Search results for: HIV drug regimen

Authors: K. K. Balavenkatraman, B. Bertschi, K. Bigot, A. Grevot, A. Doelemeyer, S. D. Chibout, A. Wolf, F. Pognan, N. Manevski, O. Kretz, P. Swart, K. Litherland, J. Ashton-Chess, B. Ling, R. Wettstein, D. J. Schaefer

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Skin toxicity is poorly detected during preclinical studies, and drug-induced side effects in humans such as rashes, hyperplasia or more serious events like bullous pemphigus or toxic epidermal necrolysis represent an important hurdle for clinical development. In vitro keratinocyte-based epidermal skin models are suitable for the detection of chemical-induced irritancy, but do not recapitulate the biological complexity of full skin and fail to detect potential serious side-effects. Normal healthy skin explants may represent a valuable complementary tool, having the advantage of retaining the full skin architecture and the resident immune cell diversity. This study investigated several conditions for the maintenance of good morphological structure after several days of culture and the retention of phase II metabolism for 24 hours in skin explants in vitro. Human skin samples were collected with informed consent from patients undergoing plastic surgery and immediately transferred and processed in our laboratory by removing the underlying dermal fat. Punch biopsies of 4 mm diameter were cultured in an air-liquid interface using transwell filters. Different cultural conditions such as the effect of calcium, temperature and cultivation media were tested for a period of 14 days and explants were histologically examined after Hematoxylin and Eosin staining. Our results demonstrated that the use of Williams E Medium at 32°C maintained the physiological integrity of the skin for approximately one week. Upon prolonged incubation, the upper layers of the epidermis become thickened and some dead cells are present. Interestingly, these effects were prevented by addition of EGFR inhibitors such as Afatinib or Erlotinib. Phase II metabolism of the skin such as glucuronidation (4-methyl umbeliferone), sulfation (minoxidil), N-acetyltransferase (p-toluidene), catechol methylation (2,3-dehydroxy naphthalene), and glutathione conjugation (chlorodinitro benzene) were analyzed by using LCMS. Our results demonstrated that the human skin explants possess metabolic activity for a period of at least 24 hours for all the substrates tested. A time course for glucuronidation with 4-methyl umbeliferone was performed and a linear correlation was obtained over a period of 24 hours. Longer-term culture studies will indicate the possible evolution of such metabolic activities. In summary, these results demonstrate that human skin explants maintain a normal structure for several days in vitro and are metabolically active for at least the first 24 hours. Hence, with further characterisation, this model may be suitable for the study of drug-induced toxicity.

Keywords: human skin explant, phase II metabolism, epidermal growth factor receptor, toxicity

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Authors: Aly Kassem, Eman Sapet, Eman Abdelbaset, Hosam Mahmoud

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Objective: Hypertension is an important public health challenge being one of the most common worldwide disease-affecting human. Our aim is to study the clinical characteristics, therapeutic regimens, treatment compliance, and risk factors in a sector of of hypertensive patients at Sohag City. Subject and Methods: A cross sectional study; conducted in Sohag city; it involved 520 patients; males (45.7 %) and females (54.3 %). Their ages ranged between 35-85 years. BP measurements, BMI, blood glucose, Serum creatinine, urine analysis, serum Lipids, blood picture and ECG were done all the studied patients. Results: Hypertension presented more between non-smokers (72.55%), females (54.3%), educated patients (50.99%) and patients with low SES (54.9%). CAD presented in (51.63%) of patients, while laboratory investigations showed hyperglycaemia in (28.7%), anemia in (18.3%), high serum creatinine level in (8.49%) and proteinuria in (10.45%) of patient. Adequate BP control was achieved in (49.67%); older patients had lower adequacy of BP control in spite of the extensive use of multiple-drug therapy. Most hypertensive patients had more than one coexistent CV risk factor. Aging, being a female (54.3%), DM (32.3%), family history of hypertension (28.7%), family history of CAD (25.4%), and obesity (10%) were the common contributing risk factors. ACE-inhibitors were prescribed in (58.16%), Beta-blockers in (34.64%) of the patients. Monotherapy was prescribed for (41.17%) of the patients. (75.81%) of patients had regular use of their drug regimens. (49.67%) only of patients had their condition under control, the number of drugs was inversely related to BP control. Conclusion: Hypertensive patients in Sohag city had a profile of high CV risks, and poor blood pressure control particularly in the elderly. A multidisciplinary approach for routine clinical check-up, follow-up, physicians and patients training, prescribing simple once-daily regimens and encouraging life style modifications are recommended. Anti hypertensives, hypertension, elderly patients, risk factors, treatment compliance.

Keywords: anti hypertensives, hypertension, elderly patients, risk factors, treatment compliance

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Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

Abstract:

Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential Cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L were in-silico screened using molecular docking, pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect towards the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interactions stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries towards the rational development of potent anti-Alzheimer agents.

Keywords: alzheimer’s disease, molecular docking, cannabis sativa l, cholinesterase inhibitors

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Authors: Shanakr Bhattarai, V. S. Tiwari, Barak Akabayov

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The plummeting number of infections and death is due to the development of drug-resistant bacteria. In addition, the number of approved antibiotic drugs by the Food and Drug Administration (FDA) is insufficient. Therefore, developing new drugs and finding novel targets for central metabolic pathways in bacteria is urgently needed. One of the promising targets is DNA replication machinery which consists of many essential proteins and enzymes. DnaG primase is an essential enzyme and a central part of the DNA replication machinery. DnaG primase synthesizes short RNA primers that initiate the Okazaki fragments by the lagging strand DNA polymerase. Therefore, it is reasonable to assume that inhibition of primase activity will stall DNA replication and prevent bacterial proliferation. We did the expression and purification of eight different bacterial DnaGs (Mycobacterium tuberculosis(Mtb), Bacillus anthracis (Ba), Mycobacterium smegmatis (Msmeg), Francisella tularencis (Ft), Vibrio cholerae (Vc) and Yersinia pestis (Yp), Staphylococcus aureus(Saureus), Escherichia coli(Ecoli)) followed by the radioactive activity assay. After obtaining the pure and active protein DnaG, we synthesized the inhibitors for them. The inhibitors were divided into five different groups, each containing five molecules, and the cocktail inhibition assay was performed against each DnaGs. The groups of molecules inhibiting the DnaGs were further tested with individual molecules belonging to inhibiting groups. Each molecule showing inhibition was titrated against the corresponding DnaGs to find IC50. We got a molecule(VS167) that acted as broad inhibitors, inhibiting all eight DnaGs. Molecules VS180 and VS186 inhibited seven DnaGs (except Saureus). Similarly, two molecules(VS 173, VS176) inhibited five DnaGs (Mtb, Ba, Ft, Yp, Ecoli). VS261 inhibited four DnaGs (Mtb, Ba, Ft, Vc). MS50 inhibited Ba and Vc DnaGs. And some of the inhibitors inhibited only one DnaGs. Thus we found the broad and specific inhibitors for different bacterial DnaGs, and their Structure-activity analysis(SAR) was done. Further, We tried to explain the similarities among the enzyme DnaGs from different bacteria based on their inhibition pattern.

