Search results for: sickle disease

Authors: Mohamed Moussaoui, Mouna Baassi, Soukayna Baammi, Hatim Soufi, Mohammed Salah, Rachid Daoud, Achraf EL Allali, Mohammed Elalaoui Belghiti, Said Belaaouad

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The present study aims to investigate the quantitative structure-activity relationship (QSAR) of a series of Thiazole derivatives reported as anticancer agents (hepatocellular carcinoma), using principally the electronic descriptors calculated by the density functional theory (DFT) method and by applying the multiple linear regression method. The developed model showed good statistical parameters (R²= 0.725, R²ₐ𝒹ⱼ= 0.653, MSE = 0.060, R²ₜₑₛₜ= 0.827, Q²𝒸ᵥ = 0.536). The energy of the highest occupied molecular orbital (EHOMO) orbital, electronic energy (TE), shape coefficient (I), number of rotatable bonds (NROT), and index of refraction (n) were revealed to be the main descriptors influencing the anti-cancer activity. Additional Thiazole derivatives were then designed and their activities and pharmacokinetic properties were predicted using the validated QSAR model. These designed molecules underwent evaluation through molecular docking (MD) and molecular dynamic (MD) simulations, with binding affinity calculated using the MMPBSA script according to a 100 ns simulation trajectory. This process aimed to study both their affinity and stability towards Cyclin-Dependent Kinase 2 (CDK2), a target protein for cancer disease treatment. The research concluded by identifying four CDK2 inhibitors - A1, A3, A5, and A6 - displaying satisfactory pharmacokinetic properties. MDs results indicated that the designed compound A5 remained stable in the active center of the CDK2 protein, suggesting its potential as an effective inhibitor for the treatment of hepatocellular carcinoma. The findings of this study could contribute significantly to the development of effective CDK2 inhibitors.

Keywords: QSAR, ADMET, Thiazole, anticancer, molecular docking, molecular dynamic simulations, MMPBSA calculation

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Authors: Owonikoko Abayomi Dele

Abstract:

Epilepsy is an unresolved disease that needs urgent attention. It is a brain disorder that affects over sixty-five (65) million people around the globe. Despite the availability of commercial anti-epileptic drugs, the war against this unmet condition is yet to be resolved. Most epilepsy patients are resistant to available anti-epileptic medications thus the need for affordable novel therapy against epilepsy is a necessity. Numerous phytochemicals have been reported for their potency, efficacy and safety as therapeutic agents against many diseases. This study investigated 99 isolated phytochemicals from Chasmanthera dependens and Carissa edulis against carbonic anhydrase (ii) drug target. The absorption, distribution, metabolism, excretion and toxicity (ADMET) of the isolated compounds were examined using admet SAR-2 web server while Swiss ADME was used to analyze the oral bioavailability, drug-likeness and lead-likeness properties of the selected leads. PASS web server was used to predict the biological activities of selected leads while other important physicochemical properties and interactions of the selected leads with the active site of the target after successful molecular docking simulation with the pyrx virtual screening tool were also examined. The results of these study identified seven lead compounds; C49- alpha-carissanol (-7.6 kcal/mol), C13- Catechin (-7.4 kcal/mol), C45- Salicin (-7.4 kcal/mol), C6- Bisnorargemonine (-7.3 kcal/mol), C36- Pallidine (-7.1 kcal/mol), S4- Lacosamide (-7.1 kcal/mol), and S7- Acetazolamide (-6.4 kcal/mol) for CA II (3HS4 receptor). These leads compounds are probable inhibitors of this drug target due to the observed good binding affinities and favourable interactions with the active site of the drug target, excellent ADMET profiles, PASS Properties, drug-likeness, lead-likeness and oral bioavailability properties. The identified leads have better binding energies as compared to the binding energies of the two standards. Thus, seven identified lead compounds can be developed further towards the development of new anti-epileptic medications.

Keywords: drug-likeness, phytochemicals, carbonic anhydrases, metalloeazymes, active site, ADMET

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Authors: Valeria Arcucci, Musarat Ishaq, Steven A. Stacker, Greg J. Goodall, Marc G. Achen

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Metastasis is the lethal aspect of cancer for most patients. Remodelling of lymphatic vessels associated with a tumour is a key initial step in metastasis because it facilitates the entry of cancer cells into the lymphatic vasculature and their spread to lymph nodes and distant organs. Although it is clear that vascular endothelial growth factors (VEGFs), such as VEGF-C and VEGF-D, are key drivers of lymphatic remodelling, the means by which many signaling pathways in endothelial cells are coordinately regulated to drive growth and remodelling of lymphatics in cancer is not understood. We seek to understand the broader molecular mechanisms that control cancer metastasis, and are focusing on microRNAs, which coordinately regulate signaling pathways involved in complex biological responses in health and disease. Here, using small RNA sequencing, we found that a specific microRNA, miR-132, is upregulated in expression in lymphatic endothelial cells (LECs) in response to the lymphangiogenic growth factors. Interestingly, ectopic expression of miR-132 in LECs in vitro stimulated proliferation and tube formation of these cells. Moreover, miR-132 is expressed in lymphatic vessels of a subset of human breast tumours which were previously found to express high levels of VEGF-D by immunohistochemical analysis on tumour tissue microarrays. In order to dissect the complexity of regulation by miR-132 in lymphatic biology, we performed Argonaute HITS-CLIP, which led us to identify the miR-132-mRNA interactome in LECs. We found that this microRNA in LECs is involved in the control of many different pathways mainly involved in cell proliferation and regulation of the extracellular matrix and cell-cell junctions. We are now exploring the functional significance of miR-132 targets in the biology of LECs using biochemical techniques, functional in vitro cell assays and in vivo lymphangiogenesis assays. This project will ultimately define the molecular regulation of lymphatic remodelling by miR-132, and thereby identify potential therapeutic targets for drugs designed to restrict the growth and remodelling of tumour lymphatics resulting in metastatic spread.

Keywords: argonaute HITS-CLIP, cancer, lymphatic remodelling, miR-132, VEGF

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Authors: Les Moncrieff

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In a world awash with potent opioids flaming an international crisis, the need to explore safe alternatives has never been more urgent. Bio-electrode Therapy is a novel adjunctive treatment method for relieving acute opioid withdrawal symptoms and many types of complex acute and chronic pain (often the underlying cause of opioid dependence). By combining the science of developmental bioelectricity with Traditional Chinese Medicine’s theory of meridians, rapid relief from pain is routinely being achieved in the clinical setting. Human body functions are dependent on electrical factors, and acupuncture points on the body are known to have higher electrical conductivity than surrounding skin tissue. When tiny gold- and silver-plated electrodes are secured to the skin at specific acupuncture points using established Chinese Medicine principles and protocols, an enhanced microcurrent and electrical field are created between the electrodes, influencing the entire meridian and connecting meridians. No external power source or electrical devices are required. Endogenous DC electric fields are an essential fundamental component for development, regeneration, and wound healing. Disruptions in the normal ion-charge in the meridians and circulation of blood will manifest as pain and development of disease. With the application of these simple electrodes (gold acting as cathode and silver as anode) according to protocols, the resulting microcurrent is directed along the selected meridians to target injured or diseased organs and tissues. When injured or diseased cells have been stimulated by the microcurrent and electrical fields, the permeability of the cell membrane is affected, resulting in an immediate relief of pain, a rapid balancing of positive and negative ions (sodium, potassium, etc.) in the cells, the restoration of intracellular fluid levels, replenishment of electrolyte levels, pH balance, removal of toxins, and a re-establishment of homeostasis.

