost in MetS group. Deficiency state end-products of both B₉ and B₁₂ may interfere with the expected profiles of MetS components. In this study, the alterations in MetS components affected vitamin B₁₂ metabolism and also its associations with anthropometric body measurements. Further increases in vitamin B₁₂ and vitamin B₉ deficiency in MetS associated with the increased vitamin B₁₂ as well as vitamin B₉ deficiency metabolites may add to MetS parameters.

Keywords: children, cobalamin, folate, metabolic syndrome, obesity

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Authors: Sundaresan Soundararajan, Chor Ngee Tan

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Introduction: Pyogenic spondylitis, otherwise treated conservatively with long term antibiotics, would require surgical debridement and reconstruction in about 10% to 20% of cases. The classical approach adopted many surgeons have always been anterior approach in ensuring thorough and complete debridement. This, however, comes with high rates of morbidity due to the nature of its access. Direct lateral retroperitoneal approach, which has been growing in usage in degenerative lumbar diseases, has the potential in treating pyogenic spondylitis with its ease of approach and relatively low risk of complications. Aims/Objectives: The objective of this study was to evaluate the effectiveness and clinical outcome of using lateral approach surgery in the surgical management of pyogenic spondylitis of the lumbar spine. Methods: Retrospective chart analysis was done on all patients who presented with pyogenic spondylitis (lumbar discitis/vertebral osteomyelitis) and had undergone direct lateral retroperitoneal lumbar vertebral debridement and posterior instrumentation between 2014 and 2016. Data on blood loss, surgical operating time, surgical complications, clinical outcomes and fusion rates were recorded. Results: A total of 6 patients (3 male and 3 female) underwent this procedure at a single institution by a single surgeon during the defined period. One patient presented with infected implant (PLIF) and vertebral osteomyelitis while the other five presented with single level spondylodiscitis. All patients underwent lumbar debridement, iliac strut grafting and posterior instrumentation (revision of screws for infected PLIF case). The mean operating time was 308.3 mins for all 6 cases. Mean blood loss was reported at 341cc (range from 200cc to 600cc). Presenting symptom of back pain resolved in all 6 cases while 2 cases that presented with lower limb weakness had improvement of neurological deficits. One patient had dislodged strut graft while performing posterior instrumentation and needed graft revision intraoperatively. Infective markers normalized for all patients subsequently. All subjects also showed radiological evidence of fusion on 6 months follow up. Conclusions: Lateral approach in treating pyogenic spondylitis is a viable option as it allows debridement and reconstruction without the risk that comes with other anterior approaches. It allows efficient debridement, short surgical time, moderate blood loss and low risk of vascular injuries. Clinical outcomes and fusion rates by this approach also support its use as practical MIS option surgery for such infection cases.

Keywords: lateral approach, minimally invasive, pyogenic spondylitis, XLIF

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Authors: E. O. Egieyeh, N. Butler, R. Coetzee, M. Van Huyssteen, A. Bheekie