Keywords: DNA replication, DnaG, okazaki fragments, antibiotic drugs

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Authors: Julie Connelly, Tanvi Toprani, Xin Xie, Dhinoth Kumar Bangarusamy, Kris C. Gunsalus

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The overuse of antibiotics worldwide has contributed to the development of multi-drug resistant (MDR) pathogenic bacterial strains. There is an increasing urgency to discover antibiotics to combat MDR pathogens. The microbiome of the Arabian Gulf is a largely unexplored and potentially rich source of novel bioactive compounds. Microbes that inhabit the Abu Dhabi coastal regions adapt to extreme environments with high salinity, hot temperatures, large temperature fluctuations, and acute exposure to solar energy. The microbes native to this region may produce unique metabolites with therapeutic potential as antibiotics and antifungals. We have isolated 200 pure bacterial strains from mangrove sediments, cyanobacterial mats, and coral reefs of the Abu Dhabi region. In this project, we aim to screen the marine bacterial strains to identify antibiotics, in particular undocumented compounds that show activity against existing antibiotic-resistant strains. We have acquired the ESKAPE pathogen panel, which consists of six antibiotic-resistant gram-positive and gram-negative bacterial pathogens that collectively cause most clinical infections. Our initial efforts of the primary screen using colony-picking co-culture assay have identified several candidate marine strains producing potential antibiotic compounds. We will next apply different assays, including disk-diffusion and broth turbidity growth assay, to confirm the results. This will be followed by bioactivity-guided purification and characterization of target compounds from the scaled-up volume of candidate strains, including SPE fraction, HPLC fraction, LC-MS, and NMR. For antimicrobial compounds with unknown structures, our final goal is to investigate their mode of action by identifying the molecular target.

Keywords: marine bacteria, natural products, drug discovery, ESKAPE panel

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Authors: Mouna Baassi, Mohamed Moussaoui, Sanchaita Rajkhowa, Hatim Soufi, Said Belaaouad

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The objective of this paper is to address the challenging task of targeting Human Immunodeficiency Virus type 1 Reverse Transcriptase (HIV-1 RT) in the treatment of AIDS. Reverse Transcriptase inhibitors (RTIs) have limitations due to the development of Reverse Transcriptase mutations that lead to treatment resistance. In this study, a combination of statistical analysis and bioinformatics tools was adopted to develop a mathematical model that relates the structure of compounds to their inhibitory activities against HIV-1 Reverse Transcriptase. Our approach was based on a series of compounds recognized for their HIV-1 RT enzymatic inhibitory activities. These compounds were designed via software, with their descriptors computed using multiple tools. The most statistically promising model was chosen, and its domain of application was ascertained. Furthermore, compounds exhibiting comparable biological activity to existing drugs were identified as potential inhibitors of HIV-1 RT. The compounds underwent evaluation based on their chemical absorption, distribution, metabolism, excretion, toxicity properties, and adherence to Lipinski's rule. Molecular docking techniques were employed to examine the interaction between the Reverse Transcriptase (Wild Type and Mutant Type) and the ligands, including a known drug available in the market. Molecular dynamics simulations were also conducted to assess the stability of the RT-ligand complexes. Our results reveal some of the new compounds as promising candidates for effectively inhibiting HIV-1 Reverse Transcriptase, matching the potency of the established drug. This necessitates further experimental validation. This study, beyond its immediate results, provides a methodological foundation for future endeavors aiming to discover and design new inhibitors targeting HIV-1 Reverse Transcriptase.

Keywords: QSAR, ADMET properties, molecular docking, molecular dynamics simulation, reverse transcriptase inhibitors, HIV type 1

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Authors: Parimalakrishnan Sundararjan, Madheswaran Murugan, Dhanya Dharman, Yatindra Kumar, Sudhir Singh Gangwar, Guru Prasad Mohanta

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Antibiotic resistance AR is a global issue, India started to redress the issues of antibiotic resistance late and it plans to have: active surveillance of microbial resistance and promote appropriate use of antibiotics. The present study attempted to achieve appropriate use of antibiotics through pharmacists’ intervention at practice point. In a quasi-experimental prospective cohort study, the cases with bacteremia from four hospitals were identified during 2015 and 2016 for intervention. The pharmacists centered intervention: active screening of each prescription and comparing with the selection of antibiotics with susceptibility of the bacteria. Wherever irrationality noticed, it was brought to the notice of the treating physician for making changes. There were two groups: intervention group and control group without intervention. The active screening and intervention in 915 patients has reduced therapeutic regimen time in patients with bacteremia. The intervention group showed the decreased duration of hospital stay 3.4 days from 5.1 days. Further, multivariate modeling of patients who were in control group showed that patients in the intervention group had a significant decrease in both duration of hospital stay and infection-related mortality. Unlike developed countries, pharmacists are not active partners in patient care in India. This unique attempt of pharmacist’ invention was planned in consultation with hospital authorities which proved beneficial in terms of reducing the duration of treatment, hospital stay, and infection-related mortality. This establishes the need for a collaborative decision making among the health workforce in patient care at least for promoting rational use of antibiotics, an attempt to combat resistance.

Keywords: antibiotics resistance, intervention, bacteremia, multivariate modeling

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Authors: Haftay Abraha Tadesse