Keywords: bioelectricity, electrodes, electrical fields, acupuncture meridians, complex pain, opioid withdrawal management

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Authors: Raviv Harris, Maggie Levy

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Natural product-based pesticides may serve as an alternative to the traditional synthetic pesticides, which have a potentially damaging effect, both to human health and for the environment. Along with plants, microorganisms are a prospective source of such biological pesticides. A unique and active strain of P. aphidis (designated isolate L12, Israel 2004), an epiphytic and non-pathogenic basidiomycete yeast, was isolated in our lab from strawberry leaves. P. aphidis L12 secretions were found to inhibit broad range of plant pathogens. This work demonstrates that metabolites isolated from the biocontrol agent P. aphidis (isolate L12) can inhibit varied fungal and bacterial phytopathogens. Biologically active metabolites were extracted from P. aphidis biomass, using the organic solvent ethyl acetate. The antimicrobial activity of the extract was demonstrated, both in vitro and in planta. Using disk diffusion assays, the following inhibition zones were obtained: 43cm² for Pseudomonas syringae pv. tomato, 28.5cm² for Xanthomonas campestris pv. vesicatoria, 59cm² for Clavibacter michiganensis subsp. michiganensis, 34cm² for Erwinia amylovora and 34cm² for Agrobacterium tumefaciens. Additionally, strong inhibitory activity of the extract against fungi mycelial growth was established, with IC₅₀ values of 606µg ml⁻¹ for Botrytis cinerea, 221µg ml⁻¹ for Pythium spp., 519µg ml⁻¹ for Rhizoctonia solani, 455µg ml⁻¹ for Sclerotinia sclerotiorum, 2270µg ml⁻¹ for Fusarium oxysporum f. sp. lycopersici, and 2038µg ml⁻¹ for Alternaria alternata. The results of the in planta experiments demonstrated a dose-dependent reduction in disease infection. Significant inhibition of B. cinerea lesions on tomato plants was obtained when a spore suspension of this pathogen was treated with extract concentrations higher than 4.2mg ml⁻¹. Concentration of 7mg ml⁻¹ caused a reduction of over 95% in the lesion size of B. cinerea on tomato plants. The strong antimicrobial activity demonstrated both in vitro and in planta against varied phytopathogens, may indicate that the extracted antimicrobial metabolites have potential to serve as natural pesticides in the field.

Keywords: antimicrobial, B. cinerea, metabolites, natural pesticides, P. aphidis

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Authors: Kathleen Cravero, Amanda Nace, Samantha Ski

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The Violence Against Children Surveys (VACS) is nationally representative surveys of male and female youth ages 13-24, designed to measure the burden of sexual, physical, and emotional violence experienced in childhood and adolescence. As of 2019, 24 countries implemented or are in the process of implementing a VACS, covering over ten percent of the world’s child population. Since the first article using VACS data from Swaziland was published in 2009, several peer-reviewed articles have been published on the VACS. However, no publications to date have analyzed the breadth of the work and analyzed how the data are represented in the peer-reviewed literature. In this study, we conducted a literature review of all peer-reviewed research that used VACS data or discussed the implementation and methodology of the VACS. The literature review revealed several important findings. Between 2009 and July 2019, thirty-five peer-reviewed articles using VACS data from 12 countries have been published. Twenty of the studies focus on one country, while 15 of the studies focus on two or more countries. Some countries are featured in the literature more than others, for example Kenya (N=14), Malawi (N=12), and Tanzania (N=12). A review of the research by gender demonstrates that research on violence against boys is under-represented. Only two studies specifically focused on boys/young men, while 11 studies focused only on violence against girls. This is despite research which suggests boys and girls experience similar rates of violence. A review of the publications by type of violence revealed significant differences in the types of violence being featured in the literature. Thirteen publications specifically focused on sexual violence, while three studies focused on physical violence, and only one study focused on emotional violence. Almost 70% of the peer-reviewed articles (24 of the 35) were first-authored by someone at the U.S. Centers for Disease Control and Prevention. There were very few first authors from VACS countries, which raises questions about who is leveraging the data and the extent to which capacities for data liberation are being developed within VACS countries. The VACS provide an unprecedented amount of information on the prevalence and past-year incidence of violence against children. Through a review of the peer-reviewed literature on the VACS we can begin to identify trends and gaps in how the data is being used as well as identify areas for further research.

Keywords: data to action, global health, implementation science, violence against children surveys

Procedia PDF Downloads 133

Authors: Elizabeth Behrens, Anne Timmermann, Alexander Yerkan, Joshua Thomas, Deborah Katz, Agne Paner, Melissa Larson, Shivi Jain, Seo-Hyun Kim, Celalettin Ustun, Ankur Varma, Parameswaran Venugopal, Jamile Shammo

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Coronavirus Disease-2019 (COVID-19) causes persistent concern for poor outcomes in vulnerable populations. Patients with hematologic malignancies (HM) have been found to have higher COVID-19 case fatality rates compared to those without malignancy. While cytopenias are common in patients with HM, especially in those undergoing chemotherapy treatment, hemoglobin (Hgb) and platelet count have not yet been studied, to our best knowledge, as potential prognostic indicators for patients with HM and COVID-19. The goal of this study is to identify factors that may increase the risk of mortality in patients with HM and COVID-19. In this single-center, retrospective, observational study, 65 patients with HM and laboratory confirmed COVID-19 were identified between March 2020 and January 2021. Information on demographics, laboratory data the day of COVID-19 diagnosis, and prognosis was extracted from the electronic medical record (EMR), chart reviewed, and analyzed using the statistical software SAS version 9.4. Chi-square testing was used for categorical variable analyses. Risk factors associated with mortality were established by logistic regression models. Non-Hodgkin lymphoma (37%), chronic lymphocytic leukemia (20%), and plasma cell dyscrasia (15%) were the most common HM. Higher Hgb level upon COVID-19 diagnosis was related to decreased mortality, odd ratio=0.704 (95% confidence interval [CI]: 0.511-0.969; P = .0263). Platelet count the day of COVID-19 diagnosis was lower in patients who ultimately died (mean 127 ± 72K/uL, n=10) compared to patients who survived (mean 197 ±92K/uL, n=55) (P=.0258). Female sex was related to decreased mortality, odd ratio=0.143 (95% confidence interval [CI]: 0.026-0.785; P = .0353). There was no mortality difference between the patients who were on treatment for HM the day of COVID-19 diagnosis compared to those who were not (P=1.000). Lower Hgb and male sex are independent risk factors associated with increased mortality of HM patients with COVID-19. Clinicians should be especially attentive to patients with HM and COVID-19 who present with cytopenias. Larger multi-center studies are urgently needed to further investigate the impact of anemia, thrombocytopenia, and demographics on outcomes of patients with hematologic malignancies diagnosed with COVID-19.

Keywords: anemia, COVID-19, hematologic malignancy, prognosis

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Authors: Juan S. Vera, Miguel A. Gomez, Omar Gelvez

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Water is Earth's most valuable resource, and the lack of it is currently a critical problem in today’s society. Non-treated wastewaters contribute to this situation, especially those coming from industrial activities, as they reduce the quality of the water bodies, annihilating all kind of life and bringing disease to people in contact with them. An effective solution for this problem is distillation, which removes most contaminants. However, this approach must also be energetically efficient in order to appeal to the industry. In this endeavour, most water distillation treatments fail, with the exception of the Mechanical Vapor Compression (MVC) distillation system, which has a great efficiency due to energy input by a compressor and the latent heat exchange. This paper presents the process of design, construction, and evaluation of a Mechanical Vapor Compression (MVC) distillation system for the main Colombian poultry company Avidesa Macpollo SA. The system will be located in the principal slaughterhouse in the state of Santander, and it will work along with the Gas Energy Mixing system (GEM) to treat the wastewaters from the plant. The main goal of the MVC distiller, rarely used in this type of application, is to reduce the chlorides, Chemical Oxygen Demand (COD) and Biological Oxygen Demand (BOD) levels according to the state regulations since the GEM cannot decrease them enough. The MVC distillation system works with three components, the evaporator/condenser heat exchanger where the distillation takes place, a low-pressure compressor which gives the energy to create the temperature differential between the evaporator and condenser cavities and a preheater to save the remaining energy in the distillate. The model equations used to describe how the compressor power consumption, heat exchange area and distilled water are related is based on a thermodynamic balance and heat transfer analysis, with correlations taken from the literature. Finally, the design calculations and the measurements of the installation are compared, showing accordance with the predictions in distillate production and power consumption, changing the temperature difference of the evaporator/condenser.