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Background: High rate of maternal and child mortality is a global concern. Nationally, it constitutes one of South Africa’s quadruple burdens of diseases. Pharmacists have a crucial role in maternal and child health care delivery and as such should be equipped with adequate knowledge and skill required to contribute to maternal and child well-being. The International Pharmaceutical Federation statement of policy (2013) outlines pharmacist-led interventions in accordance with the World Health Organisation’s interventions in maternal, new-born and child health care. The South African Pharmacy Council’s guideline on Good Pharmacy Practice (2010) also stipulates the minimum standards required to participate in reproductive, maternal and child care. Pharmacy schools are obliged to train pharmacy students to meet priority health needs of the population so that graduates are ‘fit for purpose’. The purpose of the study is to evaluate the knowledge and skill of final year pharmacy students at a university in South Africa to determine their preparedness to contribute effectively to maternal and child health care. Method: A quantitative, descriptive, non-randomized baseline study was conducted among the final year students at the School of Pharmacy. Data was collected using a questionnaire designed in sections to assess knowledge of contraception, maternal and child health directed at the primary care level and framed within the scope of practice required of an entry-level generalist pharmacist. Participants’ skill in infant growth assessment was assessed in a section of the questionnaire in a written format. Participants ticked the topics they had been exposed to on a curriculum content assessment tool which was not graded. A pilot study examined the clarity and suitability of question items, and duration to complete the questionnaire. A score of 50% in each section of the questionnaire indicated a pass. The questionnaire was delivered in campus lecture venue. Results: Of the 102 students in final year, 53 (52%) students consented to participate in the study. Only 13.2% of participants scored above 50% in each section. Forty five (85%) participants scored above 50% in the contraception section while 40 (75%) scored less than 50% in the skills assessment. Less than half (45.3%) of the participants had a total score above 50%. Being a parent or working part-time as pharmacist assistance did not have any influence on the performance of the participants. Evaluation of participants’ curriculum content exposure showed differences in exposure to the various topics. Exposure to contraception teaching received the most recognition. Conclusion: Maternal and child health curriculum content should be reviewed at the university to enhance the knowledge and skill of pharmacy graduates.

Keywords: final year pharmacy students, knowledge and skill, maternal and child health, South Africa

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Authors: Henry Acurio, Alvaro Corral, Juan Fonseca

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In Ecuador, subventions on fossil fuels for the road transportation sector have always been part of its economy throughout time, mainly because of demagogy and populism from political leaders. It is clearly seen that the government cannot maintain the subsidies anymore due to its commercial balance and its general state budget; subsidies are a key barrier to implementing the use of cleaner technologies. However, during the last few months, the elimination of subsidies has been done gradually with the purpose of reaching international prices. It is expected that with this measure, the population will opt for other means of transportation, and in a certain way, it will promote the use of private electric vehicles and public, e.g., taxis and buses (urban transport). Considering the three main elements of sustainable development, an analysis of the social, economic, and environmental impacts of eliminating subsidies will be generated at the country level. To achieve this, four scenarios will be developed in order to determine how the subsidies will contribute to the promotion of electro-mobility: 1) A Business as Usual (BAU) scenario; 2) the introduction of 10 000 electric vehicles by 2025; 3) the introduction of 100 000 electric vehicles by 2030; 4) the introduction of 750 000 electric vehicles by 2040 (for all the scenarios, buses, taxis, lightweight duty vehicles, and private vehicles will be introduced, as it is established in the National Electro Mobility Strategy for Ecuador). The Low Emissions Analysis Platform (LEAP) will be used, and it will be suitable to determine the cost for the government in terms of importing derivatives for fossil fuels and the cost of electricity to power the electric fleet that can be changed. The elimination of subventions generates fiscal resources for the state that can be used to develop other kinds of projects that will benefit Ecuadorian society. It will definitely change the energy matrix, and it will provide energy security for the country; it will be an opportunity for the government to incentivize a greater introduction of renewable energies, e.g., solar, wind, and geothermal. At the same time, it will also reduce greenhouse gas emissions (GHG) from the transportation sector, considering its mitigation potential, which as a result, will ameliorate the inhabitant quality of life by improving the quality of air, therefore reducing respiratory diseases associated with exhaust emissions, consequently, achieving sustainability, the Sustainable Development Goals (SDGs), and complying with the agreements established in the Paris Agreement COP 21 in 2015. Electro-mobility in Latin America and the Caribbean can only be achieved by the implementation of the right policies by the central government, which need to be accompanied by a National Urban Mobility Policy (NUMP), and can encompass a greater vision to develop holistic, sustainable transport systems at local governments.