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Background: Staphylococcus is a genus of worldwide distributed bacteria correlated to several infectious of different sites in humans and animals. They are among the most important causes of infection that are associated with the consumption of contaminated food. Objective: The objective of this study was to determine the isolates, antimicrobial susceptibility patterns and Public Health Significance of Staphylococcus aureus in raw meat from butchery and abattoir houses of Mekelle, Northern Ethiopia. Methodology: A cross-sectional study was conducted from April to October 2019. Socio-demographic data and Public Health Significance were collected using a predesigned questionnaire. The raw meat samples were collected aseptically in the butchery and abattoir houses and transported using an ice box to Mekelle University, College of Veterinary Sciences, for isolating and identification of Staphylococcus aureus. Antimicrobial susceptibility tests were determined by the disc diffusion method. Data obtained were cleaned and entered into STATA 22.0 and a logistic regression model with odds ratio was calculated to assess the association of risk factors with bacterial contamination. A P-value < 0.05 was considered statistically significant. Results: In the present study, 88 out of 250 (35.2%) were found to be contaminated with Staphylococcus aureus. Among the raw meat specimens, the positivity rate of Staphylococcus aureus was 37.6% (n=47) and (32.8% (n=41), butchery and abattoir houses, respectively. Among the associated risks, factories not using gloves reduces risk was found to (AOR=0.222; 95% CI: 0.104-0.473), Strict Separation b/n clean & dirty (AOR= 1.37; 95% CI: 0.66-2.86) and poor habit of hand washing (AOR=1.08; 95%CI: 0.35 3.35) was found to be statistically significant and have associated with Staphylococcus aureus contamination. All isolates of thirty-seven of Staphylococcus aureus were checked and displayed (100%) sensitive to doxycycline, trimethoprim, gentamicin, sulphamethoxazole, amikacin, CN, Co trimoxazole and nitrofurantoi. Whereas the showed resistance to cefotaxime (100%), ampicillin (87.5%), Penicillin (75%), B (75%), and nalidixic acid (50%) from butchery houses. On the other hand, all isolates of Staphylococcus aureus isolate 100% (n= 10) showed sensitive chloramphenicol, gentamicin and nitrofurantoin, whereas they showed 100% resistance of Penicillin, B, AMX, ceftriaxone, ampicillin and cefotaxime from abattoirs houses. The overall multi-drug resistance pattern for Staphylococcus aureus was 90% and 100% of butchery and abattoir houses, respectively. Conclusion: 35.3% Staphylococcus aureus isolated were recovered from the raw meat samples collected from the butchery and abattoirs houses. More has to be done in the development of hand washing behavior and availability of safe water in the butchery houses to reduce the burden of bacterial contamination. The results of the present finding highlight the need to implement protective measures against the levels of food contamination and alternative drug options. The development of antimicrobial resistance is nearly always a result of repeated therapeutic and/or indiscriminate use of them. Regular antimicrobial sensitivity testing helps to select effective antibiotics and to reduce the problems of drug resistance development towards commonly used antibiotics.

Keywords: abattoir house, AMR, butchery house, S. aureus

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Authors: Sadhana Sharma, Neha Sharma, Hardik Khandelwal, Arti Sharma

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Background: It is widely acknowledged globally that parents must advocate for their children's drug and substance abuse prevention. However, many parents find it difficult to advocate due to systemic and logistical barriers. Alternatives to introducing advocacy, awareness, and support for the prevention of drug and substance abuse to children could occur in schools. However, little research has been conducted on the development of advocates for substance abuse in school settings. Objective: to evaluate the effectiveness of a school-based addiction prevention and control created as part of the Rajasthan Addiction Prevention Project (a partnership between state-community initiative). Methods: We conducted an evaluation in this study to determine the impact of a RAPP on a primary outcome (substance abuse knowledge) and other outcomes (family–school partnership, empowerment, and support). Specifically, between September-December 2022, two schools participated in the intervention group (advocacy training), and two schools participated in the control group (waiting list). The RAPP designed specialised 2-hrs training to equip teachers-parents with the knowledge and skills necessary to advocate for their own children and those of other families. All participants were required to complete a pre- and post-survey. Results: The intervention group established school advocates in schools where trained parents volunteered to lead support groups for high-risk children. Compared to the participants in the wait list control group, those in the intervention group demonstrated greater education knowledge, P = 0.002, and self-mastery, P = 0.04, and decreased family–school partnership quality, P = 0.002.Conclusions: The experimental evaluation of school-based advocacy programme revealed positive effects on substance abuse that persist over time. The approach wa s deemed feasible and acceptable by both parents and the school.

Keywords: prevention, school based, addiction, advocacy

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Authors: Mohammad Ranjbar, Mohammad Bazyar, Blake Angell, Thomas Lung, Yibeltal Assefa

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Background: Current health insurance programs in Iran suffer from low enrolment and are not sufficient to attain the country to universal health coverage (UHC). We hypothesize that improving the enrollment rate and moving towards a more sustainable UHC can be achieved by improving the benefits package and providing new incentives. The objective of this study is to assess public preferences and willingness to pay (WTP) for social health insurance (SHI) in Iran. Methods: A discrete choice experiment (DCE) was conducted in 2021, using a self-administered questionnaire on 500 participants to estimate WTP and determine individual preferences for the SHI in Yazd, Iran. Respondents were presented with an eight-choice set and asked to select their preferred one. In each choice set, scenarios were described by eight attributes with varying levels. The conditional logit regression model was used to analyze the participants' preferences. Willingness to pay for each attribute was also calculated. Results: Most included attributes were significant predictors of the choice of a health insurance package. The maximum coverage of hospitalization costs in the private sector, ancillary services such as glasses, canes, etc., as well as coverage for hospitalization costs in the public sector and drug costs, were the most important determining factors for this choice. Coverage of preventive dental care did not significantly influence respondent choices. Estimating WTP showed that individuals are willing to pay more for higher financial protection, particularly against private sector costs; the WTP to increase the coverage of hospitalization costs in the private sector from 50% to 90% is estimated at 362,068 IR, Rials per month. Conclusion: This study identifies the key factors that the population value with regard to health insurance and the tradeoffs they are willing to make between them. Hospitalization, drugs, and ancillary services were the most important determining factors for their choice. The data suggest that additional resources coming into the Iranian health system might best be prioritized to cover hospitalization and drug costs and those associated with ancillary services.

Keywords: social health insurance, preferences, discrete choice experiment, willingness to pay

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Authors: Noshaba Dilbar, Hina Ashraf

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Medicinal plants are considered as rich source of ingredients which can be used in drug development and synthesis. Moreover, these plants play a vital role in the development of human culture of using ayurvedic medicines around the whole world. Among all plants, dessert plants are being proved as effective source of ayurvedic medicines and remedy against many diseases. Considering the fact, two plant species Limium indicum and Euphorbia granulata were taken from Cholistan dessert of Bahawalpur, Pakistan. Firstly, phytochemical screening was done by making dry and fresh plant extracts in five different solvents i.e Petroleum ether, benzene, chloroform, ethanol and methanol. Standard confirmation tests for all compounds were applied for analysis. Results revealed the presence of high range of bioactive compounds such as alakaloids, terpenoids, glycosides, steroids, flavonoids, saponins, phytosterols, oxalic acid, anthocyanin and quinone in both plants. Best results were obtained by methanolic, chloroform and petroleum ether extracts and methanolic, ethanolic and benzene extracts of Limium indicum and Euphorbia granulate respectively. Considering the results, methanolic extracts of both plants were further analysed for antibacterial activity. Plants were analysed against four pathogens including Escherchia coli, Proteus vulgaris, Klebsiella pneumonia and Pseudomonas aruginosa using disc diffusion method. Limium indicum showed highly significant activity against all pathogens while Euphorbia granulata showed significant activity against Klebsiella pneumonia and Proteus vulgaris but lesser against Escherchia coli and Pseudomonas aruginosa. MIC of extracts against each positive bacterium was calculated and recorded. Present plants can be considered for making useful drugs but further studies are needed to isolate active agents from plant extracts for drug development.