Keywords: mechanical vapor compression, distillation, wastewater, design, construction, evaluation

Procedia PDF Downloads 159

Authors: Wan-Ling Jiang, Hsin Chi, Jia-Lu Cheng, Ming-Fang Cheng

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Background: Investigating the risk factors for the fecal carriage of third-generation cephalosporin-resistant E.coli could contribute to further disease prevention. Previous research on third-generation cephalosporin-resistant prevalence in children in different regions of Taiwan is limited. This project aims to explore the risk factors and regional differences in the prevalence of third-generation cephalosporin-resistant and other antibiotic-resistant E. coli in the northern, southern, and eastern regions of Taiwan. Methods: We collected data from children aged 0 to 18 from community or outpatient clinics from July 2022 to May 2023 in southern, northern, and eastern Taiwan. The questionnaire was designed to survey the characteristics of participants and possible risk factors, such as clinical information, household environment, drinking water, and food habits. After collecting fecal samples and isolating stool culture with E.coli, antibiotic sensitivity tests and MLST typing were performed. Questionnaires were used to analyze the risk factors of third-generation cephalosporin-resistant E. coli in the three different regions of Taiwan. Results: In the total 246 stool samples, third-generation cephalosporin-resistant E.coli accounted for 37.4% (97/246) of all isolates. Among the three different regions of Taiwan, the highest prevalence of fecal carriage with third-generation cephalosporin-resistant E.coli was observed in southern Taiwan (42.7%), followed by northern Taiwan (35.5%) and eastern Taiwan (28.4%). Multi-drug resistant E. coli had prevalence rates of 51.9%, 66.3%, and 37.1% in the northern, southern, and eastern regions, respectively. MLST typing revealed that ST131 was the most prevalent type (11.8%). The prevalence of ST131 in northern, southern, and eastern Taiwan was 10.1%, 12.3%, and 13.2%, respectively. Risk factors analysis identified lower paternal education, overweight status, and non-vegetarian diet as statistical significance risk factors for third-generation cephalosporin-resistant E.coli. Conclusion: The fecal carriage rates of antibiotic-resistant E. coli among Taiwanese children were on the rise. This study found regional disparities in the prevalence of third-generation cephalosporin-resistant and multi-drug-resistant E. coli, with southern Taiwan having the highest prevalence. Lower paternal education, overweight, and non-vegetarian diet were the potential risk factors of third-generation cephalosporin-resistant E. coli in this study.

Keywords: Escherichia coli, fecal carriage, antimicrobial resistance, risk factors, prevalence

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Authors: Catherine Mary Abou-Zaid, Sandra Goodwin

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This study was conducted in a cardiac center in Bahrain. The rise in the amount of obese patients’ both men and women, being admitted for surgical procedures has become an issue to the nurses and doctors as these patients pose a high risk of major complications arising from their problem. The cessation of obesity in the country is very high and obesity-related diseases has been the cause of concern among men and women, also related individual diseases such as cardiovascular, diabetes and chronic respiratory diseases are rising dramatically within Bahrain in the last 10 years. Rationale for the Study: The ontological approach will help to understand and assess the true nature of the social world and how the world looks at obesity. Obesity has to be looked at as being a realistic ongoing issue. The epistemological approach will look at the theory of the origins of the nature of knowledge, set the rule of validating and learning in the social world of what can be done to curb this concept and how this can help prevent otherwise preventable diseases. Design Methodology: The qualitative design methodology took the form of an ontological/epistemological approach using phenomenology as a framework. The study was based on a social research issue, therefore, ontological ‘realism and idealism’ will feature as the nature of the world from a social and natural context. Epistemological positions of the study will be how we as researchers will find the actual social world and the limiting of that knowledge. The one-to-one interviews will be transcribed and the taped verbatim will be coded and charted giving the thematic analytic results. Recommendations: The significance of the research brought many recommendations. These recommendations were taken from the themes and sub-themes and were presented to the centers management and the necessary arrangements for updating knowledge and attitudes towards obesity in cardiac patients was then presented to the in-service education department. Workshops and training sessions on promoting health education were organized and put into the educational calendar for the next academic year. These sessions would look at patient autonomy, the patients’ rights, healthy eating for patients and families and the risks associated with obesity in cardiac disease processes.

Keywords: cardiac patients, diabetes, education & training, obesity cessation, qualitative

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Authors: Arman Kishan, Sanjay Kubsad, Steve Li, Mark Haft, Duc Nguyen, Dawn Laporte

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Objective: Carpal tunnel syndrome can be managed surgically with endoscopic or open carpal tunnel release (CTR). Rheumatoid arthritis (RA) is a known risk factor for Carpal Tunnel Syndrome (CTS) and is believed to be related to compression of the median nerve secondary to inflammation. We aimed to analyze national trends, outcomes, and patient-specific comorbidities associated with ECTR and OCTR in patients with RA. Methods: A retrospective cohort study was conducted using the PearlDiver database, identifying 683 RA patients undergoing ECTR and 4234 undergoing OCTR between 2010 and 2014. Demographic data, comorbidities, and complication rates were analyzed. Univariate and multivariable analyses assessed differences between the treatment methods. Results:  Patients with RA undergoing ECTR in comparison to OCTR had no significant differences in medical comorbidities such as hypertension, obesity, chronic kidney disease, hypothyroidism and diabetes mellitus. Patients in the ECTR group reported a risk ratio of 1.44 (95%CI: 1.10-1.89, p=0.01) of requiring repeat procedures within 90 days of the initial procedure. Five-year trends in ECTR and OCTR procedures reported a combined annual growth rate of 5.6% and 13.15, respectively. Conclusion: Endoscopic and open approaches to CTR are important considerations in surgical planning. RA and ECTR have previously been identified as independent risk factors for revision CTR. Our study has identified the 90-day risk of repeat procedures to be elevated in the ECTR group in comparison to the OCTR group. Additionally, the growth of OCTR procedures has outpaced the growth of ECTR procedures in the same period, likely in response to the trend of ECTR leading to higher rates of repeat procedures. The need for revision following ECTR in patients with RA could be related to chronic inflammation leading to transverse carpal ligament thickening and concomitant tenosynovitis. Future directions could include further characterization of repeat procedures performed in this subset of patients. 