Keywords: electro mobility, energy, policy, sustainable transportation

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Authors: J. Manuel Bello-López, Julieta Rojo-Medina

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Introduction: The transplant of Umbilical Cord Blood Units (UCBU) are a therapeutic possibility for patients with oncohaematological disorders, especially in children. In Mexico, 48.5% of oncological diseases in children 1-4 years old are leukemias; whereas in patients 5-14 and 15-24 years old, lymphomas and leukemias represent the second and third cause of death in these groups respectively. Therefore it is necessary to have more registries of UCBU in order to ensure genetic diversity in the country; the above because the search for appropriate a UCBU is increasingly difficult for patients of mixed ethnicity. Objective: To estimate the genetic diversity (polymorphisms) of Human Leucocyte Antigen (HLA) Class I (A, B) and Class II (DRB1) in UCBU cryopreserved for transplant at Cord Blood Bank of the NCBT. Material and Methods: HLA typing of 533 UCBU for transplant was performed from 2003-2012 at the Histocompatibility Laboratory from the Research Department (evaluated by Los Angeles Ca. Immunogenetics Center) of the NCBT. Class I HLA-A, HLA-B and Class II HLA-DRB1 typing was performed using medium resolution Sequence-Specific Primer (SSP). In cases of an ambiguity detected by SSP; Sequence-Specific Oligonucleotide (SSO) method was carried out. A strict analysis of populations genetic parameters were done in 5 representative UCBU populations. Results: 46.5% of UCBU were collected from Mexico City, State of Mexico (30.95%), Puebla (8.06%), Morelos (6.37%) and Veracruz (3.37%). The remaining UCBU (4.75%) are represented by other states. The identified genotypes correspond to Amerindian origins (HLA-A*02, 31; HLA-B*39, 15, 48), Caucasian (HLA-A*02, 68, 01, 30, 31; HLA-B*35, 15, 40, 44, 07 y HLA-DRB1*04, 08, 07, 15, 03, 14), Oriental (HLA-A*02, 30, 01, 31; HLA-B* 35, 39, 15, 40, 44, 07,48 y HLA-DRB1*04, 07,15, 03) and African (HLA-A*30 y HLA-DRB1*03). The genetic distances obtained by Cavalli-Sforza analysis of the five states showed significant genetic differences by comparing genetic frequencies. The shortest genetic distance exists between Mexico City and the state of Puebla (0.0039) and the largest between Veracruz and Morelos (0.0084). In order to identify significant differences between this states, the ANOVA test was performed. This demonstrates that UCBU is significantly different according to their origin (P <0.05). This is shown by the divergence between arms at the Dendogram of Neighbor-Joining. Conclusions: The NCBT provides UCBU in patients with oncohaematological disorders in all the country. There is a group of patients for which not compatible UCBU can be find due to the mixed ethnic origin. For example, the population of northern Mexico is mostly Caucasian. Most of the NCBT donors are of various ethnic origins, predominantly Amerindians and Caucasians; although some ethnic minorities like Oriental, African and pure Indian ethnics are not represented. The NCBT is, therefore, establishing agreements with different states of Mexico to promote the altruistic donation of Umbilical Cord Blood in order to enrich the genetic diversity in its files.

Keywords: cord blood, genetic diversity, human leucocyte antigen, transplant

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Authors: Muhammad Fiaz Qamar, Uzma Mehreen, Muhammad Arfan Zaman, Kazim Ali