Keywords: antibacterial activity, Euphorbia granulata, Limium indicum, medicinal plants, phytochemical screening

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Authors: Kushal Patel, Manasa Dittakavi, Cyrus Falsafi, Gretchen Lovett

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Rural America has seen a surge in opioid addiction rates and overdose deaths in recent years, becoming a significant public health crisis. This may be due to a variety of factors, such as lack of access to healthcare or other economic and social factors that can contribute to addiction such as poverty, unemployment, and social isolation. As the opioid epidemic has disproportionately affected rural communities, pregnant women in these areas may be highly susceptible and face additional difficulties in facing the appropriate care they need. Opioid use disorder has many negative effects on prenatal infants. These include changes in their microbiome, mental health, neurodevelopment and cognition. These can affect how the child performs in various activities in life and how they interact with others. It has been demonstrated that using cognitive behavioral therapy improves not just pain-related results but also mobility, quality of life, disability, and mood outcomes. This indicates that cognitive behavioral therapy (CBT) may be a useful therapeutic strategy for enhancing general health and wellbeing in people with opioid use problems. In terms of treating psychiatric diseases, CBT carries fewer dangers than opioids. One study that illustrates the potential for CBT to promote a reduction in opioid use disorder used self-reported drug use patterns 6 months prior to and during their pregnancy. At the beginning of the study, participants reported an average of 3.78 drug or alcohol use days in the previous 28 days, which decreased to 1.63 days after treatment. The study also found a decrease in depression scores, as measured by IDS scores, from 23.9 to 17.1 at the end of treatment. These and other results show that CBT can have meaningful impacts on pregnant women in Rural America who struggle with an opioid use disorder. This project has been approved by the West Virginia School of Osteopathic Medicine- Office of Research and Sponsored Programs and deemed non-research scholarly work.

Keywords: appalachia, CBT, opiods, pregnancy

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Authors: Malay K. Das, Bhupen Kalita

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The poor oral bioavailability of resveratrol (RSV) due to presystemic metabolism can be avoided via dermal route of administration. The hydrophilic-lipophilic nature of resveratrol-phospholipid complex (RSVPs) favors the delivery of resveratrol via the skin. The RSVPs embedded polymeric patch with moderate adhesiveness was developed for dermal application for sustained anti-inflammatory effect. The prepared patches were evaluated for various physicochemical properties, surface morphology by SEM, TEM, and compatibility of patch components by FT-IR and DSC studies. The dermal flux of the optimized patch formulation was found to be at 4.28 ± 0.48 mg/cm2/24 h. The analysis of skin extract after permeation study revealed the presence of resveratrol, which confirmed the localization of RSVPs in the skin. The stability of RSVPs in the polymeric patch and the physiologic environment was confirmed by FE-SEM studies on the patches after drug release and skin permeation studies. The RSVPs particles released from the polymer matrix maintaining the structural integrity and permeate the keratinized horney layer of skin. The optimized patch formulation showed sustained anti-inflammatory effect (84.10% inhibition of inflammation at 24 h) in carrageenan-induced rat paw edema model compared to marketed diclofenac sodium gel (39.58% inhibition of inflammation at 24 h). The CLSM study confirmed the localization of RSVPs for a longer period, thus enabling drug targeting to the dermis for sustained anti-inflammatory effect. Histological studies with phase contrast trinocular microscope suggested no alteration of skin integrity and no evidence of the presence of inflammatory cells after exposure to the permeants. The patch was found to be safe for skin application as evaluated by Draize method for skin irritation scoring in a rabbit model. These results suggest the therapeutic efficacy of the developed patch in both acute and chronic inflammatory diseases.

Keywords: resveratrol-phospholipid complex, skin delivery, sustained anti-inflammatory effect, inflammatory diseases, dermal patch

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Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

Abstract:

Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L. were in-silico screened using molecular docking and pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect on the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer's therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interaction stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is a spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries toward the rational development of potent anti-Alzheimer agents.

Keywords: Alzheimer’s disease, molecular docking, Cannabis sativa L., cholinesterase inhibitors, molecular dynamics, ADMET, MM-PBSA

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Authors: Athini Ntloko

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Mycobacterium bovis and other species of Mycobacterium tuberculosis complex (MTBC) can result to a zoonotic infection known as Bovine tuberculosis (bTB). MTBC has members that may contaminate an extensive range of hosts, including wildlife. Diverse wild species are known to cause disease in domestic livestock and are acknowledged as TB reservoirs. It has been a main study worldwide to deliberate on bTB risk factors as a result and some studies focused on particular parts of risk factors such as wildlife and herd management. The significance of the study was to determine the incidence of Mycobacterium tuberculosis complex that is associated with soil, hayfeed and water. Questionnaires were administered to thirty (30) smallholding farm owners in the two villages (kwaMasele and Qungqwala) and three (3) three commercial farms (Fort Hare dairy farm, Middledrift dairy farm and Seven star dairy farm). Detection of M. tuberculosis complex was achieved by Polymerase Chain Reaction using primers for IS6110; whereas a genotypic drug resistance mutation was detected using Genotype MTBDRplus assays. Nine percent (9%) of respondents had more than 40 cows in their herd, while 60% reported between 10 and 20 cows in their herd. Relationship between farm size and vaccination for TB differed from forty one percent (41%) being the highest to the least five percent (5%). The highest number of respondents who knew about relationship between TB cases and cattle location was ninety one percent (91%). Approximately fifty one percent (51%) of respondents had knowledge about wild life access to the farms. Relationship between import of cattle and farm size ranged from nine percent (9%) to thirty five percent (35%). Cattle sickness in relation to farm size differed from forty three (43%) being the highest to the least three percent (3%); while thirty three percent (33%) of respondents had knowledge about health management. Respondents with knowledge about the occurrence of TB infections in farms were forty-eight percent (48%). The frequency of DNA isolation from samples ranged from the highest forty-five percent (45%) from water to the least twenty two percent (22%) from soil. Fort Hare dairy farm had the highest number of positive samples, forty four percent (44%) from water samples; whereas Middledrift dairy farm had the lowest positive from water, seventeen percent (17%). Twelve (22%) out of 55 isolates showed resistance to INH and RIF that is, multi-drug resistance (MDR) and nine percent (9%) were sensitive to either INH or RIF. The mutations at rpoB gene differed from 58% being the highest to the least (23%). Fifty seven percent (57%) of samples showed a S315T1 mutation while only 14% possessed a S531L in the katG gene. The highest inhA mutations were detected in T8A (80 %) and the least was observed in A16G (17%). The results of this study reveal that risk factors for bTB in cattle and dairy farm workers are a serious issue abound in the Eastern Cape of South Africa; with the possibility of widespread dissemination of multidrug resistant determinants in MTBC from the environment.