Keywords: endoscopic treatment of carpal tunnel syndrome, open treatment of carpal tunnel syndrome, rheumatoid arthritis, trends analysis, carpal tunnel syndrome

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Authors: Ishfaq A. Bukhari, Bassem Yousef Sheikh, Abdulrahman Almotrefi, Osama Yousaf, Amer Mahmood

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Olive oil is the primary source of fat in the Mediterranean diet which is associated with a low mortality for cardiovascular disease. Olive oil is rich in monounsaturated fatty acids, and has been reported for variety of beneficial cardiovascular effects including blood pressure lowering, anti-platelet, anti-diabetic and anti-inflammatory effects. Growing number evidences from preclinical and clinical studies have shown that olive oil improves insulin resistance, decrease vessels stiffness and prevent thromboembolism. We evaluated the effects of olive against streptozotocin-induced physiological disorders in the animal models of diabetes and ischemia and reperfusion (I/R)- induced cardiac arrhythmias. Diabetes was induced in male rats with a single intraperitoneal injection of streptozotocin (60 mg/kg), rats were treated for two months with olive oil (1 ml/kg p.o). Control animals received saline. Blood glucose, body weight were monitored every 14 days. At the end of the treatment rats were sacrificed hearts were isolated for mounting on langedorff’s apparatus. The blood glucose and body weight was not significantly different in the control and olive treated animals. The control diabetic animals exhibited 100% incidence of I/R –induced ventricular fibrillation which was reduced to 0% with olive oil, treatment. The duration of ventricular fibrillation reduced from 98.8± 2.3 (control) to 0 seconds in the olive oil treated group. Diltiazem, a calcium channel blocker (1 µm/L) showed similar results and protected the I/R-induced cardiac disorders. The biochemical analysis of the cardiac tissues showed that diabetes and I/R produce marked pathological changes in the cardiomyocytes including decreased glutathione (GSH) and increased oxidative stress (Malondialdehyde; MDA). Pretreatment of animals with olive oil (1 ml/kg p.o) increased GSH and MDA levels. Olive oil also improved the diabetic-induced histopathological changes in the cardiomyocytes. These finding indicates that olive possesses cardiac protective properties. Further studies are under way in our lab to explore the mechanism of the cardio-protective effect of olive oil.

Keywords: diabeties, ischemia-reperfusion, olive oil, rats heart

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Authors: Kalpana Gupta

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Sexually transmitted infections (STIs) are infections that are spread primarily through sexual contact. In our daily practice, we see gonorrhea, chancroid, syphilis, and chlamydial infections that can be cured, as well as HIV, genital herpes, HPV, and hepatitis B infections that cannot be cured but can be managed with available treatments. Many people in India are infected with Sexually transmitted diseases (STDs), and the figures are quite high because of a lack of awareness and communication, as well as a taboo against these diseases. Numerous taboos and associated stigma shape patients’ lives and have a significant impact on health care policies, medical research, and current issues in medical ethics. Current statistics emphasize the importance of delivering sex education to this important demographic promptly. The long-standing tradition of girls marrying very young, especially in rural areas, and often too much older men, causes a slew of STIs. Stigma and HIV have a cyclical relationship; people who experience stigma and discrimination are marginalized and made more vulnerable to HIV/STDs, while those living with HIV are more vulnerable to stigma and discrimination. As urban pressures have grown, so have slums - and they have fast become ideal breeding grounds for STDs. In developed countries, strict laws have been enacted requiring people suffering from STDs to seek immediate treatment as well as contact the health department. Unfortunately, because of the stigma associated with the disease, patients in India are reluctant to reveal the source of infection. With various schemes, India is attempting to promote sex education and awareness. For example, the Ministry of Health and Family Welfare developed the National Adolescent Health Programme (also known as the Rashtriya Kishor Swasthya Karyakram) in partnership with the United Nations Population Fund (UNFPA). Whereas, National AIDS Control Organisation was set up so that every person living with HIV has access to quality care and is treated with dignity and breaking all taboos. It becomes clear that research and healthcare policies will not be effective in assisting patients with STDs unless these "nonscientific" elements are taken into account.

Keywords: sexually transmitted diseases, sexually transmitted infections, taboo, stigma, HIV/STDs, sex education and awareness, treatment, quality care, medications, healthcare policies

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Authors: Arpit Kumar Shrivastava, Subrat Kumar, Rajani Kanta Mohapatra, Priyadarshi Soumyaranjan Sahu

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Computational approaches to predict structure, function and other biological characteristics of proteins are becoming more common in comparison to the traditional methods in drug discovery. Cryptosporidiosis is a major zoonotic diarrheal disease particularly in children, which is caused primarily by Cryptosporidium hominis and Cryptosporidium parvum. Currently, there are no vaccines for cryptosporidiosis and recommended drugs are not effective. With the availability of complete genome sequence of C. hominis, new targets have been recognized for the development of effective and better drugs and/or vaccines. We identified a unique hypothetical epitopic protein in C. hominis genome through BLASTP analysis. A 3D model of the hypothetical protein was generated using I-Tasser server through threading methodology. The quality of the model was validated through Ramachandran plot by PROCHECK server. The functional annotation of the hypothetical protein through DALI server revealed structural similarity with human Transportin 3. Phylogenetic analysis for this hypothetical protein also showed C. hominis hypothetical protein (CUV04613) was the closely related to human transportin 3 protein. The 3D protein model is further subjected to virtual screening study with inhibitors from the Zinc Database by using Dock Blaster software. Docking study reported N-(3-chlorobenzyl) ethane-1,2-diamine as the best inhibitor in terms of docking score. Docking analysis elucidated that Leu 525, Ile 526, Glu 528, Glu 529 are critical residues for ligand–receptor interactions. The molecular dynamic simulation was done to access the reliability of the binding pose of inhibitor and protein complex using GROMACS software at 10ns time point. Trajectories were analyzed at each 2.5 ns time interval, among which, H-bond with LEU-525 and GLY- 530 are significantly present in MD trajectories. Furthermore, antigenic determinants of the protein were determined with the help of DNA Star software. Our study findings showed a great potential in order to provide insights in the development of new drug(s) or vaccine(s) for control as well as prevention of cryptosporidiosis among humans and animals.

Keywords: cryptosporidium hominis, hypothetical protein, molecular docking, molecular dynamics simulation

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Authors: Estelle Démoulin, Dionysios Adamopoulos, Tornike Sologashvili, Mathieu Van Steenberghe, Jalal Jolou, Haran Burri, Christoph Huber, Mustafa Cikirikcioglu

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Background & objective: Mitral valve surgeries are mainly performed by median sternotomy with conventional direct atriotomy. Good exposure to the mitral valve is challenging, especially for acute pathologies, where left atrium dilation does not occur. Other atriotomies, such as transseptal or superior septal, are used as they allow better access and visualization. Peri- and postoperative outcomes of these three different left atriotomies were compared. Methods: Patients undergoing mitral valve surgery between January 2010 and December 2020 were included and divided into three groups: group 1 (conventional direct, n=115), group 2 (transseptal, n=33) and group 3 (superior septal, n=59). To improve the sampling size, all patients underwent mitral valve surgery with or without associated procedures (CABG, aortic-tricuspid surgery, Maze procedure). The study protocol was approved by SwissEthics. Results: No difference was shown for the etiology of mitral valve disease, except endocarditis, which was more frequent in group 3 (p = 0.014). Elective surgeries and isolated mitral valve surgery were more frequent in group 1 (p = 0.008, p = 0.011) and aortic clamping and cardiopulmonary bypass were shorter (p = 0.002, p<0.001). Group 3 had more emergency procedures (p = 0.011) and longer lengths of intensive care unit and hospital stay (p = 0.000, p = 0.003). There was no difference in permanent pacemaker implantation, postoperative complications and mortality between the groups. Conclusion: Mitral valve surgeries can be safely performed using those three left atriotomies. Conventional direct may lead to shorter aortic clamping and cardiopulmonary bypass times. Superior septal is mostly used for acute pathologies, and it does not increase postoperative arrhythmias and permanent pacemaker implantation. However, intensive care unit and hospital lengths of stay were found to be longer in this group. In our opinion, this outcome is more related to the pathology and type of surgery than the incision itself.