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Ovine Theileriosis is a world-wide concern, especially in tropical and subtropical areas, due to having tick abundance that has received less awareness in different developed and developing areas due to less worth of sheep, low to the middle level of infection in different small ruminants herd. Across Asia, the prevalence reports have been conducted to provide equivalent calculation of flock and animal level prevalence of Theileriosisin animals. It is a challenge for veterinarians to timely diagnosis & control of Theileriosis and famers because of the nature of the organism and inadequacy of restricted plans to control. All most work is based upon the development of such a technique which should be farmer-friendly, less expensive, and easy to perform into the field. By the timely diagnosis of this disease will decrease the irrational use of the drugs, and other plan was to determine the prevalence of Theileriosis in District Jhang by using the conventional method, PCR and qPCR, and LAMP. We quantify the molecular epidemiology of T.lestoquardiin sheep from Jhang districts, Punjab, Pakistan. In this study, we concluded that the overall prevalence of Theileriosis was (32/350*100= 9.1%) in sheep by using Giemsa staining technique, whereas (48/350*100= 13%) is observed by using PCR technique (56/350*100=16%) in qPCR and the LAMP technique have shown up to this much prevalence percentage (60/350*100= 17.1%). The specificity and sensitivity also calculated in comparison with the PCR and LAMP technique. Means more positive results have been shown when the diagnosis has been done with the help of LAMP. And there is little bit of difference between the positive results of PCR and qPCR, and the least positive animals was by using Giemsa staining technique/conventional method. If we talk about the specificity and sensitivity of the LAMP as compared to PCR, The cross tabulation shows that the results of sensitivity of LAMP counted was 94.4%, and specificity of LAMP counted was 78%. Advances in scientific field must be upon reality based ideas which can lessen the gaps and hurdles in the way of scientific research; the lamp is one of such techniques which have done wonders in adding value and helping human at large. It is such a great biological diagnostic tools and has helped a lot in the proper diagnosis and treatment of certain diseases. Other methods for diagnosis, such as culture techniques and serological techniques, have exposed humans with great danger. However, with the help of molecular diagnostic technique like LAMP, exposure to such pathogens is being avoided in the current era Most prompt and tentative diagnosis can be made using LAMP. Other techniques like PCR has many disadvantages when compared to LAMP as PCR is a relatively expensive, time consuming, and very complicated procedure while LAMP is relatively cheap, easy to perform, less time consuming, and more accurate. LAMP technique has removed hurdles in the way of scientific research and molecular diagnostics, making it approachable to poor and developing countries.

Keywords: distribution, thelaria, LAMP, primer sequences, PCR

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Authors: Aziza Barnawi

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Background: Regular exercise reduces risk factors associated with cardiovascular diseases. Over the past decade, exercise interventions have been introduced to reduce the risk of and prevent coronary artery disease (CAD). Elevated low-density lipoproteins (LDL) contribute to the formation of atherosclerosis, its manifestations on the endothelial narrow the coronary artery and affect the endothelial function. Therefore, flow-mediated dilation (FMD) technique is used to assess the function. The results of previous studies have been inconsistent and difficult to interpret across different types of exercise programs. The relationship between exercise therapy and lipid levels has been extensively studied, and it is known to improve the lipid profile and endothelial function. However, the effectiveness of exercise in altering LDL levels and improving blood flow is controversial. Objective: This review aims to explore the evidence and quantify the impact of exercise training on LDL levels and vascular function by FMD. Methods: Electronic databases were searched PubMed, Google Scholar, Web of Science, the Cochrane Library, and EBSCO using the keywords: “low and/or moderate aerobic training”, “blood flow”, “atherosclerosis”, “LDL mediated blood flow”, “Cardiac Rehabilitation”, “low-density lipoproteins”, “flow-mediated dilation”, “endothelial function”, “brachial artery flow-mediated dilation”, “oxidized low-density lipoproteins” and “coronary artery disease”. The studies were conducted for 6 weeks or more and influenced LDL levels and/or FMD. Studies with different intensity training and endurance training in healthy or CAD individuals were included. Results: Twenty-one randomized controlled trials (RCTs) (14 FMD and 7 LDL studies) with 776 participants (605 exercise participants and 171 control participants) met eligibility criteria and were included in the systematic review. Endurance training resulted in a greater reduction in LDL levels and their subfractions and a better FMD response. Overall, the training groups showed improved physical fitness status compared with the control groups. Participants whose exercise duration was ≥150 minutes /week had significant improvement in FMD and LDL levels compared with those with <150 minutes/week.Conclusion: In conclusion, although the relationship between physical training, LDL levels, and blood flow in CAD is complex and multifaceted, there are promising results for controlling primary and secondary prevention of CAD by exercise. Exercise training, including resistance, aerobic, and interval training, is positively correlated with improved FMD. However, the small body of evidence for LDL studies (resistance and interval training) did not prove to be significantly associated with improved blood flow. Increasing evidence suggests that exercise training is a promising adjunctive therapy to improve cardiovascular health, potentially improving blood flow and contributing to the overall management of CAD.