Keywords: hayfeed, isoniazid, multi-drug resistance, mycobacterium tuberculosis complex, polymerase chain reaction, rifampicin, soil, water

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Authors: Abhay Vir Singh Kanwar

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The pharmaceutical industry today is a multi-billion dollar business and yet disadvantages people in many corners of the globe who are still dying in large numbers from curable illnesses for lack of access to drugs. The astronomical prices of essential and life-saving drugs is not just an economic problem that can be settled through clever market strategies but is an ethical issue, given the accumulated wealth of today’s humanity and the sense of global justice that it increasingly comes to share. In this paper, I make a very practical argument for what I shall call ‘the ethical healthcare paradigm’, which, I propose, can replace the economistic paradigm that can still drive the healthcare sector without creating spillover effects on the market. Taking off from the ethical-philosophical argument for recognizing every individual’s right to capability to be healthy, I shall come to the focused practical proposal of the cost-rationalization and universal availability of essential, life-saving drugs through the undertaking of research and development funding for drug innovation by the business establishment as such in terms of the concept of CSR. The paper will first expose the concepts of basic and fundamental capabilities in relation to education and health, after which it will focus on the right to capability to be healthy of every person. In the third section, it will discuss the ‘ethical healthcare paradigm’ as opposed to the economistic health paradigm and will argue that the patient will have to be considered the primary stakeholder of this paradigm or the very ‘subject’ of healthcare. The next section will be on an ethical-historical critique of the pharmaceutical industry’s profit driven economism. The section after that will look at the business operation and the stages in the life cycle of a drug that comes to the market in order to understand the risks, strengths and problems of the pharmaceutical industry. Finally, the paper will discuss the concept of CSR in relation to the ethical healthcare paradigm in order to propose CSR funding in research and development for innovation on drugs so that life-saving drugs can be made available to every sick person cost-effectively.

Keywords: capability approach, healthcare, CSR, patient

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Authors: Animesh Pan, Geoffrey D. Bothun

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With the development of nanotechnology, research in multifunctional delivery systems has a new pace and dimension. An incipient challenge is to design an all-in-one delivery system that can be used for multiple purposes, including tumor targeting therapy, radio-frequency (RF-), near-infrared (NIR-), light-, or pH-induced controlled release, photothermal therapy (PTT), photodynamic therapy (PDT), and medical diagnosis. In this regard, various inorganic nanoparticles (NPs) are known to show great potential as the 'functional components' because of their fascinating and tunable physicochemical properties and the possibility of multiple theranostic modalities from individual NPs. Magnetic, luminescent, and plasmonic properties are the three most extensively studied and, more importantly biomedically exploitable properties of inorganic NPs. Although successful attempts of combining any two of them above mentioned functionalities have been made, integrating them in one system has remained challenge. Keeping those in mind, controlled designs of complex colloidal nanoparticle system are one of the most significant challenges in nanoscience and nanotechnology. Therefore, systematic and planned studies providing better revelation are demanded. We report a multifunctional delivery platform-based liposome loaded with drug, iron-oxide magnetic nanoparticles (MNPs), and a gold shell on the surface of liposomes, were synthesized using a lipid with polyelectrolyte (layersomes) templating technique. MNPs and the anti-cancer drug doxorubicin (DOX) were co-encapsulated inside liposomes composed by zwitterionic phophatidylcholine and anionic phosphatidylglycerol using reverse phase evaporation (REV) method. The liposomes were coated with positively charge polyelectrolyte (poly-L-lysine) to enrich the interface with gold anion, exposed to a reducing agent to form a gold nanoshell, and then capped with thio-terminated polyethylene glycol (SH-PEG2000). The core-shell nanostructures were characterized by different techniques like; UV-Vis/NIR scanning spectrophotometer, dynamic light scattering (DLS), transmission electron microscope (TEM). This multifunctional system achieves a variety of functions, such as radiofrequency (RF)-triggered release, chemo-hyperthermia, and NIR laser-triggered for photothermal therapy. Herein, we highlight some of the remaining major design challenges in combination with preliminary studies assessing therapeutic objectives. We demonstrate an efficient loading and delivery system to significant cell death of human cancer cells (A549) with therapeutic capabilities. Coupled with RF and NIR excitation to the doxorubicin-loaded core-shell nanostructure helped in securing targeted and controlled drug release to the cancer cells. The present core-shell multifunctional system with their multimodal imaging and therapeutic capabilities would be eminent candidates for cancer theranostics.

Keywords: cancer thernostics, multifunctional nanostructure, photothermal therapy, radiofrequency targeting

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Authors: C. Panebianco, K. Adamberg, S. Adamberg, C. Saracino, M. Jaagura, K. Kolk, A. Di Chio, P. Graziano, R. Vilu, V. Pazienza

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Background/Aims: Despite recent advances in treatment options, a modest impact on the outcome of the pancreatic cancer (PC) is observed so far. Short-term fasting cycles have the potential to improve the efficacy of chemotherapy against PC. However, diseased people may refuse to follow the fasting regimen and fasting may worsen the weight loss often occurring in cancer patients. Therefore, alternative approaches are needed. The aim of this study was to assess the effect of Engineered Low glycemic food ELGIF mimicking diet on growth of cancer cell lines in vitro and in an in vivo pancreatic cancer mouse xenograft model. Materials and Methods: BxPC-3, MiaPaca-2 and Panc-1 cells were cultured in control and ELGIF mimicking diet culturing condition to evaluate the tumor growth and proliferation pathways. Pancreatic cancer xenograft mice were subjected to ELGIF to assess the tumor volume and weight as compared to mice fed with control diet. Results: Pancreatic cancer cells cultured in ELGIF mimicking medium showed decreased levels of proliferation as compared to those cultured in the standard medium. Consistently, xenograft pancreatic cancer mice subjected to ELGIF diet displayed a significant decrease in tumor growth. Conclusion: A positive effect of ELGIF diet on proliferation in vitro is associated with the decrease of tumor progression in the in vivo PC xenograft mouse model. These results suggest that engineered dietary interventions could be supportive as synergistic approach to enhance the efficacy of existing cancer treatments in pancreatic cancer patients.

Keywords: functional food, microbiota, mouse model, pancreatic cancer

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Authors: Aniya Everette

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In June of 1971, President Richard Nixon made his first public declaration regarding the “War on Drugs,” deeming it America’s number one public enemy. Since then, the drug war has been a divisive topic in the US. Black and brown children have been unfairly targeted and imprisoned at alarming rates as a result of this policy, which has had a negative effect on them. Black and Latino youth have faced significant obstacles that have impacted their educational opportunities, employment prospects, and general quality of life due to harsh mandatory sentences, aggressive policing tactics, and racial profiling.