Keywords: Mitral valve surgery, cardiac surgery, atriotomy, Operative outcomes

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Authors: M. Shemis, O. Maher, G. Casterou, F. Gauffre

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Hepatitis C virus (HCV) is a major cause of chronic liver disease with a global 170 million chronic carriers at risk of developing liver cirrhosis and/or liver cancer. Egypt reports the highest prevalence of HCV worldwide. Currently, two classes of assays are used in the diagnosis and management of HCV infection. Despite the high sensitivity and specificity of the available diagnostic assays, they are time-consuming, labor-intensive, expensive, and require specialized equipment and highly qualified personal. It is therefore important for clinical and economic terms to develop a low-tech assay for the direct detection of HCV RNA with acceptable sensitivity and specificity, short turnaround time, and cost-effectiveness. Such an assay would be critical to control HCV in developing countries with limited resources and high infection rates, such as Egypt. The unique optical and physical properties of gold nanoparticles (AuNPs) have allowed the use of these nanoparticles in developing simple and rapid colorimetric assays for clinical diagnosis offering higher sensitivity and specificity than current detection techniques. The current research aims to develop a detection assay for HCV RNA using gold nanoparticles (AuNPs). Methods: 200 anti-HCV positive samples and 50 anti-HCV negative plasma samples were collected from Egyptian patients. HCV viral load was quantified using m2000rt (Abbott Molecular Inc., Des Plaines, IL). HCV genotypes were determined using multiplex nested RT- PCR. The assay is based on the aggregation of AuNPs in presence of the target RNA. Aggregation of AuNPs causes a color shift from red to blue. AuNPs were synthesized using citrate reduction method. Different sets of probes within the 5’ UTR conserved region of the HCV genome were designed, grafted on AuNPs and optimized for the efficient detection of HCV RNA. Results: The nano-gold assay could colorimetrically detect HCV RNA down to 125 IU/ml with sensitivity and specificity of 91.1% and 93.8% respectively. The turnaround time of the assay is < 30 min. Conclusions: The assay allows sensitive and rapid detection of HCV RNA and represents an inexpensive and simple point-of-care assay for resource-limited settings.

Keywords: HCV, gold nanoparticles, point of care, viral load

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Authors: Charles Bijjah Nkhata, Memory Nekati Mvula, Milton Masautso Kalongonda, Martha Masamba, Isaac Thom Shawa

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Viral Hepatitis is a serious public health concern globally with deaths estimated at 1.4 million annually due to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatitis B and C are the most common viruses that cause liver damage. However, the majority of infected individuals are unaware of their serostatus. Viral Hepatitis has contributed to maternal and neonatal morbidity and mortality. There is no updated data on the Epidemiology of hepatitis B and C among pregnant mothers in Malawi. To assess the epidemiology of Hepatitis B and C viruses among pregnant women at Queen Elizabeth Central Hospital. Specific Objectives • To determine sero-prevalence of HBsAg and Anti-HCV in pregnant women at QECH. • To investigate risk factors associated with HBV and HCV infection in pregnant women. • To determine the distribution of HBsAg and Anti-HCV infection among pregnant women of different age group. A descriptive cross-sectional study was conducted among pregnant women at QECH in last quarter of 2021. Of the 114 pregnant women, 96 participants were consented and enrolled using a convenient sampling technique. 12 participants were dropped due to various reasons; therefore 84 completed the study. A semi-structured questionnaire was used to collect socio-demographic and behavior characteristics to assess the risk of exposure. Serum was processed from venous blood samples and tested for HBsAg and Anti-HCV markers utilizing Rapid screening assays for screening and Enzyme Linked Immunosorbent Assay for confirmatory. A total of 84 pregnant consenting pregnant women participated in the study, with 1.2% (n=1/84) testing positive for HBsAg and nobody had detectable anti-HCV antibodies. There was no significant link between HBV and HCV in any of the socio-demographic data or putative risk variables. The findings indicate a viral hepatitis prevalence lower than the set range by the WHO. This suggests that HBV and HCV are rare in pregnant women at QECH. Nevertheless, accessible screening for all pregnant women should be provided. The prevention of MTCT is key for reduction and prevention of the global burden of chronic viral Hepatitis.

Keywords: viral hepatitis, hepatitis B, hepatitis C, pregnancy, malawi, liver disease, mother to child transmission

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Authors: Matt S. Van Deren, Michael Papenfus

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Seattle is one of the hundreds of cities in the United States that relies on a combined sewer system to collect and convey municipal wastewater. By design, these systems convey all wastewater, including industrial and commercial wastewater, human sewage, and stormwater runoff, through a single network of pipes. Serious problems arise for combined sewer systems during heavy precipitation events when treatment plants and storage facilities are unable to accommodate the influx of wastewater needing treatment, causing the sewer system to overflow into local waterways through sewer outfalls. CSOs (Combined Sewer Overflows) pose a serious threat to human and environmental health. Principal pollutants found in CSO discharge include microbial pathogens, comprising of bacteria, viruses, parasites, oxygen-depleting substances, suspended solids, chemicals or chemical mixtures, and excess nutrients, primarily nitrogen and phosphorus. While concentrations of these pollutants can vary between overflow events, CSOs have the potential to spread disease and waterborne illnesses, contaminate drinking water supplies, disrupt aquatic life, and effect a waterbody’s designated use. This paper estimates the economic impact of CSOs on residential property values. Using residential property sales data from Seattle, Washington, this paper employs a hedonic valuation model that controls for housing and neighborhood characteristics, as well as spatial and temporal effects, to predict a consumer’s willingness to pay for improved water quality near their homes. Initial results indicate that a 100,000-gallon decrease in the average annual overflow discharged from a sewer outfall within 300 meters of a home is associated with a 0.053% increase in the property’s sale price. For the average home in the sample, the price increase is estimated to be $18,860.23. These findings reveal some of the important economic benefits of improving water quality by reducing the frequency and severity of combined sewer overflows.

Keywords: benefits, hedonic, Seattle, sewer

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Authors: Teris Cheung, Joyce Yuen Ting Lam, Kwan Hin Fong, Calvin Pak-Wing Cheng, Julie Sittlington, Yu-Tao Xiang, Tim Man Ho Li

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Insomnia is one of the most common health problems in the general population. Insomnia can be acute, intermittent, and become chronic, often due to comorbidity with other physical and mental health conditions. Although there are conventional pharmaceutical and psychotherapeutic treatments to treat symptoms of insomnia, however; there is no robust and novel randomized controlled trial (RCT) using transdermal neurostimulation on individuals with insomnia symptoms. This gives us the impetus to execute the first nationwide RCT. Aim: To evaluate the efficacy of Electrical Vestibular Stimulation (VeNS) on individuals with insomnia in Hong Kong. Design: This study was a two-armed, double blinded, randomized, sham-controlled trial. Sampling: 60 community-dwelling adults aged 18 and 60 years with moderate insomnia symptoms or above (Insomnia Severity Index > 14) were recruited. All subjects were computerized randomized into either the active VeNS group or the sham VeNS group on a 1:1 ratio. Intervention: All participants received a home-use VeNS device and used 30-min VeNS sessions during five consecutive days across a 4-week period (total treatment hours: 10). Baseline measurements and post-VeNS evaluation of the psychological outcomes, including 1) insomnia severity, 2) sleep quality, and 3) quality of life were investigated. The short-and long-term sustainability of the VeNS intervention was assessed immediately after poststim and at a 1-month and 3-month follow-up period. Data analysis: A mixed GEE model was used to analyze the repeated measures data. Missing data were managed by multiple imputations. The level of significance was set to p < 0.05. Significance of the study: This is the first trial to examine the efficacy and safety of VeNS among adults with insomnia symptoms in Hong Kong. Findings that emerged were used to determine whether this VeNS device can be considered a self-help technological device to reduce the severity of insomnia in the community setting and to reduce the global disease burden. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT04452981.