Keywords: exercise training, low density lipoprotein, flow mediated dilation, coronary artery disease

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Authors: Alan N. A. Heberle, Salatiel W. Da Silva, Valentin Perez-Herranz, Andrea M. Bernardes

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Contaminants of emerging concern are substances widely used, such as pharmaceutical products. These compounds represent risk for both wild and human life since they are not completely removed from wastewater by conventional wastewater treatment plants. In the environment, they can be harm even in low concentration (µ or ng/L), causing bacterial resistance, endocrine disruption, cancer, among other harmful effects. One of the most common taken medicine to treat cardiocirculatory diseases is the Atenolol (ATL), a β-Blocker, which is toxic to aquatic life. In this way, it is necessary to implement a methodology, which is capable to promote the degradation of the ATL, to avoid the environmental detriment. A very promising technology is the advanced electrochemical oxidation (AEO), which mechanisms are based on the electrogeneration of reactive radicals (mediated oxidation) and/or on the direct substance discharge by electron transfer from contaminant to electrode surface (direct oxidation). The hydroxyl (HO•) and sulfate (SO₄•⁻) radicals can be generated, depending on the reactional medium. Besides that, at some condition, the peroxydisulfate (S₂O₈²⁻) ion is also generated from the SO₄• reaction in pairs. Both radicals, ion, and the direct contaminant discharge can break down the molecule, resulting in the degradation and/or mineralization. However, ATL molecule and byproducts can still remain in the treated solution. On this wise, some efforts can be done to implement the AEO process, being one of them the use of a cationic membrane to separate the cathodic (reduction) from the anodic (oxidation) reactor compartment. The aim of this study is investigate the influence of the implementation of a cationic membrane (Nafion®-117) to separate both cathodic and anodic, AEO reactor compartments. The studied reactor was a filter-press, with bath recirculation mode, flow 60 L/h. The anode was an Nb/BDD2500 and the cathode a stainless steel, both bidimensional, geometric surface area 100 cm². The solution feeding the anodic compartment was prepared with ATL 100 mg/L using Na₂SO₄ 4 g/L as support electrolyte. In the cathodic compartment, it was used a solution containing Na₂SO₄ 71 g/L. Between both solutions was placed the membrane. The applied currents densities (iₐₚₚ) of 5, 20 and 40 mA/cm² were studied over 240 minutes treatment time. Besides that, the ATL decay was analyzed by ultraviolet spectroscopy (UV/Vis). The mineralization was determined performing total organic carbon (TOC) in TOC-L CPH Shimadzu. In the cases without membrane, the iₐₚₚ 5, 20 and 40 mA/cm² resulted in 55, 87 and 98 % ATL degradation at the end of treatment time, respectively. However, with membrane, the degradation, for the same iₐₚₚ, was 90, 100 and 100 %, spending 240, 120, 40 min for the maximum degradation, respectively. The mineralization, without membrane, for the same studied iₐₚₚ, was 40, 55 and 72 %, respectively at 240 min, but with membrane, all tested iₐₚₚ reached 80 % of mineralization, differing only in the time spent, 240, 150 and 120 min, for the maximum mineralization, respectively. The membrane increased the ATL oxidation, probably due to avoid oxidant ions (S₂O₈²⁻) reduction on the cathode surface.