Keywords: war, drugs, crime, racial profiling

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Authors: Said Abdirasak Abidrahman, Ibrahim Mohamed

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Background: Urinary Tract Infections (UTIs) are the commonest infections described among diabetes mellitus patients. More often, empirical antimicrobial therapy is initiated before the laboratory results are made available with minimal treatment success. The knowledge of the etiology and antibiotic susceptibility patterns of the organisms causing urinary tract infections among diabetes mellitus patients remains scarce, despite its vitality. This study sought to determine the prevalence, bacteria species, and drug susceptibility patterns of common causes of urinary tract infections among diabetes mellitus patients attending Bosaso health centers. Materials and methods: We conducted a cross-sectional study involving adult diabetic patients at Bosaso health centers between the months of May and July 2020. Laboratory assay of mid-stream urine samples was done to isolate bacteria causes of UTIs. These were biochemically identified using Gram stain, Kligler iron agar (KIA), Indole test, citrate, urea, coagulase, catalase, motility agar, and lysine iron agar. Their antibiotic susceptibility pattern for the isolated organisms was made for Ampicillin 10μg, Ciprofloxacin 5μg, Cotrimoxazole 25μg, Gentamycin 10μg, Ceftriaxone 10μg, and determined using the Kirby Bauer Disc Diffusion method. Results: Of 177 participants, 69 (39.0%) were males and 108 (61.0%) were females. Their mean age was 33.1 years (range; 18-67 years). Of these, 14.7% (26/177) of the samples revealed significant growth (>= 105 CFU/mL) giving a prevalence of 14.9 % (95% CI: 10.6 to 16.3). The organisms isolated were Escherichia coli -50% (N=13), Klebsiella pneumonia 30.8% (N=8), Staphylococcus aureus 15.4% (N=4), and unidentified organism 3.8% (N=1), and these were associated with such socio-demographic factors like history of catheterization and sexual activity. Antibiotic susceptibility to the commonly used agents for treating UTIs indicated higher sensitivity to Gentamicin and Ceftriaxone.

Keywords: antimicrobials, bacteria, urinary tract infections, diabetes

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Authors: Syeda Sahra, Abdullah Jahangir, Rachelle Hamadi, Ahmad Jahangir, Allison Glaser

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Background: Antimicrobial resistance is on the rise. The use of redundant and inappropriate antibiotics is contributing to recurrent infections and resistance. Newer antibiotics with more robust coverage for gram-negative bacteria are in great demand for complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), hospital-acquired bacterial pneumonia (H.A.B.P.), and ventilator-associated bacterial pneumonia (V.A.B.P.). Objective: We performed this meta-analysis to evaluate the efficacy and safety profile of a new antibiotic, Imipenem/cilastatin/relebactam, compared to other broad-spectrum antibiotics for complicated infections. Search Strategy: We conducted a systemic review search on PubMed, Embase, and Central Cochrane Registry. Selection Criteria: We included randomized clinical trials (R.C.T.s) with the standard of care as comparator arm with Imipenem/cilastatin/relebactam as intervention arm. Analysis: For continuous variables, the mean difference was used. For discrete variables, we used the odds ratio. For effect sizes, we used a confidence interval of 95%. A p-value of less than 0.05 was used for statistical significance. Analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic. Results: The authors observed similar efficacy at clinical and microbiologic response levels on early follow-up and late follow-up compared to the established standard of care. The incidence of drug-related adverse events, serious adverse events, and drug discontinuation due to adverse events were comparable across both groups. Conclusion: Imipenem/cilastatin/relebactam has a non-inferior safety and efficacy profile compared to peer antibiotics to treat severe bacterial infections (cUTIs, cIAIs, H.A.B.P., V.A.B.P.).

Keywords: bacterial pneumonia, complicated intra-abdominal infections, complicated urinary tract infection, Imipenem, cilastatin, relebactam

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Authors: Sathvika Reddy, Devi Revathi

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Background: In India, deliberate self-harm (DSH) with poisoning agents carries a significant impact on morbidity and mortality. Changes in the patterns of poisoning vary across various geographical locations. It is important to know the patterns in a given region in order to facilitate rapid clinical diagnosis, appropriate treatment to reduce associated morbidity and mortality. Aim and Objective: To study the patterns, treatment outcomes of acute poisoning in patients admitted to emergency wards in a tertiary care hospital and to provide poison information services. Materials and Methods: This study was conducted at M.S Ramaiah Memorial and Teaching Hospital from November 2016 to March 2017. The patient’s data was obtained from patient case sheet, interaction with health care professionals, interviewing patients and their caretakers (if possible), and were documented in a suitably designed form. Results: The study involved 131 patients with a mean age of 27.76 ± 15.5 years. Majority of the patients were in the age group 21-30 years, literates (n=53) dwelling in urban (n=113) areas belonging to upper middle class (n=50). Analgesics and antipyretics were commonly utilized in intentional drug overdosage (n=49). Envenomation constituted n=21(16.03%). Furthermore, a significant relationship was observed between marital status and self-poisoning (n=64) (P < 0.001) which commonly occurred through oral ingestion. The outcomes were correlated with the GCS and PSS system and n=85 recovered, n=17 were discharged against medical advice, and n=4 died, and n=4 were lost to follow up respectively. The poison information queries include drug overdose (n=29) and management related queries (n=22) provided majorly by residents (n=45) to update knowledge (n=11) and for better patient care (n=40). Conclusion: The trend in poisoning is dynamic. Medications were identified as the main cause of poisoning in urban areas of India. Educational programs with more emphasis on preventive measures are necessary to create awareness among the general public.

Keywords: poisoning, suicides, clinical pharmacist, envenomation, poison information services

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Authors: Shrawan Baghel, Helen Cathcart, Biall J. O'Reilly

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Amorphous drug formulations have great potential to enhance solubility and thus bioavailability of BCS class II drugs. However, the higher free energy and molecular mobility of the amorphous form lowers the activation energy barrier for crystallization and thermodynamically drives it towards the crystalline state which makes them unstable. Accurate determination of the crystallization tendency/kinetics is the key to the successful design and development of such systems. In this study, dipyridamole (DPM) and cinnarizine (CNZ) has been selected as model compounds. Thermodynamic fragility (m_T) is measured from the heat capacity change at the glass transition temperature (Tg) whereas dynamic fragility (m_D) is evaluated using methods based on extrapolation of configurational entropy to zero 〖(m〗_(D_CE )), and heating rate dependence of Tg 〖(m〗_(D_Tg)). The mean relaxation time of amorphous drugs was calculated from Vogel-Tammann-Fulcher (VTF) equation. Furthermore, the correlation between fragility and glass forming ability (GFA) of model drugs has been established and the relevance of these parameters to crystallization of amorphous drugs is also assessed. Moreover, the crystallization kinetics of model drugs under isothermal conditions has been studied using Johnson-Mehl-Avrami (JMA) approach to determine the Avrami constant ‘n’ which provides an insight into the mechanism of crystallization. To further probe into the crystallization mechanism, the non-isothermal crystallization kinetics of model systems was also analysed by statistically fitting the crystallization data to 15 different kinetic models and the relevance of model-free kinetic approach has been established. In addition, the crystallization mechanism for DPM and CNZ at each extent of transformation has been predicted. The calculated fragility, glass forming ability (GFA) and crystallization kinetics is found to be in good correlation with the stability prediction of amorphous solid dispersions. Thus, this research work involves a multidisciplinary approach to establish fragility, GFA and crystallization kinetics as stability predictors for amorphous drug formulations.