Keywords: adults, insomnia, neuromodulation, rct, vestibular stimulation

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Authors: Michely Vargas Delpupo, José Geraldo Romanello Bueno

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The right to basic sanitation, was elevated to the category of fundamental right by the Brazilian Constitution of 1988 to protect the ecologically balanced environment, ensuring social rights to health and adequate housing warranting dignity of the human person as a principle of the Brazilian Democratic State. Because of their essentiality to the Brazilian population, this article seeks to understand why universal access to basic sanitation is a goal so difficult to achieve in Brazil. Therefore, this research uses the deductive and analytical method. Given the nature of the research literature, research techniques were centered in specialized books on the subject, journals, theses and dissertations, laws, relevant law case and raising social indicators relating to the theme. The relevance of the topic stems, among other things, the fact that sanitation services are essential for a dignified life, i.e. everyone is entitled to the maintenance of the necessary existence conditions are satisfied. However, the effectiveness of this right is undermined in society, since Brazil has huge deficit in sanitation services, denying thus a worthy life to most of the population. Thus, it can be seen that the provision of water and sewage services in Brazil is still characterized by a large imbalance, since the municipalities with lower population index have greater disability in the sanitation service. The truth is that the precariousness of water and sewage services in Brazil is still very concentrated in the North and Northeast regions, limiting the effective implementation of the Law 11.445/2007 in the country. Therefore, there is urgent need for a positive service by the State in the provision of sanitation services in order to prevent and control disease, improve quality of life and productivity of individuals, besides preventing contamination of water resources. More than just social and economic necessity, there is even a an obligation of the government to implement such services. In this sense, given the current scenario, to achieve universal access to basic sanitation imposes many hurdles. These are mainly in the field of properly formulated and implemented public policies, i.e. it requires an excellent institutional organization, management services, strategic planning, social control, in order to provide answers to complex challenges.

Keywords: fundamental rights, health, sanitation, universal access

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Authors: Clinton Adas

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Antibiotic resistance has been identified by the World Health Organisation as a real possibility for the 21st Century. While many factors contribute to this, one of the more significant is industrial animal farming and its effect on the food chain and environment. Livestock consumes a significant portion of antibiotics sold globally, and these are used to make animals grow faster for profit purposes, to prevent illness caused by inhumane living conditions, and to treat disease when it breaks out. Many of these antibiotics provide little benefit to animals, and most are the same as those used by humans - including those deemed critical to human health that should therefore be used sparingly. Antibiotic resistance contributes to growing numbers of illnesses and death in humans, and the excess usage of these medications results in waste that enters the environment and is harmful to many ecological processes. This combination of antimicrobial resistance and environmental degradation furthermore harms the economic well-being and prospects of many. Using an interdisciplinary approach including medical, environmental, economic, and legal studies, the paper evaluates the dynamic between animal welfare and commerce and argues that while animal welfare is not of great concern to many, this approach is ultimately harming human welfare too. It is, however, proposed that both could be addressed under a One Health and Welfare approach, as we cannot continue to ignore the linkages between animals, the environment, and people. The evaluation of industrial animal farming is therefore considered through three aspects – the environmental impact, which is measured by pollution that causes environmental degradation; the human impact, which is measured by the rise of illnesses from pollution and antibiotics resistance; and the economic impact, which is measured through costs to the health care system and the financial implications of industrial farming on the economic well-being of many. These three aspects are considered in light of the Sustainable Development Goals that provide additional tangible metrics to evidence the negative impacts. While the research addresses the welfare of farmed animals, there is potential for these principles to be extrapolated into other contexts, including wildlife and habitat protection. It must be noted that while the question of animal rights in industrial animal farming is acknowledged and of importance, this is a separate matter that is not addressed here.

Keywords: animal and human welfare, industrial animal farming, one health and welfare, sustainable development goals

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Authors: Seunghwan Seo, Woo-Seok Lee, Ji-Sun Shin, Young Kyoung Rhee, Chang-Won Cho, Hee-Do Hong, Kyung-Tae Lee

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Doenjang, known as traditional Korean food, is product of a natural mixed fermentation process carried out by lactic acid bacteria (LAB). Lactobacillus sakei K040706 (K040706) has been accepted as the most populous LAB in over ripened doenjang. Recently, we reported the immunostimulatory effects of K040706 in RAW 264.7 macrophages and in a cyclophosphamide-induced mouse model. In this study, we investigated the ameliorative effects of K040706 in a dextran sulfate sodium (DSS)-induced colitis mouse model. We induced colitis using DSS in 5-week-ICR mice over 14 days with or without 0.1, 1 g/kg/day K040706 orally. The body weight, stool consistency, and gross bleeding were recorded for determination of the disease activity index (DAI). At the end of treatment, animals were sacrificed and colonic tissues were collected and subjected to histological experiments and myeloperoxidase (MPO) accumulation, cytokine determination, qRT-PCR and Western blot analysis. Results showed that K040706 significantly attenuated DSS-induced DAI score, shortening of colon length, enlargement of spleen and immune cell infiltrations into colonic tissues. Histological examinations indicated that K040706 suppressed edema, mucosal damage, and the loss of crypts induced by DSS. These results were correlated with the restoration of tight junction protein expression, such as, ZO-1 and occludin in K040706-treated mice. Moreover, K040706 reduced the abnormal secretions and mRNA expressions of pro-inflammatory mediators, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). DSS-induced mRNA expression of intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in colonic tissues was also downregulated by K040706 treatment. Furthermore, K040706 suppressed the protein and mRNA expression of toll-like receptor 4 (TLR4) and phosphorylation of NF-κB and signal transducer and activator of transcription 3 (STAT3). These results suggest that K040706 has an anti-colitic effect by inhibition of intestinal inflammatory responses in DSS-induced colitic mice.

Keywords: Lactobacillus sakei, NF-κB, STAT3, ulcerative colitis

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Authors: Asif Bilal, Fouzia Tanvir, Sibtain Ahmad

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Estrogen receptor alpha, also known as estrogen receptor-1, is highly involved in risk of mammary carcinoma. The objectives of this study were to identify non-synonymous SNPs of estrogen receptor and their association with breast cancer and to identify the chemotherapeutic responses of phytochemicals against it via in-silico study design. For this purpose, different online tools. to identify pathogenic SNPs the tools were SIFT, Polyphen, Polyphen-2, fuNTRp, SNAP2, for finding disease associated SNPs the tools SNP&GO, PhD-SNP, PredictSNP, MAPP, SNAP, MetaSNP, PANTHER, and to check protein stability Mu-Pro, I-Mutant, and CONSURF were used. Post-translational modifications (PTMs) were detected by Musitedeep, Protein secondary structure by SOPMA, protein to protein interaction by STRING, molecular docking by PyRx. Seven SNPs having rsIDs (rs760766066, rs779180038, rs956399300, rs773683317, rs397509428, rs755020320, and rs1131692059) showing mutations on I229T, R243C, Y246H, P336R, Q375H, R394S, and R394H, respectively found to be completely deleterious. The PTMs found were 96 times Glycosylation; 30 times Ubiquitination, a single time Acetylation; and no Hydroxylation and Phosphorylation were found. The protein secondary structure consisted of Alpha helix (Hh) is (28%), Extended strand (Ee) is (21%), Beta turn (Tt) is 7.89% and Random coil (Cc) is (44.11%). Protein-protein interaction analysis revealed that it has strong interaction with Myeloperoxidase, Xanthine dehydrogenase, carboxylesterase 1, Glutathione S-transferase Mu 1, and with estrogen receptors. For molecular docking we used Asiaticoside, Ilekudinuside, Robustoflavone, Irinoticane, Withanolides, and 9-amin0-5 as ligands that extract from phytochemicals and docked with this protein. We found that there was great interaction (from -8.6 to -9.7) of these ligands of phytochemicals at ESR1 wild and two mutants (I229T and R394S). It is concluded that these SNPs found in ESR1 are involved in breast cancer and given phytochemicals are highly helpful against breast cancer as chemotherapeutic agents. Further in vitro and in vivo analysis should be performed to conduct these interactions.