Keywords: contaminants of emerging concern, advanced electrochemical oxidation, atenolol, cationic membrane, double compartment reactor

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Authors: Belgheis Ebrahimi, Jun Lu

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In recent years, there has been a growing recognition of the potential of marine-based functional foods and combination therapies in promoting a healthy lifestyle and exploring their effectiveness in preventing or treating diseases. The combination of marine bioactive compounds or extracts offers synergistic or enhancement effects through various mechanisms, including multi-target actions, improved bioavailability, enhanced bioactivity, and mitigation of potential adverse effects. Both the green-lipped mussel (GLM) and fucoidan derived from brown seaweed are rich in bioactivities. These two, mussel and fucoidan, have not been previously formulated together. This study aims to combine GLM oil from Perna canaliculus with low molecular weight fucoidan (LMWF) extracted from Undaria pinnatifida to investigate the unique mixture’s anti-inflammatory and antioxidant properties. The cytotoxicity of individual compounds and combinations was assessed using the MTT assay in (THP-1 and RAW264.7) cell lines. The anti-inflammatory activity of mussel-fucoidan was evaluated by treating LPS-stimulated human monocyte and macrophage (THP1-1) cells. Subsequently, the inflammatory cytokines released into the supernatant of these cell lines were quantified via ELISA. Antioxidant activity was determined by using the free radical scavenging assay (DPPH). DPPH assay demonstrated that the radical scavenging activity of the combinations, particularly at concentrations exceeding 1 mg/ml, showed a significantly higher percentage of inhibition when compared to the individual component. This suggests an enhancement effect when the two compounds are combined, leading to increased antioxidant activity. In terms of immunomodulatory activity, the individual compounds exhibited distinct behaviors. GLM oil displayed a higher ability to suppress the cytokine TNF- compared to LMWF. Interestingly, the LMWF fraction, when used individually, did not demonstrate TNF- suppression. However, when combined with GLM, the TNF- suppression (anti-inflammatory) activity of the combination was better than GLM or LWMF alone. This observation underscores the potential for enhancement interactions between the two components in terms of anti-inflammatory properties. This study revealed that each individual compound, LMWF, and GLM, possesses unique and notable bioactivity. The combination of these two individual compounds results in an enhancement effect, where the bioactivity of each is enhanced, creating a superior combination. This suggests that the combination of LMWF and GLM has the potential to offer a more potent and multifaceted therapeutic effect, particularly in the context of antioxidant and anti-inflammatory activities. These findings hold promise for the development of novel therapeutic interventions or supplements that harness the enhancement effects.

Keywords: combination, enhancement effect, perna canaliculus, undaria pinnatifida

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Authors: Lena Lapidot, Amir Amnon, Rita Nosenko, Veitsman Ella, Cohen-Ezra Oranit, Davidov Yana, Segev Shlomo, Koren Omry, Safran Michal, Ben-Ari Ziv