Keywords: amorphous, fragility, glass forming ability, molecular mobility, mean relaxation time, crystallization kinetics, stability

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Authors: Zehour Rahmani, Messouda Dekmouche, Mohamed Hadjadj, Mokhtar Saidi

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In the last decades of the nineteenth century, the study of disease – causing microorganisms became concentrated on bacteria and largely institutionalized. In earlier years, the scientists interested in bacteria had originally been chemists like Pasteur, physicists like Tyndall, or botanists like Cohn and ward. For this reason, the objective of this research was to evaluate the potential of some dithiolethiones on standard microorganism strains as well as multi-drug resistant bacteria, which were isolated from hospitals. Recent studies have demonstrated, that several dithiolethione compounds, particularly (3H-1,2-dithiole-3-thione), exhibit the biological activities against several bacteria.

Keywords: bacteria, dithiolethiones, microorganism, potential

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Authors: Adel S. El-Azab, Alaa A. M. Abdel-Aziz, Ibrahim A. Al-Suwaidan, Amer M. Alanazi

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A novel series of 2,3,6-trisubstitute quinazolinone were designed, synthesized, and evaluated for their in-vitro antitumor activity. 3 (Benzylideneamino)-6-chloro-2-p-tolylquinazolin-4(3H)-One, 2-[(4-oxo-3-phenethyl-3,4-dihydroquinazolin-2-yl)thio]-N-(3,4;5-trimethoxyphenyl) acetamide and 3-(3-benzyl-6-methyl-4-oxo-3, 4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl) propanamide have shown amazing broad spectrum antitumor activity with mean GI50; 15.8, 3.16, and 7.4 μM respectively compared to known Quinazoline Derivatives antitumor drug 5-FU mean GI50=22.6 μM.

Keywords: quinazoline derivatives, in vitro antitumor, synthesis, 5-FU, NCI

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Authors: Sina Alimohammadi, Mahnaz Banihashemi, Maryam Poursharif

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Demodex is a mandatory parasite of pilosebaceous. D. folliculorum lives as a single parasite or as a number of parasites in hair follicles, and D. brevis as a single parasite living in sebaceous glands. Transmission of Demodex from one person to another requires direct skin contact; it also has a greater density in the forehead, cheeks, nose, and nasolabial folds. Demodex can cause some clinical symptoms such as follicular pityriasis, rosacea-like demodicosis, postural folliculitis, papules, seborrheic dermatitis, blepharitis, dermatitis around the lips, and hyperpigmented spots. In this study, the prevalence of Demodex species in patients referred to the dermatology department of Sayad Shirazi Hospital Gorgan, Iran, in the years 2019-2020 was investigated. Material and Methods: The study population consisted of 242 samples taken from the people referred to the dermatology department of Sayad Shirazi Hospital during the years 2019-2020, which were sampled by adhesive tape. All of the participants completed the questionnaires. The samples were examined microscopically for the presence of Demodex. Results: Out of 242 participants, 67 (27.68%) were infected with Demodex. Most cases of infection were observed in the group of 21 to 30 years (28 people; 11.57%) and then in the group of 31 to 40 years (21 people; 8.67%). Also, in the group of people under 10 years and over 60 years, no positive cases (0%) of Demodex were observed in microscopic examinations. Out of 11 variables, there was a statistically significant difference in relation to the three variables of age (P = 0.000003), use of cleansing solutions (P = 0.002), and the presence of acne (P = 0.0013). Conclusion: According to the results of this study, it was found that the incidence of Demodex in one group of acne patients is higher than in others, which emphasizes the possible role of Demodex in the pathogenesis of acne. In this study, there was an inverse relationship between the incidence of Demodex and the use of skin cleansing solutions. Also, the prevalence of Demodex is higher in the group of 20-30 years, and its prevalence does not increase with age. Due to the possibility of drug resistance in the future, regular studies on genotyping and drug resistance are recommended.

Keywords: acne, demodex, mite, prevalence

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Authors: Rawia M. Khalil, Ahmed A. Abd El Rahman, Mahfouz A. Kassem, Mohamed S. El Ridi, Mona M. Abou Samra, Ghada E. A. Awad, Soheir S. Mansy

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Solid lipid nanoparticles (SLNs) have gained great attention for the topical treatment of skin associated fungal infection as they facilitate the skin penetration of loaded drugs. Our work deals with the preparation of nystatin loaded solid lipid nanoparticles (NystSLNs) using the hot homogenization and ultrasonication method. The prepared NystSLNs were characterized in terms of entrapment efficiency, particle size, zeta potential, transmission electron microscopy, differential scanning calorimetry, rheological behavior and in vitro drug release. A stability study for 6 months was performed. A microbiological study was conducted in male rats infected with Candida albicans, by counting the colonies and examining the histopathological changes induced on the skin of infected rats. The results showed that SLNs dispersions are spherical in shape with particle size ranging from 83.26±11.33 to 955.04±1.09 nm. The entrapment efficiencies are ranging from 19.73±1.21 to 72.46±0.66% with zeta potential ranging from -18.9 to -38.8 mV and shear-thinning rheological Behavior. The stability studies done for 6 months showed that nystatin (Nyst) is a good candidate for topical SLN formulations. A least number of colony forming unit/ ml (cfu/ml) was recorded for the selected NystSLN compared to the drug solution and the commercial Nystatin® cream present in the market. It can be fulfilled from this work that SLNs provide a good skin targeting effect and may represent promising carrier for topical delivery of Nyst offering the sustained release and maintaining the localized effect, resulting in an effective treatment of cutaneous fungal infection.