Keywords: breast cancer, ESR1, phytochemicals, molecular docking

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Authors: M. Mirmohammadi, S. Taghdisi, F. Anali

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Gossypol is a yellow anti-nutritional compound found in the cotton plant. This substance exists in the cottonseed and other parts of the cotton plant, such as bark, leaves, and stems. Chemically, gossypol is a very active polyphenolic aldehyde compound, and due to this polyphenolic structure, it has antioxidant and therapeutic properties. On the other hand, this compound, especially in free form, has many toxic effects, that its excessive consumption can be very dangerous for humans and animals. In this study, gossypol was extracted as a derivative compound of gossypol acetic acid from cottonseed using the n-hexane solvent with an efficiency of 0.84 ± 0.04, which compared to the Gossypol extracted from cottonseed oil with the same method (cold press) showed a significant difference with its efficiency of 1.14 ± 0.06. Therefore, it can be suggested to use cottonseed oil to extract this valuable compound. In the other part of this research, cottonseed extracts and cotton bolls extracts were obtained by two methods of soaking and Soxhlet with hydroalcoholic solvent taken with a ratio of (25:75), then by using extracts and corn starch powder, four herbal medicine code was created and after receiving the code of ethics (IR.SSU.REC.1398.136) the therapeutic effect of each one on the Cutaneous leishmaniasis resistant to drugs (caused by the leishmaniasis parasite) was investigated in real patients and its results was compared with the common drug glucantime (local ampoule) (n = 36). Statistical studies showed that the use of herbal medicines prepared with cottonseed extract and cotton bolls extract has a significant positive effect on the treatment of the disease’s wounds (p-value > 0.05) compared to the control group (only ethanol). Also, by comparing the average diameter of the wounds after a two-month treatment period, no significant difference was found between the use of ointment containing extracts and local glucantime ampoules (p-value < 0.05). Bolls extract extracted with the Soxhlet method showed the best therapeutic effects, although there was no significant difference between them (p-value < 0.05). Therefore, there is acceptable reliability to recommend this medicine for the treatment of Cutaneous leishmaniasis resistant to drugs without the side effects of the chemical drug glucantime and the pain of injecting the ampoule.

Keywords: cottonseed oil, gossypol, cotton boll, cutaneous leishmaniasis

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Authors: Muhammad Asif Syed, Mirza Amir Baig

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Background: Pakistan is one of the two remaining polio-endemic countries, posing a significant public health challenge for global polio eradication due to failure to interrupt polio transmission. Country specific seroprevalence studies help in the evaluation of immunization program performance, the susceptibility of population against polio virus and identification of existing level of immunity with factors that affect seroconversion of the oral polio vaccine (OPV). The objective of the study was to find out factors associated with seroconversion of the OPV among children 6-59 months in Pakistan. Methods: A Hospital based cross-sectional serosurvey was undertaken in May-June 2015 at District Mirpurkhas, Sindh-Pakistan. Total 180 children aged 6–59 months were selected by using systematic random sampling from Muhammad Medical College Hospital, Mirpurkhas. Demographic, vaccination history and risk factors information were collected from the parents/guardian. Blood sample was collected and tested for the detection of poliovirus IgG antibodies by using ELISA Kit. The IgG titer <10 IU/ml, 50 to <150 IU/ml and >150 IU/ml was defined as negative, weak positive and positive immunity respectively. Pearson Chi-square test was used to determine the difference in seroprevalence in univariate analysis. Results: A total of 180 subjects were enrolled mean age was 23 months (7 -59 months). Off these 160 (89%) children were well and 18 (10%) partially protected against polio virus. Two (1.1%) children had no protection against polio virus as they had <10 IU/ml poliovirus IgG antibodies titer. Both negative cases belong from the female gender, age group 12-23 months, urban area and BMI <50 percentile. There was a difference between normal and the wasting children; it did attain statistical significance (χ2= 35.5, p=0.00). The difference in seroconversion was also observed in relation to the gender (χ2=6.23, p=0.04), duration of breast feeding (χ2=18.6, p=0.04), history of diarrheal disease before polio vaccine administration (χ2=7.7, p=0.02), and stunting (χ2= 114, p=0.00). Conclusion: This study demonstrated that near 90% children achieve seroconversion of OPV and well protected against polio virus. There is an urgent need to focus on factors like duration of breast feeding, diarrheal diseases and malnutrition (acute and chronic) among the children as an immunization strategy.

Keywords: seroconversion, oral polio vaccine, Polio, Pakistan

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Authors: Mohammad Javad Mehrabanpour, Mohammad Hosein Hosseini, Ali Shirazi, Dorsa Mehrabanpour

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Respiratory infections are the most important diseases that affect poultry. Ornithobacterium rhinotracheale is a bacterium that causes respiratory infections including alveolar inflation and pneumonia in birds. The aim of this study was to evaluated antibody titer against Ornitobacterium rhinotracheal in layer chicken sera after vaccination with an experimental ORT vaccine that produced in Razi Vaccine and Serum Research Institute. Cultured bacteria were inactivated by formalin, and controlled tests were conducted on it. The obtained antigens were formulated using Montanide oil and were homogenized using homogenizer. Eighty SPF chickens were kept until the age of 14 days under existing standards for temperature, humidity, and light. At the age of 14 days, chickens were divided into 3 groups. The first group included 50 chickens injected with prepared ORT vaccine, the second group, as control group, included 15 chickens injected with sterile PBS to get stress of infection and the third group included 15 chickens with no injection performed to them. All 3 groups were kept in separate cages at same room. Blood samples were regularly taken from the chickens every week for serum separation and evaluation of antibody titer. During the fifth week post vaccination, booster vaccine was injected into the chickens of vaccinated group. The chickens were inspected every day in terms of mortality as well as any injection site reactions. Three weeks after the booster injection, blood samples were taken from all chickens of all groups, and sera were isolated. The sera of immunized (vaccinated) SPF chickens with ORT vaccine as well as that of SPF chickens in the control groups were reviewed according to the recommendations of ELISA kit manufacturer to examine the chicken’s humeral immune response to the studied vaccine. Potency, stability and sterility tests were also performed on the above mentioned vaccine. Results obtained indicate high antibody titer in sera of chickens vaccinated with experimental ORT vaccine as compared with the control groups that emphasize the ability of experimentally prepared ORT vaccine to stimulate humoral immune response of chicken. After the second injection, antibody titer increased and remained almost stable up to 9 weeks after the injection. ORT vaccine can cause potency in chickens and can protect them against disease.

Keywords: antibody, layer chicken, Ornithobactrium rhinotracitis, vaccine

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Authors: Pampita Chakraborty, Sukumar Mukherjee

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People with diabetes mellitus are more susceptible to developing infections, as high blood sugar levels can weaken the patient's immune system defences. People with diabetes are more adversely affected when they get an infection than someone without the disease, because you have weakened immune defences in diabetes. People who have minimally elevated blood sugar levels experience worse outcomes with infections. Diabetic patients in hospitals do not necessarily have a higher mortality rate due to infections, but they do face longer hospitalisation and recovery times. A study was done in a tertiary care unit in eastern India. Patients with type 2 diabetes mellitus infection were recruited in the study. A total of 520 cases of Type 2 Diabetes Mellitus were recorded out of which 200 infectious cases was included in the study. All subjects underwent detailed history & clinical examination. Microbiological samples were collected from respective site of the infection for microbial culture and antibiotic sensitivity test. Out of the 200 infectious cases urinary tract infection(UTI) was found in majority of the cases followed by diabetic foot ulcer (DFU), respiratory tract infection(RTI) and sepsis. It was observed that Escherichia coli was the most commonest pathogen isolated from UTI cases and Staphylococcus aureus was predominant in foot ulcers followed by other organisms. Klebsiella pneumonia was the major organism isolated from RTI and Enterobacter aerogenes was commonly observed in patients with sepsis. Isolated bacteria showed differential sensitivity pattern against commonly used antibiotics. The majority of the isolates were resistant to several antibiotics that are usually prescribed on an empirical basis. These observations are important, especially for patient management and the development of antibiotic treatment guidelines. It is recommended that diabetic patients receive pneumococcal and influenza vaccine annually to reduce morbidity and mortality. Appropriate usage of antibiotics based on local antibiogram pattern can certainly help the clinician in reducing the burden of infections.