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Introduction: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related mortality worldwide. Liver Cirrhosis is the main predisposing risk factor for the development of HCC. The factor(s) influencing disease progression from Cirrhosis to HCC remain unknown. Gut microbiota has recently emerged as a major player in different liver diseases, however its association with HCC is still a mystery. Moreover, there might be an important association between the gut microbiota, nutrition, life style and the progression of Cirrhosis and HCC. The aim of our study was to characterize the gut microbial signature in association with life style and nutrition of patients with Cirrhosis, HCC-Cirrhosis and healthy controls. Design: Stool samples were collected from 95 individuals (30 patients with HCC, 38 patients with Cirrhosis and 27 age, gender and BMI-matched healthy volunteers). All participants answered lifestyle and Food Frequency Questionnaires. 16S rRNA sequencing of fecal DNA was performed (MiSeq Illumina). Results: There was a significant decrease in alpha diversity in patients with Cirrhosis (qvalue=0.033) and in patients with HCC-Cirrhosis (qvalue=0.032) compared to healthy controls. The microbiota of patients with HCC-cirrhosis compared to patients with Cirrhosis, was characterized by a significant overrepresentation of Clostridium (pvalue=0.024) and CF231 (pvalue=0.010) and lower expression of Alphaproteobacteria (pvalue=0.039) and Verrucomicrobia (pvalue=0.036) in several taxonomic levels: Verrucomicrobiae, Verrucomicrobiales, Verrucomicrobiaceae and the genus Akkermansia (pvalue=0.039). Furthermore, we performed an analysis of predicted metabolic pathways (Kegg level 2) that resulted in a significant decrease in the diversity of metabolic pathways in patients with HCC-Cirrhosis (qvalue=0.015) compared to controls, one of which was amino acid metabolism. Furthermore, investigating the life style and nutrition habits of patients with HCC-Cirrhosis, we found significant correlations between intake of artificial sweeteners and Verrucomicrobia (qvalue=0.12), High sugar intake and Synergistetes (qvalue=0.021) and High BMI and the pathogen Campylobacter (qvalue=0.066). Furthermore, overweight in patients with HCC-Cirrhosis modified bacterial diversity (qvalue=0.023) and composition (qvalue=0.033). Conclusions: To the best of the our knowledge, we present the first report of the gut microbial composition in patients with HCC-Cirrhosis, compared with Cirrhotic patients and healthy controls. We have demonstrated in our study that there are significant differences in the gut microbiome of patients with HCC-cirrhosis compared to Cirrhotic patients and healthy controls. Our findings are even more pronounced because the significantly increased bacteria Clostridium and CF231 in HCC-Cirrhosis weren't influenced by diet and lifestyle, implying this change is due to the development of HCC. Further studies are needed to confirm these findings and assess causality.

Keywords: Cirrhosis, Hepatocellular carcinoma, life style, liver disease, microbiome, nutrition

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Authors: Wenhsuan Lee, Yachi Chang, Yingyih Shih

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In clinical practices, it is common that while facing the unknown progress of their disease, palliative care patients may easily feel anxious and depressed. These types of reactions are a cause of psychosomatic diseases and may also influence treatment results. However, the purpose of palliative care is to provide relief from all kinds of pains. Therefore, how to make patients more comfortable is an issue worth studying. This study adopted the “bio-psycho-social model” proposed by Engel and applied spontaneous breathing training, in the hope of seeing patients’ psychological state changes caused by their physiological state changes, improvements in their anxious conditions, corresponding adjustments of their cognitive functions, and further enhancement of their social functions and the social support system. This study will be a one-year study. Palliative care outpatients will be recruited and assigned to the experimental group or the control group for six outpatient visits (once a month), with 80 patients in each group. The patients of both groups agreed that this study can collect their physiological quantitative data using an HRV device before the first outpatient visit. They also agreed to answer the “Beck Anxiety Inventory (BAI)”, the “Taiwanese version of the WHOQOL-BREF questionnaire” before the first outpatient visit, to fill a self-report questionnaire after each outpatient visit, and to answer the “Beck Anxiety Inventory (BAI)”, the “Taiwanese version of the WHOQOL-BREF questionnaire” after the last outpatient visit. The patients of the experimental group agreed to receive the breathing training under HRV monitoring during the first outpatient visit of this study. Before each of the following three outpatient visits, they were required to fill a self-report questionnaire regarding their breathing practices after going home. After the outpatient visits, they were taught how to practice breathing through an HRV device and asked to practice it after going home. Later, based on the results from the HRV data analyses and the pre-tests and post-tests of the “Beck Anxiety Inventory (BAI)”, the “Taiwanese version of the WHOQOL-BREF questionnaire”, the influence of the breathing training in the bio, psycho, and social aspects were evaluated. The data collected through the self-report questionnaires of the patients of both groups were used to explore the possible interfering factors among the bio, psycho, and social changes. It is expected that this study will support the “bio-psycho-social model” proposed by Engel, meaning that bio, psycho, and social supports are closely related, and that breathing training helps to transform palliative care patients’ psychological feelings of anxiety and depression, to facilitate their positive interactions with others, and to improve the quality medical care for them.

Keywords: palliative care, breathing training, bio-psycho-social model, heart rate variability

Procedia PDF Downloads 259