Keywords: candida infections, hot homogenization, nystatin, solid lipid nanoparticles, stability, topical delivery

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Authors: Hanna Teklu Gebregziabher

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Background: A variety of techniques for medical termination of second-trimester pregnancy can be used, but there is no consensus about which is the best. Even though most evidence suggests the combined use of intracervical Foley catheter and vaginal misoprostol is safe, effective, and acceptable method for termination of second-trimester pregnancy, which is comparable to mifepristone-misoprostol combination regimen with lower cost and no additional maternal risks. The use of mifepristone and misoprostol alone with no other procedure is still the most common procedure in different institutions for 2nd-trimester pregnancy. Methods: A cross-sectional comparative prospective study design is employed on women who were admitted for 2nd-trimester medical abortion and medical abortion failed or if there was no change in cervical status after 24 hours of 1st dose of misoprostol. The study was conducted at St. Paulose Hospital Millennium Medical College. A sample of 44 participants in each arm was necessary to give a two-tailed test, a type 1 error of 5%, 80% statistical power, and a 1:1 ratio among groups. Thus, a total of 94 cases, 47 from each arm, were recruited. Data was entered and cleaned by using Epi-info and analyzed using SPSS version 29.0 statistical software and was presented in descriptive and tabular forms. Different variables were cross-tabulated and compared for significant differences and statistical analysis using the chi-square test and independent t-test, to conclude. Result: There was a significant difference between the two groups on induction to expulsion time and number of doses used. The mean ± SD of induction to expulsion time for those used misoprostol alone was 48.09 ± 11.86 and those who used trans-cervical catheter sequentially with misoprostol were 36.7 ±6.772. Conclusion: The use of a trans-cervical Foley catheter in conjunction with misoprostol in a sequential manner is a more effective, safe, and easily accessible procedure. In addition, the cost of utilizing the catheter is less compared to the cost of misoprostol and is readily available. As a good substitute, we advised using Trans-cervical Catether even for medical abortions performed in the second trimester.

Keywords: second trimester, medical abortion, catheter, misoprostol

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Authors: P. Mukhopadhyay, N. C. Dey

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Occupational health hazard is a very common term in every emerging country. Along with the unorganized sector, most organized sectors including government industries are suffering from this affliction. In addition to workload, the seasonal changes also have some impacts on working environment. With this focus in mind, one hundred male industrial workers, who are directly involved to the task of Periodic Overhauling (POH) in a fabricating workshop in the public domain are selected for this research work. They have been studied during work periods throughout different seasons in a year. For each and every season, the participants working heart rate (WHR) is measured and compared with the standards given by different national and internationally recognized agencies i.e., World Health Organization (WHO) and American Conference of Governmental Industrial Hygienists (ACGIH) etc. The different environmental parameters i.e. dry bulb temperature (DBT), wet bulb temperature (WBT), globe temperature (GT), natural wet bulb temperature (NWB), relative humidity (RH), wet bulb globe temperature (WBGT), air velocity (AV), effective temperature (ET) are recorded throughout the seasons to critically observe the effect of seasonal changes on the WHR of the workers. The effect of changes in environment to the WHR of the workers is very much surprising. It is found that the percentages of workers who belong to the ‘very heavy’ workload category are 83.33%, 66.66% and 16.66% in the summer, rainy and winter seasons, respectively. Ongoing undertaking of this type of job profile forces the worker towards occupational disorders causing absenteeism. This occurrence results in lower production rates, and on the other hand, costs due to medical claims also weaken the industry’s economic condition. In this circumstance, the authors are trying to focus on some remedial measures from the ergonomic angle by proposing a new work/ rest regimen and introducing engineering controls along with management controls which may help the worker, and consequently, the management also.

Keywords: workload, working heart rate, occupational health hazard, industrial worker

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Authors: Haftay Abraha Tadesse

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Background: Staphylococcus is a genus of worldwide distributed bacteria correlated to several infectious of different sites in human and animals. They are among the most important causes of infection that are associated with the consumption of contaminated food. Objective: The objective of this study was to determine the isolates, antimicrobial susceptibility patterns and public health significance for Staphylococcus aureus in raw meat from butchery and abattoir houses of Mekelle, Northern Ethiopia. Methodology: A cross-sectional study was conducted from April to October 2019. Sociodemographic data and public health significance were collected using predesigned questionnaire. The raw meat samples were collected aseptically in the butchery and abattoir houses and transported using ice box to Mekelle University, College of Veterinary Sciences for isolating and identification of Staphylococcus aureus. Antimicrobial susceptibility tests were determined by disc diffusion method. Data obtained were cleaned and entered in to STATA 22.0 and logistic regression model with odds ratio were calculated to assess the association of risk factors with bacterial contamination. P-value < 0.05 was considered as statistically significant. Results: In present study, 88 out of 250 (35.2%) were found to be contamination with Staphylococcus aureus. Among the raw meat specimens to be positivity rate of Staphylococcus aureus were 37.6% (n=47) and (32.8% (n=41), butchery and abattoir houses, respectively. Among the associated risk factories not using gloves reduces risk was found to (AOR=0.222; 95% CI: 0.104-0.473), Strict Separation b/n clean & dirty (AOR= 1.37; 95% CI: 0.66-2.86) and poor habit of hand washing (AOR=1.08; 95%CI: 0.35-3.35) were found to be statistically significant and ha ve associated with Staphylococcus aureus contamination. All isolates thirty sevevn of Staphyloco ccus aureus were checked displayed (100%) sensitive to doxycycline, trimethoprim, gentamicin, sulphamethoxazole, amikacin, CN, Co trimoxazole and nitrofurantoi. whereas the showed resistance of cefotaxime (100%), ampicillin (87.5%), Penicillin (75%), B (75%), and nalidixic acid (50%) from butchery houses. On the other hand, all isolates of Staphylococcus aur eu isolate 100% (n= 10) showed sensitive chloramphenicol, gentamicin and nitrofurantoin whereas the showed 100% resistance of Penicillin, B, AMX, ceftriaxone, ampicillin and cefotaxime from abattoirs houses. The overall multi drug resistance pattern for Staphylococcus aureus were 90% and 100% of butchery and abattoirs houses, respectively. Conclusion: 35.3% Staphylococcus aureus isolated were recovered from the raw meat samples collected from the butchery and abattoirs houses. More has to be done in the developed of hand washing behavior, and availability of safe water in the butchery houses to reduce burden of bacterial contamination. The results of the present finding highlight the need to implement protective measures against the levels of food contamination and alternative drug options. The development of antimicrobial resistance is nearly always as a result of repeated therapeutic and/or indiscriminate use of them. Regular antimicrobial sensitivity testing helps to select effective antibiotics and to reduce the problems of drug resistance development towards commonly used antibiotics. Key words: abattoir houses, antimicrobial resistance, butchery houses, Ethiopia,

Keywords: abattoir houses, antimicrobial resistance, butchery houses, Ethiopia, staphylococcus aureuse, MDR

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