Keywords: antimicrobial resistance, diabetic foot ulcer, respiratory tract infection, urinary tract infection

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Authors: Michael P. Mannino, Gerald W. Hart

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The majority of glucose metabolism proceeds through glycolytic pathways such as glycolysis or pentose phosphate pathway, however, about 5% is shunted through the hexosamine biosynthetic pathway, producing uridine diphosphate N-acetyl glucosamine (UDP-GlcNAc). This precursor can then be incorporated into complex oligosaccharides decorating the cell surface or remain as an intracellular post-translational-modification (PTM) of serine/threonine residues (O-GlcNAcylation, OGN), which has been identified on over 4,000 cytosolic or nuclear proteins. Intracellular OGN has major implications on cellularprocesses, typically by modulating protein localization, protein-protein interactions, protein degradation, and gene expression. Additionally, OGN is known to have an extensive cross-talk with phosphorylation, be in a competitive or cooperative manner. Unlike other PTMs there are only two cycling enzymes that are capable of adding or removing the GlcNAc moiety, O-linked N-aceytl glucosamine Transferase (OGT) and O-linked N-acetyl glucoamidase (OGA), respectively. The activity of OGT has been shown to be sensitive to cellular UDP-GlcNAc levels, even changing substrate affinity. Owing to this and that the concentration of UDP-GlcNAc is related to the metabolisms of glucose, amino acid, fatty acid, and nucleotides, O-GlcNAc is often referred to as a nutrient sensing rheostat. Indeed OGN is known to regulate several signaling pathways as a result of nutrient levels, such as insulin signaling. Dysregulation of OGN is associated with several disease states such as cancer, diabetes, and neurodegeneration. Improvements in glycomics over the past 10-15 years has significantly increased the OGT substrate pool, suggesting O-GlcNAc’s involvement in a wide variety of signaling pathways. However, O-GlcNAc’s role at the receptor level has only been identified in a case-by-case basis of known pathways. Examining the OGN of the plasma membrane (PM) may better focus our understanding of O-GlcNAc-effected signaling pathways. In this current study, PM fractions were isolated from several cell types via ultracentrifugation, followed by purification and MS/MS analysis in several cell lines. This process was repeated with or without OGT/OGA inhibitors or with increased/decreased glucose levels in media to ascertain the importance of OGN. Various pathways are followed up on in more detailed studies employing methods to localize OGN at the PM specifically.

Keywords: GlcNAc, nutrient sensitive, post-translational-modification, receptor

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Authors: Vincenzo Piemonte

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The liver is a complex, large-scale biochemical reactor which plays a unique role in the human physiology. When liver ceases to perform its physiological activity, a functional replacement is required. Actually, liver transplantation is the only clinically effective method of treating severe liver disease. Anyway, the aforementioned therapeutic approach is hampered by the disparity between organ availability and the number of patients on the waiting list. In order to overcome this critical issue, research activities focused on liver support device systems (LSDs) designed to bridging patients to transplantation or to keep them alive until the recovery of native liver function. In recirculating albumin dialysis devices, such as MARS (Molecular Adsorbed Recirculating System), adsorption is one of the fundamental steps in albumin-dialysate regeneration. Among the albumin-bound toxins that must be removed from blood during liver-failure therapy, bilirubin and tryptophan can be considered as representative of two different toxin classes. The first one, not water soluble at physiological blood pH and strongly bounded to albumin, the second one, loosely albumin bound and partially water soluble at pH 7.4. Fixed bed units are normally used for this task, and the design of such units requires information both on toxin adsorption equilibrium and kinetics. The most common adsorptive media used in LSDs are activated carbon, non-ionic polymeric resins and anionic resins. In this paper, bilirubin adsorption isotherms on different adsorptive media, such as polymeric resin, albumin-coated resin, anionic resin, activated carbon and alginate beads with entrapped albumin are presented. By comparing all the results, it can be stated that the adsorption capacity for bilirubin of the five different media increases in the following order: Alginate beads < Polymeric resin < Albumin-coated resin < Activated carbon < Anionic resin. The main focus of this paper is to provide useful guidelines for the optimization of liver support devices which implement adsorption columns to remove albumin-bound toxins from albumin dialysate solutions.

Keywords: adsorptive media, adsorption equilibrium, artificial liver devices, bilirubin, mathematical modelling

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Authors: Joana Gato, Ahmed Abotabekh, Panayoti Bachkangi

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Introduction: Oestrogen is an essential gonadal hormone that plays a vital role in the reproductive system of women1. The average age of menopause in the UK is 512. Women who go through premature menopause should be offered Hormone replacement therapy (HRT). Similarly, women who undergo surgical menopause should be offered HRT, unless contraindicated, depending on the indication of their surgery2,3. Aim: To assess if the patients in our department are counselled regarding HRT after surgical treatment and if HRT was prescribed. Methodology: A retrospective audit in a busy district hospital, examining all the patients who had a hysterectomy. The audit examined if HRT was discussed pre-operatively, prescribed on discharge and if a follow up was arranged. For women with contraindication to HRT, the audit assessed if the reasons were discussed pre-operatively and communicated to the Inclusion criteria: woman having a total or subtotal hysterectomy, with or without bilateral salpingo-ophorectomy (BSO), between April and September 2022. Exclusion criteria: woman having a vaginal hysterectomy. Results: 40 patients in total had hysterectomy; 27 (68%) were under the age of 51. 15 out of 27 patients bad BSO. 9 women were prescribed HRT, but 8 were offered HRT immediately, and 1 of them were offered a follow up. Of women who underwent surgical menopause, 7 were not given any HRT. The HRT choice was diverse, however, the majority was prescribed oral HRT. 40% of women undergoing surgical menopause did not have a discussion about HRT prior to their surgery. In postmenopausal women (n=13; 33%), still two were given HRT for preexisting menopausal symptoms. Discussion: Only 59% of the pre-menopausal patients had oophorectomy, therefore undergoing surgical menopause. Of these, 44% were not given any HRT, and 40% had no discussion about HRT prior to surgery. Interestingly, the majority of these women have no obvious contraindication to HRT. The choice of HRT was diverse, but the majority was commenced on oral HRT. Our unit is still working towards meeting all the NICE guidance standards of offering HRT and information prior to surgery to women planning to undergo surgical menopause. Conclusion: Starting HRT at the onset of menopause has been shown to improve quality of life and reduce the risk of cardiovascular disease and osteoporotic fractures4. Our unit still has scope for improvement to comply with the current NICE guidance. All pre-menopausal women undergoing surgical menopause should have a discussion regarding HRT prior to surgery and be offered it if there are no contraindications. This discussion should be clearly documented in the notes. At the time of this report, some of the patients have not yet had a follow up, which we recognize as a limitation to our audit.

Keywords: hormone replacement therapy, menopause, premature ovarian insufficiency, surgical management

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